Acute Kidney Injury (AKI) (see Acute Kidney Injury)

Epidemiology

• Mechanical Ventilation is Associated with an Increased Risk of Acute Kidney Injury
  • BEST Kidney Trial (JAMA, 2005) [MEDLINE]: n = 29,269 critically ill patients
    • Positive-Pressure Mechanical Ventilation was an Independent Risk Factor for Acute Kidney Injury (Odds Ratio 2.11, 95% CI: 1.58-2.82)

Mechanism

• May Be Related to Increased Release of Inflammatory Mediators (Such as IL-6), Impaired Renal Perfusion Associated with Decreased Cardiac Output, Increased Sympathetic Tone, and/or Humoral Pathway Activation (Crit Care Med, 2005) [MEDLINE]

Arytenoid Cartilage Dislocation

Epidemiology

• Arytenoid Cartilage Dislocation Has Been Reported as a Rare Complication of Intubation (Br J Anaesth, 1978) [MEDLINE]
• Risk Factors for Arytenoid Cartilage Dislocation/Subluxation (Ann Card Anaesth, 2017) [MEDLINE]: Japanese retrospective review of 19,437 adult patients
  • Cardiovascular Surgery (Odds Ratio: 9.9, p<0.001)
  • Difficult Intubation (Odds Ratio: 12.1, p=0.018)
• BMI is a Risk Factor for Arytenoid Cartilage Dislocation ( J Voice, 2018) [MEDLINE]

Mechanisms

• Laryngoscopic Trauma to Arytenoids

Clinical

• Hoarseness (see Hoarseness): typically manifests only after the patient is extubated

Aspiration Pneumonia (see Aspiration Pneumonia)

Epidemiology

• Aspiration of Oropharyngeal Secretions is Common with Endotracheal Tubes and Tracheostomy Tubes
• Polyurethane Endotracheal Tube Cuffs Decrease the Amount of Leakage Around the Cuff, as Compared to Polyvinyl Chloride Cuff Endotracheal Tubes (Crit Care Med, 2008) [MEDLINE]

Mechanisms

• Delayed Triggering of the Swallowing Response (Crit Care Med, 1990) [MEDLINE]
• Pharyngeal Pooling of Secretions Above the Airway Cuff (Crit Care Med, 1990) [MEDLINE]
  • Risk of Aspiration is Correlated with the Amount of Oropharyngeal Secretions

Auto-Positive End-Expiratory Airway Pressure (Auto-PEEP or Intrinsic PEEP) (see PEEP+Auto-PEEP) (Am Rev Respir Dis, 1982) [MEDLINE]

• See Above

Dental/Lingual/Orolabial/Pharyngeal/Laryngeal Mucosal Injury

• See Above

Endotracheal Tube Tip Malpositioning

• See Above

Esophageal Injury/Perforation

Mechanisms

• Trauma Due to Inadvertent Esophageal Intubation: trauma may result from either the endotracheal tube stylet or the endotracheal tube itself

Clinical

• Ranges from Esophageal Mucosal Injury to Overt Esophageal Perforation (see Esophageal Perforation) (Anaesthesia, 1994) [MEDLINE]

Gastrointestinal Complications

Acalculous Cholecystitis (see Acalculous Cholecystitis)

• Epidemiology
  • Acalculous Cholecystitis Has Been Reported on Occur in 0.2-3% of Mechanically-Ventilated Patients (Chest, 2001) [MEDLINE]

Constipation (see Constipation)

• Epidemiology
  • Constipation Has Been Reported on Occur in 15% of Mechanically-Ventilated Patients (Chest, 2001) [MEDLINE]

Diarrhea (see Diarrhea)

• Epidemiology
  • Diarrhea Has Been Reported on Occur in 15-51% of Mechanically-Ventilated Patients (Chest, 2001) [MEDLINE]
• Mechanisms
  • Tube Feedings (Related to Hyperosmolar Tube Feedings, High Infusion Rate, and/or Dietary Lipids)
  • Clostridium Difficile Infection (see Clostridium Difficile)
  • Medications (Such as Antibiotics, Magnesium-Based Antacids, H2-Receptor Antagonists)
  • Hypoalbuminemia (Especially Chronic Severe Hypoalbuminemia <2.6 g/dL)
  • Prolonged Fasting >5 Days: interferes with bile acid homeostasis, due to intestinal mucosal atrophy

Erosive Esophagitis (see Esophagitis)

• Epidemiology
  • Erosive Esophagitis Has Been Reported to Occur in 48% of Mechanically-Ventilated Patients (Chest, 2001) [MEDLINE]

Gastrointestinal Stress Ulceration (see Peptic Ulcer Disease)

• Epidemiology
  • Stress-Related Mucosal Damage is the Most Common Etiology of Gastrointestinal Hemorrhage in Mechanically-Ventilated Patients
  • Endoscopically-Identified But Asymptomatic Stress Ulceration Has Been Reported to Occur in 74-100% of Mechanically-Ventilated Patients (Chest, 2001) [MEDLINE]
  • Clinically Evident Gastrointestinal Hemorrhage Due to Stress Ulceration Has Been Reported to Occur in 5-25% of Mechanically-Ventilated Patients (Chest, 2001) [MEDLINE]
  • Clinically Significant Gastrointestinal Hemorrhage Due to Stress Ulceration Has Been Reported to Occur in 3-4% of Mechanically-Ventilated Patients (Chest, 2001) [MEDLINE]
• Mechanisms
  • Positive-Pressure Mechanical Ventilation is Associated with Decreased Splanchnic Perfusion, Possibly Related to Decreased Cardiac Output (Intensive Care Med, 2000) [MEDLINE] (Intensive Care Med, 2000) [MEDLINE]: decreased splanchnic perfusion results in increased levels of aminotransferases and lactate dehydrogenase (LDH)
• Clinical
  • Mucosal Lesions Tend to Be Multiple and Occur Predominantly in the Fundus of the Stomach (Typically Sparing the Antrum)
  • Distal (Antral and Duodenal) Mucosal Erosions and/or Ulcers May Also Occur
    • Distal (Antral and Duodenal) Mucosal Erosions Tend to Appear Later
    • Distal (Antral and Duodenal) Mucosal Erosions Tend to Be Deeper
    • Distal (Antral and Duodenal) Mucosal Erosions May Be Associated with a Higher Incidence of Gastrointestinal Hemorrhage

Ileus (and Gastrointestinal Hypomotility) (see Ileus)

• Epidemiology
  • Decreased Bowel Sounds Have Been Reported on Occur in 50% of Mechanically-Ventilated Patients (Chest, 2001) [MEDLINE]
  • High Gastric Residuals Have Been Reported to Occur in 39% of Mechanically-Ventilated Patients (Chest, 2001) [MEDLINE]
  • Ileus Has Been Reported to Occur in 4-10% of Mechanically-Ventilated Patients (Chest, 2001) [MEDLINE]
• Mechanisms
  • Gastrointestinal Dysmotility Has Been Demonstrated in Mechanically-Ventilated Patients (Crit Care Med, 1994) [MEDLINE]
• Clinical
  • Hypomotility with Tube Feeding Intolerance/Ileus
• Management
  • Avoid Medications Which Impair Gastrointestinal Motility

