General

• Australia/New Zealand Study of Severe Sepsis and Septic Shock Mortality Rates (JAMA 2014) [MEDLINE]
  • From 2000 to 2012, there was a Decrease in the Absolute Sepsis Mortality Rate from 35.0% (95% CI, 33.2%-36.8%; 949/2708) to 18.4% (95% CI, 17.8%-19.0%; 2300/12,512; P <0.001)
• Systematic Review of the Global Incidence and Mortality of Sepsis (Am J Respir Crit Care Med, 2016) [MEDLINE]
  • In Articles Restricted to the Last 10 Years, Incidence Rate was 437/100k for Sepsis and 270/100k for Severe Sepsis
  • In Articles Restricted to the Last 10 Years, Hospital Mortality Rate was 17% for Sepsis and 26% for Severe Sepsis
• Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3: Society of Critical Care Medicine and European Society of Intensive Care Medicine) (JAMA, 2016) [MEDLINE]
  • Sepsis Mortality Rate: 10%
  • Septic Shock Mortality Rate: >40%

Prognostic Value of Sepsis Scoring Systems

• Study of SIRS Criteria in Defining Severe Sepsis (NEJM, 2015) [MEDLINE]
  • Sepsis Mortality Rate Increases Linearly with the Sepsis Disease Severity
• Australian/New Zealand Retrospective Cohort Analysis Examining the Accuracy of Sepsis Scoring Criteria in Predicting In-Hospital Mortality of Patients with Suspected Infection Admitted to the Intensive Care Unit (JAMA, 2017) [MEDLINE]: n = 184,875
  • Most Common Diagnosis was Bacterial Pneumonia (Accounted for 17.7% of Cases)
  • Overall, 18.7% of Patients Died in the Hospital
  • Increase in SOFA Score of ≥2 Had Greater Prognostic Accuracy for In-Hospital Mortality than SIRS Criteria or qSOFA Score
• Systematic Review and Meta-Analysis of Sepsis Scoring with Quick-SOFA and Systemic Inflammatory Response Syndrome Criteria for the Diagnosis of Sepsis and Prediction of Mortality (Chest, 2018) [MEDLINE]: n = 229,480 patients (from 10 studies)
  • SIRS Criteria were Significantly Superior to the qSOFA for the Diagnosis of Sepsis
    • Meta-Analysis of Sensitivity for the Diagnosis of Sepsis Comparing the qSOFA Criteria and SIRS Criteria was in Favor of SIRS Criteria (risk ratio [RR], 1.32; 95% CI, 0.40-2.24; P < .0001; I2 = 100%)
  • qSOFA Criteria were Slightly Better than the SIRS Criteria in Predicting Hospital Mortality
    • Meta-Analysis of the Area Under the Receiver Operating Characteristic Curve of 6 Studies Comparing the qSOFA Criteria and SIRS Criteria Favored the qSOFA Criteria (RR, 0.03; 95% CI, 0.01-0.05; P = .002; I2 = 48%) as a Predictor of In-Hospital Mortality
• Systematic Review/Meta-Analysis of the Prognostic Accuracy of qSOFA Scoring in Predicting Sepsis Mortality (Ann Intern Med, 2018) [MEDLINE]: n = 385, 333 (from 38 studies)
  • Overall, qSOFA Score Had Poor Sensitivity (60.8%) and Moderate Specificity (72.0%) for Predicting Short-Term (28-Day or 30-Day) Sepsis Mortality
    • Sensitivity of qSOFA in Predicting Sepsis Mortality was Higher in the ICU Population (87.2% [CI, 75.8%-93.7%]) than the non-ICU Population (51.2% [CI, 43.6%-58.7%])
    • Specificity of qSOFA in Predicting Sepsis Mortality was Higher in the Non-ICU Population (79.6% [CI, 73.3%-84.7%]) than the ICU Population (33.3% [CI, 23.8%-44.4%]
  • SIRS Criteria Had High Sensitivity (88.1%) and Low Specificity (25.8%) for Predicting Short-Term (28-Day or 30-Day) Sepsis Mortality

