Invasive Mechanical Ventilation-General

Indications for Endotracheal Intubation and Invasive Mechanical Ventilation (see also Endotracheal Intubation)

Inability to Maintain Airway Patency and/or Reflexes

Upper Airway Obstruction

Lower Airway Obstruction

  • Mucous Plugging with Inability to Clear Secretions
  • Massive Hemoptysis (see Hemoptysis)

Respiratory Failure (see Respiratory Failure)

Type I Hypoxemic Respiratory Failure

Type II Hypoxemic, Hypercapnic Respiratory Failure

  • Acute Hypoxemic, Hypercapnic Respiratory Failure (Acute Hypoventilation, Acute Ventilatory Failure)
    • Decreased Ventilatory Drive
    • Decreased Ventilatory Output Due to Neuromuscular Disease
    • Decreased Ventilatory Output Due to Excessive Ventilatory Demand
  • Chronic Hypoxemic, Hypercapnic Respiratory Failure (Chronic Hypoventilation, Chronic Ventilatory Failure)
    • Decreased Ventilatory Drive
    • Decreased Ventilatory Output Due to Neuromuscular Disease
    • Decreased Ventilatory Output Due to Excessive Ventilatory Demand

Physiology

Physiologic/Clinical Benefits of Positive-Pressure Mechanical Ventilation

Positive-Pressure Mechanical Ventilation Decreases the Work of Breathing

  • Increased Work of Breathing (with the Development of Respiratory Muscle Fatigue) is a Common Feature of Various Types of Respiratory Failure
  • Depending on the Mode/Settings Utilized, Mechanical Ventilation Can Assume Part or All of the Work of Breathing, Allowing the Respiratory Muscles Time to Recover from Fatigue (Am J Med, 1982) [MEDLINE] (Intensive Care Med, 1998) [MEDLINE]

Positive-Pressure Mechanical Ventilation Improves V/Q Mismatch

  • Improvement in V/Q Mismatch on Positive-Pressure Mechanical Ventilation is a Summation of the Following Two Competing Mechanisms
    • Positive-Pressure Mechanical Ventilation Worsens Physiologic (Alveolar) Dead Space (by Distending Alveoli Which May Be Poorly Perfused, Resulting in High V/Q Areas of the Lung)
      • Dead Space = Anatomic Dead Space + Physiologic (Alveolar) Dead Space
      • Note that Positive-Pressure Mechanical Ventilation Does Not Alter the Anatomic Dead Space
    • Positive-Pressure Mechanical Ventilation (Especially with the Application of PEEP) Decreases Atelectasis, Resulting in Decreased Physiologic Shunt
      • Shunt = areas of the lung which are underventilated, relative to perfusion (i.e. areas with low V/Q ratios)

Positive-Pressure Mechanical Ventilation Improves Left Ventricular Failure (see Congestive Heart Failure)

  • Positive-Pressure Mechanical Ventilation Decreases Venous Return to the Right Side of the Heart (Preload) and Decreases Left Ventricular Afterload (NEJM, 1991) [MEDLINE]
    • Hemodynamic Effects of Positive-Pressure Mechanical Ventilation are Due to Transmission of the Airway Pressure to the Adjacent Thoracic Structures
      • Transmission is Greatest When There is Low Chest Wall Compliance (Due to Fibrothorax, etc) or High Chest Wall Compliance (Due to COPD, etc)
      • Transmission is Least When There is High Chest Wall Compliance (Due to Sternotomy, etc) or Low Lung Compliance (Due to ARDS, Pulmonary Edema, etc)

Heterogeneity of Ventilation While on Positive-Pressure Mechanical Ventilation

  • Distribution of Ventilation (While on Positive-Pressure Mechanical Ventilation) is Heterogenous Due to Regional Differences in Alveolar Compliance, Airway Resistance, and Dependency (Upper Lung Zone vs Lower Lung Zone)
    • More Compliant Lung Zones with Low Airway Resistance Will Be the Most Ventilated (and Most Distended), While Less Compliant Lung Zones with High Airway Resistance Will Be the Least Ventilated (and Least Distended)

Technique

Negative Pressure Ventilation vs Positive Pressure Ventilation

  • Negative Pressure Ventilation
    • Concept
      • Negative Pressure is Created Around the Chest Wall, Resulting in Negative Intrapleural Pressure
      • “Pulls” Air into the Airways
    • Examples:
      • Cuirass Ventilation
      • Iron Lung Ventilation
    • Advantages
      • Mimics the Normal Respiratory Physiologic Function Which Normally Occurs with Diaphragmatic Contraction
    • Disadvantages
      • Negative Pressure within the Airway During Inspiration (without an Endotracheal Tube) Predisposes Upper Airway Collapse
      • Lack of Endotracheal Tube Impairs Access to the Lower Airways (Via Bronchoscopy, etc) to Facilitate Sampling and Secretion Clearance
  • Positive Pressure Ventilation
    • Concept
      • Positive Pressure is Created at Mouth or Proximal End of Endotracheal Tube, Resulting in Positive Intra-Airway Pressure
      • “Pushes” Air into the Airways
    • Examples
    • Advantages
      • Presence of Endotracheal Tube Allows Protection of Upper Airway and Access to Lower Airways (Via Bronchoscopy, etc) to Facilitate Sampling and Clearance)
    • Disadvantages
      • Less Physiologic, as Compared to Normal Respiratory Physiologic Function
      • Requires Close Monitoring of Pressure and Volume Being Utilized to Avoid Lung Injury

Volume-Cycled vs Pressure-Cycled Ventilation

  • Volume-Cycled Ventilation
    • Mechanism of Delivery: delivers a pre-determined volume (VT) at a set inspiratory flow rate and respiratory rate (RR), allowing exhalation when volume is reached (resultingly, airway pressure is determined by lung mechanics or patient effort)
    • Advantages
      • Providers are More Familiar with Volume-Cycled Ventilator Modes, Facilitating Troubleshooting
      • Decreased Lung Compliance (Pneumothorax, etc) During Volume-Cycled Ventilation Results in Easily Recognizable Increase in Peak Inspiratory Pressure (PIP)
    • Disadvantages
      • Inappropriately Large Tidal Volume (VT) May Result in High Peak Inspiratory Pressure (PIP) and Increased Plateau Pressure (Pplat), the Latter of Which is Most Associated with an Increased Risk of Barotrauma)
    • Examples of Volume-Cycled Ventilation Modes
      • Assist-Control (AC)
      • Synchronous Intermittent Mandatory Ventilation (SIMV)
      • Pressure-Regulated Volume Control (PRVC)
  • Pressure-Cycled Ventilation
    • Mechanism of Delivery: delivers a pre-determined pressure (resultingly, VT is determined by lung mechanics or patient effort)
    • Advantages
      • Increased Patient Comfort
    • Disadvantages
      • Providers are Less Familiar with Volume-Cycled Ventilator Modes, Complicating Troubleshooting
      • Decreased Lung Compliance (Pneumothorax, etc) During Pressure-Cycled Ventilation Results in a Less Recognizable Decrease in Tidal Volume (VT)
    • Examples of Pressure-Cycled Ventilation Modes
      • Pressure-Control (PC)
      • Pressure Support (PS)
  • Clinical Efficacy: data suggest no significant differences in work of breathing, mortality rate, or oxygenation between volume-cycled vs pressure-cycled ventilation
    • Randomized Trial of Volume-Cycled vs Pressure-Cycled Ventilation in Severe Respiratory Failure (Crit Care Med, 1994) [MEDLINE]
      • Early Initiation of Pressure-Limited Ventilation was Associated with Lower Peak Airway Pressure and More Rapid Clinical Improvement in Static Thoracic Compliance than Volume-Cycled Ventilation
    • Prospective, Observational Study of Pressure-Cycled vs Volume-Cycled Ventilation in ARDS (Chest, 2002) [MEDLINE]
      • Pressure Control Ventilation Generated Lower Peak Pressures and May Have Homogenized Gas Distribution and Avoided Regional Overdistention
    • Trial of Pressure-Cycled vs Volume-Cycled Ventilation in Acute Respiratory Failure (Eur Respir J, 2002) [MEDLINE]
      • No Difference in Work of Breathing and Gas Exchange (at a Fixed Tidal Volume and Peak Inspiratory Flow)

Variables Involved in Positive-Pressure Ventilation

  • Trigger (What Initiates the Breath)
    • Patient Effort (Detected as Either a Pressure or Flow Change): this is the trigger for patient-initiated breaths
    • Set Machine Timer at a Set Respiratory Rate: this is the trigger for ventilator-initiated breaths
  • Target (What Controls Gas Delivery During the Breath)
    • Set Flow Rate (Such as the Peak Inspiratory Flow Rate)
    • Set Inspiratory Pressure
  • Cycle (What Terminates the Breath)
    • Set Tidal Volume
    • Set Inspiratory Time
    • Set Flow Rate
    • Airway Pressure: may be used a backup safety cycle variable in some cases

Trigger

  • General Comments
    • Trigger Should Be Set to Allow the Patient to Easily Trigger the Initiation of a Breath (Anesthesiology, 1988) [MEDLINE]
  • Pressure Triggering: patient attempting to initiate a breath results in a negative airway pressure with sensing by the demand valve
    • Trigger Sensitivity is Typically Set at -1 to -3 cm H2O): ventilator-assisted breaths will be initiated when the alveolar pressure decreases to 1-3 cm H2O below atmospheric pressure
    • Pressure Triggering May Be Used in AC and SIMV Modes
    • Problems with Pressure Triggering
      • Trigger Sensitivity Set Too High (i.e -1 cm H2O) May Result in the Inappropriate Triggering in Response to Cardiac Oscillations, Patient Movement, Water Moving in the Ventilator Tubing, etc
      • Trigger Sensitivity Set Too Low (i.e. -4 cm H2O) May Result in Increased Work of Breathing or a Delay for the Patient to Trigger a Breath (and Therefore, Dyssynchrony)
      • Presence of Auto-PEEP Impairs Pressure Triggering (and Therefore, Can Produce Dyssynchrony), Since the Patient Needs to First Overcome the Positive End-Expiratory Pressure to Trigger the Breath
  • Flow Triggering: uses monitoring of a continuous flow of gas through the ventilator circuit, such that when the patient attempts to initiate a breath with generation of negative airflow, the ventilator breath is initiated when the return flow is less than the delivered flow
    • Trigger Sensitivity is Typically set at 2L/min
    • Flow Triggering May Be Used in CPAP, PS, AC, and SIMV Modes
    • Flow Triggering
      • Flow Triggering Decreases Work of Breathing in CPAP and During Spontaneous Breaths in SIMV (Crit Care Med, 1989) [MEDLINE] (Crit Care Med, 1994) [MEDLINE] (Am J Respir Crit Care Med, 1995) [MEDLINE] (Crit Care Med, 2000) [MEDLINE]
      • Flow Triggering Decreases Work of Breathing During IMV (Crit Care Med, 1994) [MEDLINE]
      • Flow Triggering Decreases Work of Breathing During PS (Am J Respir Crit Care Med, 1998) [MEDLINE]
      • Flow Triggering Does Not Decrease the Work of Breathing During AC (Am J Respir Crit Care Med, 1998) [MEDLINE]

Tidal Volume

Clinical Efficacy-Tidal Volume Setting in Patients without Acute Respiratory Distress Syndrome (ARDS)

  • Randomized IMPROVE Trial Examining Intraoperative Low Tidal Volume Ventilation in Patients Undergoing Major Abdominal Surgery (NEJM, 2013) [MEDLINE]
    • Intraoperative Low Tidal Volume Ventilation (6-8 mL/kg PBW, PEEP 6-8 cm H2O, Recruitment Maneuvers q30 min) was Associated with Decreased Adverse Pulmonary/Extrapulmonary Events, Decreased Need for Mechanical Ventilation and Decreased Hospital Length of Stay in Intermediate and High-Risk Patients Undergoing Major Abdominal Surgery
    • Lung Protective Strategy Did Not Decrease the Development of ARDS or Impact the Mortality Rate
  • Meta-Analysis of Low Tidal Volume Ventilation in Non-ARDS Patients (JAMA, 2012) [MEDLINE]: n= 2,822 (20 studies)
    • Low Tidal Volume Ventilation Decreased the Development of Lung Injury and Decreased the Mortality Rate
  • Systematic Review of Low Tidal Volume Ventilation in Non-ARDS Patients (Crit Care Med, 2015) [MEDLINE]
    • Low Tidal Volume Ventilation Decreased Pulmonary Complications
  • Meta-Analysis of Low Tidal Volume Ventilation in Patients without ARDS (Intensive Care Med, 2014) [MEDLINE]
    • Use of Lower Tidal Volumes in Patients without ARDS at the Onset of Mechanical Ventilation Could Be Associated with a Shorter Duration of Ventilation
    • Use of Lower Tidal Volumes Seems No to Affect Sedation or Analgesia Needs, But This Must Be Confirmed in a Robust, Well-Powered Randomized Controlled Trial
  • Meta-Analysis of Efficacy of Intraoperative Low Tidal Volume Ventilation in Preventing Postoperative Pulmonary Complications (Ann Surg, 2016) [MEDLINE]: n = 1054 (16 studies)
    • Intraoperative Low Tidal Volume Ventilation in Conjunction with PEEP and Recruitment Maneuvers Improved Clinical Pulmonary Outcomes (Atelectasis, Lung Infection, Acute Lung Injury) and Decreased Hospital Length of Stay in Otherwise Healthy Patients Undergoing General Surgery
  • PReVENT Trial Comparing Low (7 mL/kg PBW) vs Intermediate (9 mL/kg PBW) Tidal Volume Ventilation in ICU Patients at Risk for ARDS (JAMA, 2018) [MEDLINE]: n = 961 (6 centers)
    • Study Design
      • Randomized Patients Not Expected to Be Extubated within 24 hrs (Majority were Randomized within 1 hr of Start of Mechanical Ventilation)
      • Low Tidal Volume Group Used Higher Tidal Volume (7 mL/kg PBW) than in Other Similar Studies (Which Generally Used 6 mL/kg PBW), Because Pressure Support was Used More Frequently in this Group
      • By Day 1, 58% of Patients in the Low Tidal Volume Group were Receiving Pressure Support Ventilation (Which Allowed Large Spontaneous Tidal Volumes if the Patients were on Minimal Ventilatory Support)
      • On Day 1, 59% of Patient in the Low Tidal Volume Group Received a Tidal Volume >6 mL/kg PBW and 14% of Patients Received a Tidal Volume >9.5 mL/kg PBW
      • On Days 1 and 2, Respectively, Estimates Suggest that Only 25% of Patients in the Intermediate Tidal Volume Group Received Tidal Volumes >10 mL/kg PBW
    • In ICU Patients without ARDS, There was No Difference Between Low Tidal Volume Ventilation Strategy (7 mL/kg PBW) and Intermediate Tidal Volume Ventilation Strategy (9 mL/kg PBW), in Terms of Ventilator-Free Days at Day 28
    • In ICU Patients without ARDS, There was No Difference Between Low Tidal Volume Ventilation Strategy (7 mL/kg PBW) and Intermediate Tidal Volume Ventilation Strategy (9 mL/kg PBW), in Terms of ICU Length of Stay, Hospital Length of Stay, 90-Day Mortality, Incidence of ARDS, Incidence of Pneumonia, Incidence of Severe Atelectasis, and Incidence of Pneumothorax
    • Possible Explanations for Lack of Effect of the Low Tidal Volume Ventilation Strategy
      • The Low Tidal Volume Ventilation Strategy was Associated with Respiratory Acidosis, Which Might Have Influenced the Duration of Ventilation
      • Driving Pressure in the Intermediate Volume Ventilation Strategy was Still within a Protective Range for Patients without ARDS
    • Critique
      • Some Experts Have Suggested that the PReVENT Trial Demonstrates that a Negative Trial May Be the Result of Inadequate Separation Between Interventions
  • Spanish Randomized iPROVE Trial of Multiple Ventilation Strategies in Patients Undergoing Abdominal Surgery (Lancet Respir Med, 2018) [MEDLINE]: n = 1,012
    • Strategies: individualized intraoperative ventilation with individualized PEEP after a lung recruitment maneuver plus individualized postoperative CPAP, individualized intraoperative ventilation plus postoperative CPAP, and standard intraoperative ventilation plus postoperative CPAP, or standard intraoperative ventilation plus standard postoperative oxygen therapy
    • Ventilation Strategy Did Not Impact the Postoperative Complication Rate

Recommendations-Tidal Volume Setting in Patients without Acute Respiratory Distress Syndrome (ARDS)

  • Lung-Protective Ventilation Strategy with Low Tidal Volume Ventilation (6-8 mL/kg PBW) and Low Plateau Pressure (<30 cm H2O) is Probably Recommended

Clinical Efficacy-Tidal Volume Setting in Patients with Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome)

  • The Acute Respiratory Distress Syndrome Network (ARDSNet) Multicenter Randomized Trial Comparing High Tidal Volume (12 mL/kg PBW and Plateau Pressure <50 cm H2O) with Low Tidal Volume (6 mL/kg PBW and Plateau Pressure <30 cm H2O) Ventilation (NEJM, 2000) [MEDLINE]: n = 861
    • Trial was Stopped Prematurely Due to Mortality Benefit and Increased Ventilator-Free Days in Low Tidal Volume Ventilation Group
    • Low Tidal Volume Group Had Decreased Mortality Rate (31%), as Compared to High Tidal Volume Group (39.8%)
      • However, Tidal Volumes Between 6 and 12 mL/g PBW were Not Studied
    • Low Tidal Volume Group Had Increased Ventilator-Free Days During the First 28 Days (12 +/- 11), as Compared to the High Tidal Volume Group (10 +/- 11)
    • Mean Tidal Volumes Achieved on Days 1-3 in Low Tidal Volume Group were Lower (6.2 +/- 0.8 mL/kg PBW), as Compared to High Tidal Volume Group (11.8 +/- 0.8 mL/kg PBW)
    • Mean Plateau Pressures Achieved in Low Tidal Volume Group were Lower (25 +/- 6 cm H2O), as Compared to High Tidal Volume Group (33 +/- 8 cm H2O)
    • Arterial pCO2 was 4-7 mm Hg Higher in Low Tidal Volume Group, But pCO2 Never Exceeded 44 mm Hg: this is likely not clinically significant
    • FIO2 was Higher in the Low Tidal Volume Group on Days 1 and 3, Becoming Equivalent by Day 7: this suggests that the institution of low tidal volumes resulted in a transient worsening of oxygenation
    • Auto-PEEP was Higher in the Low Tidal Volume Group (Who Had Higher Respiratory Rates), Although the Difference in Median Auto-PEEP was <1 cm H2O: this is likely not clinically significant (Crit Care Med, 2005) [MEDLINE]
  • Review of Animal/Human Data from ARDS Clinical Trials Network (and Original Data) Examining if There is a Safe Upper Limit of Plateau Pressure in ARDS (Am J Respir Crit Care Med, 2005)
    • Authors Could Not Identify a Safe Upper Limit for Plateau Pressure in ARDS
  • Study of Sedative Use During Low Tidal Volume Ventilation (Crit Care Med, 2005) [MEDLINE]
    • Low Tidal Volume Ventilation Does Not Result in Increased Use of Sedatives, Opiates, or Paralytics
  • Meta-Analysis of Low Tidal Volume and Limited Airway Pressure or Higher PEEP in ALI/ARDS (Ann Intern Med, 2009) [MEDLINE]
    • Decreased Mortality with Routine Use of Low Tidal Volume, But Not High PEEP Ventilation, in Unselected Patients with ARDS or Acute Lung Injury
    • High PEEP May Help to Prevent Life-Threatening Hypoxemia in Selected Patients
  • Systematic Review of Pressure/Volume-Limited Strategies (PLoS One, 2011) [MEDLINE]: the ARDS Network trial [MEDLINE] contributed 21.4% of the weight toward the summary estimate of effect in this analysis
    • Pressure/Volume-Limited Strategies Decrease Mortality Rate and are Associated with Increased Use of Paralytics
  • Cochrane Database Review of Lung Protective Ventilation Strategies in ARDS (Cochrane Database Syst Rev, 2013) [MEDLINE]
    • Lung Protective Strategies (Low Tidal Volume or Plateau Pressure <30 cm H2O) Decrease Mortality
  • Trial Examining Predictors of Ventilator-Induced Lung Injury in ARDS (Anesthesiology, 2013) [MEDLINE]
    • Rationale: stress index describes the shape of the airway pressure-time curve profile and may indicate tidal recruitment or tidal overdistension (convex downward pressure curve indicates initial low compliance with better compliance later in the breath due to recruitment, while convex upward curve indicates overdistention -> optimal curve is straight diagonal initial pressure waveform)
    • Plateau Pressure Partitioned to the Respiratory System (Pplat,Rs) >25 cm H20 and Stress Index Partitioned to the Respiratory System (SI,Rs) >1.05 were Most Associated with Injurious Ventilation
  • Systematic Review/Meta-Analysis of Morbidity/Mortality in Post-Operative Acute Lung Injury (Lancet Respir Med, 2014) [MEDLINE]
    • Lung Protective Mechanical Ventilation Strategies (Applied During Surgery) Decrease the Incidence of Post-Operative Acute Lung Injury, But Do Not Decrease the Mortality Rate
  • Study of Contribution of Driving Pressure to Mortality in ARDS (NEJM, 2015) [MEDLINE]: study used data from 9 prior randomized trials
    • Rationale: lower tidal volume, lower plateau pressure, and higher PEEP are all believed to decrease mechanical stresses on the lung in ARDS (which can induce ventilator-associated lung injury)
      • However, There is an Uncertainty When Optimizing One Component Adversely Affects Another (Example: Increasing PEEP May Undesirably Increase the Plateau Pressure), Which this Study Attempted to Address
      • Authors Theorized in Their Study that Optimizing the Tidal Volume/Respiratory System Compliance Ratio (Known as the Driving Pressure = Delta P) Would Provide a Better Predictor of Outcome in ARDS
    • Driving Pressure (Plateau Pressure – PEEP or Delta P) was the Best Predictor of Survival
      • Decreases in Tidal Volume or Increases in PEEP Were Beneficial Only if They Resulted in a Decrease in Delta P (In Other Words, PEEP Increments are Protective Only When They are Associated with an Improvement in Respiratory System Compliance, So that the Same Tidal Volume Can Be Delivered with a Lower Delta P)
      • Further Trials Using Specific Manipulation of Delta P are Required Before Recommending this Strategy as a Standard
    • Caveat: Delta P Can Only Be Accurately Assessed in Non-Breathing Patients

Recommendations-Tidal Volume Setting in Patients with Acute Respiratory Distress Syndrome (ARDS) (American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice Guidelines for Mechanical Ventilation in ARDS) (Am J Respir Crit Care Med, 2017) [MEDLINE]

  • Lung-Protective Ventilation Strategy with Low Tidal Volume Ventilation (4-8 mL/kg PBW) and Low Plateau Pressure (<30 cm H2O) is Recommended (Strong Recommendation, Moderate Confidence)
    • Predicted Body Weight (PBW)
      • Male: PBW = 50 + 2.3 (ht in inches – 60)
      • Female: PBW = 45.5 + 2.3 (ht in inches – 60)
    • Maintaining the Plateau Pressure (Pplat) <35 cm H2O Decreases the Risk of Barotrauma (Since Plateau Pressure is the Best Clinical Estimate of Mean Alveolar Pressure)
      • Driving Pressure = Plateau Pressure – PEEP
    • In Some Cases of ARDS, Low Tidal Volume Ventilation May Require the Use of Permissive Hypercapnia (Which Occurs Due to an Increase in the Relative Amount of Dead Space)