Impaired Mucociliary Motility

Physiology

• Positive-Pressure Mechanical Ventilation Impairs Airway Mucociliary Clearance, Increasing the Risk of Secretion Retention and Pneumonia (Chest, 1994) [MEDLINE]

Management

• Nebulized N-Acetylcysteine (Mucomyst) (see N-Acetylcysteine)
  • Randomized Trial of Routine vs On-Demand Nebulized N-Acetylcysteine with Salbutamol in Mechanically-Ventilated Patients (≥24hrs) in the ICU (JAMA, 2018) [MEDLINE]: n = 922
    • Routine Nebulized N-Acetylcysteine with Salbutamol Did Not Decrease the Number of Ventilator-Free Days, as Compared to On-Demand Nebulized N-Acetylcysteine with Salbutamol
    • There was No Difference in Length of Stay, Mortality, or the Proportion of Patients Developing Pulmonary Complications Between the Groups
    • Routine Nebulized N-Acetylcysteine Increased the Risk of Tachyarrhythmias and Agitation

Intensive Care Unit-Acquired Weakness (see Intensive Care Unit-Acquired Weakness)

Epidemiology

• Weakness is Common in Mechanically-Ventilated Patients (Chest, 2007) [MEDLINE]
  • However, it is Unclear as to Whether Mechanical Ventilation Itself Independently Causes Weakness

Mechanisms

• Critical Illness
• Prolonged Immobilization
• Prolonged Sedative Administration (see Sedation)
• Administration of Neuromuscular Junction Antagonists (see Neuromuscular Junction Antagonists)

Management

• Early Physical Therapy/Mobilization
  • Randomized Trial of Early Mobilization in Mechanically-Ventilated Patients (Lancet, 2009) [MEDLINE]
    • Early Mobilization within 72 hrs of Intubation was Safe, Well-Tolerated, and Associated with Improved Functional Outcomes at Hospital Discharge, Shorter Duration of Delirium, and More Ventilator-Free Days, as Compared to Standard Care

Recommendations (Related to Early Mobilization) (Society of Critical Care Medicine Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU) (Crit Care Med, 2018) [MEDLINE]

• Assuming Stability of the Following Parameters, Rehabilitation or Mobilization is Recommended in Critically Ill Adults (Conditional Recommendation, Low Quality Evidence)
  • Cardiovascular Stability Criteria
    • Heart Rate 60-130 bpm
    • Systolic Blood Pressure 90-180 mm Hg (or Mean Arterial Pressure 60-100 mm Hg)
    • Absence of New/Symptomatic Arrhythmia
    • Absence of Chest Pain Due to Myocardial Ischemia
  • Respiratory Stability Criteria
    • Respiratory Rate 5-40 breaths/min
    • SpO2 ≥88%
    • FiO2 <60% and Positive End-Expiratory Pressure <10 cm H2O
    • Endotracheal Tube/Tracheostomy is Adequately Secured
  • Neurologic Stability Criteria
    • Able to Open Eyes to Voice
    • Absence of Unstable Spinal Injury/Lesion
  • Other Stability Criteria
    • Absence of Unstable Fracture and Active/Uncontrolled Gastrointestinal Hemorrhage
    • Mobilization May Be Performed with Femoral Vascular Access Devices (Except Femoral Sheaths in Which Hip Mobilization is Generally Avoided), Continuous Renal Replacement Therapy, and Infusion of Vasoactive Medications
• Serious Safety Events or Harms are Uncommon During Physical Rehabilitation/Early Mobilization (Ungraded Statement)
• Indicators for Stopping Physical Rehabilitation/Early Mobilization Include the Development of New Cardiovascular, Respiratory, or Neurologic Instability (Ungraded Statement)
  • Cardiovascular Instability
    • Deviation from Above Stability Criteria
  • Pulmonary Instability
    • Deviation from Above Stability Criteria
    • Ventilator Dyssynchrony
  • Neurologic Instability
    • Change in Level of Consciousness (Not Following Directions, Lightheadedness, Combative Behavior, or Agitation)
  • Other Instability
    • Fall
    • Hemorrhage
    • Medical Device Removal or Malfunction
    • Patient Distress

Laryngeal Injury

Epidemiology

• Endotracheal Tube-Associated Laryngeal Injury is the Most Common Complication Associated with Endotracheal Tube Placement
  • Laryngeal Edema/Inflammation is Observed Post-Extubation in >50% of Intubations (Chest, 1989) [MEDLINE] and (Intensive Care Med, 2010) [MEDLINE]
    • However, Not All Cases are Significantly Symptomatic
  • Clinically Significant Laryngeal Edema Occurs in 5-13% of Extubated Patients, But Only 1% Require Reintubation (Anesthesiology, 1992) [MEDLINE]
  • Study of Cuff Leak Volume and Risk of Post-Extubation Stridor (Chest, 1996) [MEDLINE]
    • Approximately 6% of Extubations Resulted in Post-Extubation Stridor
  • Fiberoptic Study of Endotracheal Intubation-Associated Laryngeal Injuries (Intensive Care Med, 2010) [MEDLINE]: prospective study of n = 136 patients extubated after >24 hrs of mechanical ventilation (median duration of intubation = 3 days)
    • Approximately 73% of Patients Demonstrated a Laryngeal Injury
    • The Most Common Lesions were Edema (67% of Cases) and Abnormal Vocal Mobility (67% of Cases)
  • Incidence of Postextubation Stridor Has Been Reported to Be Between 6-37% (J Evid Based Med, 2011) [MEDLINE]
• Sex
  • Laryngeal Injuries are More Common in Females than Males (Anesthesiology, 1992) [MEDLINE]
• Obesity
  • Obesity Does Not Appear to Increase the Risk of Laryngeal Injury, Although it Increases the Risk for Difficult Intubation (Intern Emerg Med, 2013) [MEDLINE]
• Risk Factors Associated with Endotracheal Tube-Associated Laryngeal Injury (Otolaryngol Head Neck Surg, 1994) [MEDLINE] and (Intensive Care Med, 2010) [MEDLINE]
  • Absence of Use of Neuromuscular Blockade During Intubation (see Neuromuscular Junction Antagonists)
  • Aspiration (see Aspiration Pneumonia)
  • Emergency Intubation
  • Prolonged Intubation (Studies Define this Variably as ≥36 hrs to ≥3 Days)
  • Traumatic Intubation
  • Unplanned Extubation
  • Use of Large Endotracheal Tube
    • Male: >8 mm
    • Female: >7 mm
  • Use of Nasogastric/Orogastric Tube (see Nasogastric/Orogastric Tube)
• Risk Factors Not Associated with the Severity of Endotracheal Tube-Associated Laryngeal Injury (Laryngoscope, 2011) [MEDLINE]
  • Duration of Intubation
  • Endotracheal Tube Size: including use of endotracheal tubes with subglottic suction ports