Poor Prognostic Factors

• Atrial Fibrillation (see Atrial Fibrillation)
  • Study of New-Onset Atrial Fibrillation in Severe Sepsis (JAMA, 2011) [MEDLINE]
    • Patients with New-Onset AF and Severe Sepsis are at 4x Increased Risk of In-Hospital CVA and a 7% Increased Risk of Death, as Compared with Patients with No AF and Patients with Preexisting AF
    • Possible Mechanisms for Increased Risk of CVA in New-Onset AF in Severe Sepsis: new-onset AF might just be a marker for the sickest patients with greatest inherent CVA risk, sepsis itself might result in an increased risk for CVA (by hemodynamic collapse, coagulopathy, or systemic inflammation), or new-onset AF might be a source of cardioembolic CVA
    • Patients with Severe Sepsis Had a 6x Increased Risk of In-Hospital CVA, as Compared with Hospitalized Patients without Severe Sepsis
    • Patients with Severe Sepsis and Preexisting AF Did Not Have an Increased Risk of CVA, as Compared with Patients without AF
  • Prospective Observational Study of Atrial Fibrillation as a Predictor of Mortality in Critically Ill Patients (Crit Care Med, 2016) [MEDLINE]
    • AF in Critical Illness (Whether New-Onset or Recurrent) is Independently Associated with Increased Hospital Mortality (31% vs 17%), Especially in Patients without Sepsis
    • New-Onset AF (But Not Recurrent AF) was Associated with Increased Diastolic Dysfunction and Vasopressor Use and a Greater Cumulative Positive Fluid Balance
  • Dutch Cohort Study of the Incidence, Predictors, and Outcomes of New-Onset Atrial Fibrillation in Critically Ill Patients with Sepsis (Am J Respir Crit Care Med, 2017) [MEDLINE]
    • Atrial Fibrillation is a Common Complication of Sepsis and is Independently Associated with Excess Mortality
• Cancer
  • Study of Hospitalized Patients with Cancer and Severe Sepsis (Crit Care, 2004) [MEDLINE]
    • Cancer Increases the Risk of Hospitalization with Severe Sepsis (Relative Risk 3.96)
    • As Compared with the General Population, Cancer Patients are Much More Likely to Be Hospitalized (Relative Risk, 2.77; 95% CI, 2.77-2.78) and to Be Hospitalized with Severe Sepsis (Relative Risk, 3.96; 95% CI, 3.94-3.99)
    • The In-Hospital Mortality Rate for Cancer Patients with Severe Sepsis was 37.8%
    • Sepsis is Associated with 8.5% of All Cancer Deaths at a Cost of $3.4 Billion Per Year
  • Study of Epidemiology of Sepsis in Patients with Cancer (Chest, 2006) [MEDLINE]
    • Patients with a History of Cancer are at Increased Risk for Acquiring and Dying from Sepsis, as Compared to the General Population: although incidence and fatality rates are decreasing over time
    • There are Significant Racial and Gender Disparities in the Incidence and Outcome of Sepsis Among Cancer Patients
• Coagulopathy (see Coagulopathy)
  • Cohort Study of Coagulation in Severe Sepsis (Intensive Care Med, 2015) [MEDLINE]
    • Progressive Coagulopathy (as Defined by Thromboelastography Variables) was Associated with an Increased Risk of Death and Increased Risk of Hemorrhage
• Delayed Antibiotic Therapy
  • Delayed Antibiotic Therapy is Associated with Increased Sepsis Mortality (Am J Med, 1980) [MEDLINE] and (Crit Care Med, 2011) [MEDLINE]
• Ethanol Abuse (see Ethanol)
  • Study of the Impact of Ethanol Abuse on Sepsis Mortality (Crit Care Med, 2007) [MEDLINE]
    • Ethanol Dependence Increased the Risk of Sepsis, Septic Shock, and Organ Failure
    • Ethanol Dependence Increased Hospital Mortality in ICU Patients
• Failure of Serum Procalcitonin to Decrease (see Serum Procalcitonin)
  • Prospective, Multicenter Procalcitonin MOnitoring SEpsis (MOSES) Study of Procalcitonin in Sepsis (Crit Care Med, 2017) [MEDLINE]
    • Inability to Decrease Serum Procalcitonin by >80% was a Significant Independent Predictor of Mortality
• Hyperchloremia (see Hyperchloremia
  • Study of Effect of Hyperchloremia of Hospital Mortality in Critically Ill Sepsis Patients (Crit Care Med, 2015) [MEDLINE]