Recommendations-Tidal Volume Setting in Patients with Acute Respiratory Distress Syndrome (ARDS) Associated with Sepsis (2016 Surviving Sepsis Guidelines; Intensive Care Med, 2017) [MEDLINE]

  • Low Tidal Volume (6 mL/kg PBW) is Recommended Over High Tidal Volume (12 mL/kg PBW) in Sepsis-Associated ARDS (Strong Recommendation, High Quality of Evidence)
  • Low Tidal Volume (6 mL/kg PBW) is Recommended Over High Tidal Volume (12 mL/kg PBW) in Sepsis-Associated Respiratory Failure without ARDS (Weak Recommendation, Low Quality of Evidence)
  • Plateau Pressure Upper Limit of 30 cm H2O is Recommended in Sepsis-Associated Severe ARDS (Strong Recommendation, Moderate Quality of Evidence)
  • Respiratory Rate Max Should Be 35 Breaths/min (Recognizing that Some Patients May Experience Hypercapnia)
    • Hypercapnia is Generally Well-Tolerated in the Absence of Contraindications (Such as Increased Intracranial Pressure, Sickle Cell Crisis, etc)

“Lost Volume” on Ventilator

  • Lost Volume is a Disparity Between the Inspiratory Tidal and Expiratory Tidal Volume (i.e. Expiratory Tidal Volume < Inspiratory Tidal Volume)
  • Etiology of Lost Volume on the Ventilator
    • Bronchopleural Fistula (see Bronchopleural Fistula)
      • Air Leak from the Chest Tube is Present
    • Endotracheal Tube (ETT) Cuff Leak
      • Air Leak Around the Endotracheal Tube Cuff is Frequently Audible or Manifested by Secretions Bubbling Out from the Patient’s Mouth During Exhalation
    • Inadvertent Extubation
      • May Occur After Patient Turning or Repositioning
      • May Be Accompanied by Respiratory Distress or Precipitous Oxygen Desaturation
    • Inadvertent Nasogastric (NG)/Orogastric (OG) Tube Placement into the Trachea/Mainstem Bronchus (with Suction Applied) (see Nasogastric/Orogastric Tube)
      • Diagnosis Can Be Made by Chest X-Ray or Bronchoscopy, Demonstrating Nasogastric/Orogastric Tube in the Trachea/Mainstem Bronchus
    • Leak in Ventilator Circuit
      • Due to a Loose Connection or Fractured Ventilator Tubing
    • Ventilator Malfunction

Respiratory Rate (RR)

  • Respiratory Rate Should Be Adjusted to Maintain Appropriate pCO2 and pH
    • Respiratory Rate Should Be Set to Allow an Adequate Minute Ventilation, Should the Patient Become Apneic
    • In ARDS, the Maximum Respiratory Rate Should Be ≤35 Breaths/min
    • When Increasing the Respiratory Rate in Some Modes of Ventilation, Inspiratory Flow Rate Can Be Increased to Maintain the I/E Ratio: to prevent the development of auto-PEEP
    • When Increasing the Respiratory Rate, the Patient Should Be Monitored for the Development of Auto-PEEP
      • High Respiratory Rates in Patients Mechanically-Ventilated for Acute Respiratory Failure Can Produce Dynamic Hyperinflation (with Development of Auto-PEEP), Increase the Dead Space/Tidal Volume Ratio, and Impair Right Ventricular Ejection with a Decrease in the Cardiac Output (Crit Care Med, 2002) [MEDLINE]: n = 14
      • In a Patient Who Develops Auto-PEEP on a Respiratory Rate Which Achieves a Normal pH, Respiratory Rate Can Be Decreased and “Permissive Hypercapnia” Utilized

Minute Ventilation (VE)

  • Physiologic Definition
    • VE = VA + VD
      • Minute Ventilation (VE): expressed in L/min
      • Alveolar Ventilation (VA): expressed in L/min
      • Dead Space Ventilation (VD): expressed in L/min
        • Not on the Ventilator: VD is equivalent to approximately 1/3 of resting tidal volume (or approximately 2.2 ml/kg)
        • On the Ventilator with Lung Pathology: VD/VT ratio is variable
  • Clinical Definition
    • VE = RR x VT
      • Minute Ventilation (VE): expressed in L/min
      • Respiratory Rate (RR): expressed in breaths/min
      • Tidal Volume (VT): expressed in L/breath

Positive End-Expiratory Pressure (PEEP)

Definitions

  • Extrinsic PEEP: PEEP applied by the clinician
  • Auto-PEEP (Intrinsic PEEP): PEEP which develops due to intrinsic properties of the lungs and/or airways
  • Total PEEP = Extrinsic PEEP + Auto-PEEP

Physiology

  • Use of PEEP in Severe Asthma/COPD Exacerbation with Airway Obstruction
    • During Severe Asthma/COPD Exacerbation (with Airway Obstruction), the Airways Behave Like a Starling Resistor (Chest, 1989) [MEDLINE]
      • Ohmic Resistor (i.e. One Which Follows Ohm’s Law)
        • With an Ohmic Resistor, if Extrinsic PEEP is Decreased, the Peak Airway Pressure (PIP) Would Be Expected to Decrease by a Similar Amount: this is one would expect with normal lungs
      • Starling Resistor: flow rate in the airways is not dependent on the amount extrinsic PEEP applied
        • Example Using a “Waterfall” Analogy: the flow rate of a waterfall is not impacted by the level of the pool of water below (of course, until the pool of water rises to the level of the waterfall)
        • With a Starling Resistor, When Extrinsic PEEP is Decreased, the Peak Airway Pressure (PIP) Does Not Decrease by a Similar Amount: this is due to the fact that flow is determined by upstream events only

Beneficial Effects of Positive End-Expiratory Pressure (PEEP)

  • PEEP Decreases End-Expiratory Alveolar Derecruitment (Collapse), Rather than Increasing Alveolar Recruitment
    • End-Expiratory Alveolar Collapse Occurs in Intubated Patients Due to the Fact that the Endotracheal Tube Bypasses the Glottis
    • Derecruited Lung is Correlated with Intrapulmonary Shunt (Am J Respir Crit Care Med, 2017) [MEDLINE]
      • Improvement in Oxygenation with Increased PEEP Generally Reflects Lung Recruitment
      • However, Oxygenation is Also Influenced by Other Factors Which May Be Affected by PEEP (Cardiac Output, etc)
    • Decreased End-Expiratory Alveolar Derecruitment Can Mitigate Ventilator-Induced Lung Injury (VILI) (Am J Respir Crit Care Med, 2017) [MEDLINE]
    • In ARDS, a Combination of Physiologic Variables (pO2/FIO2 Ratio <150 at a PEEP 5 cm H2O, a Decrease in Dead Space, and an Increase in Respiratory System Compliance with an Increase in PEEP to 15 cm H2O) Predicted a Higher Percentage of Potentially Recruitable Lung (NEJM, 2006) [MEDLINE]
    • Quantification of the Amount of Recruitable Lung Can Be Achieved Using Chest Computed Tomography (CT), Helium Dilution/Nitrogen Washout Techniques, Electrical Impedance Tomography, or Construction of Airway Pressure-Volume Curves at Tidal Ventilation with Different Levels of PEEP (Am J Respir Crit Care Med, 2017) [MEDLINE]
      • Estimates of Recruitability from Helium Dilution and Pressure–Volume Curves are Strongly Correlated with Each Other, But Both are Poorly Correlated with Estimates of Recruitability Obtained from Chest CT Scanning
      • This Discrepancy May Be Accounted for by the Fact that CT Measures the Opening of Previously Collapsed Lung Units, While the Helium Dilution and Pressure–Volume Curve Techniques Measure the Volume of Gas Entering Newly Recruited Lung Units Together with Previously Opened Lung Units
  • PEEP Decreases Intrapulmonary Shunting
    • PEEP is Transmitted to the Most Compliant Lung Regions and Therefore, is Most Useful for Diffuse Lung Processes (Multilobar Pneumonia, ARDS, Cardiogenic Pulmonary Edema, etc) and is Less Useful for Localized Lung Processes
      • In Patients with Focal Lung Disease (Pneumonia, etc), PEEP Compresses Alveolar Capillaries in the Uninvolved Regions of the Lung (Causing Dead Space with High V/Q Ratio in That Region), Diverting Blood Flow to the Injured Lung Region (Causing Low V/Q Ratio in That Region) (J Appl Physiol Respir Environ Exerc Physiol, 1982) [MEDLINE]
  • PEEP Improves Lung Compliance (Am J Respir Crit Care Med, 2017) [MEDLINE]
    • PEEP Increases the Number of Aerated Alveoli Participating in Tidal Ventilation, Decreasing Tidal Lung Stress and Strain (i.e. Improving Lung Compliance)
  • PEEP Decreases the Risk of Ventilator-Associated Pneumonia (VAP) (see Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia) (Crit Care Med, 2008) [MEDLINE]
    • PEEP Decreases the Passage of Posterior Pharyngeal Secretions Around the Endotracheal Tube Cuff into the Lungs (Crit Care Med, 2008) [MEDLINE]
  • PEEP Promotes More Homogeneous Ventilation
    • PEEP Distributes Ventilation and Blood Flow Differently in the Supine vs Prone Position (Anesthesiology, 2010) [MEDLINE]
      • PEEP Might Be Less Effective and Worsen V/Q Mismatch During Prone Ventilation
  • PEEP Decreases Dynamic Airway Compression (Intensive Care Med, 1993) [MEDLINE]
  • At Lower Levels, PEEP Improves Cardiac Output (NEJM, 1975) [MEDLINE]

Adverse Effects of Positive End-Expiratory Pressure (PEEP)

  • At Higher Levels, PEEP Decreases Cardiac Output and May Result in Hypotension (Chest, 2005) [MEDLINE]
    • Mechanism: at higher levels, PEEP increases Intrathoracic pressure (and increasing right atrial pressure), decreasing to the right side of the heart, culminating in a decrease in cardiac output
      • Decreased Mixed Venous pO2
      • Decreased Arterial pO2
    • However, PEEP of 10-20 cm H2O Has Been Demonstrated to Be Well-Tolerated in Most ARDS Patients (Crit Care, 2004) [MEDLINE]
  • PEEP May Undesirably Cause Alveolar Overdistention
    • While PEEP is Generally Thought to Have Beneficial Effects When Used in ARDS, PEEP May Result in Predominant Alveolar Recruitment, Predominant Alveolar Overdistention, or a Combination of Both Recruitment and Overdistention
      • Consequently, PEEP Could Theoretically Increase Contribute to Ventilator-Induced Lung Injury with Overdistention Propagating Lung Inflammation and Injury (Similar to the Effects of Excessive Tidal Volume)
      • Lung Recruitability is a Critical Determinant Which Will Determine the Effect of PEEP on the Injured Lung and the Amount of Lung Which Can Be Recruited Varies Widely in Patients with ARDS (NEJM, 2006) [MEDLINE]
        • In Patients with High Lung Recruitability, Much of the Increase in End-Expiratory Lung Volume (EELV) with PEEP Results from Opening of Collapsed Lung Units, Decreasing Cyclic Lung Collapse/Reopening anf Decreasing Dynamic Strain in Aerated Lung Units (Due to an Increase in Aerated Lung Volume Available for Tidal Volume Distribution)
        • In Patients with Low Lung Recruitability, PEEP Results in Additional Distention of Already Aerated Lung Tissue, Possibly Causing Overdistention Injury
        • Personalized PEEP Titration, Based on Recruitability, Oxygenation Response After Increases in PEEP (a Marker Lung Recruitment) Predicted a Lower Mortality Rate in ARDS (Am J Respir Crit Care Med, 2014) [MEDLINE]
  • PEEP May Increase Pulmonary Vascular Resistance (PVR) by Narrowing or Occluding Alveolar Septal Vessels, Which are Surrounded by Alveolar Pressure (Even When Using Low Tidal Volumes) (Crit Care Med, 2010) [MEDLINE]
    • Consequently, Increased PVR Increases the Right Ventricular Afterload, Further Decreasing Cardiac Output
  • PEEP Can Worsen Alveolar Dead Space by Increasing the Volume of Lung in Which Alveolar Pressure Exceeds Pulmonary Capillary Pressure (NEJM, 1975) [MEDLINE]
  • PEEP Increases Peak Inspiratory Pressure (PIP)
    • The Addition of PEEP Will Generally Increase the PIP by an Equivalent Amount, Except in the Presence of Auto-PEEP
    • In Fact, the Failure of the PIP to Increase with Application of Extrinsic PEEP is Evidence for the Presence of Auto-PEEP
  • PEEP Can Increase the Plateau Pressure (Pplat)
  • PEEP Exacerbates Right-to-Left Shunting Through a Patent Foramen Ovale (PFO) (see Patent Foramen Ovale) (Ann Intern Med, 1993) [MEDLINE]
  • PEEP May Increase Intracranial Pressure (Controversial) (see Increased Intracranial Pressure)
    • Mechanism: PEEP may decrease cerebral venous outflow
      • In Patients with Stroke, PEEP Did Not Increase the Intracranial Pressure (Stroke, 2001) [MEDLINE]
      • In Severe Traumatic Brain Injury, PEEP Did Not Decrease Cerebral Perfusion (J Trauma, 2002) [MEDLINE]
      • In Animal Studies and Patients with SAH, PEEP Did Not Directly Increase the Intracranial Pressure, But Did So Only by Inducing Hypotension (Crit Care Med, 2005) [MEDLINE]

Techniques/Strategies to Set the Optimum Amount of PEEP

  • FIO2/PEEP Table Strategy
    • The ARDSNet Trial Standardized FIO2/PEEP Table is the One Most Commonly Used [ARDSNet] (NEJM, 2000) [MEDLINE]
    • The ALVEOLI Trial Compared Low PEEP and High PEEP and Found that Oxygenation Improved in the Higher PEEP Group, Suggesting that There was Greater Recruitment with Higher PEEP (NEJM, 2004) [MEDLINE]
      • Oxygenation Responses Vary Widely Between Patients with ARDS
    • While PEEP is Generally Set at a Minimum of 5 cm H2O and Titrated up, the Optimal Level of PEEP in a Patient with ARDS May Depend on the Tidal Volume Being Used (Crit Care, 2018) [MEDLINE]
    • In a Comparative Study of 4 Bedside Methods to Optimize PEEP (FIO2/PEEP Table, Open Lung Strategy Limited by Plateau Pressure, Stress Index, and a Higher FIO2/PEEP Table), the ARDSNet PEEP/FIO2 Table was the Only Strategy Which Consistently Provided Higher PEEP Levels in Patients with Severe ARDS and Greater Recruitability, and Provided Lower PEEP Levels in Patients with Mild ARDS and Less Recruitability (Crit Care Med, 2014) [MEDLINE]
    • Conclusion
      • FIO2/PEEP Tables are Easy and Reasonable to Use, But They Do Not Necessarily Guarantee an Optimal PEEP Setting in an Individual Patient
  • Open Lung Strategy Used in the EXPRESS Trial with High PEEP Until Plateau Pressure Reached 28-30 cm H2O (Not Exceeding This Level to Avoid Overdistention) (JAMA, 2008) [MEDLINE]
    • However, This Technique Did Not Demonstrate a Mortality Benefit
      • Higher PEEP Group Had Higher Ventilator-Free Days and Higher Organ Failure–Free Days
    • Randomized Trial of Open Lung Approach in ARDS (Crit Care Med, 2016) [MEDLINE]
      • Open Lung Approach Improved Oxygenation and Driving Pressure, without Detrimental Effects on Mortality, Ventilator-Free Days, or Barotrauma
    • Conclusion
      • This Strategy Does Not Always Result in the Optimal PEEP for an Individual Patient
  • Strategy to Optimize Lung Compliance (NEJM, 1975) [MEDLINE]
    • Conclusion
      • Unclear Benefit of This Strategy
  • Driving Pressure-Targeted Strategy
    • In Meta-Analysis, Low Driving Pressure (Plateau Pressure – PEEP Difference) <13-15 cm H2O was Associated with Decreased Mortality Rate in ARDS (NEJM, 2015) [MEDLINE]
    • Conclusion
      • While Promising, This Strategy Needs Prospective Trials to Determine if it Indeed Improves the ARDS Mortality Rate
  • Strategy to Maintain PEEP to Keep Tidal Ventilation Above the Lower Inflection Point on the Static Pressure-Volume Curve of the Lung (Am J Respir Crit Care Med, 1999) [MEDLINE]
    • Note: this is the Static Curve, Not the Dynamic Curve Obtained During Mechanical Ventilation
    • This May reduce the Potential for Sheer Forces Exacerbating Lung Injury in ARDS
    • However, this Technique is Cumbersome (Requiring Deep Sedation and/or Neuromuscular Blockade) and Trials Do Not Indicate that it Has a Mortality Benefit
  • Strategy Using the Stress Index to Determine the Optimal Amount of PEEP
    • Stress Index is a Software-Derived Value Obtained During a Constant Flow Breath (to Determine the Pressure-Time Curve) in a Sedated Patient (i.e. with No Patient Effort) (Anesthesiology, 2013) [MEDLINE] (Respir Care, 2018) [MEDLINE]
    • Optimal Stress Index is a Straight Diagonal (i.e. 1.0) Reflecting Unchanging Compliance Throughout the Breath
      • If Recruitment/Derecruitment is Occurring During the Breath, the Stress Index Curve is Concave Bowing Upward (Low Compliance Early, Followed by High Compliance Later in the Breath) -> Stress Index <1
      • If Overdistention is Occurring During the Breath, the Stress Index Curve is Concave Bowing Downward (High Compliance Early, Followed by Low Compliance Later in the Breath) -> Stress Index >1
  • Strategy Using Transpulmonary Pressure
    • This Technique is Based on Fact that Airway Pressures are Not a Reliable Indicator of Lung Stress
      • Conditions Which Increase Chest Wall Elastance (Edema, Kyphoscoliosis, Abdominal Compartment Syndrome) or Shift the Pressure–Volume Curve of the Respiratory System or the Chest Wall to the Right (Obesity) Will Increase the Airway Pressure
    • Difficult to Measure in Clinical Practice (Requires Esophageal Manometry)
  • Strategy Using Oxygen Delivery to Determine the Optimal Amount of PEEP
    • The Level of PEEP Which Optimizes Oxygen Delivery May Not Correlate with the Level of PEEP Which Maximizes Arterial Oxygenation (Br J Anaesth, 2016) [MEDLINE]
  • CT/Ultrasound/Electrical Impedance Tomography Imaging-Guided Strategy
    • None of These Have Been Widely Adopted

Clinical Efficacy-Positive End-Expiratory Pressure (PEEP) in Patients without Acute Respiratory Distress Syndrome (ARDS)

  • Randomized IMPROVE Trial Examining Intraoperative Low Tidal Volume Ventilation in Patients Undergoing Major Abdominal Surgery (NEJM, 2013) [MEDLINE]
    • Intraoperative Low Tidal Volume Ventilation (6-8 mL/kg PBW, PEEP 6-8 cm H2O, Recruitment Maneuvers q30 min) was Associated with Decreased Adverse Pulmonary/Extrapulmonary Events, Decreased Need for Mechanical Ventilation and Decreased Hospital Length of Stay in Intermediate and High-Risk Patients Undergoing Major Abdominal Surgery
    • Lung Protective Strategy Did Not Decrease the Development of ARDS or Impact the Mortality Rate
  • Randomized PROVHILO Trial of PEEP During Abdominal Surgery (Lancet, 2014) [MEDLINE]
    • High PEEP (12 cm H20) and Recruitment Strategy During Abdominal Surgery Did Not Decrease Postoperative Pulmonary Complications, as Compared to Low PEEP Strategy (2 cm H2O)
    • High PEEP Group Required More Vasopressors to Treat Intraoperative Hypotension
  • Randomized Trial of PEEP in Patients Undergoing Elective Cardiac Surgery and Ventilated for Hypoxemia (JAMA, 2017) [MEDLINE]: n = 320
    • Alveolar Recruitment with PEEP Decreased Pulmonary Complications, ICU Length of Stay, and Decreased Mortality Rate without Increasing the Risk of Barotrauma
  • Spanish Randomized iPROVE Trial of Multiple Ventilation Strategiesin Patients Undergoing Abdominal Surgery (Lancet Respir Med, 2018) [MEDLINE]: n = 1,012
    • Strategies: individualized intraoperative ventilation with individualized PEEP after a lung recruitment maneuver plus individualized postoperative CPAP, individualized intraoperative ventilation plus postoperative CPAP, and standard intraoperative ventilation plus postoperative CPAP, or standard intraoperative ventilation plus standard postoperative oxygen therapy
    • Ventilation Strategy Did Not Impact the Postoperative Complication Rate
  • Conclusions
    • Overall
      • Optimal Level of PEEP in Mechanically-Ventilated Patients without ARDS is Unknown
    • Severe Airway Obstruction (Asthma/COPD Exacerbation, etc)
      • Use of Extrinsic PEEP in Patients with Auto-PEEP Should Not Exceed 50-80% of the Amount of Auto-PEEP
    • Cardiogenic Pulmonary Edema (see Cardiogenic Pulmonary Edema)
      • PEEP Does Not Appear to Have a Clinical Benefit Above that of Positive-Pressure Ventilation Alone in Patients with Cardiogenic Pulmonary Edema (Chest, 1998) [MEDLINE]
    • Flail Chest (see Flail Chest)
      • PEEP Has Unclear Clinical Benefit
    • Tracheobronchomalacia (see Tracheobronchomalacia)
      • PEEP Has an Unclear Clinical Benefit

Clinical Efficacy-Positive End-Expiratory Pressure (PEEP) in Patients with Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome)