Mechanisms

• Trauma Due to the Laryngoscopy Blade, Endotracheal Tube Stylet, or the Endotracheal Tube During Intubation
• Direct Endotracheal Tube Pressure on the Larynx and Surrounding Tissues (with//without Associated Inflammation)

Diagnosis

• Endotracheal Tube Cuff Leak Test (see Endotracheal Tube Cuff Leak Test)
  • Clinical Data
    • Study of Cuff Leak Volume and Risk of Post-Extubation Stridor (Chest, 1996) [MEDLINE]
      • Cuff Leak Volume = Inspiratory Tidal Volume – Expiratory Tidal Volume with Endotracheal Tube Cuff Deflated
      • Cuff Leak Volume was Significantly Lower in Those Who Developed Post-Extubation Stridor (180 +/- 157 mL), as Compared to Those Who Did Not (360 mL +/- 157 mL)
      • Positive Predictive Value for Cuff Leak <110 mL was 80%
      • Sensitivity for the Absence of Post-Extubation Stridor with a Cuff Leak Volume >110 mL was 98% and the Specificity was 99%
    • Study of Cuff Leak Testing in Predicting Post-Extubation Laryngeal Edema (Intensive Care Med, 2002) [MEDLINE]: n = 76
      • Best Cutoff Value for Cuff Leak was 15.5% of Tidal Volume with Sensitivity of 75%, Specificity of 72.1%, Positive Predictive Value of 25%, Negative Predictive Value of 96.1%
    • Study of Post-Extubation Stridor and Value of Cuff Leak Test (Intensive Care Med, 2003) [MEDLINE]
      • Low Cuff Leak Volume (<130 mL or 12% of Tidal Volume) Can Identify Patients at Risk for Post-Extubation Stridor with Sensitivity of 85%/Specificity of 95%
    • Study of Endotracheal Tube Cuff Leak Test and Risk for Post-Extubation Stridor (Respir Care, 2005) [MEDLINE]
      • Female Patients, Patients with ETT Size/Laryngeal Diameter Ratio >45%, and Patients Intubated for >6 Days Were More Likely to Develop Post-Extubation Stridor
      • Failing the Cuff Leak Test was Not an Accurate Predictor for Post-Extubation Stridor
    • Systematic Review and Meta-Analysis of Cuff Leak Test (Intensive Care Med, 2009) [MEDLINE]
      • Cuff Leak Test Had Pooled Sensitivity of 63% and Pooled Specificity of 86%
      • Cuff Leak Test Had Positive Likelihood Ratio of 4.04 (95% CI: 2.21-7.40) and a Negative Likelihood Ratio of 0.46 (95% CI: 0.26-0.82)
    • Study of Endotracheal Tube Cuff Leak Test and Prediction of Post-Extubation Stridor (J Intensive Care Med, 2017) [MEDLINE]: n = 362
      • Endotracheal Tube Cuff Leak Testing (4 Different Tests) Demonstrated Sensitivity of 27-46%/Specificity of 70-88%, Positive Predictive Value of 14-19%, and Negative Predictive Value of 92-93% for Post-Extubation Stridor
      • Given High Rate of False Positives, Routine Leak Testing May Expose Patients to Undue Prolonged Mechanical Ventilation
    • American Thoracic Society/American College of Physicians Clinical Practice Guideline for Liberation from Mechanical Ventilation in Critically Ill Adults with Meta-Analysis of Cuff Leak Test (Am J Respir Crit Care Med, 2017) [MEDLINE]
      • Cuff Leak Testing Decreased the Rate of Reintubation (2.4% vs 4.2%) and Post-Extubation Stridor (4% vs 7%), But at the Expense of Delayed Extubation (9% Absolute Increase)
• Cough Testing: can be used in addition to cuff leak testing
  • Absence of Both an Audible Cough and Cuff Leak Indicates that the Patient is 10x More Likely to Develop Post-Extubation Stridor (J Crit Care, 2004) [MEDLINE]
• Laryngeal Ultrasound (see Laryngeal Ultrasound): promising, but requires further study (J Crit Care, 2013) [MEDLINE]

Clinical

• Dysphagia (see Dysphagia)
• Dysphonia (see Dysphonia)
• Hoarseness (see Hoarseness)
• Pharyngitis (see Pharyngitis)
• Stridor (see Stridor)

Treatment

• Generally Resolves within 24-48 hrs After Extubation
• Careful Consideration of Extubation Technique, in Case Reintubation is Required
  • Extubation Over an Airway Exchange Catheter Can Be Considered in Selected Patients (Anesth Analg, 2007) [MEDLINE]
• Racemic Epinephrine (see Epinephrine)
• HELIOX (see Heliox)
• Corticosteroids (see Corticosteroids)
  • Clinical Efficacy
    • Study of Intravenous Methylprednisolone to Prevent Post-Extubation Stridor (Crit Care Med, 2006) [MEDLINE]
      • Decreased Cuff Leak Volume was a Reliable Indicator to Identify Patients at High Risk for Post-Extubation Stridor
      • Cuff Leak Volume Increased After Methylprednisolone Doses (After a 2nd Injection in the One Dose Group and After the 2nd-4th Injection in the Four Dose Group), as Compared to Control
      • Single/Four Methylprednisolone Doses Effectively Decrease the Occurrence of Post-Extubation Stridor: however, there was no difference between the single and four methylprednisolone dose groups
    • Prospective Randomized Trial of Prophylactic Multiple Dose Dexamethasone to Decrease the Incidence of Post-Extubation Stridor in Adult Patients at High Risk for Laryngeal Edema (Crit Care, 2007) [MEDLINE]: n = 86
      • Prophylactic Dexamethasone (q6hrs x 4 Doses Throughout the Day Prior to Extubation) was Effective in Increasing the Cuff Leak Volume and Decreasing the Incidence of Post-Extubation Stridor (10% vs 27.5%) in Adult Patients at High Risk for Laryngeal Edema (Patients Intubated >48 hrs and with Cuff Leak Volume <110 mL): increase in cuff leak volume continued to occur 24 hrs after the last dexamethasone dose
      • No Significant Difference in Reintubation Rate Between the Two Groups (2.5% vs 5%)
    • French Randomized Trial of Methylprednisolone for the Prevention of Post-Extubation Laryngeal Edema (Lancet, 2007) [MEDLINE]: n = 761
      • In Patients Ventilated >36 hrs and Undergoing Planned Extubation, Methylprednisolone (20 mg Given 12 hrs and Then q4hrs Until Extubation) Decreased the Incidence of Post-Extubation Laryngeal Edema (3% vs 22%) and Need for Reintubation
    • Meta-Analysis of Prophylactic Intravenous Steroids to Prevent Post-Extubation Airway Complications in Adults (BMJ, 2008) [MEDLINE]
      • Prophylactic Intravenous Steroids Before Planned Extubation Decreased the Incidence of Laryngeal Edema and the Reintubation Rate (with Few Adverse Events)
    • Systematic Review of Corticosteroids to Prevent or Treat Post-Extubation Stridor (Cochrane Database Syst Rev, 2009) [MEDLINE]
      • Multiple Doses of Corticosteroids Begun 12-24 hrs Prior to Extubation Appear to Be Beneficial in Patients with a High Likelihood of Post-Extubation Stridor
    • Randomized Trial of Methylprednisolone to Prevent Post-Extubation Stridor and Reintubation (Minerva Anestesiol, 2011) [MEDLINE]: n = 71
      • In Patients with Cuff Leak Percentage <24% of Tidal Volume, a Single Methylprednisolone Dose 4 hrs Prior to Planned Extubation Decreased the Incidence of Post-Extubation Stridor and the Reintubation Rate
  • Recommendations: corticosteroids can be considered in selected patients with a decreased endotracheal tube cuff leak and high risk for post-extubation stridor
• Reintubation: may be required