    • In Critically Ill Sepsis Patients, Hyperchloremia (Serum Cl ≥110 mEq/L) on ICU Admission, as Well as Higher Serum Chloride and within Subject Worsening of Hyperchloremia at 72 hrs of the ICU Stay were Associated with Increased All-Cause Hospital Mortality
      • The Associations were Independent of Base Deficit, Cumulative Fluid Balance, Acute Kidney Injury, and Other Critical Illness Parameters
• Hyperglycemia (see Hyperglycemia)
  • Study of Admission Hyperglycemia in Critically Ill Sepsis Patients (Crit Care Med, 2016) [MEDLINE]
    • Admission Hyperglycemia was Associated with Adverse Sepsis Outcome of Irrespective of the Presence or Absence of Preexisting Diabetes Mellitus
      • Mechanism Appears to Be Unrelated to Exaggerated Inflammation or Coagulation
• Hypothermia/Lack of Fever (Temperature <35.5 Degrees C)(see Fever)
  • Study of Sepsis Definitions (Chest, 1992) [MEDLINE]
    • Failure to Develop a Fever (Defined as a Temperature <35.5ºC) was More Frequent in Sepsis Non-Survivors (17%) than Sepsis Survivors (5%)
• Immunosuppression
  • Study of Sepsis Mortality Risk Factors in Immunosuppressed Patients (Scand J Infect Dis, 2009) [MEDLINE]
    • Immunosuppressed Patients Had a Higher 28-Day Sepsis Mortality Rate, as Compared to Immunocompetent Patients (Adjusted Relative Risk 1.62, 95% CI 1.38-1.91)
      • Septic Shock, Hypothermia, Cancer and Invasive Fungal Infections were Associated with Increased Mortality in Immunosuppressed Patients
      • Black Race and the Presence of Rigors were Independent Predictors of Survival in Immunosuppressed Patients
  • Study of Immunologic Status in Sepsis and Septic Shock (Chest, 2014) [MEDLINE]
    • Immunodeficiency is Common in Severe Sepsis and Septic Shock
      • Non-Neutropenic Hematologic Malignancy
      • Non-Neutropenic Solid Tumor
      • Neutropenia (of Any Etiology)
    • Immunodeficiency is Associated with Increased Short-Term Mortality After Multivariate Analysis (Subdistribution Hazard Ratio, 1.37; 95% CI, 1.12-1.67)
    • AIDS (Subdistribution Hazard Ratio 1.9), Non-Neutropenic Solid Tumors (Subdistribution Hazard Ratio 1.8), Non-Neutropenic Hematologic Malignancy (Subdistribution Hazard Ratio 1.4), and Neutropenia (Subdistribution Hazard Ratio 1.7) were Associated with an Increased Risk of Death
• Inadequate Sepsis Resuscitation
  • Inadequate Sepsis Resuscitation is Associated with Increased Sepsis Mortality (NEJM, 2001) [MEDLINE]
  • Severe Hyperlactatemia (>10 mmol/L) is Associated with Extremely High ICU Mortality (78.2%) in Sepsis, Especially When There is No Marked Lactate Clearance within 12 hrs (Intensive Care Med, 2016) [MEDLINE]
  • VOLUME-CHASERS Multicenter Prospective Study of the Impact of Vasopressor Dosing Intensity on the Mortality Rate in Septic Shock (Crit Care Med, 2020) [MEDLINE]: n = 616 (33 hospitals: 32 in US and 1 in Jordan)
    • Norepinephrine was the Most Common Vasopressor Used (Used in 93% of Cases)
    • Patients Received a Median of 3,400 mL (Interquartile Range: 1,851-5,338 mL) During the 24 hrs After Shock Diagnosis
    • Median Vasopressor Dosing Intensity During the First 24 hrs of Shock Onset was 8.5 μg/min Norepinephrine Equivalents (Range: 3.4-18.1 μg/min Norepinephrine Equivalents)
    • In the First 6 hrs, Increasing Vasopressor Dosing Intensity was Associated with Increased Odds Ratio of 30-Day In-Hospital Mortality (with the Strength of Association Dependent on Concomitant Fluid Administration)
    • Over the Entire 24 hr Period, Every 10 μg/min Increase in Vasopressor Dosing Intensity was Associated with an Increased Risk of 30-Day Mortality (Adjusted Odds Ratio: 1.33; 95% CI: 1.16-1.53), and This Association Did Not Vary with the Amount of Fluid Administration
    • Compared to an Early High/Late Low Vasopressor Dosing Strategy, an Early Low/Late High or Sustained High Vasopressor Dosing Strategy was Associated with Higher Mortality Rate
• Leukopenia (see Leukopenia)
  • Study of Gram-Negative Bacteremia (Am J Med, 1980) [MEDLINE]
    • Leukopenia <4k was More Common in Non-Survivors (15%) than Non-Survivors (7%) in Gram-Negative Sepsis
• Liver Disease (see Cirrhosis)