  • ARDSNet ALVEOLI Study (NEJM, 2004) [MEDLINE]
    • In Patients with ALI/ARDS Who Receive Low Tidal Volume Ventilation (6 ml/kg PBW) and Plateau Pressure Limit of 30 cm H2O, Lower or Higher PEEP Levels Had No Impact on Mortality Rate, ICU Length of Stay, Weaning from the Ventilator, Ventilator-Free Days, or Organ Failure-Free Days
  • Expiratory Pressure (EXPRESS) Study (JAMA, 2008) [MEDLINE]: French multicenter RCT (n = 767)
    • Setting PEEP Aimed at Increasing Alveolar Recruitment While Limiting Hyperinflation Had No Impact on Mortality Rate
    • However, it Improved Lung Function, Increased Ventilator-Free Days, and Decreased Non-Pulmonary Organ Failure-Free Days
  • Lung Open Ventilation (LOV) Study (JAMA, 2008) [MEDLINE]
    • Open Lung Ventilation Had No Impact on Mortality Rate
    • However, There was Decreased Need for Salvage Therapies and Lower Incidence of Refractory Hypoxemia
  • Systematic Review and Meta-Analysis of PEEP Levels in ARDS (JAMA, 2010) [MEDLINE]
    • Higher PEEP was Not Associated with Improved Hospital Survival, as Compared to Lower PEEP
    • However, in the Subset of ARDS Patients with pO2/FiO2 Ratio <200 mm Hg, PEEP Improved Survival
  • Trial Examining Predictors of Ventilator-Induced Lung Injury in ARDS (Anesthesiology, 2013) [MEDLINE]
    • Rationale: stress index describes the shape of the airway pressure-time curve profile and may indicate tidal recruitment or tidal overdistension (convex downward pressure curve indicates initial low compliance with better compliance later in the breath due to recruitment, while convex upward curve indicates overdistention -> optimal curve is straight diagonal initial pressure waveform)
    • Plateau Pressure Partitioned to the Respiratory System (Pplat,Rs) >25 cm H20 and Stress Index Partitioned to the Respiratory System (SI,Rs) >1.05 were Most Associated with Injurious Ventilation
  • Study of Contribution of Driving Pressure to Mortality in ARDS (NEJM, 2015) [MEDLINE]: study used data from 9 prior randomized trials
    • Rationale: lower tidal volume, lower plateau pressure, and higher PEEP are all believed to decrease mechanical stresses on the lung in ARDS (which can induce ventilator-associated lung injury)
      • However, There is an Uncertainty When Optimizing One Component Adversely Affects Another (Example: Increasing PEEP May Undesirably Increase the Plateau Pressure), Which this Study Attempted to Address
      • Authors Theorized in Their Study that Optimizing the Tidal Volume/Respiratory System Compliance Ratio (Known as the Driving Pressure = Delta P) Would Provide a Better Predictor of Outcome in ARDS
    • Driving Pressure (Plateau Pressure – PEEP or Delta P) was the Best Predictor of Survival
      • Decreases in Tidal Volume or Increases in PEEP Were Beneficial Only if They Resulted in a Decrease in Delta P (In Other Words, PEEP Increments are Protective Only When They are Associated with an Improvement in Respiratory System Compliance, So that the Same Tidal Volume Can Be Delivered with a Lower Delta P)
      • Further Trials Using Specific Manipulation of Delta P are Required Before Recommending this Strategy as a Standard
    • Caveat: Delta P Can Only Be Accurately Assessed in Non-Breathing Patients
  • Randomized Trial of Open Lung Approach in ARDS (Crit Care Med, 2016) [MEDLINE]: n = 200
    • Open Lung Approach Improved Oxygenation and Driving Pressure, without Detrimental Effects on Mortality, Ventilator-Free Days, or Barotrauma
  • Study of Driving Pressure and Lung Stress in ARDS (Crit Care, 2016) [MEDLINE]
    • The Applied Tidal Volume (mL/kg of Ideal Body Weight) was Not Related to Lung Gas Volume (r2 = 0.0005; p = 0.772)
    • At Both PEEP Levels, the higher Airway Driving Pressure Group Had a Significantly Higher Lung Stress, Respiratory System and Lung Elastance, as Compared to the Lower Airway Driving Pressure Group
    • Airway Driving Pressure was Significantly Related to Lung Stress (at PEEP +5, r2 = 0.581; p < 0.0001/at PEEP +15, r2 = 0.353; p < 0.0001)
    • For a Lung Stress of 24 and 26 cmH2O, the Optimal Cutoff Values for the Airway Driving Pressure were 15.0 cm H2O (ROC AUC 0.85, 95 % CI: 0.782-0.922) and 16.7 (ROC AUC 0.84, 95 % CI: 0.742-0.936)
  • Systematic Review and Meta-Analysis of Driving Pressure and Mortality Rate in ARDS (Crit Care Med, 2018) [MEDLINE]: n = 6,062 (7 studies)
    • Median (Interquartile Range) Driving Pressure Between Higher and Lower Driving Pressure Groups was 15 cm H2O (14-16 cm H2O)
    • Higher Driving pressure was Associated with a Significantly Higher Mortality Rate (Pooled Risk Ratio 1.44; 95% CI: 1.11-1.88; I = 85%)
    • Sensitivity Analysis Restricted to the Three Studies with Similar Driving Pressure Cutoffs (13-15 cm H2O) Demonstrated Similar Results (Pooled Risk Ratio, 1.28; 95% CI: 1.14-1.43; I = 0%)
  • Trial of PEEP in ARDS (Crit Care, 2018) [MEDLINE]
    • Optimal PEEP (as Determined by Stress Index on the Ventilator) Depended on Tidal Volume
  • Phase 2 Randomized EPVent-2 Trial Evaluating Esophageal Pressure-Guided Positive End-Expiratory Pressure (PEEP) Titration Strategy in ARDS (JAMA, 2019) [MEDLINE]: n = 200 (14 hospitals in North America)
    • In Moderate-Severe ARDS (with Standard Low Tidal Volume Ventilation), Esophageal Pressure-Guided PEEP Titration Strategy Did Not Improve Mortality Rate or Ventilator-Free Days, as Compared to a Standard Empirical FIO2/PEEP Strategy

General Recommendations for Patients with Acute Respiratory Distress Syndrome (ARDS)

  • PEEP of 0 cm H2O is Generally is Accepted to Be Harmful in ARDS
  • PEEP of 8-15 cm H2O is Appropriate in Most Patients with ARDS: although higher PEEP levels might be used in patients for whom a greater potential for recruitment can be demonstrated
  • Although Further Trials are Required Before This Strategy Can Be Recommended, Increasing PEEP May Only Be Beneficial if it Results in a Decrease in the Delta P (Plateau Pressure – PEEP)

Recommendations for Patients with Acute Respiratory Distress Syndrome (ARDS) (American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice Guidelines for Mechanical Ventilation in ARDS) (Am J Respir Crit Care Med, 2017) [MEDLINE]

  • Higher PEEP (Rather Than Lower PEEP) is Recommended in Adults with Moderate-Severe ARDS (Conditional Recommendation, Moderate Confidence)

Recommendations for Patients with Acute Respiratory Distress Syndrome (ARDS) Associated with Sepsis (2016 Surviving Sepsis Guidelines; Intensive Care Med, 2017) [MEDLINE]

  • Higher PEEP is Recommended Over Lower PEEP in Adults with Sepsis-Associated Moderate-Severe ARDS (Weak Recommendation, Moderate Quality of Evidence)
    • The Optimal Method for Selecting PEEP is Unclear
    • Potential Methods Include Titrating PEEP Upward on a Tidal Volume of 6 mL/kg Until the Plateau Pressure is 28 cm H20, Titrating PEEP to Optimize Thoracoabdominal Compliance with the Lowest Driving Pressure, Titrating PEEP Based on Decreasing the FIO2 to Maintain Adequate Oxygenation, etc

Flow Rate and Pattern

  • Physiology
    • Peak Flow Rate Should Be Set at a Level Sufficient to Overcome the Pulmonary and Ventilator Impedance
      • Insufficient Flow Rates Result in Increased Work of Breathing, Dyspnea, Spuriously Low Peak Inspiratory Pressure, and/or Scalloping of the Inspiratory Pressure Curve (NEJM, 1994) [MEDLINE]
    • Flow Waveform
      • Square (Constant Flow) Waveform
      • Decelerating (Ramp) Flow Waveform: may distribute ventilation more evenly than other patterns of flow, especially in the setting of airway obstruction (Intensive Care Med, 1985) [MEDLINE]
        • This Waveform Decreases the Peak Airway Pressure, Physiologic Dead Space, and pCO2, While Leaving Oxygenation Unchanged (Chest, 2002) [MEDLINE]
      • Sinusoidal Waveform
  • Application
    • Set Peak Flow Rates Typically Range from 60 L/min to 100 L/min
      • High Peak Flow Rates are Commonly Used in Patients with Obstructive Lung Disease: these allow shorter inspiratory times with longer expiratory times (i.e. lower I/E ratio), decreasing the risk of dynamic hyperinflation (Intensive Care Med, 1996) [MEDLINE]
        • Normal I/E Ratio: 1:2
        • Typical I/E Ratio Employed During Mechanical Ventilation of Patient with Obstructive Lung Disease: 1:3 to 1:5
      • Use of High Inspiratory Flow Rate During Assist Control Ventilation is Associated with an Increase in the Respiratory Rate (During Both Wakefulness and Sleep and in Health and Disease States) (Curr Opin Crit Care, 2003) [MEDLINE]: such changes occur before changes in the arterial blood gas, consistent with either Hering-Breuer reflex activity or effects of flow-sensitive receptors
  • Adverse Effects of High Flow Rate
    • Increased Peak Inspiratory Pressure (PIP) (Eur Respir J, 2002) [MEDLINE]
    • Decreased Inspiratory Time with Decreased Mean Airway Pressure (Which May Result in Worsened Oxygenation)

Fraction of Inspired Oxygen (FIO2)

  • Clinical Efficacy
    • Randomized Trial of Conservative Oxygen Strategy in Mechanically-Ventilated Patients (Am J Respir Crit Care Med, 2016) [MEDLINE]
      • Conservative Oxygen Strategy (SpO 88-92%) Did Not Impact the ICU or 90-Day Mortality Rate or Risk of Organ Dysfunction, as Compared to Liberal Oxygen Strategy (SpO2 ≥96%)
    • Italian Oxygen-ICU Trial of Conventional Oxygen Strategy (pO2 Up to 150 mm Hg or SaO2 97-100%) vs Conservative Oxygen Strategy (pO2 70-100 or SaO2 94-98%) in a General ICU Population (Stay of ≥72 hrs) (JAMA, 2016) [MEDLINE]: trial had unplanned, early termination
      • Conservative Oxygen Strategy Decreased Mortality Rate, as Compared to the Conventional Oxygen Strategy
    • French HYPERS2S Trial of Hyperoxia and Hypertonic Saline in Septic Shock (Lancet Respir Med, 2017) [MEDLINE]
      • Trial Stopped Prematurely for Safety Reasons
      • Setting FiO2 to 100% to Induce Arterial Hyperoxia Might Increase the Mortality Rate in Septic Shock
      • Hypertonic (3%) Saline Resuscitation Did Not Decrease the Mortality Rate in Septic Shock
    • Improving Oxygen Therapy in Acute-illness (IOTA) Systematic Review and Meta-Analysis of Conservative vs Liberal Oxygen Strategy in Critically Ill Patients (Lancet, 2018) [MEDLINE]: n = 25 trials (in patients with sepsis, critical illness, stroke, trauma, myocardial infarction, cardiac arrest, and emergency surgery)
      • In Acutely Ill Adults, Liberal Oxygen Therapy Strategy (Median SaO2 96%, Range 94-99%) Increases the 30-Day (and Longest Follow-Up) Mortality Rate, as Compared to a Conservative Oxygen Therapy Strategy (Relative Risk at 30 Days was 1.21, 95% CI 1.03-1.43)
        • Supplemental Oxygen Might Become Unfavorable with SaO2 >94-96%
    • Post Hoc Analysis of HYPERS2S Trial Data (Ann Intensive Care, 2018) [MEDLINE]
      • Hyperoxia May Be Associated with a Increased Mortality Rate in Patients with Septic Shock Using the Sepsis-3 Criteria (with Serum Lactate > 2 mmol/L), But Not in Patients with Hypotension Alone
        • In Patients with Serum Lactate ≤2 mmol/L, Hyperoxia Had No Effect on the Mortality Rate, Nor on Other Outcomes
    • Observational Study of Hyperoxia in the Emergency Department in Patients with Acute Respiratory Failure (Crit Care, 2018) [MEDLINE]: n = 688
      • Emergency Department Exposure to Hyperoxia is Common and Associated with Increased Mortality in Mechanically Ventilated Patients Achieving Normoxia After Admission
      • This Suggests that Hyperoxia in the Immediate Post-Intubation Period Could Be Particularly Injurious and Targeting Normoxia from Initiation of Mechanical Ventilation May Improve Outcome
  • Recommendations (British Thoracic Society Emergency Oxygen Guidelines, 2017) (Thorax, 2017) [MEDLINE]
    • Oxygen Should Be Prescribed to Achieve a Target Saturation of 94–98% for Most Acutely Ill Patients or 88–92% or Patient-Specific Target Range for Those at Risk of Hypercapnic Respiratory Failure
    • Best Practice is to Prescribe a Target Range for All Hospitalized Patients at the Time of Hospital Admission So that Appropriate Oxygen Therapy Can Be Started in the Event of Unexpected Clinical Deterioration with Hypoxemia and Also to Ensure that the Oximetry Section of the Early Warning Score Can Be Scored Appropriately
  • Recommendations (British Medical Journal-Oxygen Therapy for Acutely Ill Medical Patients: Clinical Practice Guideline, 2018) (BMJ, 2018) [MEDLINE]
    • Supplemental Oxygen Therapy Should Be Titrated to SpO2 ≤96% (Strong Recommendation)
      • SpO2 >96% is Likely Associated with a Small, But Important, Increased Risk of Death without Plausible Clinical Benefit

Recruitment Maneuvers

  • Rationale
    • Ventilatory Strategy that Transiently Increases the Transpulmonary Pressure to Reopen the Recruitable Lung Units in ARDS (see Acute Respiratory Distress Syndrome)
      • There is a Large-Scale Loss of Aerated Lung and Once the End-Inspiratory Pressure Surpasses the Regional Critical Opening Pressure of the Lung Units, those Lung Units are Likely to Reopen
  • Clinical Efficacy in Patients with ARDS
    • Study of Lung Recruitment Using CT Scanning with Breath Holding at Various Airway Pressures in ARDS (NEJM, 2006) [MEDLINE]
      • The Percentage of Recruitable Lung was Extremely Variable in ARDS: on average, 24% of lung could not be recruited
      • The Percentage of Recruitable Lung was Associated with the Response to PEEP
    • Cochrane Database Review of Recruitment Maneuvers in Patients with ARDS (Cochrane Database Syst Rev, 2009) [MEDLINE]
      • No Clinical Benefit of Recruitment Maneuvers in Either Mortality or Length of Mechanical Ventilation
    • Randomized Trial of Recruitment in Moderate-Severe ARDS (JAMA, 2017) [MEDLINE]: n = 1010
      • In Moderate-Severe ARDS, Lung Recruitment and Titrated PEEP Strategy Increased 28-Day All-Cause Mortality, as Compared to Low PEEP Strategy
      • Lung Recruitment and Titrated PEEP Strategy Decreased the Number of Ventilator-Free Days, Increased the Risk of Pneumothorax Requiring Chest Tube Drainage), and Increased the Risk of Barotrauma, as Compared to Low PEEP Strategy
      • Lung Recruitment and Titrated PEEP Strategy Had No Impact on ICU Length of Stay, Hospital Length of Stay, or In-Hospital Mortality Rate, as Compared to Low PEEP Strategy
  • Recommendations for Patients with ARDS (American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice Guidelines for Mechanical Ventilation in ARDS) (Am J Respir Crit Care Med, 2017) [MEDLINE]
    • Recruitment Maneuvers are Recommended in Adults with ARDS (Conditional Recommendation, Low-Moderate Confidence)
      • Recruitment Maneuvers Should Be Used with Caution in Patients with Pre-Existing Hypovolemia/Shock Due to Concern About Causing Hemodynamic Compromise
  • Recommendations for Patients with ARDS Associated with Sepsis (2016 Surviving Sepsis Guidelines; Intensive Care Med, 2017) [MEDLINE]
    • Recruitment Maneuvers are Recommended in Sepsis-Associated ARDS (Weak Recommendation, Moderate Quality of Evidence)
      • Selected Patients with Severe Hypoxemia May Benefit from Recruitment Maneuvers in Conjunction with Higher Levels of PEEP

Humidification of the Ventilator Circuit

  • Rationale for Humidification
    • The Upper Airway Provides 75% of the Heat and Moisture Supplied to the Alveoli
    • When the Upper Airway is Bypassed with an Endotracheal Tube, the Humidifier Needs to Supply the Missing Heat/Moisture
  • Types of Humidification
    • Active Humidification Via a Heated Humidifier: actively increase the heat and water vapor content of inspired gas
    • Passive Humidification Via a Heat and Moisture Exchanger: operate passively by storing heat and moisture from a patient’s exhaled gas (and subsequently releasing it into the inhaled gas)
  • Clinical Efficacy
    • Review and Clinical Practice Guideline for the Use of Humidification with Mechanical Ventilation (Respir Care, 2012) [MEDLINE]
  • Recommendations (Respir Care, 2012) [MEDLINE]
    • Humidification is Recommended for Every Patient on Invasive Mechanical Ventilation (Grade 1A Recommendation)
    • Active Humidification is Recommended when Using NIPPV, as it May Improve Adherence and Comfort (Grade 2B Recommendation)
      • Passive Humidification is Not Recommended for NIPPV (Grade 2C Recommendation)
    • Invasive Mechanical Ventilation
      • When Providing Humidification to Patients with Low Tidal Volumes (i.e. Those on Lung-Protective Ventilation Strategies), Heat and Moisture Exchangers are Not Recommended Because They May Contribute to Additional Dead Space, Which Can Increase the Ventilation Requirement and pCO2
    • Heat and Moisture Exchanger Should Not Be Used for the Prevention of Ventilator-Associated Pneumonia (VAP) (Grade 2B Recommendation)

Sedation (see Sedation)

  • Recommendations for Patients with ARDS Associated with Sepsis (2016 Surviving Sepsis Guidelines; Intensive Care Med, 2017) [MEDLINE]
    • Continuous or Intermittent Sedation Should Be Minimized (with Specific Sedation Endpoints) in Sepsis-Associated Mechanically-Ventilated Respiratory Failure (Best Practice Statement)

Pressures on the Ventilator

Peak Inspiratory Pressure (PIP)

  • Peak Inspiratory Pressure is is the Maximal Airway Pressure (as Measure at the Ventilator) Achieved During Gas Delivery
    • During Volume-Cycled Ventilation: where tidal volume is manually set
      • Peak Airway Pressure is Dependent on the Following
        • Airway Resistance
        • Inspiratory Flow Rate/Pattern
        • Static Lung Compliance
        • Tidal Volume
      • Peak Airway Pressure is the Arithmetic Sum of the Following Pressures
        • Flow-Related Pressure
        • Pressure Related to Elastic System Recoil
        • End-Expiratory Pressure (PEEP + Auto-PEEP)
    • During Pressure-Cycled Ventilation
      • Delta P is Manually Set and PIP is Not Used

Plateau Pressure

  • Plateau Pressure (Pplat) is End-Inspiratory Pressure at a Point of Zero Inspiratory Airflow
    • Technique: measure during an inspiratory hold maneuver (0.5-1 sec)
    • Physiology
      • Pressure is the Pressure Which is Applied by the Mechanical Ventilator to the Small Airways and Alveoli During Positive-Pressure Mechanical Ventilation
      • Etiology of Increased Plateau Pressure
        • High PEEP
        • High Inspiratory Flow Rate
        • High Tidal Volume
    • Clinical
      • Plateau Pressure is the Airway Pressure Which is Best Correlated with the Risk of Barotrauma

Mean Alveolar Pressure

  • Mean Alveolar Pressure is Pressure Averaged Over the Entire Ventilatory Cycle
    • Mean Alveolar Pressure Cannot Be Measured Clinically, But it Best Estimated by the Plateau Pressure
    • Mean Alveolar Pressure is the Most Important Determinant of Oxygenation
    • Mean Alveolar Pressure Correlates with the Risk of Ventilator-Associated Barotrauma

Mean Airway Pressure

  • Mean Airway Pressure is Airway Pressure Averaged Over the Entire Ventilatory Cycle
    • Mean Airway Pressure Usually Underestimates the Mean Alveolar Pressure, But it Correlates with Oxygenation

End-Expiratory Pressure

  • End-Expiratory Pressure is Airway Pressure at the End of Expiration
    • If the End-Expiratory Airway Pressure is Positive, This is Termed Positive End-Expiratory Airway Pressure (PEEP)
      • Extrinsic PEEP: PEEP applied by the clinician
      • Auto-PEEP (Intrinsic PEEP): PEEP which develops due to intrinsic properties of the lungs and/or airways
      • Total PEEP = Extrinsic PEEP + Auto-PEEP

Driving Pressure

  • Driving Pressure = Plateau Pressure – PEEP
  • Clinical Data
    • Study of Contribution of Driving Pressure to Mortality in ARDS (NEJM, 2015) [MEDLINE]: study used data from 9 prior randomized trials
      • Rationale: lower tidal volume, lower plateau pressure, and higher PEEP are all believed to decrease mechanical stresses on the lung in ARDS (which can induce ventilator-associated lung injury)
        • However, There is an Uncertainty When Optimizing One Component Adversely Affects Another (Example: Increasing PEEP May Undesirably Increase the Plateau Pressure), Which this Study Attempted to Address
        • Authors Theorized in Their Study that Optimizing the Tidal Volume/Respiratory System Compliance Ratio (Known as the Driving Pressure = Delta P) Would Provide a Better Predictor of Outcome in ARDS
      • Driving Pressure (Plateau Pressure – PEEP or Delta P) was the Best Predictor of Survival
        • Decreases in Tidal Volume or Increases in PEEP Were Beneficial Only if They Resulted in a Decrease in Delta P (In Other Words, PEEP Increments are Protective Only When They are Associated with an Improvement in Respiratory System Compliance, So that the Same Tidal Volume Can Be Delivered with a Lower Delta P)
        • Further Trials Using Specific Manipulation of Delta P are Required Before Recommending this Strategy as a Standard
      • Caveat: Delta P Can Only Be Accurately Assessed in Non-Breathing Patients
  • Recommendations
    • Maintain the Driving Pressure ≤13-15 cm H2O (NEJM, 2015) [MEDLINE]

Troubleshooting Respiratory Decompensation on the Ventilator Using Airway Pressures

  • Decreased Peak Inspiratory Pressure (PIP)
    • Bronchopleural Fistula (see Bronchopleural Fistula)
      • Clinical Features
        • Air Leak from the Chest Tube is Present
    • Endotracheal Tube Cuff Leak
      • Clinical Features
        • Lost Volume on the Ventilator (i.e. Expiratory Tidal Volume < Inspiratory Tidal Volume)
        • Decreased Peak Inspiratory Pressure (PIP)
        • Air Leak Around the Endotracheal Tube Cuff is Frequently Audible or Manifested by Secretions Bubbling Out from the Patient’s Mouth During Exhalation
    • Inadvertent Extubation
      • Clinical Features
        • Often Occurs After Patient Turning or Repositioning
        • May Be Accompanied by Respiratory Distress or Precipitous Oxygen Desaturation
        • Lost Volume on the Ventilator (i.e. Expiratory Tidal Volume < Inspiratory Tidal Volume)
        • Intra-Breath Drop in Airway Pressure May Occur in Cases Where the Cuff has Herniated Above the Vocal Cords, as Air Begins to Leak Past the Cuff
    • Inadvertent Nasogastric (NG)/Orogastric (OG) Tube Placement into the Trachea/Mainstem Bronchus (with Suction Applied) (see Nasogastric/Orogastric Tube)
      • Diagnosis
        • Chest X-Ray or Bronchoscopy, Demonstrating Nasogastric/Orogastric Tube in the Trachea/Mainstem Bronchus
      • Clinical Features
        • Lost Volume on the Ventilator (i.e. Expiratory Tidal Volume < Inspiratory Tidal Volume)
        • Airway Pressure May Be Decreased Continuously (if on Continuous Suction) or Intermittently (if on Intermittent Suction)
    • Leak in Ventilator Circuit
      • Physiology
        • Due to a Loose Connection or Fractured Ventilator Tubing
      • Clinical Features
        • Lost Volume on the Ventilator (i.e. Expiratory Tidal Volume < Inspiratory Tidal Volume)
        • Decreased Peak Inspiratory Pressure (PIP)
    • Patient’s Inspiratory Effort Exceeding the Peak Flow Rate Set on the Ventilator
      • Clinical Features
        • Decreased Peak Inspiratory Pressure (PIP)
        • Normal or Increased Exhaled Tidal Volume
    • Tracheoesophageal Fistula (see Tracheoesophageal Fistula)
      • Clinical Features
        • Lost Volume on the Ventilator (i.e. Expiratory Tidal Volume < Inspiratory Tidal Volume)
        • Decreased Peak Inspiratory Pressure (PIP)
  • Normal Peak Inspiratory Pressure (PIP)
  • Increased Peak Inspiratory Pressure (PIP)