Neurologic Complications

Cervical Spinal Cord Injury (SCI) (see Spinal Cord Injury)

• Mechanisms
  • Intubation in Patient with Atlantoaxial Instability (see Atlantoaxial Instability)
    • Ankylosing Spondylitis (see Ankylosing Spondylitis) (Anesthesiology, 1989) [MEDLINE]
    • Down Syndrome (see Down Syndrome)
    • Rheumatoid Arthritis (RA) (see Rheumatoid Arthritis)
  • Intubation in Patient with Unstable Cervical Spine Fracture (see Cervical Spine Fracture)

Hypoxic-Ischemic Brain Injury (see Hypoxic-Ischemic Brain Injury)

• Mechanisms
  • Prolonged Hypoxia During Attempted Intubation

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

• Mechanism
  • Positive-Pressure Mechanical Ventilation Increases Intracranial Pressure (Likely Mediated by Impairment of Cerebral Venous Outflow)

Neuronal Damage

• Mechanism
  • Positive-Pressure Mechanical Ventilation Has Been Demonstrated to Cause Hippocampal Apoptosis in Animal Studies (Am J Respir Crit Care Med, 2013) [MEDLINE]
  • Hippocampal Changes May Be Related to the Development of Delirium

Oxygen Toxicity (see Oxygen)

Epidemiology

• Prior Exposure to Bleomycin Increases the Risk of Toxicity from Hyperoxia (Am Rev Respir Dis. 1984) [MEDLINE] (see Bleomycin)

Physiology

• Mechanisms by Which Hyperoxia Contributes to the Development of Lung Injury
  • Absorptive Atelectasis
    • High FIO2 Causes a Washout of Alveolar Nitrogen and Replacement by Oxygen, Resulting in Absorption of Alveolar Oxygen into the Blood
  • Formation of Reactive Oxygen Intermediates (Such as Superoxide Anion, Hydroxyl Radical, and Hydrogen Peroxide) Which Overwhelm the Cell’s Antioxidant Defense Mechanisms
    • Concentration of Reactive Oxygen Intermediates In Exhaled Gas Increases After Only 1 hr of Breathing 28% FIO2, Regardless of the Presence of Lung Disease (Thorax, 2004) [MEDLINE]
    • Reactive Oxygen Intermediates React with Various Intracellular Macromolecules (Impairing Their Function), Resulting in Cell Death
  • Impairment of Bactericidal Function of Immune Cells, Resulting in an Increased Risk of Infection
  • Impairment of Mucociliary Clearance, Resulting in an Increased Risk of Infection
  • Increased Susceptibility to Mucous Plugging
  • Induction of a Deleterious Inflammatory Response, Resulting in Secondary Apoptosis and Tissue Damage
• Volunteer Studies Breathing FIO2 100% x 6-48 hrs Variably Induced Tracheobronchitis, Substernal Burning, Chest Tightness, and a Dry Cough
  • Pulmonary Function Tests (PFT’s) (see Pulmonary Function Tests)
    • Decreased VC
    • Decreased DLCO
• Tolerance of Hyperoxia Appears to Be Related to an Ability to Generate Antioxidants: this tolerance may be genetically determined
• Phases of Oxygen Toxicity (Phases Overlap)
  • Acute/Exudative Phase: usually begins within 48-72 hrs, depending on inspired oxygen fraction (and is believed to be reversible)
    • Perivascular, Interstitial, and Alveolar Edema -> atelectasis and alveolar hemorrhage
  • Subacute/Proliferative Phase: usually begins after 4th-7th day (and is believed to be irreversible)
    • Rebsorption of Exudates
    • Hyperplasia of Type II Pneumocytes
    • Deposition of Collagen and Elastin in Interstitium and Hyaline Membrane Deposition

Clinical

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

Treatment

• Preventive Measures: maintain pO2 <80 mmHg and FIO2 <40-50%

Patient-Ventilator Dyssynchrony

Definition

• Delivery of Breath from the Ventilator Which is Not Matched by the Patient Effort

Epidemiology

• More than 10% of Breaths were Found to Be Dyssynchronous in 24% of Mechanically-Ventilated Patients in One Observational Study (Intensive Care Med, 2006) [MEDLINE]
  • Ineffective Triggering and Double-Triggering were the Most Commonly Observed Events
  • Dyssynchrony Occurred in Both Assist Control and Pressure Support Ventilation Modes
  • Dyssynchrony was Associated with a Prolonged Duration of Mechanical Ventilation (7.5 days, IQR 3-20 vs 25.5, IQR 9.5-42.5)

Factors Contributing to Patient-Ventilator Dyssynchrony

Ventilator Factors

• Extraneous Flow (From Nebulizer or Added Oxygen)
• Flow Delivery System of the Ventilator
• Flow Pattern Selected
• Flow Triggering vs Pressure Triggering of Ventilator
  • There is Not a Significant Difference in Patient Effort Required to Trigger a Breath on Either Type of Modern Ventilators
• Inappropriate Inspiratory:Expiratory (I:E) Ratio
  • Inadequate Expiration Time May Contribute to the Development of Auto-PEEP
• Pressure-Targeting Difficulties
  • Pressure Target for Ventilator to Reach is Detected at the Proximal End of the Endotracheal Tube, But Since the Endotracheal Tube is a High Resistance Tube, the Pressure at the Distal End of Endotracheal Tube Will Be Different
  • Solutions to This Problem Include Using “Tracheal Target” for Pressure (with the Sensor Located at Distal End of the Endotracheal Tube) or Adjusting Slope of Pressure Rise for Breath
  • Automatic Tube Compensation (ATC)
    • This Ventilator Feature is Purported to Overcome the Resistance of the Endotracheal Tube
• Rise Time Capability
  • Rise Time is the Rate of Valve Opening
• Sensitivity Setting