  • Study of the Impact of Ethanol Abuse on Sepsis Mortality (Crit Care Med, 2007) [MEDLINE]
    • Sepsis and Liver Disease were Associated with an Increased Mortality Rate for Alcohol-Dependent Patients, as Compared to Those without Alcohol Dependence
• Non-Urinary Tract Site of Infection
  • Urinary Tract Site of Infection is Associated with Lower Sepsis Mortality Rate (30%), as Compared to Unknown/Gastrointestinal/Pulmonary Sources (50-55%) (J Infect Dis, 1983) [MEDLINE]
  • Ischemic Bowel Source of Infection is Associated with the Highest (78%) Sepsis Mortality Rate (Am J Respir Crit Care Med, 2014) [MEDLINE]
  • Urinary Tract is Associated with the Lowest (26%) Sepsis Mortality Rate (Am J Respir Crit Care Med, 2014) [MEDLINE]
• Obesity (see Obesity)
  • Systematic Review of the Effect of Obesity on Sepsis Mortality (J Crit Care, 2015) [MEDLINE]: n = 7 studies
    • The Effect of Obesity on Sepsis Mortality Rate is Unclear
• Older Age
  • Factors in Older Patients Which Contribute to Increased Sepsis Mortality Rates
    • Association of Sepsis with Comorbid Illness
    • Impaired Immunologic Response
    • Malnutrition
    • Increased Exposure to Multidrug-Resistant Pathogens (in Nursing Homes, etc)
    • Increased Utilization of Medical Devices (Intravenous/Arterial Catheter, Pacemaker, Joint Replacement, etc)
  • Age Independently Increases Both the Risk of Sepsis and the Mortality Rate Associated with Sepsis (Crit Care Med, 2006) [MEDLINE]
    • Elderly Patients Account for 12% of the US Population, But 65% of Sepsis Cases (Relative Risk 13.1, as Compared to Younger Patients)
    • Elderly Patients are More Likely to Have Gram-Negative Infections, Particularly in Association with Pneumonia (Relative Risk 1.66, as Compared to Younger Patients)
    • Case-Fatality Rates Increase Linearly with Age
    • Age is an Independent Predictor of Mortality (Odds Ratio 2.26)
    • Elderly Sepsis Patients Died Earlier During Hospitalization*
    • Elderly Survivors of Sepsis were More Likely to Be Discharged to a Non-Acute Health Care Facility
  • Australia/New Zealand Study of Severe Sepsis and Septic Shock Mortality Rates (JAMA 2014) [MEDLINE]
    • In Patients <44 y/o without Comorbidities, the Sepsis Mortality Rate was Far Lower (<10%)
• Prior Antibiotic Therapy (in Patients with Gram-Negative Sepsis): likely due to increased risk of multidrug-resistant pathogens
  • Recent Antibiotic Exposure is Associated with Increased Hospital Mortality in Gram-Negative Bacteremia with Severe Sepsis or Septic Shock (Crit Care Med, 2011) [MEDLINE]
• Specific Pathogens
  • Patients with Hospital-Acquired or Healthcare-Associated Bloodstream Infection Had Higher Sepsis Morbidity and Mortality than Community-Acquired Bloodstream Infection (Crit Care Med, 2006) [MEDLINE]
  • Increased Sepsis Mortality is Associated with Bloodstream Infection Due to Specific (More Commonly Hospital-Acquired) Pathogens (Crit Care Med, 2006) [MEDLINE]
    • Methicillin-Resistant Staphylococcus Aureus (Odds Ratio 2.70, 95% CI 2.03-3.58)
    • Non-Candida Fungus (Odds Ratio 2.66, 95% CI 1.27-5.58)
    • Candida (Odds Ratio 2.32 95% CI 1.21-4.45)
    • Methicillin-Sensitive Staphylococcus Aureus (Odds Ratio 1.9, 95% CI 1.53-2.36)
    • Polymicrobial Infection (Odds Ratio 1.69, 95% CI 1.24-2.30)
    • Pseudomonas (Odds Ratio 1.6, 95% CI 1.04-2.47)
  • In Patients with Septic Shock Due to Candidemia, Poor Prognostic Factors Included Inadequate Source Control, Inadequate Antifungal Therapy, and 1-Point Increments in the APACHE II Score (Intensive Care Med, 2014) [MEDLINE]
• Thrombocytopenia (see Thrombocytopenia)
  • Study of Prognostic Value of Early Thrombocytopenia in Sepsis (Crit Care Med, 2016) [MEDLINE]
    • Thrombocytopenia Severity was Associated with Increased 28-Day Mortality Rate (by Kaplan-Meier Method)
      • Thrombocytopenia Severity was Associated with Increased 28-Day Mortality Rate (Hazard Ratio, 1.65; 95% CI, 1.31-2.08 for Platelet Count <50k vs>150k; p<0.0001)
    • Thrombocytopenia <100k was Associated with Increased 28-Day Mortality (by Multivariate Cox Regression)