Compliance on the Ventilator

  • Static Lung Compliance
    • Static Compliance Reflects the Distensibility of the Lungs and Chest Wall (But Not Airway Resistance, Since it is Measured at Point of No Airflow)
    • Equation
      • Static Compliance = VT/(Plateau Pressure-Total PEEP)
        • Use the Exhaled Tidal Volume Shown on the Ventilator for the VT in this Equation, Not the Preset Tidal Volume (Since Ventilator Tubing Will Expand During Positive Pressure Ventilation: Expands About 3 cc for Every 1 cm H2O Increase in the Inflation Pressure
        • Compliance is Most Accurate when Performed During Passive Ventilation (Since the Patient’s Respiratory Muscle Efforts Will Decrease the Chest Wall Compliance) (Normal = 50-80 mL/cm H2O)
  • Dynamic Lung Compliance
    • Dynamic Compliance Reflects the Distensibility of the Lungs and Chest Wall and Airway Resistance (Since it is Measured at a Point of Maximal Inspiratory Airflow)
    • Equation
      • Dynamic Compliance = VT/(PIP-Total PEEP)
        • Use the Exhaled Tidal Volume Shown on the Ventilator for the VT in this Equation, Not the Preset Tidal Volume (Since Ventilator Tubing Will Expand During Positive Pressure Ventilation: Expands About 3 cc for Every 1 cm H2O Increase in the Inflation Pressure)
        • Compliance is Most Accurate when Performed During Passive Ventilation (Since the Patient’s Respiratory Muscle Efforts Will Decrease the Chest Wall Compliance) (Normal = 50-80 mL/cm H2O)

Ventilator Breath Types

  • Volume Control
    • Ventilator-Initiated Breaths with a Set Inspiratory Flow Rate
      • Inspiration is Terminated When the Set Tidal Volume is Reached
      • Airway Pressure is Determined by the Patient’s Airway Resistance, Lung Compliance, and Chest Wall Compliance
    • Examples of Ventilator Modes Which Use Volume Control Breaths
      • Volume Assist Control
      • Volume Synchronized Mandatory Ventilation (SIMV)
  • Volume Assist
    • Patient-Initiated Breaths with a Set Inspiratory Flow Rate
      • Inspiration is Terminated When a Set Tidal Volume is Reached
      • Airway Pressure is Determined by the Patient’s Airway Resistance, Lung Compliance, and Chest Wall Compliance
    • Examples of Ventilator Modes Which Use Volume Assist Breaths
      • Volume Assist Control
      • Volume Synchronized Mandatory Ventilation (SIMV)
  • Pressure Control
    • Ventilator-Initiated Breaths with a Set Pressure Limit
      • Inspiration is Terminated When the Set Inspiratory Time Has Elapsed
      • Tidal Volume is Variable and Dependent on the Patient’s Airway Resistance, Lung Compliance, Chest Wall Compliance, and Tubing Resistance: therefore, a specific minute ventilation is not guaranteed
    • Examples of Ventilator Modes Which Use Pressure Control Breaths
      • Pressure Assist Control
      • Pressure Synchronized Mandatory Ventilation (SIMV)
  • Pressure Assist
    • Ventilator-Initiated Breaths with a Set Pressure Limit
      • Inspiration is Terminated When the Set Inspiratory Time Has Elapsed
      • Tidal Volume is Variable and Dependent on the Patient’s Airway Resistance, Lung Compliance, Chest Wall Compliance, and Tubing Resistance: therefore, a specific minute ventilation is not guaranteed
    • Examples of Ventilator Modes Which Use Pressure Assist Breaths
      • Pressure Assist Control
      • Pressure Synchronized Mandatory Ventilation (SIMV)
  • Pressure Support
    • Patient-Initiated Breaths with a Pressure Limit
      • Ventilator Provides a Driving Pressure for Each Breath, Which Determines the Maximal Flow Rate
      • Inspiration is Terminated Once the Inspiratory Flow is Decreased to a Predetermined Percentage of its Maximum Value
    • Examples of Ventilator Modes Which Use Pressure Support Breaths
      • Pressure Support (PS)

Ventilator Modes

General Comments

  • Nomenclature of Ventilator Modes Has Become Increasingly Complex
    • Proposals Have Been Made to Revise the Ventilator Naming Scheme (Respir Care, 2007) [MEDLINE]

Continuous Mandatory Ventilation (CMV)

  • Clinical Use
    • Currently, Continuous Mandatory Ventilation is Less Commonly Used in the US
  • Concept
    • Minute Ventilation is Entirely Determined by the Set Respiratory Rate and Set Tidal Volume
      • Due to Sedation/Paralysis/Coma/Lack of Incentive to Increase Minute Ventilation Above the Set Respiratory Rate and Tidal Volume, the Patient Does Not Initiate Any Breaths Above the Set Respiratory Rate (and Ventilator Does Not Deliver Any Breaths if Patient Attempts to Triggers a Breath)
    • Types of Breaths Delivered
      • Volume Control Breaths (Ventilator-Triggered)
    • Work of Breathing
      • Effectively Zero
  • Settings
    • Respiratory Rate (RR)
    • Tidal Volume (VT)
  • Monitor
    • Peak Airway Pressure (PIP)
    • Plateau Pressure (Pplat)
  • Recommendations for Patients with ARDS Associated with Sepsis (2016 Surviving Sepsis Guidelines; Intensive Care Med, 2017) [MEDLINE]
    • No Ventilator Mode is Recommended Over Another for Mechanical Ventilation in Patients with Sepsis

Volume Synchronized Intermittent Mandatory Ventilation (SIMV)

  • Clinical Use
    • Volume Synchronized Intermittent Mandatory Ventilation is Commonly Used (Am J Respir Crit Care Med, 2000) [MEDLINE]
    • However, in a Study of Ventilation Practices in Patients with ARDS, the Use of Synchronized Intermittent Mandatory Ventilation (SIMV) Decreased from 1998 (11%) to 2004 (1.6%) (Am J Respir Crit Care Med, 2008) [MEDLINE]
  • Concept
    • Mode Which Uses a Set Respiratory Rate and Tidal Volume in Which the Ventilator-Initiated Breaths are Synchronized with the Patient’s Breaths
      • Patient-Triggered Breaths Occur Over the Set Rate (and These are at a Variable Tidal Volume, Depending on the Patient’s Respiratory Mechanics)
    • Types of Breaths
      • Volume Control Breaths (Ventilator-Triggered): ventilator breaths are synchronized with the patient inspiratory effort
      • Spontaneous Unsupported Breaths (Patient-Triggered): at whatever size the patient is able to generate
    • Work of Breathing
      • Highly Variable
        • If the Respiratory Rate is Set High and the Patient is Not Triggering Any Breaths, this Mode Functions Similar to Assist Control and the Patient’s Work of Breathing Will Be Very Low
        • If the Respiratory Rate is Set Low (or at Zero) and the Patient is Triggering Most or All of the Breaths, the Work of Breathing is Increased (and if Not Properly Monitored, the Patient May Rapidly Fatigue)
  • Settings
    • Respiratory Rate (RR)
    • Tidal Volume (VT)
  • Monitor
    • Peak Airway Pressure (PIP)
    • Plateau Pressure (Pplat)
  • Advantages
    • If the Respiratory Rate is Set Low, SIMV Allows the Patient to Maintain a Higher Degree of Respiratory Muscle Function (and Increased Work of Breathing), as Compared to Assist Control Ventilation
    • Work of Breathing Can Be Gradually Increased by Weaning Down the Set Respiratory Rate: this may be advantageous in postoperative settings, etc
    • Decreased Propensity to Develop Auto-PEEP, as Compared to Assist Control Ventilation
  • Disadvantages
    • Inappropriately Low Set Respiratory Rate May Result in the Patient Having a High Work of Breathing (with Resultant Fatigue)
  • Clinical Efficacy
    • SIMV May Decrease Dyssynchrony, Better Preserve Respiratory Muscle Function, Decrease Mean Airway Pressure, and Allow Greater Control Over the Level of Support, as Compared to Assist Control Ventilation (Am Rev Respir Dis, 1983) [MEDLINE]
    • Trial of Assist Control vs Synchronized Intermittent Mandatory Ventilation in Acute Respiratory Failure (without COPD) (Crit Care Med, 1989) [MEDLINE]
      • No Clear Clinical Difference Between Modes (Although Cardiac Output, Mean Arterial Blood Pressure, Pulmonary Capillary Wedge Pressure, and Oxygen Consumption were All Better When the Level of Support Provided by SIMV was <50%)
  • Study of Intermittent Mandatory Ventilation (Anesthesiology, 1994) [MEDLINE]
    • The Respiratory Neuromuscular System Poorly Adapts to Changing Respiratory Workloads Since Muscle Contraction During Lower Levels of IMV is Similar During Both Supported (Mandatory) and Unsupported (Spontaneous) Breaths
  • Recommendations for Patients with ARDS Associated with Sepsis (2016 Surviving Sepsis Guidelines; Intensive Care Med, 2017) [MEDLINE]
    • No Ventilator Mode is Recommended Over Another for Mechanical Ventilation in Patients with Sepsis

Pressure Synchronized Intermittent Mandatory Ventilation (SIMV)

  • Clinical Use
    • However, in a Study of Ventilation Practices in Patients with ARDS, the Use of Synchronized Intermittent Mandatory Ventilation (SIMV) Decreased from 1998 (11%) to 2004 (1.6%) (Am J Respir Crit Care Med, 2008) [MEDLINE]
  • Concept
    • Mode Which Uses a Set Respiratory Rate and Driving Pressure in Which the Ventilator-Initiated Breaths are Synchronized with the Patient’s Breaths
      • Patient-Triggered Breaths Occur Over the Set Rate (and These are at a Variable Tidal Volume, Depending on the Patient’s Respiratory Mechanics)
    • Types of Breaths
      • Pressure Control Breaths (Ventilator-Triggered): ventilator breaths are synchronized with the patient inspiratory effort
      • Spontaneous Unsupported Breaths (Patient-Triggered): at whatever size the patient is able to generate
    • Work of Breathing
      • Highly Variable
        • If the Respiratory Rate is Set High and the Patient is Not Triggering Any Breaths, this Mode Functions Similar to Assist Control and the Patient’s Work of Breathing Will Be Very Low
        • If the Respiratory Rate is Set Low (or at Zero) and the Patient is Triggering Most or All of the Breaths, the Work of Breathing is Increased (and if Not Properly Monitored, the Patient May Rapidly Fatigue)
  • Settings
    • Respiratory Rate (RR)
    • Driving Pressure (Delta P)
  • Monitor
    • Tidal Volume
  • Advantages
    • If the Respiratory Rate is Set Low, SIMV Allows the Patient to Maintain a Higher Degree of Respiratory Muscle Function (and Increased Work of Breathing), as Compared to Assist Control
    • Work of Breathing Can Be Gradually Increased by Weaning Down the Set Respiratory Rate: this may be advantageous in postoperative settings, etc
  • Disadvantages
    • Inappropriately Low Set Respiratory Rate May Result in the Patient Having a High Work of Breathing: which can result in fatigue
  • Recommendations for Patients with ARDS Associated with Sepsis (2016 Surviving Sepsis Guidelines; Intensive Care Med, 2017) [MEDLINE]
    • No Ventilator Mode is Recommended Over Another for Mechanical Ventilation in Patients with Sepsis

Volume Assist Control (Assist Control, AC) Ventilation

  • Clinical Use
    • Volume Assist Control (Assist Control) Ventilation is Commonly Used (Am J Respir Crit Care Med, 2000) [MEDLINE]
  • Concept
    • Flow-Targeted, Volume-Cycled Mode
      • Patient Can Trigger Additional Breaths Above the Set Respiratory Rate (with Each Breath Consisting of a Full Tidal Volume Breath)
    • Types of Breaths
      • Volume Control Breaths (Ventilator-Triggered)
      • Volume Assist Breaths (Patient-Triggered)
    • Work of Breathing
      • Very Low: most of the patient’s work of breathing in this mode (which is generally minimal) involves triggering ventilator-delivered breaths (if the patient is not triggering any breaths, their work of breathing is effectively zero)
  • Settings
    • Respiratory Rate (RR)
    • Tidal Volume (VT)
    • Flow Rate
    • PEEP
    • FIO2
    • I/E Ratio (Usually 1:2)
  • Monitor
    • Peak Airway Pressure (PIP)
    • Plateau Pressure (Pplat)
  • Advantages
    • Provides Guaranteed Delivery of the Desired Minute Ventilation (Due to a Set Tidal Volume and Set Respiratory Rate): this is useful if the patient is heavily sedated/paralyzed or apneic for other reasons
  • Disadvantages
    • Low Respiratory Muscle Workload May Result in Ventilator-Induced Diaphragmatic Dysfunction (VIDD)
  • Recommendations for Patients with ARDS Associated with Sepsis (2016 Surviving Sepsis Guidelines; Intensive Care Med, 2017) [MEDLINE]
    • No Ventilator Mode is Recommended Over Another for Mechanical Ventilation in Patients with Sepsis

Pressure Assist Control (Pressure Control, PC)

  • Concept
    • Pressure-Targeted, Time-Cycled Mode
      • Patient Can Trigger Additional Breaths Above the Set Respiratory Rate (with Each Breath Consisting of a Full Pressure Breath)
    • Types of Breaths
      • Pressure Control Breaths: machine triggered
      • Pressure Assist Breaths: patient triggered
    • Work of Breathing
      • Very Low: most of the patient’s work of breathing in this mode (which is generally minimal) involves triggering ventilator-delivered breaths (if the patient is nor triggering any breaths, their work of breathing is effectively zero)
  • Settings
    • Respiratory Rate (RR)
    • Delta P (Driving Pressure): since driving pressure is manually set, tidal volume that occurs will depend on lung/chest wall compliance
    • PEEP: typically initially set to +5
    • FIO2: typically initially set to 100% FIO2
  • Monitor
    • Tidal Volume (VT)
  • Advantages
    • Assuming No Change in Lung/Chest Wall Compliance, Provides Guaranteed Delivery of the Desired Minute Ventilation (Due to a Set Driving Pressure and Set Respiratory Rate): this is useful if the patient is heavily sedated/paralyzed or apneic for other reasons
  • Disadvantages
    • If Lung/Chest Wall Compliance Decreases During the Course of Ventilation (Due to Hemothorax, Pneumothorax, Pulmonary Edema), Tidal Volume Will Decrease: for this reason, tidal volumes need to be monitored closely in this mode (with ventilator alarms set accordingly)
  • Recommendations for Patients with ARDS Associated with Sepsis (2016 Surviving Sepsis Guidelines; Intensive Care Med, 2017) [MEDLINE]
    • No Ventilator Mode is Recommended Over Another for Mechanical Ventilation in Patients with Sepsis

Pressure-Regulated Volume Control (PRVC)

  • History
    • 1991: development of pressure-regulated volume control (and inclusion in the Siemens Servo 300 Ventilator)
      • PRVC was Developed to Address the Shortfall of Pressure Control Ventilation Where it Cannot Guarantee a Minimum Minute Ventilation in the Setting of Changing Lung Mechanics or Patient Effort
  • Concept
    • Volume-Targeted, Pressure Control Mode
      • PRVC Uses Tidal Volume as a Feedback Control for Continuously Adjusting the Pressure Target (and Inspiratory Time): it is a type of adaptive pressure control
      • PRVC Will Attempt to Deliver the Set Tidal Volume Using the Lowest Possible Pressure: it increases or decreases the pressure by +/- 3 cm H2O per breath
        • With Improved Respiratory Mechanics or Increased Respiratory Effort by the Patient, PRVC Will Deliver a Lower Inspiratory Pressure
        • If Patient Effort is Large Enough, the Tidal Volume Will Increase Despite a Lower Inspiratory Pressure
        • With Worsened Respiratory Mechanics or Decreased Respiratory Effort by the Patient, PRVC Will Deliver a Higher Inspiratory Pressure
    • Work of Breathing
      • Very Low
  • Commercial Availability
    • Maquet Servo-i Ventilator: known as Pressure-Regulated Volume Control (PRVC)
    • Drager Evita Ventilator: known as AutoFlow
    • Hamilton Galileo Ventilator: known as Adaptive Pressure Ventilation
    • Puritan Bennett 840 Ventilator: known as Volume Control+
    • Engstrom/General Electric Ventilator: known as Volume Targeted Pressure Control, Pressure Controlled Volume Guaranteed
  • Settings
    • Respiratory Rate (RR)
    • Tidal Volume (VT)
    • Flow Rate
    • PEEP
    • FIO2
    • Inspiratory Time: resulting in an I/E ratio (typically around 1:2)
    • Inspiratory Rise Time (Slope Percent): used on some PRVC ventilators to specify the speed at which to reach the peak pressure
    • Upper Pressure Alarm (Usually at 35-40 cm H2O): maximum delivered pressure should be 5 cm H2O below this
  • Monitor
    • Peak Airway Pressure (PIP)
    • Plateau Pressure (Pplat)
  • Advantages
    • Guaranteed Delivery of a Minimum Average Tidal Volume (Unless the Pressure Alarm is Set Too Low, So that the Target Tidal Volume is Not Delivered)
    • Guaranteed Ventilation at the (Minimum) Set Respiratory Rate
    • Decreased Peak Inspiratory Pressure (PIP), Theoretically Decreasing the Risk of Barotrauma: however, risk of barotrauma is most related to the plateau pressure (Pplat)
      • However, this Decrease is Relative to Volume Control, in Which the Peak Inspiratory Pressure is a Function of Both Resistance and Compliance and Would Be Expected to Be Higher (But Does Not Reflect the Actual Lung-Distending Pressure, the Plateau Pressure)
    • Decelerating Flow Pattern (Similar to Pressure Control) May Improve the Distribution of Ventilation
    • Can Better Meet Patient’s Inspiratory Flow Demands Since it Adapts to the Patient’s Airway Resistance and Compliance on a Breath by Breath Basis (i.e. Achieves Flow Synchrony)
    • Provides Automatic Weaning of Ventilator Support (Since the Inspiratory Pressure Decreases with Increasing Patient Effort): this can be an advantage or a disadvantage, depending on the desire for the patient to be exerting these efforts
  • Disadvantages
    • Ventilator May Potentially Increase the Pressure to a Dangerously High Level as it Attempts to Maintain the Set Tidal Volume
      • The Maximum Delivered Pressure is Limited to 5 cm H2O Below the Set High Pressure Alarm Limit
      • High Pressure Alarm Limit Should Be Set at 35-40 cm H20
    • Pressure Delivered is Dependent on the Tidal Volume Achieved During the Previous Breath
    • If the Patient Intermittently Makes a Significant Inspiratory Effort, it Can Result in Variable Tidal Volumes than Can Be Higher or Lower than the Set Tidal Volume
    • If a Patient Have a High Respiratory Drive (in the Setting of Severe Metabolic Acidosis, etc), PRVC Will Decrease the Inspiratory Pressure, Inappropriately Shifting the Workload to the Patient
  • Clinical Efficacy
    • Study Comparing Patient Comfort Between PRVC vs Pressure Support Ventilation (Respir Care, 2008) [MEDLINE]
      • PRVC was Less Comfortable than Pressure Support
  • Recommendations for Patients with ARDS Associated with Sepsis (2016 Surviving Sepsis Guidelines; Intensive Care Med, 2017) [MEDLINE]
    • No Ventilator Mode is Recommended Over Another for Mechanical Ventilation in Patients with Sepsis

Automode

  • Concept
    • Ventilator Automatically Switches Between PRVC and Volume Support Mode
      • When There is No Patient Effort, Ventilator Delivers PRVC Breaths
      • When There is Patient Effort, Ventilator Delivers Volume Support Breaths
  • Commercial Availability
    • Maquet Servo-i Ventilator
  • Recommendations for Patients with ARDS Associated with Sepsis (2016 Surviving Sepsis Guidelines; Intensive Care Med, 2017) [MEDLINE]
    • No Ventilator Mode is Recommended Over Another for Mechanical Ventilation in Patients with Sepsis

Adaptive Support Ventilation (ASV) (see Adaptive Servo Ventilation)

  • History
    • 1994: adaptive support ventilation was first described by Laubscher (Int J Clin Monit Comput 1994) [MEDLINE] (IEEE Trans Biomed Eng 1994) [MEDLINE]
    • 1998: adaptive support ventilation became commercially vvailable in Europe
    • 2007: adaptive support ventilation became commercially available in the US
  • Concept
    • Assist Control, Pressure-Targeted, Time-Cycled Mode Which Utilizes Respiratory Mechanics to Automatically Set a Tidal Volume-Frequency Pattern to Achieve a Desired Minute Ventilation Using Pressure Control Breaths
      • The Ventilator Algorithm Uses an Equation to Mimimize the Work of Inspiration (Theoretically Decreasing Applied Forces to the Lungs)
        • Equation Utilizes an Expiratory Time Constant Obtained from the Expiratory Limb of the Flow-Volume Loop (on a Breath by Breath Basis) (Crit Care Med, 1995) [MEDLINE] (Intensive Care Med, 2000) [MEDLINE]
        • Patients with Long Expiratory Time Constant (COPD or Asthma Exacerbation) Will Receive a Higher Tidal Volume and Lower Respiratory Rate (Int J Artif Organs, 2004) [MEDLINE] (Intensive Care Med, 2008) [MEDLINE]
        • Patients with Short Expiratory Time Constant (Stiff Lungs Due to ARDS, etc or Stiff Chest Wall Due to Kyphoscoliosis, Morbid Obesity, Neuromuscular Disease, etc) Will Receive a Lower Tidal Volume and Higher Respiratory Rate (Int J Artif Organs, 2004) [MEDLINE] (Intensive Care Med, 2008) [MEDLINE]
      • Tidal Volume is Adjusted to Deliver Low Tidal Volumes (But High Enough Above the Dead Space Volume to Avoid Hypoventilation)
      • Exhalation Time is Adjusted to Avoid Gas Trapping
      • In a Patient without Respiratory Efforts (Paralyzed Patient, etc), Adaptive Support Ventilation Delivers Pressure Control Breaths
      • In a Patient with Respiratory Efforts, Adaptive Support Ventilation Delivers Pressure Support for the Triggered Breaths with Supplemental Pressure Control Breaths to Achieve the Desired Respiratory Rate
  • Commercial Availability
    • Hamilton Galileo Ventilator
  • Settings
    • Desired Minute Ventilation (VE)
    • Patient Height (Which is Used to Calculate the Ideal Body Weight, Which is Subsequently Used to Estimate Anatomic Dead Space, Approximately 2.2 mL/kg)
    • Patient Sex
    • Percent of Normal Predicted Minute Ventilation Goal
      • If the Patient Has Increased Minute Ventilation Requirements (Due to Sepsis, Increased Dead Space, etc), this Might Be Set >100%
      • During Weaning, this Would Typically Be Set <100%
    • FIO2
    • PEEP
  • Advantages
    • Adaptive Support Ventilation Can Be Used from Initial Support Through Weaning
      • Adapts to Changing Lung Mechanics
      • Provides Automatic Weaning
    • Less Need for Human Manipulation of the Ventilator
    • Improved Synchrony
  • Disadvantages
    • Providers May Be Unfamiliar with This Ventilator Modality
  • Clinical Efficacy
    • Randomized Trial of Adaptive Support Ventilation in Fast-Track Extubation Protocol in Cardiac Surgery Patients (Anesthesiology, 2001) [MEDLINE]
      • Weaning Protocol Based on Adaptive Support Ventilation was Predictable and May Accelerate Extubation in Fast-Track Cardiac Surgery Patients
    • Trial Comparing Adaptive Support Ventilation with Pressure Control Synchronous Intermittent Mandatory Ventilation (Crit Care Med, 2002) [MEDLINE]
      • Adaptive Support Ventilation Had Lower Inspiratory Load and Improved Synchrony
    • Randomized Trial of Adaptive Support Ventilation vs Pressure-Regulated Volume Control Ventilation with Automode in Weaning Patients After Cardiac Surgery (Anesthesiology, 2008) [MEDLINE]
      • Adaptive Support Ventilation was Associated with Earlier Extubation
    • Randomized Trial Comparing Adaptive Support Ventilation to Pressure Assist/Control Ventilation in Mechanically-Ventilated Adult Medical ICU Patients (Chest, 2015) [MEDLINE]: n = 229
      • Adaptive Support Ventilation Shortened the Duration of Weaning and Total Duration of Mechanical Ventilation with a Fewer Number of Manual Ventilator Settings
      • No Differences were Observed in Terms of 28-Day Weaning Success or Mortality Rate
  • Recommendations for Patients with ARDS Associated with Sepsis (2016 Surviving Sepsis Guidelines; Intensive Care Med, 2017) [MEDLINE]
    • No Ventilator Mode is Recommended Over Another for Mechanical Ventilation in Patients with Sepsis