Patient Factors

• Abdominal Pathology
• Auto-PEEP
  • Presence of Auto-PEEP Requires the Patient to Generate Much More Negative Pressure to Trigger the Ventilator to Overcome the Already Positive Airway Pressure
    • Example: In a Patient with Airway Obstruction, Setting the Pressure Support Level Too High During a Pressure Support Spontaneous Breathing Trial May Result in Higher Tidal Volume Breaths Which Take Longer to Exhale and Contribute to the Development of Auto-PEEP
      • In This Case, Decreasing the Amount of Pressure Support Will Decrease the Tidal Volume and Decrease the Amount of Auto-PEEP and Ventilator Dyssynchrony (Intensive Care Med, 2008) [MEDLINE]
• Circuit Leak
  • Endotracheal Tube Cuff Leak
• Endotracheal Tube/Tracheostomy Size
• Inspiratory Effort/Respiratory Drive/Neural Timing
• Pain
  • Splinting
• Respiratory System Pathology
• Secretions
• Sedation

Mechanisms (Respir Care, 2011)[MEDLINE]

• Ventilator Breath Triggering Problem
  • General Comments
    • Triggering Dyssynchronies are the Best Studied of All Forms of Dyssynchrony
    • Triggering Dyssynchronies Occur in 26-82% of All Mechanically-Ventilated Patients (Am J Respir Crit Care Med, 2001) [MEDLINE] ( J Crit Care, 2009) [MEDLINE] (Crit Care Med, 2009) [MEDLINE]
    • Triggering Dyssynchronies Occur More Commonly in Patients with COPD and Obstructive Lung Diseases (Intensive Care Med, 2012) [MEDLINE]: this can be overcome
  • Ineffective Triggering
    • Ventilator Triggering Has an Inherent Delay (Up to 100 msec or More)
    • Etiologies of Ineffective Triggering (Intensive Care Med, 2006) [MEDLINE]
      • Insensitive Inspiratory (Pressure or Flow) Trigger
      • Higher Level of Pressure Support
      • Higher Tidal Volume
      • Higher pH
    • Ventilator Triggering Sensitivity is Generally Set High Enough to Avoid to Inadvertent “Auto-Triggering” (Due to Cardiac Oscillations, etc)
  • Excessive Triggering
    • Etiologies of Excessive Triggering
      • Excessively Sensitive Inspiratory (Pressure or Flow) Trigger
      • Hiccups (see Hiccups)
    • Types of Excessive Triggering
      • Auto-Triggering
      • Breath-Stacking (When a Second Breath is Delivered Before the First Breath Has Completed)
      • Entrainment (When Ventilator-Delivered Gas Flow Elicits an Effort During the Breath)
  • Effect of Auto-PEEP on Triggering
    • In the Setting of Auto-PEEP, Triggering Requires the Patient to First Overcome the End-Expiratory Positive Pressure (This Represents an Inspiratory Load for the Patient, Increasing the Work of Breathing)
  • Cardiogenic Auto-Triggering Dyssynchrony
    • Cardiac Systole Can Result in Several Milliliters of Airflow (Which are Correlated with Changes in Intrathoracic Pressure) (Respir Physiol, 1996) [MEDLINE]
    • Cardiogenic Auto-Triggering May Therefore Occur in Some Cases
    • Cardiogenic Auto-Triggering Has Been Described in the Setting of Brain Death, Hyperdynamic Hemodynamic State, Post-Cardiac Surgery, and Hemoperitoneum (Chest, 2020) [MEDLINE]
  • Reverse Triggering Dyssynchrony
    • Reverse Triggering Dyssynchrony was First Described in 2013 (Chest, 2013) [MEDLINE]
    • Reverse Triggering Dyssynchrony May Occur in Up to 30% of Patients with ARDS (Intensive Care Med, 2019) [MEDLINE]
    • The Mechanism of Reverse Triggering is Unclear
    • Reverse Triggering May Be Observed During Deep Sedation, During Transition from Sedation to an Awakened State, or Even in a Brain Dead Patient (Am J Respir Crit Care Med, 2016) [MEDLINE]
    • Reverse Triggering Dyssynchrony is Manifested by a Ventilator-Delivered Breath Paradoxically Triggering a Diaphragmatic Contraction, Which then Initiates a Spontaneous Breath, Resulting in Breath Stacking (Chest, 2013) [MEDLINE]
    • Reverse Triggering Dyssynchrony Causes Overdistention, Increases the Work of Breathing, and May Cause Diaphragmatic Muscle Damage
    • Deepening of the Sedation Paradoxically Increases the Incidence of Reverse Triggering Dyssynchrony: this is critical, since deep sedation may be employed to prevent or manage ventilator dyssynchrony (thereby, inadvertently increasing the risk of reverse triggering dyssynchrony)
• Ventilator-Delivered Flow Pattern Problem
  • During an Interactive Breath, Inspiratory Muscles are Contracting with the Ventilator Delivering Flow Which Should Be Adequate to Provide Muscle Unloading, Achieving Flow Synchrony
  • Flow Dyssynchrony Can Occur and Manifests as a Tachypneic, Dyspneic Patient (“Flow Starvation”) and Abnormality in the Pressure Waveform on the Ventilator (Pressure Waveform is “Sucked Downward”, Often Below the Baseline)
• Breath Cycling Problem
  • Cycling Dyssynchronies Probably Occur in <10% of Mechanically-Ventilated Patients
  • Two Mechanisms
    • Ventilator-Delivered Breath Extends Beyond the Duration of the Patient Effort, Resulting in Shortened Expiratory Time (with Gas Trapping)
    • Ventilator-Delivered Breath Ends Before the Patient Effort Has Finished (“Breath Stacking”), Resulting in an Increased Inspiratory Load

Diagnosis

• Patient-Ventilator Dyssynchrony Can Be Diagnosed Using Observation of the Patient Respiratory Effort and the Ventilator Waveforms (Respir Care, 2005) [MEDLINE]
  • The Most Readily Apparent Type of Dyssynchrony is the Failure of the Ventilator to Trigger a Breath with a Patient Effort
• Reverse Triggering is Difficult to Detect without the Use of an Esophageal Balloon or Diaphragmatic Electromyogram (EMG)

Clinical

• “Breath Stacking” (Patient Triggers the Next Breath Before the Last Breath is Completed)
  • Breath Stacking was Commonly Observed in Low Tidal Volume Mechanical Ventilation for Acute Respiratory Distress Syndrome (ARDS) (Crit Care Med, 2008) [MEDLINE]
• Dynamic Hyperinflation
• Dyspnea (see Dyspnea) (Respir Care, 2000) [MEDLINE]
• Increased Work of Breathing (Intensive Care Med, 2006) [MEDLINE]
• Prolonged Duration of Mechanical Ventilation (Intensive Care Med, 2006) [MEDLINE] (Crit Care Med, 2009) [MEDLINE]
• Increased Sedative Use in Mechanically-Ventilated Patients
  • Due to Patient Fighting of the Ventilator
• Increased Intensive Care Unit (ICU) Length of Stay (Crit Care Med, 2009) [MEDLINE]
  • Resulting in Increased Healthcare Cost
• Increased Intensive Care Unit (ICU) and Hospital Mortality (Intensive Care Med, 2015) [MEDLINE]
• Muscle Damage
• Ventilation/Perfusion Problems