Factors Which Do Not Impact Sepsis Mortality Rate

Presence of Bacteremia at the Time of Sepsis Diagnosis (see Bacteremia) (Crit Care Med, 2011) [MEDLINE]

• Prognosis is Probably More Closely Associated with the Severity of the Infection and Severity of Sepsis
• Systematic Review and Meta-Analysis of Culture-Negative vs Culture-Positive Sepsis/Septic Shock (Crit Care, 2021) [MEDLINE]
  • Blood Culture-Positivity or Culture-Negativity was Not Associated with Mortality Rate
  • Furthermore, Blood Culture-Positive Patients Had Similar Intensive Care Unit Length of Stay, Mechanical Ventilation Requirements, and Renal Replacement Requirements as Culture-Negative Patients
• In a Meta-Analysis (n = 23,973, 7 Studies), There was No Significant Difference Between Blood Culture-Positive and Culture-Negative Sepsis in Terms of All-Cause Mortality, Need for Renal Replacement Therapy, Need for Mechanical Ventilation, and Length of Intensive Care Unit Stay (Cureus 15(2): e35416. doi:10.7759/cureus.35416)
  • However, the Length of Hospital Stay was Significantly Shorter in Patients with Blood Culture-Negative Sepsis, as Compared to Blood Culture-Positive Sepsis

Post-Intensive Care Syndrome (PICS) (see Post-Intensive Care Syndrome)

General Comments

• Post-Intensive Care Syndrome (PICS) Constitutes New or Worsening Function in One or More of the Cognitive, Psychiatric, and Physical Domains After a Critical Illness