Volume Support

  • Concept
    • Patient-Triggered, Pressure-Targeted, Flow-Cycled Mode
      • Adjusts the Level of Pressure Support Required to Achieve a Set Tidal Volume, Based on the Inspiratory Effort by the Patient
      • Volume Support is Essentially Pressure Support with a Guaranteed Tidal Volume
  • Recommendations for Patients with ARDS Associated with Sepsis (2016 Surviving Sepsis Guidelines; Intensive Care Med, 2017) [MEDLINE]
    • No Ventilator Mode is Recommended Over Another for Mechanical Ventilation in Patients with Sepsis

Continuous Positive Airway Pressure (CPAP)

  • Clinical Utility
    • While Many Ventilators Use a “CPAP Mode”, During Which Pressure Support Ventilation is Added (So Called “CPAP/PS”), CPAP is Rarely Used Alone in the Modern Era for Spontaneous Breathing Trials
  • Concept
    • Maintains a Continuous Level of Pressure Throughout Inspiration
  • Indications
    • Weaning from Mechanical Ventilation
  • Recommendations for Patients with ARDS Associated with Sepsis (2016 Surviving Sepsis Guidelines; Intensive Care Med, 2017) [MEDLINE]
    • No Ventilator Mode is Recommended Over Another for Mechanical Ventilation in Patients with Sepsis

Pressure Support Ventilation (PSV)

  • Concept
    • Patient-Triggered, Flow-Cycled Mode
      • Inspiratory Pressure is Delivered by the Ventilator Until the Inspiratory Flow Decreases to a Predetermined Percentage of its Peak Value (Usually 25%)
    • Types of Breaths
      • Pressure Support Breaths (Patient-Triggered)
    • Work of Breathing
      • Variable (Depending on the Level of Pressure Support)
        • Patient’s Work of Breathing is Inversely Proportional to the Amount of Pressure Support Applied (i.e. High Pressure Support = Low Work of Breathing), Assuming that the Inspiratory Flow Rate is Sufficient to Meet the Patient Demand (Crit Care Med, 1997) [MEDLINE]
        • High Pressure Support Usually Results in a Higher Tidal Volume and Lower Respiratory Rate
      • Work of Breathing is Also Inversely Proportional to the Inspiratory Flow Rate, Such that Increasing the Inspiratory Flow Rate Shortens the Time Until Maximal Airway Pressure is Reached (Crit Care Med, 2003) [MEDLINE]
  • Indications
    • Ventilator Weaning
  • Settings
    • Pressure Support Level
      • The Required Pressure Support Level Depends on the Size of the Endotracheal Tube: resistance of the endotracheal tube is related to the endotracheal tube diameter and the inspiratory flow rate (Chest, 1988) [MEDLINE]
        • For 7.5-8.0 Endotracheal Tubes, Pressure Support of 5 cm H2O is Generally Considered Adequate to Overcome the Resistance of the Tube
        • For <7.0 Endotracheal Tube, Pressure Support ≥10 cm H20 May Be Required to Overcome the Resistance of the Tube (Anesthesiology, 1991) [MEDLINE]
      • Some Ventilators Have an Automatic Tube Compensation Mode, Which is a Type of Pressure Support Ventilation that Applies an Adequate Amount of Pressure to Overcome the Work of Breathing Imparted by the Endotracheal Tube (Which Can Vary from Breath to Breath)
        • Automatic Tube Compensation May Improve Tolerance of Spontaneous Breathing Trial Over CPAP Alone (Crit Care Med, 2006) [MEDLINE]
    • PEEP
    • FIO2
  • Monitor
    • Respiratory Rate (RR)
    • Tidal Volume (VT)
    • Index of Rapid Shallow Breathing (RSBI)
  • Advantages
    • Comfortable for Patient
    • Useful (and Commonly Used) for Ventilator Weaning
    • May Be Combined with Synchronized Intermittent Mandatory Ventilation (SIMV): SIMV breaths with most of the work of breathing performed by the ventilator and PS breaths with increasing amount of work performed by the patient (as pressure support levels are gradually decreased)
  • Disadvantages
    • Lack of Guaranteed Ventilation at a (Minimum) Set Respiratory Rate, Since the Patient Must Trigger All of the Breaths (Pressure Support Relies Entirely on the Patient’s Intrinsic Respiratory Drive)
    • When Used for Full Ventilatory Support, Pressure Support Ventilation Results in Poorer Sleep (as Compared to Assist Control Ventilation (Intensive Care Med, 2007) [MEDLINE]
      • As Compared to Assist Control Ventilation, Pressure Support Results in Greater Sleep Fragmentation, Less Stage 1 and 2 Non-Rapid Eye Movement (NREM) Sleep, More Wakefulness During the First Part of the Night, and Less Stage 3 and 4 NREM Sleep During the Second Part of the Night
    • When Used for Full Ventilatory Support, Pressure Support May Result in the Development of Central Sleep Apnea (CSA) During Sleep (see Central Sleep Apnea): may occur in patient on pressure support ventilation, due to sedation which depresses the central respiratory drive, critical illness itself, or hyperventilation (with hypocapnia)
      • Study of Ventilator Mode on Quality of Sleep (Am J Respir Crit Care Med, 2002) [MEDLINE]: n = 11
        • Inspiratory Assistance from Pressure Support Causes Hypocapnia, Which Combined with the Lack of a Backup Respiratory Rate and Wakefulness Drive Can Lead to Central Apneas and Sleep Fragmentation (Especially in Patients with Heart Failure)
    • When Used for Full Ventilatory Support, Pressure Support May Result in Ventilator Dyssynchrony (Which May Prolong the Duration of Mechanical Ventilation) (Chest, 1995) [MEDLINE] (Intensive Care Med, 2006) [MEDLINE]
      • Mechanisms Include Inspiratory Response Delays Caused by the Inspiratory Triggering Mechanisms and the Ventilator Demand Flow Characteristics, Mismatch Between the Patient’s cCompletion of the Inspiration and the Ventilator’s Criterion for Terminating Pressure Support; and Restriction of Expiration Due to Resistance from the Patient’s Airways, Endotracheal Tube, and/or Expiratory Valve
    • When Used for Full Ventilatory Support, High Levels of Pressure (≥20 cm H2O) are Required to Prevent Atelectasis and to Maintain a Stable Respiratory Pattern (Intensive Care Med, 1989) [MEDLINE] (Chest, 1990) [MEDLINE]
      • Higher Levels of Pressure Support (≥20 cm H2O) are Generally Less Comfortable for Patients, as Compared to Moderate Levels of Pressure Support (10-15 cm H2O) (Chest, 2004) [MEDLINE]
    • Pressure Support is Relatively Contraindicated in the Setting of Increased Airway Resistance (COPD or Asthma Exacerbation)
      • Due to Decreased Airflow Resulting in Termination of Inspiration After a Smaller than Optimal Tidal Volume Has Been Achieved (J Appl Physiol, 1985) [MEDLINE] (Chest, 1993) [MEDLINE]
      • Due to Pressure Support Not Preventing the Development of Auto-PEEP (Am J Respir Crit Care Med, 1995) [MEDLINE]
        • In This Setting, Selecting a Higher Percentage of the Peak Inspiratory Flow as the Trigger to Terminate Inspiration May Slightly Improve Auto-PEEP (Crit Care Med, 2007) [MEDLINE]
  • Clinical Efficacy-Weaning
    • Cochrane Database Systematic Review of Pressure Support vs T-Piece Weaning from Mechanical Ventilation in Adults (Cochrane Database Syst Rev, 2014) [MEDLINE]
      • Due to Low Quality Studies, the Effects on Weaning Success, ICU Mortality Rate, Reintubation Rate, ICU Length of Stay, and Pneumonia Rate were Imprecise
      • Pressure Support was More Effective than T-Piece for Successful Spontaneous Breathings Trials Among Patients with Simple Weaning
      • Based on 3 Trials, Pressure Support Use Shortened Weaning, While 1 Trial Demonstrated that T-Piece Use Shortened Weaning
    • Trial of Neurally Adjusted Ventilatory Assist vs Pressure Support (Crit Care Med, 2016) [MEDLINE]
      • In Patients Recovering from Acute Respiratory Failure, Levels of Neurally Adjusted Ventilatory Assist Between 0.5-2.5 cm H2O/μvolt are Comparable to Pressure Support Levels from 7-25 cm H2O in Terms of Respiratory Muscle Unloading
      • Neurally Adjusted Ventilatory Assist Provides Better Patient-Ventilator Interaction, But Can Be Sometimes Excessively Sensitive to Electrical Activity of the Diaphragm in Terms of Triggering
    • Comparative Trial of Pressure Support vs Proportional Assist Ventilation (Respir Care, 2017) [MEDLINE]
      • Mechanical Ventilation Dyssynchrony was Influenced by Patient Effort, Respiratory Mechanics, Ventilator Type, and Ventilation Mode
      • In Pressure Support Mode, Delayed Cycling was Associated with Shorter Effort in Obstructive Respiratory Mechanics Profiles, Whereas Premature Cycling was More Common with Longer Effort and a Restrictive Profile
      • Proportional Assist Ventilation-Plus (PAV+) Prevented Premature Cycling But Not Delayed Cycling, Especially in Obstructive Respiratory Mechanics Profiles, and it was Associated with a Lower Tidal Volume
  • Recommendations for Patients with ARDS Associated with Sepsis (2016 Surviving Sepsis Guidelines; Intensive Care Med, 2017) [MEDLINE]
    • No Ventilator Mode is Recommended Over Another for Mechanical Ventilation in Patients with Sepsis

Proportional Assist Ventilation (PAV) (see Proportional Assist Ventilation)

  • History
    • 1992: proportional assist ventilation was first developed by Younes (Am Rev Respir Dis, 1992) [MEDLINE] (Am Rev Respir Dis, 1992) [MEDLINE]
    • 1999: proportional assist ventilation first became available in Europe
    • 2006: proportional assist ventilation first became available in the US
  • Concept
    • Useful for a Spontaneously Breathing Patient with Normal Respiratory Drive
    • Proportional Assist Ventilation is Similar to Pressure Support Ventilation, Except that the Pressure Applied is a Function of the Patient Effort
      • Using the Servo, the Greater the Inspiratory Effort, the Greater the Increase in Applied Pressure
      • In Contrast, Pressure Support Ventilation Delivers a Constant Pressure Throughout Inspiration (as Pressure Controlled Breaths Via a Servo), Regardless of the Patient’s Inspiratory Effort
        • Pressure Rises to a Preset Level Which is Held Constant Until a Cycling Criterion is Met (Percent of the Maximum Inspiratory Flow is Reached): the inspiratory flow and tidal volume is the result of the patient’s inspiratory effort, the level of pressure applied, and the respiratory system mechanics
  • Indications
    • Ventilator Weaning
  • Commercial Availability
    • Puritan Bennett 840 Ventilator: known as proportional assist ventilation
    • Drager Ventilator: known as proportional pressure support
  • Settings
    • Airway Type (Endotracheal Tube vs Tracheostomy)
    • Airway Size (Inner Diameter)
    • Percentage of Work Supported (Assist Range: 5-95%)
    • Tidal Volume Limit
    • Pressure Limit
    • Expiratory Sensitivity: this parameter tells the ventilator at what flow to end the inspiration (since, normally, as inspiration ends, flow should stop)
  • Advantages
    • Decreased Work of Breathing
    • Improved Synchrony
    • Adapts to Changing Respiratory Mechanics and Patient Effort
    • Decreased Need for Ventilator Manipulation
    • Decreased Need for Sedation
    • Similar Hemodynamic Profile to Pressure Support Ventilation
  • Disadvantages
    • All Breaths are Spontaneous (Similar to Pressure Support)
      • Not Useful in a Patient with Decreased Respiratory Drive
    • The Patient Controls the Timing and Size of the Breath
      • While There are No Preset Volume, Pressure, or Flow Goals, Safety Limits Can Be Set for the Volume and Pressure
    • Not Useful in a Patient with Large Air Leak (Due to a Bronchopleural Fistula, etc)
    • Cautious Use in Patient with Airway Obstruction/Dynamic Hyperinflation (as the Ventilator May Not Sense the Prolonged Exhalation)
    • Cautious Use in Patient with High Ventilatory Drive (as the Ventilator May Overestimate the Respiratory System Mechanics and May Provide Overassistance, Even if the Patient Has Stopped Inspiration)
  • Clinical Efficacy
    • Trial Comparing Proportional Assist Ventilation to Pressure Support Ventilation (J Appl Physiol, 1996) [MEDLINE]
      • Proportional Assist Ventilation Decreased the Work of Breathing More than Pressure Support Ventilation
    • Trial Comparing Proportional Assist Ventilation to Pressure Support Ventilation in COPD Patients (Intensive Care Med, 1999) [MEDLINE]
      • Proportional Assist Ventilation Decreased the Work of Breathing More than Pressure Support Ventilation
    • Trial Comparing Proportional Assist Ventilation to Pressure Support Ventilation (Am J Respir Crit Care Med, 2000) [MEDLINE]
      • Proportional Assist Ventilation Decreased the Work of Breathing More than Pressure Support Ventilation
    • Study of the Effects of Pressure Support and Proportional Assist Ventilation in Hypercapnic COPD Patients with Acute Respiratory Failure (Respiration, 2003) [MEDLINE]
      • In Hypercapnic COPD Patients with Acute Respiratory Failure, Pressure Support May Cause Missing Efforts, Whereas Proportional Assist Ventilation May Cause “Runaway” Phenomenon, Due to Distinct Patient-Ventilator Interactions
      • However, These Phenomenon Do Not Limit the Improvement in Arterial Blood Gases with the Use of Both Modes
    • Trial Comparing Proportional Assist Ventilation to Pressure Support Ventilation (Intensive Care Med, 2006) [MEDLINE]
      • Proportional Assist Ventilation Decreased the Work of Breathing More than Pressure Support Ventilation
    • Trial of Pressure Support and Proportional Assist Ventilation in Patients with ARDS (Anesthesiology, 2006)[MEDLINE]
      • In Patients with ARDS Due to Sepsis, Respiratory Rate and Cardiac Index were Slightly Higher, as Compared to Pressure-Support Ventilation
      • Tidal Volumes were Variable, But within the Lung Protective Range (6-8 mL/kg with Plateau Pressure <30 cm H2O)
    • Trial of Pressure Support and Proportional Assist Ventilation in Mechanically-Ventilated Patients (Crit Care Med, 2007) [MEDLINE]
      • Proportional Assist Ventilation was More Efficacious than Pressure Support Ventilation in Terms of Matching Ventilatory Requirements with Ventilator Assistance, Resulting in Less Patient-Ventilator Dyssynchrony and Better Quality of Sleep
    • Trial of Pressure Support and Proportional Assist Ventilation in Mechanically-Ventilated Critically Ill Patients (Intensive Care Med, 2008) [MEDLINE]
      • Tidal Volumes were Variable, But within the Lung Protective Range (6-8 mL/kg with Plateau Pressure <30 cm H2O)
      • Proportional Assist Ventilation Increase Synchrony, as Compared to Pressure Support
  • Recommendations for Patients with ARDS Associated with Sepsis (2016 Surviving Sepsis Guidelines; Intensive Care Med, 2017) [MEDLINE]
    • No Ventilator Mode is Recommended Over Another for Mechanical Ventilation in Patients with Sepsis

Inverse Ratio Ventilation (IRV)

  • Concept
    • While Not a Ventilator Mode, this is a Ventilatory Strategy (Employed During Volume-Limited or Pressure-Limited Ventilation) with the Induction of Inspiratory Time > Expiratory Time (i.e. Inversion of the I:E Ratio)
      • Inverse Ratio Ventilation Strategy is Most Commonly Used in Conjunction with Pressure Ventilation (as Pressure Control-Inverse Ratio Ventilation), But There is No Clinical Difference Between its Use with Either of Volume-Cycled or Pressure-Cycled Ventilation (Chest, 2000) [MEDLINE]
      • The Clinical Goal is to Increase the Mean Airway Pressure to Potentially Improve Oxygenation
  • Indications
    • Refractory Hypoxemia in the Setting of ARDS
  • Technique
    • Inverse Ratio Ventilation Usually Requires Heavy Sedation with Paralysis to Facilitate Inversion of the Ratio (Since the Ratio is Typically Uncomfortable for the Patient)
    • Use of Inverse Ratio Ventilation with Volume-Cycled Ventilation
      • With a Ramp Wave Flow Pattern: peak inspiratory flow rate is initially set at least 4x higher than the minute ventilation and then slowly decreased until the inspiratory time exceeds the expiratory time
      • With a Square Wave Flow Pattern: end-inspiratory pause is added (usually 0.2 sec) and then slowly increased until the inspiratory time exceeds the expiratory time
    • Use of Inverse Ratio Ventilation with Pressure-Cycled Ventilation
      • Gradually Increase the I:E Ratio Until the Inspiratory Time Exceeds the Expiratory Time
      • When Inverse Ratio Ventilation is Used with Pressure Control, this Strategy Will Assure that a Maximal Plateau Pressure Will Not Be Exceeded (Protecting Against Ventilator-Induced Lung Injury and Barotrauma)
      • While Unproven, Development of Auto-PEEP May Be Less Common with Pressure Control-Inverse Ratio Ventilation than it is with Volume Control-Inverse Ratio Ventilation (Intensive Care Med, 1992) [MEDLINE]
  • Disadvantages
    • Development of Auto-PEEP (with Consequences Including Barotrauma, Hypotension, etc) (Chest, 1988) [MEDLINE]
    • Development of Barotrauma (Independent of the Development of Auto-PEEP)
      • Risk of Pneumothorax Has Been Reported to Be as High as 29% (Despite the Presence of Auto-PEEP) (Crit Care Med, 1995) [MEDLINE]
  • Clinical Efficacy
    • Observational Study of Pressure Control-Inverse Ratio Ventilation in Severe Adult Respiratory Failure (Chest, 1988) [MEDLINE]: n = 31
      • IRV was Associated with a Significant Increase in the Mean Airway Pressure and the pO2 (from 69 to 80 mm Hg), Despite a Decrease in PEEP
    • Study of Effects of Inverse Ratio Ventilation on Hemodynamics and Pulmonary Parameters (Chest, 1992) [MEDLINE]
      • IRV is Usually Well-Tolerated Hemodynamically
    • Trial of IRV in ARDS (Crit Care Med, 2001) ([MEDLINE]
      • In ARDS, Extending the End-Inspiratory Pause without Inducing a Clinically Significant Increase in PEEPi, Does Not Consistently Improve Arterial Oxygenation But Enhances Carbon Dioxide Elimination
  • Recommendations for Patients with ARDS Associated with Sepsis (2016 Surviving Sepsis Guidelines; Intensive Care Med, 2017) [MEDLINE]
    • No Ventilator Mode is Recommended Over Another for Mechanical Ventilation in Patients with Sepsis

Airway Pressure Release Ventilation (APRV) (see Airway Pressure Release Ventilation)