Management

• Set Ventilator Triggering Sensitivity to a Setting as Low as Possible without Inducing Auto-Triggering
  • If Double-Triggering is Occurring, Decrease the Trigger Sensitivity (e.g. from -1 to -3 cm H2O)
• Treat Auto-PEEP (If Present): prolong the expiratory time, decrease tidal volume, decrease respiratory rate, bronchodilators, etc
• Avoid Modes Which Deliver Multiple Different Breath Types (SIMV, etc)
• Adjust Flow Magnitude and Profile (Sine, Square, Decelerating), If Flow-Targeted Breaths are Desired
  • Increasing the Flow Rate When Increasing the Tidal Volume Will Ensure that the Inspiratory Time Remains Constant (Am J Respir Crit Care Med, 1995) [MEDLINE]
• Set Breath Duration Using the Cycle Variable (Volume, Time, Flow) to Optimize Comfort
• Proportional Assist Ventilation (PAV): may be useful
• Neurally-Adjusted Ventilatory Assistance (NAVA): may be useful

Pharyngitis (see Pharyngitis)

Epidemiology

• Common
  • Pharyngitis is Common and Occurs in Anywhere from 14-57% of Patients Intubated for Operative General Anesthesia (J Clin Anesth, 2010) [MEDLINE] (J Int Med Res, 2017) [MEDLINE]
• Risk Factors for Postoperative Endotracheal Intubation-Associated Pharyngitis
  • Cough During Emergence from General Anesthesia (J Int Med Res, 2017) [MEDLINE]
  • Female Sex (Br J Anaesth, 2002) [MEDLINE]
  • Greater Area of Endotracheal Tube Contact with the Tracheal Mucosa (Anesthesiology, 1983) [MEDLINE]
  • Higher Endotracheal Tube Cuff Pressure (J Int Med Res, 2017) [MEDLINE]
  • Large Endotracheal Tube (Anesthesiology, 1987) [MEDLINE] (Acta Anaesthesiol Scand, 2010) [MEDLINE]
  • Use of Nasogastric Tube During Surgery

Mechanisms

• Mild Trauma to Upper Airway Mucosa

Clinical

• Sore Throat

Prevention

• Preoperative Use of Magnesium Lozenges
• Preoperative Use of Zinc Lozenges (Anesth Analg. 2018) [MEDLINE]
  • Note: Topical Lidocaine Applied to Upper Airway Structures or the Endotracheal Tube May Actually Increase the Risk of Postoperative Pharyngitis Due to the Endotracheal Tube (Can Anaesth Soc J, 1980) [MEDLINE] (Acta Anaesthesiol Scand, 1992) [MEDLINE]
• Use of Conical-Shaped Endotracheal Tube Cuff (As Compared to Cylindrical-Shaped Cuff) (Anesth Analg, 2017) [MEDLINE]
• Use the Lowest Effective Endotracheal Tube Cuff Pressure: generally <20 mm Hg
  • Use of Nitrous Oxide During Surgery Results in the Nitrous Oxide Diffusing into the Endotracheal Tube Cuff (and Undesirably Increasing the Endotracheal Tube Cuff Pressure)
  • Head Down Positioning During Surgery Increases the Endotracheal Tube Cuff Pressure
• Use the Appropriate Endotracheal Tube Size (for Patient Sex and Size)
  • Female: 7-7.5 mm (internal diameter), which may require adjustment for patient size
  • Male: 7.5-8 mm (internal diameter), which may require adjustment for patient size

Treatment

• Usually Self-Limited: lasting <48 hrs (Acta Anaesthesiol Scand, 2010) [MEDLINE]
  • In Cases with Persistent or Severe Hoarseness/Dysphagia, Otolaryngologic Evaluation May Be Warranted to Evaluate for Specific Intubation-Associated Injury

Positive Pressure-Induced Artifacts Introduced into the Measurement of Hemodynamic Pressures

Mechanism

• Airway Pressure Transmission to Thoracic Structures, Resulting in Artifactual Elevation of Hemodynamic Pressure Measurements: this occurs because (by convention) most hemodynamic pressures are assessed at end-expiration (when PEEP is the predominant determinant of airway pressure)

Clinical

• PEEP Artifactually Elevates the Pulmonary Capillary Wedge Pressure (PCWP) (see Hemodynamics)
  • Correction of PEEP Consists of Subtracting Approximately One Half of the PEEP Level from the PCWP if the Lung Compliance is Normal (or One Quarter of the PEEP Level if the Lung Compliance is Decreased) (J Appl Physiol Respir Environ Exerc Physiol, 1982) [MEDLINE]
  • Correction of the PCWP for the Amount of PEEP Can More Accurately Done Using the Index of Transmission (Crit Care Med, 2000) [MEDLINE]
    • Index of Transmission = (End Inspiratory PCWP – End Expiratory PCWP) / (Plateau Pressure – Total PEEP)
    • Transmural PCWP = End-Expiratory PCWP – (Index of Transmission x Total PEEP)
    • This Estimation Can Be Unreliable if the Respiratory Variation of the PCWP is Greater than that of the Pulmonary Arterial Pressure Tracing
• PEEP May Also Artifactually Elevate the Central Venous Pressure (CVP) (see Hemodynamics)

Sleep Disruption

Epidemiology

• Sleep Disruption is Common in Mechanically-Ventilated Patients (Chest, 2000) [MEDLINE]

Mechanisms (Am J Respir Crit Care Med, 2003) [MEDLINE]

• Patient-Related Factors (Anxiety, Fear, Hospital Attire, Disorientation, Lack of Privacy, Loneliness, Lack of Familiarity with Staff, Lack of Understanding of Medical Terms, etc)
• Environment-Related Factors (Noise, Light, Comfort of Bed, Disrupted Circadian Rhythms, Visitors, Room Ventilation, Bad Odor, Hand Washing by Providers, etc)
• Disease-Related Factors (Pain, Dyspnea, Coughing, Thirst, Nausea, Need to Use Bedpan/Urinal, etc)
• Treatment-Related Factors (Nursing Care, Patient Procedures, Vital Sign Measurement, Medication Administration, Oxygen Mask, Endotracheal Tube, Urinary Catheter, Mode of Mechanical Ventilation, etc)
  • Specific Ventilator Modes Might Contribute Differentially to Sleep Disruption (Am J Respir Crit Care Med, 2002) [MEDLINE] (Crit Care Med, 2008) [MEDLINE]

Diagnosis

• Identification of Sleep in Critically Ill Patients is Difficult with Standard Criteria (Sleep Med, 2012) [MEDLINE]

General Management

• Sound Reduction Strategies May Be Useful to Improve Sleep in ICU Patients (Crit Care, 2013) [MEDLINE]
• Pressure Support Ventilation Should Be Avoided in Patients with Central Sleep Apnea (Especially Those with Congestive Heart Failure and Chronic Respiratory Failure) (Intensive Care Med, 2016) [MEDLINE]

Recommendations (Society of Critical Care Medicine Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU) (Crit Care Med, 2018) [MEDLINE]