Clinical Studies

• Canadian Clinical Trials Group 5-Year Study of Acute Respiratory Distress Syndrome (ARDS) Sequelae (NEJM, 2011) [MEDLINE]: ARDS survivors (n = 109) studied at at 3, 6, and 12 months and at 2, 3, 4, and 5 years after discharge from the intensive care unit
  • Exercise Limitation (Decreased 6-Minute Walk Test) and Physical Dysfunction May Persist for Up to 5 yrs After ARDS
  • Pulmonary Function was Near Normal-Normal
  • Psychological Problems May Persist for Up to 5 years after ARDS
• Acute Respiratory Distress Syndrome (ARDS) Cognitive Outcomes Study (Am J Respir Crit Care Med, 2012) [MEDLINE]: study of ARDS survivors (n = 213)
  • Long-Term Cognitive Impairment was Present in 55% of Subjects
  • Anxiety was Present in 62% of Subjects
  • Depression was Present in 36% of Subjects
  • Post-Traumatic Stress Disorder (PTSD) was Present in 39% of Subjects
  • Impact of Hypoxemia
    • Presence of Hypoxemia is a Risk Factor for Long-Term Cognitive and Psychiatric Impairment
  • Impact of Fluid Management Strategy
    • Conservative Fluid Management Strategy is a Potential Risk Factor for Long-Term Cognitive Impairment
      • However, This Finding Requires Further Studies for Confirmation
• BRAIN-ICU Study of Patients with Respiratory Failure or Shock in the Medical/Surgical Intensive Care Unit (NEJM, 2013) [MEDLINE]: n = 821
  • Delirium Developed in 74% of Cases During Hospital Stay
  • Outcomes At 3 Months
    • 40% of Patients Had Impaired Global Cognition Scores that Were 1.5 Standard Deviations (SD) Below the Population Mean, Similar to Scores for Patients with Moderate Traumatic Brain Injury
    • 26% of Patients Had Scores 2 Standard Deviations (SD) Below the Population Mean (Similar to Scores for Patients with Mild Alzheimer’s Disease)
  • Outcomes At 12 Months
    • Similar Persistent Cognitive Dysfunction Occurs as in Those with Moderate Traumatic Brain Injury
    • Similar Persistent Cognitive Dysfunction Occurs as in Those with Mild Alzheimer’s Disease
  • Impact of Duration of Delirium
    • Longer Duration of Delirium was Significantly Associated with Worse Global Cognition at 3 and 12 Months and Worse Executive Function at 3 and 12 Months
  • Impact of Sedative Use
    • Use of Sedatives or Analgesics was Not Associated with Cognitive Impairment at 3 and 12 Months
  • Cognitive Dysfunction was Also Independent of Age, Pre-Existing Cognitive Impairment, Presence or Severity of Coexisting Conditions, and Organ Failure During Intensive Care Unit Stay
• Longitudinal Cohort Study of Depression, Posttraumatic Stress Disorder, and Functional Disability in Intensive Care Survivors from the BRAIN-ICU Study (Lancet Respir Med, 2014) [MEDLINE]: n = 821
  • At 3 Months
    • Approximately 37% of Patients Reported at Least Mild Depression (Depression was Mainly Due to Somatic Symptoms, Rather than Cognitive-Affective Symptoms)
      • Depressive Symptoms were Common Even in Patients without a History of Depression (Occurred in 30% of These Patients at 3 Months)
    • Approximately 7% of Patients Reported Posttraumatic Stress Disorder at 3 Months
    • Approximately 32% of Patients were Disabled in Their Activities of Daily Living (ADL’s)
    • Approximately 26% of Patients were Disabled in Their Instrumental Activities of Daily Living (IADL’s)
    • After Adjusting for Covariates, Younger Age was Associated with a Probability of Worse Posttraumatic Stress Disorder
  • At 12 Months
    • Approximately 33% of Patients Reported at Least Mild Depression (Depression was Mainly Due to Somatic Symptoms, Rather than Cognitive-Affective Symptoms)
      • Depressive Symptoms were Common Even in Patients without a History of Depression (Occurred in 29% of These Patients at 12 Months)
    • Approximately 7% of Patients Reported Posttraumatic Stress Disorder at 12 Months
    • Approximately 27% of Patients were Disabled in Their Activities of Daily Living (ADL’s)
    • Approximately 23% of Patients were Disabled in Their Instrumental Activities of Daily Living (IADL’s)
    • After Adjusting for Covariates, Younger Age was Associated with a Probability of Worse Posttraumatic Stress Disorder
• NHLBI ARDS Network Prospective Longitudinal (1 Year) Multicenter Study of Physical Impairment in Acute Respiratory Distress Syndrome (ARDS) Survivors (Am J Respir Crit Care Med, 2014) [MEDLINE]
  • ARDS Survivors Demonstrated Impairment in 6-Minute Walk Test Distance (Distance was 64% Predicted at 6 Months, 67% Predicted at 1 Year) and Short Form-36 (SF-36) Physical Function Outcome Measures
  • Impairment Appeared to Be Correlated with Mean Daily Corticosteroid Dose and ICU Length of Stay
• Prospective Longitudinal (2 Year) Multicenter Study of Physical Impairment in Acute Respiratory Distress Syndrome (ARDS) Survivors (Crit Care Med, 2014) [MEDLINE]
  • Muscle Weakness is Common at Hospital Discharge Following ARDS, Usually Recovering Within 1 Year
  • Muscle Weakness is Associated with Substantial Impairment in Physical Function and Health-Related QOL, Which Continue Beyond 12 Months
  • Corticosteroid Dose and Use of Neuromuscular Blockade Were Not Associated with the Development of Weakness
• SMOOTH Trial in Germany Employing a Primary Care Management Strategy in Sepsis Survivors (JAMA, 2016) [MEDLINE]
  • Primary Care Management Strategy in Sepsis Survivors Did Not Improve Mental Health-Related Quality of Life at 6 Months