  • Concept
    • Inverse Ratio, Pressure Controlled, Intermittent Mandatory Ventilation with Unrestricted Spontaneous Breathing
      • Alveolar Recruitment is Maximized by the High Continuous Positive Airway Pressure During the P high Phase (Crit Care Med, 1987) [MEDLINE] (Crit Care Med, 1987) [MEDLINE]
      • The Transition from P high to P low Deflates the Lungs and Results in the Elimination of Carbon Dioxide
      • The Difference Between P high and P low is the Driving Pressure
      • Airway Pressure Release Ventilation Allows the Patient to Breathe Spontaneously While Receiving High Airway Pressure with an Intermittent Pressure Release
      • Historically, Airway Pressure Release Ventilation Has Been Viewed as “Alternating Levels of CPAP”: this gave rise to the P high, P low, etc terminology for settings
    • Confusion Exists in the Literature Regarding the Distinction Between APRV and Bi-Level Ventilation
      • Review of 50 Published Studies Noted that 78% of Them Described APRV, While 22% Described Bi-Level Ventilation (Intensive Care Med, 2008) [MEDLINE]
      • Proprietary Modes Vary by Manufacturer
        • Airway Pressure Release Ventilation (APRV): Drager Evita ventilators
        • BiLevel: Puritan-Bennett 840 ventilator (by Covidien)
        • BiPhasic: CareFusion ventilators
        • Bi-Vent: Maquet Servo-i ventilators
        • DuoPAP: Hamilton C-1 ventilator
      • Similarities
        • Both Modes Allow Unrestricted Spontaneous Breathing During and Between the Mandatory Breaths
      • Differences
        • APRV Uses Extreme I:E Ratios (>2:1), While Bi-Level Ventilation Usually Does Not
        • APRV Usually Keeps the Duration of T low at ≤1.5 sec, While Bi-Level Ventilation Has No Restriction on T low (Consequently, Bi-Level Ventilation Allows More Spontaneous Breaths to Occur at P low)
        • APRV Results in Higher Mean Airway Pressure, But Lower Minute Ventilation (VE) than Bi-Level Ventilation
        • In Intermittent Mandatory Airway Pressure Release Ventilation (IMPRV), Cyclic Inflations and Deflations are Synchronized to Occur After Every Few Spontaneous Breaths (Intensive Care Med, 1992) [MEDLINE]
  • Indications
  • Contraindications
    • Obstructive Lung Disease (COPD or Asthma Exacerbation) or High Minute Ventilation Requirement
      • Due to Increased Risk of Hyperinflation, High Alveolar Pressure, and Pulmonary Barotrauma
  • Physiology
    • Time Ratio
      • Airway Pressure Release Ventilation Time Ratios Reported in Literature: 1:1 to 9:1
      • The Greater the Percentage of the Total Time Spent at High Pressure (80-95%), the Greater the Alveolar Recruitment
      • The Lesser the Percentage of the Total Time Spent at Low Pressure (Usually 0.2-0.8 sec in Adults), the Less Alveolar De-Recruitment Occurs
      • If the Time Spent at Low Pressure is Too Short, Expiration Will Be Incomplete and Auto-PEEP Will Develop
        • However, Some APRV Regimens Use P Low of 0 cm H2O with the Required Development of Auto-PEEP
        • There is a Theoretical Concern About Developing Auto-PEEP, Since (Unlike Applied PEEP Which Distributes Evenly) Auto-PEEP Distributes Predominantly to Lung Units with the Highest Airway Resistance and Lowest Compliance (Chest, 1995) [MEDLINE]
        • Lung Units with Partially Obstructed Airways and Atelectatic Lung Units Will Consequently Have Higher PEEP than the Set P low
    • Clinical Determinants of Tidal Volume
      • Driving Pressure
      • Lung/Chest Wall Compliance (Which Includes the Airway Resistance)
      • Timing and Duration of Pressure Release
    • Clinical Determinants of Oxygenation (pO2)
      • FIO2
      • Amount of P high
      • Time Spent at T high
    • Clinical Determinants of Ventilation (pCO2)
      • Driving Pressure or Delta P (P high – P low)
        • Larger Delta P = More Volume Per Release = More CO2 Excretion Per Release
      • Patient’s Spontaneous Breathing
        • While Spontaneous Breathing May Occur at Both P high and P low, it Typically Occurs During the P high Phase (Due to the Short Duration of Time Spent at P low)
  • Technique
  • Ventilator Settings/Terminology
    • P high is the Upper Pressure Level
    • P low or PEEP is the Lower Pressure Level
    • T high is the Time Spent at P high
    • T low is the Time Spent at T low
    • Release Rate is the Number of Cycles (or Releases) Per Minute: increasing the release rate will decrease the pCO2
      • T high 4.0 sec + T low 0.5 sec (cycle length = 4.5 sec) -> release rate = 13.3/min
      • T high 4.5 sec + T low 0.5 sec (cycle length = 5.0 sec) -> release rate = 12.0/min
      • T high 5.0 sec + T low 0.5 sec (cycle length = 5.5 sec) -> release rate = 10.9/min
      • T high 6.0 sec + T low 0.5 sec (cycle length = 6.5 sec) -> release rate = 9.23/min
  • General Approach is to Ventilate the Lung on the Steep Portion of the Pressure-Volume Curve (Where Mean Lung Volume and Pressures are Adequate for Oxygenation and Ventilation and the Tidal Volume Lies Between the Lower and Upper Inflection Points of the Curves)
    • This Strategy Improves Lung Compliance, Venous Admixture, and pO2 in ARDS
    • This Strategy Also Protects the Lung in ARDS by Avoiding Collapse During Expiration (Atelectrauma) and Stretch-Related Lung Injury During Inspiration (Volutrauma, Barotrauma)
  • Sedation Should Be Minimized (Although, Some Sedation is Usually Required)
  • Paralytics Should Be Avoided, Since Using Paralytics Will Eliminate the Spontaneous Breaths (One of the Purported Benefits of APRV)
  • Initial Settings
    • No Consensus Exists with How to Set the Initial APRV Parameters: both of the following approaches are probably grossly equivalent
      • Approach #1: use short T low + P low of 0 cm H2O -> prolongs I:E ratio and creates auto-PEEP
      • Approach #2: use longer T low (to eliminate auto-PEEP) + higher P low (to avoid alveolar collapse)
    • Initial P high is Set Using the Plateau Pressure of the Current Volume-Controlled Mode (Preferably 20-30 cm H2O)
      • Target Tidal Volume Should Be Approximately 6 ml/kg PBW
      • Avoid Using P high >35 cm H2O, Unless the Patient Has Obesity/Ascites/etc
    • Initial P low Should Be Set at 0 cm H2O
    • Initial T high Should Be Set at 4.5 sec
    • Initial T low Should Be Set at 0.5 sec
  • Subsequent Changes
    • Wait 4-6 hrs for Clinical Response After a Change in Ventilator Settings
    • To Increase pO2
      • Increase FIO2
      • Increase P high (Adjust in 2 cm H2O Increments, Range: 20-30 cm H2O)
      • Increase T high (Adjust in 0.5 sec Increments, Range: 4.0-6.0 sec): this will decrease the release rate
      • Decrease T low: note that as the T high:T low ratio increases, auto-PEEP can develop (which will decrease effective delta P and VT)
      • Lung Recruitment Maneuvers
    • To Decrease pO2
      • Decrease FIO2
      • Decrease T high: this will increase the release rate
      • Increase T low (Adjust in 0.1 sec Increments, Range: 0.5-0.8 sec): this will increase the time spent at release
    • To Decrease pCO2
      • Increase P high (Adjust in 2 cm H2O Increments, Usual Range: 20-30 cm H2O): this will increase the delta P (P high – P low)
      • Decrease T high (Adjust in 0.5 sec Increments): this will increase the release rate
      • Increase T low (Adjust in 0.1 sec Increments, Range: 0.5-0.8 sec): this will increase the time spent at release
      • Optimize Spontaneous Breathing*
    • To Increase pCO2
      • Increase T high (Adjust in 0.5 sec Increments, Range: 4.0-6.0 sec): this will decrease the release rate
      • Decrease P high (Adjust in 2 cm H2O Increments, Usual Range: 20-30 cm H2O): this will decrease the delta P (P high – P low) and may undesirably decrease the pO2
  • Advantages
    • Alveolar Recruitment Due to High Airway Pressure and Diaphragmatic Contraction During Spontaneous Breathing
    • Improved Oxygenation, as Spontaneous Breaths Allow More Even Distribution of Ventilation (Decreasing Intrapulmonary Shunt)
    • Preservation of Spontaneous Breathing
      • With Spontaneous Breathing, APRV is Better Tolerated than Inverse Ratio Ventilation (Without the Need for Deep Sedation/Paralysis)
      • However, in the Absence of Spontaneous Breathing (i.e. During Paralysis), APRV is Functionally Equivalent to Inverse Ratio Ventilation (Due to the Relatively Long Times Spent at High Pressure)
    • Improved Hemodynamics: spontaneous breaths augment cardiac filling
    • Potential Lung-Protective Effects (Exp Ther Med, 2017) [MEDLINE]
    • No Significant Impact on Intracranial Pressure in the Setting of Traumatic Brain Injury and ARDS (J Crit Care, 2019) [MEDLINE]
  • Disadvantages
    • Risk of Volutrauma Due to Spontaneous Breathing During High Pressure (with Concomitant generation of Large Tidal Volumes and Large Negative Pleural Pressure Swings)
    • Increased Work of Breathing
    • Increased Energy Expenditure Due to Patient Taking Spontaneous Breaths
  • Clinical Efficacy
    • Trial of APRV vs Pressure Control Ventilation in Trauma Patients with ARDS (Am J Respir Crit Care Med, 2001) [MEDLINE]: n = 30
      • APRV was Associated with Increased Respiratory System Compliance, Increased Arterial pO2, Increased Cardiac Index, Increased Oxygen Delivery, Decreased Venous Admixture (QVA/QT), and Decreased Oxygen Extraction
      • Pressure Control Ventilation was Associated with Decreased Respiratory System Compliance, Decreased Arterial pO2, Decreased Cardiac Index, Decreased Oxygen Delivery, Increased Venous Admixture (QVA/QT), Increased Need for Sufentanil/Midazolam/Norepinephrine/Dobutamine
      • APRV was Associated with a Shorter Duration of Ventilatory Support and ICU Length of Stay
      • No Difference in Mortality Rates
    • Large Randomized Controlled Trial of APRV (Acta Anaesthesiol Scand, 2004) [MEDLINE]: RCT (n = 58) comparing APRV with SIMV with PS (study was terminated early for futility)
      • No 28-Day or 1-Year Mortality Benefit
      • No Difference in Ventilator-Free Days at 28 Days
      • However, Proning was Used in Both Arms and its Effects May Have Overshadowed the Potential Effects of APRV in this Study
    • Randomized Trial of APRV in Adult Trauma Patients with Respiratory Failure (J Trauma, 2010) [MEDLINE]: n= 63
      • For Adult Trauma Patients Requiring Mechanical Ventilation >72 hrs, APRV Had a Similar Safety Profile as Low Tidal Volume Ventilation
      • Trends for APRV Patients to Have Increased Ventilator Days, ICU Length of Stay, and Ventilator-Associated Pneumonia May Be Explained by Initial Higher Acute Physiology and Chronic Health Evaluation II Scores
    • Retrospective Review of APRV in Trauma Patients (J Trauma Acute Care Surg, 2012) [MEDLINE]
      • After Controlling for Confounding Factors, APRV Mode Increased the Number of Ventilator Days in Trauma Patients
    • Animal Study of APRV in Traumatized Pigs with Combined Brain and Lung Trauma (J Trauma Acute Care Surg, 2015) [MEDLINE]
      • Microdialysis Data Suggested a Trend Toward Increased Cerebral Ischemia Associated with APRV Over Time
    • Trial of APRV vs Standard Low Tidal Volume Ventilation in ARDS (Intensive Care Med, 2017) [MEDLINE]: n = 148
      • Early Application of APRV in ARDS Improved Oxygenation, Improved Respiratory System Compliance, Decreased Pplat, Decreased Duration of Mechanical Ventilation, and Decreased the ICU Length of Stay
    • Prospective Randomized Intermountain Trial of Low Tidal vs Traditional APRV and Volume Control Ventilation Protocols (Crit Care Med, 2018) [MEDLINE]: n = 246 planned (study stopped early because of low enrollment and inability to consistently achieve tidal volumes <6.5 mL/kg in the low tidal volume-airway pressure release ventilation arm)
      • APRV Often Resulted in Release Volumes >12 mL/kg Despite a Protocol Targeting Low Tidal Volume Ventilation
      • Current APRV Protocols are Unable to Achieve Consistent and Reproducible Delivery of Low Tidal Volume Ventilation Goals
    • Systematic Review and Meta-Analysis of APRV in Acute Hypoxemic Respiratory Failure (Ann Intensive Care, 2019) [MEDLINE]: n = 330 (5 RCT’s)
      • Evidence was Low Quality with Moderate Heterogeneity
      • APRV was Associated with a Higher Number of Ventilator-Free Days at Day 28
      • APRV was Associated with a Lower Hospital Mortality Rate
      • APRV was Not Associated with Any Negative Hemodynamic Impact or Increased Risk of Barotrauma
  • Recommendations for Patients with ARDS Associated with Sepsis (2016 Surviving Sepsis Guidelines; Intensive Care Med, 2017) [MEDLINE]
    • No Ventilator Mode is Recommended Over Another for Mechanical Ventilation in Patients with Sepsis

Neurally Adjusted Ventilatory Assist (NAVA) Ventilation (see Neurally Adjusted Ventilatory Assist)

  • Concept
    • Ventilator Mode in Which the Electrical Discharge from the Diaphragm (i.e. Diaphragmatic Excitation = EAdi) is Used to Trigger a Ventilator-Delivered Breath (Respir Care, 2011) [MEDLINE]
      • When a Deflection in the EAdi Signal Greater than the Set Threshold (Usually >0.5 μvolts) is Detected by a Sensor in a Gastric Tube Catheter, a Ventilator Breath is Delivered
      • Degree of Assist is Proportional to the Amplitude of the EAdi Signal and the Set Assist Level
      • Set Assist Level is Determined with the Assist Level Being Increased to Achieve a Comfortable and Consistent Tidal Volume and an EAdi Signal Which Remains Flat
      • Neuroventilator Coupling (Time Between a Spontaneous Diaphragmatic Effort and the Delivery of a Ventilator Breath) is Faster with NAVA than with Conventional Ventilator Modes
  • Advantages
    • XXXX
  • Disadvantages
    • Requires the Patient to Have an Intact Respiratory Drive
  • Clinical Efficacy
    • French Prospective Study of NAVA vs Pressure Support in Spontaneously Breathing Acute Respiratory Failure Patients in the ICU (Intensive Care Med, 2011) [MEDLINE]: n= 22
      • NAVA Decreased Ventilator Dyssynchrony
    • Trial of NAVA vs Proportional Assist Ventilation (Crit Care, 2015) [MEDLINE]: n = 16
      • NAVA vs Proportional Assist Ventilation Both Prevented Overdistention, Improved Neuromechanical Coupling, Improved the Variability of the Respiratory Pattern, and Decrease Ventilator Dyssynchrony
    • Trial of Neurally Adjusted Ventilatory Assist vs Pressure Support (Crit Care Med, 2016) [MEDLINE]
      • In Patients Recovering from Acute Respiratory Failure, Levels of Neurally Adjusted Ventilatory Assist Between 0.5-2.5 cm H2O/μvolt are Comparable to Pressure Support Levels from 7-25 cm H2O in Terms of Respiratory Muscle Unloading
      • Neurally Adjusted Ventilatory Assist Provides Better Patient-Ventilator Interaction, But Can Be Sometimes Excessively Sensitive to Electrical Activity of the Diaphragm in Terms of Triggering
    • French Multicenter Randomized Trial of NAVA vs Pressure Support Ventilation in the Early Phase of Ventilator Weaning (Intensive Care Med, 2016) [MEDLINE]: n = 125
      • NAVA Did Not Increase the Probability of Remaining in a Partial Ventilatory Mode (Either NAVA or Pressure Support) throughout the First 48 hrs
      • NAVA Did Not Increase Ventilator-Free Days at Day 28 or the 28-Day Mortality Rate
      • NAVA Decreased Ventilator Dyssynchrony
      • NAVA Resulted in Less Frequent Application of Postextubation Noninvasive Mechanical Ventilation
  • Recommendations for Patients with ARDS Associated with Sepsis (2016 Surviving Sepsis Guidelines; Intensive Care Med, 2017) [MEDLINE]
    • No Ventilator Mode is Recommended Over Another for Mechanical Ventilation in Patients with Sepsis

High-Frequency Ventilation (see High-Frequency Ventilation)

  • Concept
    • Ventilation Mode Employing the Use of High Respiratory Rates
  • Technique
    • General Comments: all techniques utilize respiratory rates >100 breaths/min
    • Conventional Mechanical Ventilation with Small Tidal Volumes and Rapid Respiratory Rates
    • Chest Wall Oscillation
    • High-Frequency Percussive Ventilation (HFPV): flow-regulated, pressure-limited, and time-cycled ventilator that delivers a series of high-frequency small volumes (at 200-900 cycles/min) in a successive stepwise stacking pattern
    • High-Frequency Jet Ventilation
    • High-Frequency Oscillation Ventilation (HFOV): most widely used type of high-frequency ventilation used in adult critical care -> delivers a small tidal volume by oscillating a bias gas flow in the airway
  • Clinical Efficacy
    • Randomized, Controlled Multicenter Oscillatory Ventilation For Acute Respiratory Distress Syndrome Trial) MOAT Trial of High-Frequency Oscillation Ventilation (Am J Respir Crit Care Med, 2002) [MEDLINE]
      • While the Study was Not Powered to Evaluate Mortality Differences, But an Insignificant Trend Toward Improved Overall 30-Day Mortality Rate in the High-Frequency Oscillation Ventilation Group, as Compared with the Conventional Ventilation Group (37% vs 52% 30-Day Mortality, p=0.098)
      • There Were No Significant Difference Between Groups in New or Worsening Barotrauma, Endotracheal Tube Obstruction, or Adverse Hemodynamic Effects
    • Retrospective Chart Review of High-Frequency Oscillation Ventilation for Rescue Therapy in Medical-Surgical ICU Patients (Chest, 2004) [MEDLINE]: n = 156
      • High-Frequency Oscillation Ventilation Had Beneficial Effects on pO2/FIO2 Ratios and Oxygenation Index
      • 30-Day Mortality Rate was 61.7%
      • Pneumothorax Rate was 21.8%
    • Canadian Clinical Trials Group OSCILLATE High-Frequency Oscillation Study in ARDS (NEJM, 2013) [MEDLINE]
      • In Adults with Moderate-to-Severe ARDS, Early Application of High-Frequency Oscillation Ventilation (as Compared with a Ventilation Strategy of Low Tidal Volume and High PEEP) Did Not Decrease and May Increase, the In-Hospital Mortality Rate
  • Recommendations (American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice Guidelines for Mechanical Ventilation in ARDS) (Am J Respir Crit Care Med, 2017) [MEDLINE]
    • High Frequency Ventilation is Not Routinely Recommended in Moderate-Severe ARDS (Strong Recommendation, Moderate-High Confidence)
    • Recommendations for Patients with ARDS Associated with Sepsis (2016 Surviving Sepsis Guidelines; Intensive Care Med, 2017) [MEDLINE]
    • No Ventilator Mode is Recommended Over Another for Mechanical Ventilation in Patients with Sepsis

Esophageal Pressure-Guided Mechanical Ventilation

  • Rationale
    • Pressures
      • Esophageal Pressure is a Surrogate for Pleural Pressure
      • Transpulmonary Pressure = Alveolar Pressure – Pleural Pressure
        • Alternative, Transpulmonary Pressure = Airway Pressure – Esophageal Pressure
    • Optimal Level of PEEP Maintains Oxygenation, While Preventing Lung Injury Due to Repeated Alveolar Collapse and Overdistention
      • In Patients with Low Pleural Pressure, PEEP Can Be Maintained Low to Keep Transpulmonary Pressure Low
      • In Patients with High Pleural Pressure (Where Underinflation May Cause Hypoxemia), PEEP Can Be Increased to Maintain a Positive Transpulmonary Pressure Which Might Improve Aeration and Oxygenation without Causing Overdistention
    • Stress Index
      • Rationale: stress index calculation allows determination of the optimal PEEP
      • Technique
      • Software-Derived Dimensionless Value Obtained During a Constant Flow Breath Reflecting the Shape of the Airway Pressure vs Time Curve
      • Requires Absence of Patient Effort
      • Optimal Stress Index is a Straight Diagonal (i.e. 1.0): reflecting unchanging compliance throughout the breath
        • Alternatively, if recruitment/derecruitment is occurring during the breath, the stress index curve is concave bowing upward (low compliance early, followed by high compliance later in the breath) -> stress index <1
        • Alternatively, if overdistention is occurring during the breath, the stress index curve is concave bowing downward (high compliance early, followed by low compliance later in the breath) -> stress index >1
  • Clinical Efficacy
    • EPVent Pilot Study Using Transpulmonary Pressure (NEJM, 2008) [MEDLINE]
      • Esophageal Pressure was Used as a Surrogate for Pleural Pressure
      • PEEP Levels were Set to Maintain End-Expiratory Transpulmonary Pressure Between 0-10 cm H2O and End-Inspiratory Transpulmonary Pressure to <25 cm H2O, Based on a Sliding Scale Using the Patient’s pO2 and FIO2
        • Transpulmonary Pressure was Used to Determine the Optimal Level of PEEP Based on Lung and Chest Wall Mechanics
        • pH was Maintained Between 7.30-7.45
        • pO2 was Maintained Between 55-120 mm Hg
      • As Compared to Standard Care, a Ventilator Strategy Using Esophageal Pressures to Estimate Transpulmonary Pressure Improved Oxygenation and Respiratory System Compliance and Had a Trend Toward a Decreased Mortality Rate
    • Study of Stress Index (Using Airway Pressure vs Time) to Decrease Injurious Ventilation (as Assessed by CT Scanning Measures of Ventilator-Induced Lung Injury) in ARDS (Anesthesiology, 2013) [MEDLINE]
      • Injurious Ventilation was Most Associated with Pplat,rs >25 cm H2O and Stress Index >1.05
        • Pplat,rs = plateau pressure for the respiratory system (inspiratory)
        • Stress Index = dimensionless number obtained during a constant flow breath which describes the shape of airway pressure vs time curve and the shape of the transpulmonary pressure (PL) vs time curve
    • Recommendations for Patients with ARDS Associated with Sepsis (2016 Surviving Sepsis Guidelines; Intensive Care Med, 2017) [MEDLINE]
    • No Ventilator Mode is Recommended Over Another for Mechanical Ventilation in Patients with Sepsis

Volume Assured Pressure Support Ventilation (VAPS) (see Volume Assured Pressure Support Ventilation)

  • Recommendations for Patients with ARDS Associated with Sepsis (2016 Surviving Sepsis Guidelines; Intensive Care Med, 2017) [MEDLINE]
    • No Ventilator Mode is Recommended Over Another for Mechanical Ventilation in Patients with Sepsis

Disease-Specific Mechanical Ventilation Strategies

Asthma and Chronic Obstructive Pulmonary Disease (COPD) (see Asthma and Chronic Obstructive Pulmonary Disease)

  • Strategies
    • Use Large Size Endotracheal Tube to Minimize the Expiratory Airflow Resistance
    • Use Low Tidal Volumes and Respiratory Rates (Decreasing the Minute Ventilation), Often with Permissive Hypercapnia
      • May Require Sedation (with/without Paralysis)
    • Decrease the I:E Ratio (from 1:3 to 1:5) to Avoid the Development of Auto-PEEP
      • May Require Higher Inspiratory Flow Rate (80-100 L/min)
    • Maintain Plateau Pressure <30 cm H2O
    • Aggressively Manage Ventilator Dyssynchrony
    • Treat Bronchospasm (by Standard Means)

Hypoxemic Respiratory Failure (of Any Etiology) (see Respiratory Failure)

  • Strategies
    • Standard Lung Protective Ventilation Strategy (Low Tidal Volume with Higher PEEP)

Cardiogenic Pulmonary Edema (see Cardiogenic Pulmonary Edema)

  • Strategies
    • Standard Lung Protective Ventilation Strategy (Low Tidal Volume with Higher PEEP)

Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome)

  • Strategies
    • Standard Lung Protective Ventilation Strategy (Low Tidal Volume with Higher PEEP)
    • Early Administration of Neuromuscular Blockade: may be beneficial

Increased Intracranial Pressure (ICP) (see Increased Intracranial Pressure)

  • Strategies
    • Avoid Hypotension (as This May Decrease the Cerebral Perfusion Pressure)
    • Maintain Normocapnia with pCO2 35-40 mm Hg (and Specifically Avoid Hypercapnia)
      • While Hyperventilation May Be Used for a Brief Period of Time (1-2 hrs) to Manage an Acute Increase in Intracranial Pressure Associated with Herniation Which is Unresponsive to Other Therapies (Mannitol, Sedation/Paralysis, Cerebrospinal Fluid Drainage), Prophylactic Hyperventilation (with pCO2 ≤35 mm Hg) Should Be Avoided in the Setting of Traumatic Brain Injury (TBI), Due to the Potential to Impair Cerebral Perfusion (see Traumatic Brain Injury) (J Neurosurg, 1991)[MEDLINE] (Chest, 2005) [MEDLINE] (Crit Care Med, 2005) [MEDLINE]
      • Permissive Hypercapnia is Contraindicated
    • Maintain Normoxemia

Pregnancy (see Pregnancy)