• Features of Sleep in the Critically Ill Patient (Ungraded Statement)
  • Total Sleep Time (TST) and Sleep Efficiency are Often Normal
  • Sleep Fragmentation, the Proportion of Time Spent in Light Sleep (Stages N1 + N2), and Time Spent Sleeping During the Day (vs Night) are Higher
  • The proportion of Time Spent in Deep Sleep (Stage N3 Sleep and REM) is Lower
  • Subjective Sleep Quality is Decreased
• Influence of Delirium on Sleep (Ungraded Statement)
  • The Presence of Delirium May Not Affect Total Sleep Time, Sleep Efficiency, or Sleep Fragmentation
  • The Influence of Delirium on the Proportion of Time Spent in Light (N1 + N2) vs Deeper (N3) Sleep is Unknown
  • The Presence of Delirium Decreases REM Sleep
  • Delirium is Associated with Greater Circadian Sleep-Cycle Disruption and Increased Daytime Sleep
  • Whether Delirium Affects Reported Subjective Sleep Quality Remains Unclear
  • Although an Association Between Sleep Quality and Delirium Occurrence Exists in Critically Ill Adults, a Causal Relationship Has Not Been Established
• Influence of Mechanical Ventilation on Sleep (Ungraded Statement)
  • Use of Mechanical Ventilation in Critically Ill Adults May Worsen Sleep Fragmentation, Sleep Architecture, and Circadian Rhythm (Daytime Sleep), as Compared to Normal Sleep, But These Effects are Often Variable and Have Not Yet Been Fully Investigated
  • Use of Mechanical Ventilation (vs Periods without Mechanical Ventilation) in Patients with Respiratory Failure May Improve Sleep Efficiency and Decrease Sleep Fragmentation, But the Data are Limited
  • Unclear Association Between Sleep Quality and Duration of Mechanical Ventilation, Length of ICU Stay, and ICU Mortality in Critically Ill Adults
  • Assist-Control Ventilation is Recommended at Night (vs Pressure Support Ventilation) for Improving Sleep in Critically Ill Adults (Conditional Recommendation, Low Quality of Evidence)
  • In Patient Requiring Noninvasive Positive-Pressure Ventilation (NIPPV), Either an NIPPV-Dedicated Ventilator or a Standard ICU Ventilator May Be Used for Critically Ill Adults to Improve Sleep (Conditional Recommendation, Very Low Quality of Evidence)
• Unusual Sleep Patterns (Ungraded Statement)
  • The Prevalence of Unusual or Dissociated Sleep Patterns is Highly Variable and Depends on Patient Characteristics
• Risk Factors (Ungraded Statement)
  • Patients Who Report Poor Quality Sleep and/or Use of a Pharmacologic Sleep Aid at Home are More Likely to Report Poor Quality Sleep in the ICU
  • Pain, Environmental Stimuli, Healthcare-Related Interruptions, Psychologic Factors, Respiratory Factors, and Medications Each Affect Sleep Quality in the ICU: see above
• Monitoring of Sleep in the ICU
  • Clinical Physiologic Sleep Monitoring is Not Routinely Recommended in Critically Ill Adults (Conditional Recommendation, Very Low Quality of Evidence)
• Other Adjunctive Therapies to Improve Sleep in the ICU
  • Aromatherapy, Acupressure, and Music at Night are Not Recommended to Improve Sleep in Critically Ill Adults (Conditional Recommendation, Low Quality of Evidence for Aromatherapy and Acupressure, Very Low Quality of Evidence for Music)
  • Noise/Light Reduction Strategies are Recommended to Improve Sleep in Critically Ill Adults (Conditional Recommendation, Low Quality of Evidence)
  • No Recommendation Regarding the Use of Melatonin to Improve Sleep in Critically Ill Adults (No Recommendation, Very Low Quality of Evidence)
  • Propofol is Not Recommended to Improve Sleep in Critically Ill Adults (Conditional Recommendation, Low Quality of Evidence)
  • No Recommendation Regarding the Use of Dexmedetomidine at Night to Improve Sleep in Critically Ill Adults (No Recommendation, Low Quality of Evidence)
  • Use of a Sleep-Promoting, Multicomponent Protocol is Recommended in Critically Ill Adults (Conditional Recommendation, Very Low Quality of Evidence)
• Outcomes
  • The Effects of Sleep Quality and Circadian Rhythm Alterations on Outcomes in Critically Ill Patients After ICU Discharge are Unknown

Swallowing/Speech Impairment

Epidemiology

• Swallowing/Speech Impairment is Common Following Extubation
  • Swallowing/Speech Impairment Occurs in Approximately 50% of Patients (Range: 3-62%) (Chest, 2010) [MEDLINE]
  • However, Clinically-Significant Aspiration is Far Less Common

Mechanisms

• Laryngeal Injury is the Likely Mechanism for Speech Impairment

Clinical

• Dysphagia (see Dysphagia)

Treatment

• Formal Swallowing Evaluation (Fiberoptic Endoscopic Evaluation of Swallowing/FEES, Barium Swallowing study, etc) is Generally Recommended for Patients Who Have Been Intubated for ≥7 Days (or Who Have Other Risk Factors for Dysphagia)
• Usually Resolves Spontaneously Over Time

Temporomandibular Joint Dislocation (see Temporomandibular Joint Dislocation)

Mechanisms

• Due to Excessive Force Used to Open the Mouth During Intubation

Tracheobronchial Wall Injury

Clinical

• Bronchial Mucosal Injury: may result in hemoptysis from the site of mucosal injury
  • Bronchial Wall Mucosal Injury May Occur with Inadvertent Mainstem Intubation with a Single Lumen Tube or with Standard Use of a Double-Lumen Tube (Where the Tube Tip is Placed in Either the Right or Left Mainstem Bronchus)
• Tracheal Mucosal Injury: may result in hemoptysis from the site of mucosal injury
• Tracheal Perforation (see Tracheal Perforation)
• Tracheoesophageal Fistula (see Tracheoesophageal Fistula)

Ventilator-Associated Pneumonia (VAP)/Ventilator-Associated Tracheobronchitis (see Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia)

Mechanisms

• Bacterial Biofilm Formation within the Lumen of the Endotracheal Tube
  • Occurs within Hours of Intubation

Ventilator-Associated Sinusitis (see Acute Rhinosinusitis)

Mechanisms

• Impairment of Sinus Drainage, Resulting in Sinusitis

Ventilator-Induced Diaphragmatic Dysfunction (VIDD)

Mechanism

• Diaphragmatic Muscle Atrophy
  • Diaphragmatic Proteolysis May Develop within the First Day of Mechanical Ventilation (N Engl J Med, 2008) [MEDLINE] (Am J Respir Crit Care Med, 2011) [MEDLINE]
  • Diaphragmatic Proteolysis Appears to Be Mediated Via Oxidative Stress-Induced Mitochondrial Dysfunction (Am J Respir Crit Care Med, 2012) [MEDLINE]

Diagnosis

• Diaphragmatic Atrophy Can Be Identified by Diaphragmatic Ultrasound (Thorax, 2014) [MEDLINE]

Clinical

• Study of Diaphragm Dysfunction on Admission to the Intensive Care Unit (Am J Respir Crit Care Med, 2013) [MEDLINE]
  • Reduced Diaphragmatic Capacity to Produce Inspiratory Pressure is Frequent on Admission to the Intensive Care Unit (ICU)
  • Diaphragm Dysfunction is Associated with Sepsis and Disease Severity, Suggesting that it May Represent Another Form of Organ Failure
  • Diaphragm Dysfunction is Associated with a Poor Prognosis
• Diaphragmatic Thickening Can Predict Weaning Success (Thorax, 2014) [MEDLINE]
• Study of Association of Ventilator-Associated Diaphragmatic Atrophy with Clinical Outcomes (Am J Respir Crit Care Med, 2018) [MEDLINE]: n = 191
  • Diaphragmatic Thickness Decreased >10% in 41% of Patients by Median Day 4 (Interquartile Range: 3-5)
  • Decreased Diaphragmatic Thickness (Due to Abnormally Low Respiratory Effort) was Associated with Decreased Daily Probability of Liberation from Mechanical Ventilation (Adjusted Hazard Ratio 0.69; 95% CI: 0.54-0.87; Per 10% Decrease), Prolonged ICU Admission (Adjusted Duration Ratio 1.71; 95% CI: 1.29-2.27), and a Higher Risk of Complications (Adjusted Odds Ratio 3.00; 95% CI: 1.34-6.72)
  • Increased Diaphragmatic Thickness (Due to Excessive Inspiratory Effort) (n = 47; 24%) Also Predicted Prolonged Mechanical Ventilation (Adjusted Duration Ratio 1.38; 95% CI: 1.00-1.90)
  • Patients with Thickening Fraction Between 15-30% (Similar to Breathing at Rest) During the First 3 Days Had the Shortest Duration of Mechanical Ventilation
• Study of Diaphragmatic Dysfunction in Septic Mechanically Ventilated Patients (Ann Intensive Care, 2022) [MEDLINE]: n = 92
  • Septic Patients were Associated with a More Severe, But Reversible, Diaphragmatic Dysfunction, as Compared to Non-Septic Patients
  • Increase in Diaphragm Function was Associated with Improved 28-Day Survival

Management

• Unknown

Ventilator-Induced Lung Injury (VILI)/Barotrauma

• See Above

Vocal Cord Granuloma (see Vocal Cord Granulomas)

Epidemiology

• Vocal Cord Granuloma(s) May Occur in 30-40% of Patients Intubated for >3-4 Days (Intensive Care Med, 2010) [MEDLINE]
• Duration of Intubation and Severity of Initial Laryngeal Injury Do Not Predict the Formation of Vocal Cord Granulomas (Am Rev Respir Dis, 1992) [MEDLINE]

Diagnosis

• Fiberoptic Laryngoscopy (see Fiberoptic Laryngoscopy)
• Neck CT (see Neck Computed Tomography): may diagnose vocal cord granulomas

Physiology

• Likely a Consequence of Prior Inflammation/Ulceration

Clinical

• Hoarseness (see Hoarseness): hoarseness persisting for >7-10 days after extubation is suggestive of the diagnosis

Treatment

• May Resolve Spontaneously in Some Cases (Crit Care Med, 1983) [MEDLINE]
• Surgical Resection is Often Required

Vocal Cord Paralysis

Epidemiology

• Occurs in <1% of Intubations
• Risk Factors for Vocal Cord Paralysis (Br J Anaesth, 2007) [MEDLINE]
  • Age ≥50 y/o: 3-fold increased risk
  • Intubation ≥3-6 hrs: 2-fold increased risk
  • Intubation ≥6 hrs: 15-fold increased risk
  • Diabetes Mellitus (see Diabetes Mellitus): 2-fold increased risk
  • Hypertension (see Hypertension): 2-fold increased risk

Clinical

• Unilateral Vocal Paralysis (see Unilateral Vocal Fold Immobility)
• Bilateral Vocal Cord Paralysis (see Bilateral Vocal Fold Immobility)

Vocal Cord Ulceration

Epidemiology

• Occurs in Approximately 33% of Cases
• Most Commonly Occurs with Intubations Lasting >4 Days (Intensive Care Med, 2010) [MEDLINE]

Physiology

• Direct Pressure on Vocal Cords (with/without Associated Inflammation): usually occurs at the posteromedial aspect of the vocal cords

Diagnostic

• Fiberoptic Laryngoscopy (see Fiberoptic Laryngoscopy)

Clinical

• Asymptomatic: some cases
• Dysphonia (see Dysphonia)
• Hoarseness (see Hoarseness)
• Stridor (see Stridor)

Treatment

• Vocal Cord Ulcers Usually Resolve Spontaneously, But May Progress to Granulomas, Nodules, Interarytenoid Adhesions (Crit Care Med, 1983) [MEDLINE]

Other Complications

Decubitus Ulcer (see Decubitus Ulcer)

• Mechanisms
  • Prolonged Immobilization
  • Elevation of the Head of the Bed (Which is Standardly Used in the Mechanically-Ventilated Patient to Decrease the Risk of Aspiration) is Associated with Increased Risk of Sacral Decubitus Ulcers (Crit Care Med, 2008) [MEDLINE]

Deep Venous Thrombosis (DVT) (see Deep Venous Thrombosis)

• Epidemiology
  • Prolonged Immobilization Associated with Mechanical Ventilation is Associated with an Increased Risk of Deep Venous Thrombosis
  • Additionally, Deep Venous Thrombosis is Common in Mechanically-Ventilated Patients, Despite the Use of Pharmacologic Prophylaxis (J Thromb Thrombolysis, 2017) [MEDLINE]

Induction of Inflammatory Response

• Mechanism
  • Positive-Pressure Mechanical Ventilation Induces an Inflammatory Cytokine Response (in the Bloodstream and Bronchoalveolar Lavage Fluid), Which May Be Attenuated by a the Use of Low Tidal Volume/High PEEP Strategy to Minimize Overdistention and Recruitment/Derecruitment of the Lung (JAMA, 1999) [MEDLINE]

Insulin Resistance

• Epidemiology
  • Prolonged Bedrest Associated with Mechanical Ventilation Has Been Associated with the Development of Insulin Resistance (Arterioscler Thromb Vasc Biol, 2007) [MEDLINE]

Joint Contractures

• Epidemiology
  • Prolonged Bed Rest is Associated with the Development of Joint Contractures (CMAJ, 2008) [MEDLINE]

Tracheal Bacterial Translocation into the Bloodstream

• Mechanism
  • Positive-Pressure Mechanical Ventilation Has Been Demonstrated to Induce Translocation of Tracheal Bacteria into the Bloodstream in Animal Studies (Especially with High Tidal Volumes and Low PEEP) (Crit Care Med, 1997) [MEDLINE]