  • Strategy
    • Target a pCO2 of Approximately 32 mm Hg (Since Pregnant Patients Typically Normally Manifest a Respiratory Alkalosis)
      • Animal Studies Indicate that Decreasing the pCO2 Below this Level May Undesirably Decrease Uterine Blood Flow
      • Permissive Hypercapnia May Be Difficult to Maintain in a Pregnant Patient, But is Gdenerally Safe Up to a pCO2 of 60 mm Hg
    • Higher Levels of PEEP May Be Required in Third Trimester Patients to Prevent Atelectasis

Abdominal Compartment Syndrome (see Abdominal Compartment Syndrome)

  • Strategies
    • Permissive Hypercapnia (with/without Neuromuscular Blockade): may be required to decrease airway pressure and avoid barotrauma
    • Treat Underlying Abdominal Compartment Syndrome (as Required)

Trauma

  • Strategies
    • In the Setting of Shock, Avoid Excessive PEEP and Elevated Plateau Pressure (Both May Decrease Right Ventricular Filling and Cause Hypotension)
    • In the Setting of Lung Trauma, Use Standard Lung Protective Ventilation Strategy (Low Tidal Volume with Higher PEEP)
    • In the Setting of Increased Intracranial Pressure, See Measures Above
    • In the Setting of Abdominal Compartment Syndrome, See Measures Above

Adverse Effects and Complications

Unplanned Extubation

Definition

  • Definition of Unplanned Extubation: premature removal of endotracheal tube
    • Accidental Removal During the Course of Care
      • During Patient Transport
      • During Patient Turning
    • Purposeful Removal by Patient

Epidemiology of Unplanned Extubation

  • Unplanned Extubation is a Marker for Poor Quality of Care
  • Incidence of Unplanned Extubations
    • Study: 0.1-3.6 events per 100 ventilator days (Anesth Analg, 2012) [MEDLINE]
    • Study: 7.5 events per 1000 ventilator days (Am J Crit Care, 2014) [MEDLINE]
  • Reintubation Rate
    • Case-Control Study of the Outcome of Unplanned Extubation (Am J Respir Crit Care Med, 2000) [MEDLINE]: n = 75 patients with unplanned extubation (and 150 matched controls)
      • Of the Unplanned Extubations, 56% of Patients Required Reintubation
        • Of These, 74% Required Reintubation Immediately
        • Of These, 86% Required Reintubation within 12 hrs
      • Of the Unplanned Extubations, 44%) Occurred During Weaning Trials
      • Mortality Rate for Patients with Unplanned Extubation was 40%, as Compared to Controls (31%) (p>0.2)
      • Patients with Unplanned Extubation Had a Longer Duration of Mechanical Ventilation (19 vs 11 Days, p<0.01), Longer ICU Length of Stay ((21 vs 14 Days, p<0.05), Longer Hospital Length of Stay ((30 vs 21 Days, p<0.01), and Increased Risk to Require Chronic Care (64% vs 24%, p<0.001)
    • Systematic Review: reintubation rate was 45.8% (range: 1.8-88%) (Anesth Analg, 2012) [MEDLINE]
    • Study: reintubation rate was 27% (Am J Crit Care, 2014) [MEDLINE]
      • Those Who Required Reintubation were Older and Male

Risk Factors for Unplanned Extubation

  • Male Sex
    • Male Sex Has Been Demonstrated to Be Associated with Increased Risk for Unplanned Extubation (Crit Care, 2011) [MEDLINE]
    • Male Sex Has Been Demonstrated to Be Associated with Increased Risk for Unplanned Extubation (Odds Ratio 4.8) (Anesth Analg, 2012) [MEDLINE]
  • Lower Sedation Level
    • Ramsey Sedation Scale Category 1 and 2 Have Been Demonstrated to Be Associated with Increased Risk for Unplanned Extubation (Odds Ratios 30 and 25, Respectively) (Crit Care, 2011) [MEDLINE]
    • Lower Sedation Level Has Been Demonstrated to Be Associated with Increased Risk for Unplanned Extubation (Odds Ratio 2.0-5.4) (Anesth Analg, 2012) [MEDLINE]
    • Higher Consciousness Level Has Been Demonstrated to Be Associated with Increased Risk for Unplanned Extubation (Odds Ratio 1.4-2.0) (Anesth Analg, 2012) [MEDLINE]
    • Strategies of No Sedation (and Less So, Intermittent Sedation) Have Been Demonstrated to Be Associated with Increased Risk for Unplanned Extubation, as Compared to Patients Receiving Continuous Sedation (with Daily Sedation Vacation) (Am J Crit Care, 2014)[MEDLINE]
      • Agitation Appeared to be Highest in the Intermittent Sedation Group
  • Length of ICU Stay
    • Increased Length of ICU Stay Has Been Demonstrated to Be Associated with Increased Risk for Unplanned Extubation (Crit Care, 2011) [MEDLINE]
  • Type of Sedation
    • Midazolam Use (at the Time of Unplanned Extubation) Has Been Demonstrated to Be Associated with Increased Risk for Unplanned Extubation (Crit Care, 2011) [MEDLINE]
  • Restlessness/Agitation
    • Restlessness/Agitation Have Been Demonstrated to Be Associated with Increased Risk for Unplanned Extubation (Odds Ratio 3.3-30.6) (Anesth Analg, 2012) [MEDLINE]
  • Use of Physical Restraints
    • Use of Physical Restraints Has Been Demonstrated to Be Associated with Increased Risk for Unplanned Extubation (Odds Ratio 1.4-2.0) (Anesth Analg, 2012) [MEDLINE]
  • Nursing Care
    • Unplanned Extubation Has Been Demonstrated to Occur More Frequently on Night Shift and with the Patient Being Cared for by a Less Experienced Nurses (Anesth Analg, 2012) [MEDLINE]
  • APACHE II Score
    • High APACHE II Score (≥17) Has Been Demonstrated to Be Associated with Increased Risk for Unplanned Extubation (Odds Ratio 9.0) (Anesth Analg, 2012) [MEDLINE]
  • Presence of Chronic Obstructive Pulmonary Disease (COPD)
    • Presence of COPD Has Been Demonstrated to Be Associated with Increased Risk for Unplanned Extubation (Odds Ratio 2.3-2.4) (Anesth Analg, 2012) [MEDLINE]

Consequences of Unplanned Extubation

  • Airway Injury
  • Arrhythmias
  • Aspiration Pneumonia (see Aspiration Pneumonia)
  • Bronchospasm (see Obstructive Lung Disease)
  • Cardiorespiratory Arrest
  • Death
  • Impact on Mortality Rate
    • Patients with Unplanned Extubation Had a Lower Hospital Mortality Rate, as Compared to Patients without Unplanned Extubation (10% vs 30%) (Crit Care, 2011) [MEDLINE]
  • Increased Cost

Prevention of Unplanned Extubation

Preventative Measures

  • 24-hr Bedside Supervision
  • Avoidance of Agitation
  • Change in Method of Endotracheal Tube Securement
  • Daily Awakening Protocols: identifying patients ready for withdrawal from mechanical ventilation
  • Increased Nurse/Patient Ratio
  • Nursing Education
  • Patient Transport Protocols
  • Regular Surveillance
  • Securement of Endotracheal Tube Before Changing Patient Position
  • Sedation Protocols
  • Weaning Protocols

Clinical Efficacy

  • Quality Improvement Programs to Prevent Unplanned Extubation Reduce the Unplanned Extubation Rate by 42% (Range: 22-53%) (Anesth Analg, 2012) [MEDLINE]

Outcome of Mechanical Ventilation

Patients Undergoing Mechanical Ventilation Incur High Healthcare Costs and Sustain Prolonged Disability

  • Duke University One Year Prospective Study of the Outcomes of Patients Undergoing Mechanical Ventilation (Ann Intern Med. 2010;153(3):167 [MEDLINE]: n = 126
    • Approximately 82% of Mechanically-Ventilated Patients Survived Hospitalization
    • The Survivor Patients Had a Median of 4 Separate Hospital Transitions in Postdischarge Care Location
    • Approximately 67% of the Survivor Patients were Readmitted at Least Once
    • Survivor Patients Spent an Average of 74% of All Days Alive in a Hospital or Postacute Care Facility or Receiving Home Health Care
    • At 1 Year, 9% of Patients Had a Good Outcome (Alive with No Functional Dependency), 26% Had a Fair outcome (Alive with Moderate Functional Dependency), and 65% Had a Poor Outcome (Either Alive with Complete Functional Dependency [21%] or Dead [44%])
    • Patients with Poor Outcomes were Older, Had More Comorbid Conditions, and Were More Frequently Discharged to a Postacute Care Facility than Patients with Either Fair or Good Outcomes (P<0.05 for All)
    • Mean Cost Per Patient was $306,135 (SD: $285,467), and Total Cohort Cost was $38.1 million, for an Estimated $3.5 Million Per Independently Functioning Survivor at 1 Year

References

General

  • American Association for Respiratory Care Consensus Group. Essentials of Mechanical Ventilators. Respir Care 1992; 37:1000-1008
  • Classification for mechanical ventilators. Respir Care 1992; 37:1009-1025
  • Increased initial flow rate reduces inspiratory work of breathing during pressure support ventilation in patients with exacerbation of chronic obstructive pulmonary disease. Intensive Care Med. 1996 Nov;22(11):1147-54 [MEDLINE]
  • The treatment of acidosis in acute lung injury with tris-hydroxymethyl aminomethane (THAM). Am J Respir Crit Care Med. 2000 Apr;161(4 Pt 1):1149-53 [MEDLINE]
  • High-frequency oscillatory ventilation for acute respiratory distress syndrome in adults: A randomized, controlled trial. Am J Respir Crit Care Med 2002;166:801-808
  • Effect of inspiratory time and flow settings during assist-control ventilation. Curr Opin Crit Care. 2003 Feb;9(1):39-44 [MEDLINE]
  • High-frequency oscillatory ventilation in adults: The Toronto experience. Chest 2004;126:518 [MEDLINE]
  • Humidification during invasive and noninvasive mechanical ventilation: 2012. Respir Care. 2012 May;57(5):782-8. doi: 10.4187/respcare.01766 [MEDLINE]
  • An Official American Thoracic Society/American College of Chest Physicians Clinical Practice Guideline: Liberation from Mechanical Ventilation in Critically Ill Adults. Rehabilitation Protocols, Ventilator Liberation Protocols, and Cuff Leak Tests. Am J Respir Crit Care Med. 2017 Jan 1;195(1):120-133. doi: 10.1164/rccm.201610-2075ST [MEDLINE]
  • Official Executive Summary of an American Thoracic Society/American College of Chest Physicians Clinical Practice Guideline: Liberation from Mechanical Ventilation in Critically Ill Adults. Am J Respir Crit Care Med. 2017 Jan 1;195(1):115-119. doi: 10.1164/rccm.201610-2076ST [MEDLINE]

Physiology

  • Clinical manifestations of inspiratory muscle fatigue. Am J Med. 1982;73(3):308 [MEDLINE]
  • Hypercapnia. N Engl J Med. 1989;321(18):1223 [MEDLINE]
  • Treatment of severe cardiogenic pulmonary edema with continuous positive airway pressure delivered by face mask. N Engl J Med. 1991;325(26):1825 [MEDLINE]
  • Influence of mechanical ventilation on blood lactate in patients with acute respiratory failure. Intensive Care Med. 1998;24(9):924 [MEDLINE]

Technique

Types of Mechanical Ventilation

Pressure-Cycled vs Volume-Cycled Ventilation
  • Randomized, prospective trial of pressure-limited versus volume-controlled ventilation in severe respiratory failure. Crit Care Med. 1994;22(1):22 [MEDLINE]
  • Effects of short-term pressure-controlled ventilation on gas exchange, airway pressures, and gas distribution in patients with acute lung injury/ARDS: comparison with volume-controlled ventilation. Chest. 2002;122(4):1382 [MEDLINE]
  • Different modes of assisted ventilation in patients with acute respiratory failure. Eur Respir J. 2002;20(4):925 [MEDLINE]
Variables Involved in Positive-Pressure Ventilation
  • Optimization of respiratory muscle relaxation during mechanical ventilation. Anesthesiology. 1988;69(1):29 [MEDLINE]

Ventilator Settings

Trigger
  • Inspiratory work of breathing on flow-by and demand-flow continuous positive airway pressure. Crit Care Med. 1989;17(11):1108 [MEDLINE]
  • Influence of pressure- and flow-triggered synchronous intermittent mandatory ventilation on inspiratory muscle work. Crit Care Med. 1994;22(12):1933 [MEDLINE]
  • Patient-ventilator interaction during synchronized intermittent mandatory ventilation. Effects of flow triggering. Am J Respir Crit Care Med. 1995;151(1):1 [MEDLINE]
  • Effects of flow triggering on breathing effort during partial ventilatory support. Am J Respir Crit Care Med. 1998;157(1):135 [MEDLINE]
  • Flow triggering, pressure triggering, and autotriggering during mechanical ventilation. Crit Care Med. 2000;28(2):579 [MEDLINE]
Tidal Volume (VT)
  • Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342(18):1301 [MEDLINE]
  • Intraoperative ventilation: incidence and risk factors for receiving large tidal volumes during general anesthesia. BMC Anesthesiol. 2011;11:22 [MEDLINE]
  • Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory distress syndrome: a meta-analysis. JAMA. 2012;308(16):1651 [MEDLINE]
  • A trial of intraoperative low-tidal-volume ventilation in abdominal surgery. N Engl J Med. 2013;369(5):428 [MEDLINE]
  • Intraoperative low-tidal-volume ventilation. N Engl J Med. 2013;369(19):1861 [MEDLINE]
  • Intraoperative ventilatory strategies to prevent postoperative pulmonary complications: a meta-analysis. Curr Opin Anaesthesiol. 2013 Apr;26(2):126-33 [MEDLINE]
  • Association between tidal volume size, duration of ventilation,and sedation needs in patients without acute respiratory distress syndrome: an individual patient data meta-analysis. Intensive Care Med. 2014;40(7):950-957 [MEDLINE]
  • Lung-Protective Ventilation With Low Tidal Volumes and the Occurrence of Pulmonary Complications in Patients Without Acute Respiratory Distress Syndrome: A Systematic Review and Individual Patient Data Analysis. Crit Care Med. 2015 Oct;43(10):2155-63 [MEDLINE]
  • A Meta-analysis of Intraoperative Ventilation Strategies to Prevent Pulmonary Complications: Is Low Tidal Volume Alone Sufficient to Protect Healthy Lungs? Ann Surg. 2016 May;263(5):881-7. doi: 10.1097/SLA.0000000000001443 [MEDLINE]
  • PReVENT Trial. Effect of a Low vs Intermediate Tidal Volume Strategy on Ventilator-Free Days in Intensive Care Unit Patients Without ARDS: A Randomized Clinical Trial. JAMA. 2018 Oct 24. doi: 10.1001/jama.2018.14280 [MEDLINE]
Respiratory Rate
  • Increasing respiratory rate to improve CO2 clearance during mechanical ventilation is not a panacea in acute respiratory failure. Crit Care Med. 2002;30(7):1407 [MEDLINE]
Positive End-Expiratory Pressure (PEEP)
  • Occult positive end-expiratory pressure in mechanically ventilated patients with airflow obstruction: The auto-PEEP effect. Am Rev Respir Dis 1982; 126:166-170 [MEDLINE]
  • Effect of positive end-expiratory pressure and body position in unilateral lung injury. J Appl Physiol Respir Environ Exerc Physiol. 1982;52(1):147 [MEDLINE]
  • Physiologic PEEP. Respir Care. 1988; 33:620
  • Determination of auto-PEEP during spontaneous and controlled ventilation by monitoring changes in end-expiratory thoracic gas volume. Chest 1989; 96:613-616 [MEDLINE]
  • Should PEEP be used in airflow obstruction? Am Rev Respir Dis 1989; 140:1-3 [MEDLINE]
  • PEEP, auto-PEEP, and waterfalls. Chest. 1989 Sep;96(3):449-51 [MEDLINE]
  • Auto-PEEP during CPR: an “occult” cause of electromechanical dissociation? Chest 1991;99:492–493 [MEDLINE]
  • Physiologic effects of positive end-expiratory pressure in chronic obstructive pulmonary disease during acute ventilatory failure and controlled mechanical ventilation. Am Rev Respir Dis. 1993;147:5–13 [MEDLINE]
  • Positive end-expiratory pressure increases the right to-left shunt in mechanically ventilated patients with patent foramen ovale. Ann Intern Med 1993; 119:887-894 [MEDLINE]
  • Interaction between intrinsic positive end-expiratory pressure and externally applied positive end-expiratory pressure during controlled mechanical ventilation. Crit Care Med 1993; 21:348-356 [MEDLINE]
  • The effects of applied vs auto-PEEP on local lung unit pressure and volume in a four-unit lung model. Chest. 1995 Oct;108(4):1073-9 [MEDLINE]
  • Auto-PEEP and electromechanical dissociation. N Engl J Med 1996;335:674–675 [MEDLINE]
  • Does positive end-expiratory pressure ventilation improve left ventricular function? A comparative study by transesophageal echocardiography in cardiac and noncardiac patients. Chest. 1998;114(2):556 [MEDLINE]
  • Pressure-volume curves and compliance in acute lung injury: evidence of recruitment above the lower inflection point. Am J Respir Crit Care Med. 1999 Apr;159(4 Pt 1):1172-8 [MEDLINE]
  • Use of pulse oximetry to recognize severity of airflow obstruction in obstructive airway disease: correlation with pulsus paradoxus. Chest 1999;115:475–481 [MEDLINE]
  • Influence of positive end-expiratory pressure on intracranial pressure and cerebral perfusion pressure in patients with acute stroke. Stroke. 2001;32(9):2088 [MEDLINE]
  • Intrinsic (or auto-) positive end-expiratory pressure during spontaneous or assisted ventilation. Intensive Care Med 2002;28:1552 [MEDLINE]
  • Positive end-expiratory pressure alters intracranial and cerebral perfusion pressure in severe traumatic brain injury. J Trauma. 2002;53(3):488 [MEDLINE]
  • The National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. N Engl J Med 2004;351:327-36 [MEDLINE]
  • Effects of positive end-expiratory pressure on gastric mucosal perfusion in acute respiratory distress syndrome. Crit Care. 2004;8(5):R306 [MEDLINE]
  • Effects of positive end-expiratory pressure on regional cerebral blood flow, intracranial pressure, and brain tissue oxygenation. Crit Care Med. 2005;33(10):2367 [MEDLINE]
  • Cardiovascular issues in respiratory care. Chest. 2005;128(5 Suppl 2):592S [MEDLINE]
  • Review of ventilatory techniques to optimize mechanical ventilation in acute exacerbation of chronic obstructive pulmonary disease.  Int J Chron Obstruct Pulmon Dis  2007 Dec;2(4):441–452 [MEDLINE]
  • Positive-end expiratory pressure reduces incidence of ventilator-associated pneumonia in nonhypoxemic patients. Crit Care Med. 2008;36(8):2225 [MEDLINE]
  • Positive-end expiratory pressure setting in adult acute lung injury and acute respiratory distress syndrome: a randomized, controlled trial. JAMA 2008;299:646 [MEDLINE]
  • Effect of positive expiratory pressure and type of tracheal cuff on the incidence of aspiration in mechanically ventilated patients in an intensive care unit. Crit Care Med. 2008;36(2):409 [MEDLINE]
  • Clinical concise review: Mechanical ventilation of patients with chronic obstructive pulmonary disease. Crit Care Med. 2008 May;36(5):1614-9. doi: 10.1097/CCM.0b013e318170f0f3 [MEDLINE]
  • Positive end-expiratory pressure redistributes regional blood flow and ventilation differently in supine and prone humans. Anesthesiology. 2010;113(6):1361 [MEDLINE]
  • Cardiac output estimation using pulmonary mechanics in mechanically ventilated patients. Biomed Eng Online. 2010;9:80 [MEDLINE]
  • Dynamic hyperinflation and auto-positive end-expiratory pressure: lessons learned over 30 years. Am J Respir Crit Care Med. 2011;184:756–762 [MEDLINE]
  • Patient-ventilator interactions. Implications for clinical management. Am J Respir Crit Care Med. 2013;188:1058–1068 [MEDLINE]
  • High versus low positive end-expiratory pressure during general anaesthesia for open abdominal surgery (PROVHILO trial): a multicentre randomised controlled trial. Lancet. 2014 Aug 9;384(9942):495-503. doi: 10.1016/S0140-6736(14)60416-5. Epub 2014 Jun 2 [MEDLINE]
  • Asynchronies during mechanical ventilation are associated with mortality. Intensive Care Med. 2015;41(4): 633–641; published online Feb 2015 [MEDLINE]
  • Effect of Intensive vs Moderate Alveolar Recruitment Strategies Added to Lung-Protective Ventilation on Postoperative Pulmonary Complications: A Randomized Clinical Trial. JAMA. 2017;317(14):1422 [MEDLINE]
  • Best PEEP trials are dependent on tidal volume. Crit Care. 2018;22(1):115 [MEDLINE]
  • Individualised perioperative open-lung approach versus standard protective ventilation in abdominal surgery (iPROVE): a randomised controlled trial. Lancet Respir Med. 2018;6(3):193 [MEDLINE]
Flow Rate and Pattern
  • Decelerating inspiratory flow waveform improves lung mechanics and gas exchange in patients on intermittent positive-pressure ventilation. Intensive Care Med. 1985;11(2):68 [MEDLINE]
  • The inspiratory workload of patient-initiated mechanical ventilation. Am Rev Respir Dis. 1986;134(5):902 [MEDLINE]
  • Optimization of respiratory muscle relaxation during mechanical ventilation. Anesthesiology. 1988;69(1):29 [MEDLINE]
  • Mechanical ventilation. N Engl J Med. 1994;330(15):1056 [MEDLINE]
  • Different modes of assisted ventilation in patients with acute respiratory failure. Eur Respir J. 2002;20(4):925 [MEDLINE]
  • Effects of inspiratory flow waveforms on lung mechanics, gas exchange, and respiratory metabolism in COPD patients during mechanical ventilation. Chest. 2002;122(6):2096 [MEDLINE]
Fraction of Inspired Oxygen (FIO2)
  • Conservative versus Liberal Oxygenation Targets for Mechanically Ventilated Patients. A Pilot Multicenter Randomized Controlled Trial. Am J Respir Crit Care Med. 2016 Jan;193(1):43-51 [MEDLINE]
  • Effect of Conservative vs Conventional Oxygen Therapy on Mortality Among Patients in an Intensive Care Unit: The Oxygen-ICU Randomized Clinical Trial. JAMA. 2016 Oct 18;316(15):1583-1589. doi: 10.1001/jama.2016.11993 [MEDLINE]
  • Hyperoxia and hypertonic saline in patients with septic shock (HYPERS2S): a two-by-two factorial, multicentre, randomised, clinical trial. Lancet Respir Med. 2017 Mar;5(3):180-190. doi: 10.1016/S2213-2600(17)30046-2 [MEDLINE]
  • BTS guideline for oxygen use in adults in healthcare and emergency settings. Thorax. 2017;72(Suppl 1):ii1 [MEDLINE]
  • Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet. 2018 Apr 28;391(10131):1693-1705. doi: 10.1016/S0140-6736(18)30479-3 [MEDLINE]
  • Hyperoxia toxicity in septic shock patients according to the Sepsis-3 criteria: a post hoc analysis of the HYPER2S trial. Ann Intensive Care. 2018 Sep 17;8(1):90. doi: 10.1186/s13613-018-0435-1 [MEDLINE]
  • Emergency department hyperoxia is associated with increased mortality in mechanically ventilated patients: a cohort study. Crit Care. 2018 Jan 18;22(1):9. doi: 10.1186/s13054-017-1926-4 [MEDLINE]
  • Oxygen therapy for acutely ill medical patients: a clinical practice guideline. BMJ. 2018 Oct 24;363:k4169. doi: 10.1136/bmj.k4169. [MEDLINE]

Recruitment Maneuvers

  • Recruitment manoeuvres for adults with acute lung injury receiving mechanical ventilation. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD006667 [MEDLINE]
  • Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA. 2017 Oct 10;318(14):1335-1345. doi: 10.1001/jama.2017.14171 [MEDLINE]

Ventilator Breath Types

  • XXXX

Ventilator Modes

General
  • Randomized, prospective trial of pressure-limited versus volume-controlled ventilation in severe respiratory failure. Crit Care Med. 1994;22(1):22 [MEDLINE]
  • How is mechanical ventilation employed in the intensive care unit? An international utilization review. Am J Respir Crit Care Med. 2000;161(5):1450 [MEDLINE]
  • Characteristics and outcomes in adult patients receiving mechanical ventilation: a 28-day international study. JAMA. 2002;287(3):345 [MEDLINE]
  • Classification of ventilator modes: update and proposal for implementation. Respir Care 2007; 52:301–323 [MEDLINE]
  • Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017 Jan 18. doi: 10.1007/s00134-017-4683-6 [MEDLINE]
Continuous Mandatory Ventilation (CMV)
  • Patient comfort during pressure support and volume controlled continuous mandatory ventilation. Respir Care 2008; 53:897-902 [MEDLINE]
Synchronized Intermittent Mandatory Ventilation (SIMV)
  • Intermittent mandatory ventilation. Am Rev Respir Dis. 1983;127(5):641 [MEDLINE]
  • Demand and continuous flow intermittent mandatory ventilation systems. Chest. 1985;87(5):625 [MEDLINE]
  • External work output and force generation during synchronized intermittent mechanical ventilation. Effect of machine assistance on breathing effort. Am Rev Respir Dis. 1988;138(5):1169 [MEDLINE]
  • Assist control versus synchronized intermittent mandatory ventilation during acute respiratory failure. Crit Care Med. 1989;17(7):607 [MEDLINE]
  • Regulation of inspiratory neuromuscular output during synchronized intermittent mechanical ventilation. Anesthesiology. 1994;80(1):13 [MEDLINE]
  • Influence of pressure and flow-triggered synchronous intermittent mandatory ventilation on inspiratory muscle work. Crit Care Med. 1994;22(12):1933 [MEDLINE]
  • Synchronized intermittent mandatory ventilation with and without pressure support ventilation in weaning patients with COPD from mechanical ventilation. Chest. 1994;105(4):1204 [MEDLINE]
  • Evolution of mechanical ventilation in response to clinical research. Am J Respir Crit Care Med. 2008;177(2):17 [MEDLINE]
Assist Control (AC) Ventilation
  • Assist control versus synchronized intermittent mandatory ventilation during acute respiratory failure. Crit Care Med. 1989;17(7):607 [MEDLINE]
Pressure-Regulated Volume Control (PRVC) Ventilation
  • Patient comfort during pressure support and volume controlled continuous mandatory ventilation. Respir Care 2008; 53:897-902 [MEDLINE]
Adaptive Support Ventilation (ASV)
  • Automatic selection of tidal volume, respiratory frequency and minute ventilation in intubated ICU patients as start up procedure for closed-loop controlled ventilation. Int J Clin Monit Comput 1994; 11:19-30 [MEDLINE]
  • An adaptive lung ventilation controller. IEEE Trans Biomed Eng 1994; 699. 41:51–59 [MEDLINE]
  • Simple method to measure total expiratory time constant based on the passive expiratory flow-volume curve. Crit Care Med. 1995;23(6):1117 [MEDLINE]
  • Expiratory time constants in mechanically ventilated patients with and without COPD. Intensive Care Med. 2000;26(11):1612 [MEDLINE]
  • Adaptive support ventilation for fast tracheal extubation after cardiac surgery: a randomized controlled study. Anesthesiology 2001; 95:1339–1345 [MEDLINE]
  • Adaptive support ventilation. Respir Care Clin North Am 2001; 7:425–440 [MEDLINE]
  • Patient ventilator interactions during partial ventilatory support: a preliminary study comparing the effects of adaptive support ventilation with synchronized intermittent mandatory ventilation plus inspiratory pressure support. Crit Care Med 2002; 30:801–807 [MEDLINE]
  • Adaptive support ventilation (ASV). Minerva Anestesiol 2002; 68:365–368 [MEDLINE]
  • Automatic “respirator/weaning” with adaptive support ventilation: the effect on duration of endotracheal intubation and patient management. Anesth Analg 2003; 97:1743–1750 [MEDLINE]
  • Evaluation of adaptive support ventilation in paralysed patients and in a physical lung model. Int J Artif Organs. 2004;27(8):709 [MEDLINE]
  • Randomized controlled trial comparing adaptive-support ventilation with pressure-regulated volume-controlled ventilation with automode in weaning patients after cardiac surgery. Anesthesiology 2008; 109:81–87 [MEDLINE]
  • Automatic selection of breathing pattern using adaptive support ventilation. Intensive Care Med. 2008;34(1):75 [MEDLINE]
  • A randomized controlled trial comparing the ventilation duration between adaptive support ventilation and pressure assist/control ventilation in medical patients in the ICU. Chest. 2015 Jun;147(6):1503-1509. doi: 10.1378/chest.14-2599 [MEDLINE]
Pressure Support Ventilation (PSV)
  • Respiratory function during pressure support ventilation. Chest. 1986;89(5):677 [MEDLINE]
  • Pressure support compensation for inspiratory work due to endotracheal tubes and demand continuous positive airway pressure. Chest. 1988;93(3):499 [MEDLINE]
  • Determinants and limits of pressure-preset ventilation: a mathematical model of pressure control. J Appl Physiol (1985). 1989;67(3):1081 [MEDLINE]
  • Comparison of pressure support ventilation and assist control ventilation in patients with acute respiratory failure. Intensive Care Med. 1989;15(6):364 [MEDLINE]
  • Efficacy of pressure support ventilation dependent on extravascular lung water. Chest. 1990;97(6):1412 [MEDLINE]
  • Inspiratory pressure support compensates for the additional work of breathing caused by the endotracheal tube. Anesthesiology. 1991;75(5):739 [MEDLINE]
  • Patient and ventilator work of breathing and ventilatory muscle loads at different levels of pressure support ventilation. [MEDLINE]
  • Decreasing imposed work of the breathing apparatus to zero using pressure-support ventilation. Crit Care Med. 1993;21(9):1333 [MEDLINE]
  • Mechanical ventilation. American College of Chest Physicians’ Consensus Conference. Chest. 1993;104(6):1833 [MEDLINE]
  • An analysis of desynchronization between the spontaneously breathing patient and ventilator during inspiratory pressure support. Chest. 1995;107(5):1387 [MEDLINE]
  • Variability of patient-ventilator interaction with pressure support ventilation in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1995;152(1):12 [MEDLINE]
  • Patient-ventilator flow dyssynchrony: flow-limited versus pressure-limited breaths. Crit Care Med. 1997;25(10):1671 [MEDLINE]
  • Effect of ventilator mode on sleep quality in critically ill patients. Am J Respir Crit Care Med. 2002;166(11):1423 [MEDLINE]
  • Effect of different inspiratory rise time and cycling off criteria during pressure support ventilation in patients recovering from acute lung injury. Crit Care Med. 2003;31(11):2604 [MEDLINE]
  • Assessment of physiologic variables and subjective comfort under different levels of pressure support ventilation. Chest. 2004;126(3):85 [MEDLINE]
  • Patient-ventilator asynchrony during assisted mechanical ventilation. Intensive Care Med. 2006;32(10):1515 [MEDLINE]
  • Assist-control ventilation vs. low levels of pressure support ventilation on sleep quality in intubated ICU patients. Intensive Care Med. 2007;33(7):1148 [MEDLINE]
  • Extubation outcome following a spontaneous breathing trial with automatic tube compensation versus continuous positive airway pressure. Crit Care Med. 2006;34(3):682 [MEDLINE]
  • Effect of different cycling-off criteria and positive end-expiratory pressure during pressure support ventilation in patients with chronic obstructive pulmonary disease. Crit Care Med. 2007;35(11):2547 [MEDLINE]
  • Pressure support versus T-tube for weaning from mechanical ventilation in adults. Cochrane Database Syst Rev. 2014 May 27;(5):CD006056. doi: 10.1002/14651858.CD006056.pub2 [MEDLINE]
  • Comparison Between Neurally Adjusted Ventilatory Assist and Pressure Support Ventilation Levels in Terms of Respiratory Effort. Crit Care Med. 2016 Mar;44(3):503-11. doi: 10.1097/CCM.0000000000001418 [MEDLINE]
  • Influences of Duration of Inspiratory Effort, Respiratory Mechanics, and Ventilator Type on Asynchrony With Pressure Support and Proportional Assist Ventilation. Respir Care. 2017 May;62(5):550-557. doi: 10.4187/respcare.05025 [MEDLINE]
Proportional Assist Ventilation (PAV)
  • Proportional assist ventilation, a new approach to ventilatory support. Theory. Am Rev Respir Dis 1992; 145:114-120 [MEDLINE]
  • Proportional assist ventilation. Results of an initial clinical trial. Am Rev Respir Dis 1992; 145:121-129 [MEDLINE]
  • Patient ventilator interaction during acute hypercapnia: pressure support vs. proportional assist ventilation. J Appl Physiol 1996; 81:426-436 [MEDLINE]
  • Proportional assist versus pressure support ventilation: effects on breathing pattern and respiratory work of patients with chronic ob- structive pulmonary disease. Intensive Care Med 1999; 25:790-798 [MEDLINE]
  • Compensation for increase in respiratory workload during mechanical ventilation. Pressure support versus proportional assist ventilation. Am J Respir Crit Care Med 2000; 161:819–826 [MEDLINE]
  • Effect of different levels of pressure support and proportional assist ventilation on breathing pattern, work of breathing and gas exchange in mechanically ventilated hypercapnic COPD patients with acute respiratory failure. Respiration 2003; 70:355-361 [MEDLINE]
  • Respiratory load compensation during mechanical ventilation-proportional assist ventilation with load-adjustable gain factors versus pressure support. Intensive Care Med 2006; 32:692-699 [MEDLINE]
  • Short-term cardiorespiratory effects of proportional assist and pressure support ventilation in patients with acute lung injury/acute respiratory distress syndrome. Anesthesiology 2006; 105:703-708 [MEDLINE]
  • Patient ventilator interaction and sleep in mechanically ventilated patients: pressure support versus proportional assist ventilation. Crit Care Med 2007; 35:1048-1054 [MEDLINE]
  • Proportional assist ventilation with load-adjustable gain factors in critically ill patients: comparison with pressure support. Intensive Care Med 2008; 34:2026-2034 [MEDLINE]
  • Proportional assist ventilation and neurally adjusted ventilatory assist-better approaches to patient ventilator synchrony? Clin Chest Med 2008; 29:329-342 [MEDLINE]
  • Influences of Duration of Inspiratory Effort, Respiratory Mechanics, and Ventilator Type on Asynchrony With Pressure Support and Proportional Assist Ventilation. Respir Care. 2017 May;62(5):550-557. doi: 10.4187/respcare.05025 [MEDLINE]
Inverse Ratio Ventilation (IRV)
  • Improved oxygenation and lower peak airway pressure in severe adult respiratory distress syndrome. Treatment with inverse ratio ventilation. Chest. 1986;89(2):211 [MEDLINE]
  • Pressure controlled inverse ratio ventilation in severe adult respiratory failure. Chest. 1988;94(4):755 [MEDLINE]
  • Pressure control inverse ratio ventilation as a method to reduce peak inspiratory pressure and provide adequate ventilation and oxygenation. Chest. 1989;95(5):1081 [MEDLINE]
  • Cardiorespiratory effects of pressure controlled inverse ratio ventilation in severe respiratory failure. Chest. 1989;96(6):1356 [MEDLINE]
  • The use of pressure-controlled inverse ratio ventilation in the surgical intensive care unit. J Trauma. 1991;31(9):1211 [MEDLINE]
  • Effects of inverse ratio ventilation on cardiorespiratory parameters in severe respiratory failure. Chest. 1992;102(5):1556 [MEDLINE]
  • Open up the lung and keep the lung open. Intensive Care Med. 1992;18(6):319 [MEDLINE]
  • Cardiorespiratory effects of pressure-controlled ventilation with and without inverse ratio in the adult respiratory distress syndrome. Chest. 1993;104(3):871 [MEDLINE]
  • Should inverse ratio ventilation be used in adult respiratory distress syndrome? Am J Respir Crit Care Med. 1994;149(5):1354 [MEDLINE]
  • Long-term effects of two different ventilatory modes on oxygenation in acute lung injury. Comparison of airway pressure release ventilation and volume-controlled inverse ratio ventilation. Am J Respir Crit Care Med. 1994;149(6):1550 [MEDLINE]
  • Pressure-controlled, inverse ratio ventilation that avoids air trapping in the adult respiratory distress syndrome. Crit Care Med. 1995;23(2):279 [MEDLINE]
  • Beneficial effects of the “open lung approach” with low distending pressures in acute respiratory distress syndrome. A prospective randomized study on mechanical ventilation. Am J Respir Crit Care Med. 1995;152(6 Pt 1):1835 [MEDLINE]
  • Inverse ratio ventilation (I/E = 2/1) in acute respiratory distress syndrome: a six-hour controlled study. Am J Respir Crit Care Med. 1997;155(5):1637 [MEDLINE]
  • Prospective randomized trial comparing pressure-controlled ventilation and volume-controlled ventilation in ARDS. For the Spanish Lung Failure Collaborative Group. Chest. 2000;117(6):1690 [MEDLINE]
  • Extending inspiratory time in acute respiratory distress syndrome. Crit Care Med. 2001;29(1):40 [MEDLINE]
  • The outcome of early pressure-controlled inverse ratio ventilation on patients with severe acute respiratory distress syndrome in surgical intensive care unit. Am J Surg. 2002;183(2):151 [MEDLINE]
Airway Pressure Release Ventilation (APRV)
  • Airway pressure release ventilation: a new concept in ventilatory support. Crit Care Med. 1987;15(5):459 [MEDLINE]
  • Airway pressure release ventilation. Crit Care Med. 1987;15(5):462 [MEDLINE]
  • Airway pressure release ventilation during acute lung injury: a prospective multicenter trial. Crit Care Med. 1991;19(10):1234 [MEDLINE]
  • Continuous positive airway pressure (CPAP) vs. intermittent mandatory pressure release ventilation (IMPRV) in patients with acute respiratory failure. Intensive Care Med. 1992;18(2):69 [MEDLINE]
  • The effects of applied vs auto-PEEP on local lung unit pressure and volume in a four-unit lung model. Chest. 1995 Oct;108(4):1073-9 [MEDLINE]
  • Spontaneous breathing during ventilatory support improves ventilation-perfusion distributions in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 1999;159(4 Pt 1):1241 [MEDLINE]
  • Airway pressure release ventilation increases cardiac performance in patients with acute lung injury/adult respiratory distress syndrome. Crit Care. 2001;5(4):221 [MEDLINE]
  • Long-term effects of spontaneous breathing during ventilatory support in patients with acute lung injury. Am J Respir Crit Care Med. 2001;164(1):43 [MEDLINE]
  • Effects of spontaneous breathing during airway pressure release ventilation on renal perfusion and function in patients with acute lung injury. Intensive Care Med. 2002;28(10):1426 [MEDLINE]
  • Influence of different release times on spontaneous breathing pattern during airway pressure release ventilation. Intensive Care Med. 2002;28(12):1742 [MEDLINE]
  • Lung recruitment maneuvers in acute respiratory distress syndrome and facilitating resolution. Crit Care Med. 2003;31(4 Suppl):S265 [MEDLINE]
  • Lung computed tomography during a lung recruitment maneuver in patients with acute lung injury. Intensive Care Med. 2003;29(2):218 [MEDLINE]
  • Airway pressure release ventilation as a primary ventilatory mode in acute respiratory distress syndrome. Acta Anaesthesiol Scand. 2004;48(6):722-31 [MEDLINE]
  • Other approaches to open-lung ventilation: Airway pressure release ventilation. Crit Care Med. 2005 Mar;33(3 Suppl):S228-40 [MEDLINE]
  • Preliminary experience with airway pressure release ventilation in a trauma/surgical intensive care unit. J Trauma. 2005;59(1):71 [MEDLINE]
  • Does airway pressure release ventilation offer important new advantages in mechanical ventilatory support? Resp Care. 2007;52:452-460
  • Airway pressure release and biphasic intermittent positive airway pressure ventilation: are they ready for prime time? J Trauma. 2007;62(5):1298 [MEDLINE]
  • Airway pressure release ventilation and biphasic positive airway pressure: a systemic review of definitional criteria. Intensive Care Med 2008;34(10):1766-1773 [MEDLINE]
  • A randomized prospective trial of airway pressure release ventilation and low tidal volume ventilation in adult trauma patients with acute respiratory failure. J Trauma. 2010;69(3):501-510 [MEDLINE]
  • Comparison of APRV and BIPAP in a mechanical model of ARDS (abstract). Respir Care 2010;55(11): 1516
  • Airway pressure release ventilation: what do we know? Respir Care. 2012 Feb;57(2):282-92 [MEDLINE]
  • Compared to conventional ventilation, airway pressure release ventilation may increase ventilator days in trauma patients. J Trauma Acute Care Surg. 2012 Aug;73(2):507-10 [MEDLINE]
  • Lung protective ventilation (ARDSNet) versus airway pressure release ventilation: ventilatory management in a combined model of acute lung and brain injury. J Trauma Acute Care Surg. 2015 Feb;78(2):240-9; discussion 249-51. doi: 10.1097/TA.0000000000000518 [MEDLINE]
  • Early application of airway pressure release ventilation may reduce the duration of mechanical ventilation in acute respiratory distress syndrome. Intensive Care Med. 2017;43(11):1648 [MEDLINE]
  • Experimental study of airway pressure release ventilation in the treatment of acute respiratory distress syndrome. Exp Ther Med. 2017 Sep;14(3):1941-1946. doi: 10.3892/etm.2017.4718 [MEDLINE]
  • Randomized Feasibility Trial of a Low Tidal Volume-Airway Pressure Release Ventilation Protocol Compared With Traditional Airway Pressure Release Ventilation and Volume Control Ventilation Protocols. Crit Care Med. 2018;46(12):1943 [MEDLINE]
  • APRV for ARDS: the complexities of a mode and how it affects even the best trials. J Thorac Dis. 2018;10(Suppl 9):S1058 [MEDLINE]
  • Airway pressure release ventilation during acute hypoxemic respiratory failure: a systematic review and meta-analysis of randomized controlled trials. Ann Intensive Care. 2019 Apr 4;9(1):44. doi: 10.1186/s13613-019-0518-7 [MEDLINE]
  • Airway pressure release ventilation does not increase intracranial pressure in patients with traumatic brain injury with poor lung compliance. J Crit Care. 2019 Apr;50:118-121. doi: 10.1016/j.jcrc.2018.11.034 [MEDLINE]
Neurally Adjusted Ventilatory Assist (NAVA)
  • Neurally adjusted ventilatory assist: a ventilation tool or a ventilation toy? Respir Care. 2011 Mar;56(3):327-35 [MEDLINE]
  • Neurally adjusted ventilatory assist improves patient-ventilator interaction. Intensive Care Med. 2011 Feb;37(2):263-71 [MEDLINE]
  • Neurally adjusted ventilatory assist and proportional assist ventilation both improve patient-ventilator interaction. Crit Care. 2015;19:56 [MEDLINE]
  • Neurally adjusted ventilatory assist as an alternative to pressure support ventilation in adults: a French multicentre randomized trial. Intensive Care Med. 2016;42(11):1723 [MEDLINE]
  • Comparison Between Neurally Adjusted Ventilatory Assist and Pressure Support Ventilation Levels in Terms of Respiratory Effort. Crit Care Med. 2016 Mar;44(3):503-11. doi: 10.1097/CCM.0000000000001418 [MEDLINE]
High-Frequency Oscillatory Ventilation (HFOV)
  • High-frequency oscillatory ventilation for acute respiratory distress syndrome in adults: a randomized, controlled trial. Am J Respir Crit Care Med. 2002 Sep 15;166(6):801-8 [MEDLINE]
  • High-frequency oscillatory ventilation in adults: the Toronto experience. Chest. 2004 Aug;126(2):518-27 [MEDLINE]
Esophageal Pressure-Guided Mechanical Ventilation
  • Airway pressure-time curve profile (stress index) detects tidal recruitment/hyperinflation in experimental acute lung injury. Crit Care Med. 2004 Apr;32(4):1018-27 [MEDLINE]
  • EPVent Study. Mechanical ventilation guided by esophageal pressure in acute lung injury. N Engl J Med 2008; 359:2095– 2104 [MEDLINE]
  • Accuracy of plateau pressure and stress index to identify injurious ventilation in patients with acute respiratory distress syndrome. Anesthesiology. 2013 Oct;119(4):880-9. doi: 10.1097/ALN.0b013e3182a05bb8 [MEDLINE]
  • The application of esophageal pressure measurement in patients with respiratory failure. Am J Respir Crit Care Med 2014; 189:520–531 [MEDLINE]
  • The assessment of transpulmonary pressure in mechanically ventilated ARDS patients. Intensive Care Med 2014; 40:1670–1678 [MEDLINE]
  • Novel approaches to minimize ventilator-induced lung injury. Curr Opin Crit Care. 2015 Feb;21(1):20-5. doi: 10.1097/MCC.0000000000000172 [MEDLINE]

Disease-Specific Mechanical Ventilation Strategies

  • Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial. J Neurosurg. 1991;75(5):731 [MEDLINE]
  • Primer on medical management of severe brain injury. Crit Care Med. 2005;33(6):1392 [MEDLINE]
  • Hyperventilation in head injury: a review. Chest. 2005;127(5):1812 [MEDLINE]

Unplanned Extubation

  • Effect of unplanned extubation on outcome of mechanical ventilation. Am J Respir Crit Care Med. 2000;161(6):1912 [MEDLINE]
  • Risk factors and outcomes after unplanned extubations on the ICU: a case-control study. Crit Care. 2011;15(1):R19 [MEDLINE]
  • Unplanned endotracheal extubations in the intensive care unit: systematic review, critical appraisal, and evidence-based recommendations. Anesth Analg. 2012;114(5):1003-1014 [MEDLINE]
  • Unplanned extubation in critically ill adults: clinical review. Nurs Crit Care. 2013;18(3):123-134 [MEDLINE]
  • Influence of sedation strategies on unplanned extubation in a mixed intensive care unit. Am J Crit Care. 2014;23(4):306-314 [MEDLINE]

Outcome of Mechanical Ventilation

  • One-year trajectories of care and resource utilization for recipients of prolonged mechanical ventilation: a cohort study. Ann Intern Med. 2010;153(3):167 [MEDLINE]