Subsequent Increased Mortality Rate

• Nationwide Population-Based Study in Sepsis Survivors (Am J Respir Crit Care Med, 2016) [MEDLINE]
  • Sepsis Survivors Had Increased All-Cause Mortality Rate (Hazard Ratio, 2.18; 95% Confidence Interval, 2.14-2.22) at One Year Post-Discharge
  • Sepsis Survivors Had Increased Risk of Major Cardiovascular Events (Hazard Ratio, 1.37; 95% Confidence Interval, 1.34-1.41) at One Year Post-Discharge
  • Risk Persisted Up to 5 Years Post-Discharge
• French Cluster Analysis Study of Patient Disposition and Outcome After Critical Illness (Chest, 2022) [MEDLINE]: n = 77,132 ICU ICU survivors who spent ≥2 nights in a French ICU during 2018 and were treated with invasive mechanical ventilation or vasopressors or inotropes (trauma, burn, organ transplant, stroke, and neurosurgical patients were excluded)
  • 89% of All Patients were Able to Return to Home
    • In the Year After Discharge, These Patients Spent a Median of 330 (Interquartile Range [IQR]: 283-349) Days at Home
  • At 1 Year
    • 77% of Patients were Still at Home
    • 17% Had Died
    • 51% Had Been Re-Hospitalized
    • 10% Required Further ICU Admission
  • 48% of Patients Required Rehabilitation Facilities and 5.7% Required Hospital at Home
  • Three Clusters of Patients with Distinct Post-ICU Trajectories were Identified
    • Patients in Cluster 1 (68% of Total) Survived and Spent Most of the Year at Home (338 [323-354] Days)
    • Patients in Cluster 2 (18%) Had More Complex Trajectories, But Most Could Return Home (91%), Spending 242 (174-277) Days at Home
    • Patients in Cluster 3 (14%) Died with Only 37% Returning Home for 45 (15-90) Days

Subsequent Increased Risk of Future Sepsis

• Study of Subsequent Infections in Sepsis Survivors (J Intensive Care Med, 2014) [MEDLINE]
  • Sepsis Survivors Have an Increased Risk of Future Infections with an Associated Increased Mortality Rate

Subsequent Increased Healthcare Use

• Study of Healthcare Utilization in Sepsis Survivors (Am J Respir Crit Care Med, 2014) [MEDLINE]
  • Healthcare Use is Markedly Elevated in the First Year After Severe Sepsis
• French Cluster Analysis Study of Patient Disposition and Outcome After Critical Illness (Chest, 2022) [MEDLINE]: n = 77,132 ICU ICU survivors who spent ≥2 nights in a French ICU during 2018 and were treated with invasive mechanical ventilation or vasopressors or inotropes (trauma, burn, organ transplant, stroke, and neurosurgical patients were excluded)
  • 89% of All Patients were Able to Return to Home
    • In the Year After Discharge, These Patients Spent a Median of 330 (Interquartile Range [IQR]: 283-349) Days at Home
  • At 1 Year
    • 77% of Patients were Still at Home
    • 17% Had Died
    • 51% Had Been Re-Hospitalized
    • 10% Required Further ICU Admission
  • 48% of Patients Required Rehabilitation Facilities and 5.7% Required Hospital at Home
  • Three Clusters of Patients with Distinct Post-ICU Trajectories were Identified
    • Patients in Cluster 1 (68% of Total) Survived and Spent Most of the Year at Home (338 [323-354] Days)
    • Patients in Cluster 2 (18%) Had More Complex Trajectories, But Most Could Return Home (91%), Spending 242 (174-277) Days at Home
    • Patients in Cluster 3 (14%) Died with Only 37% Returning Home for 45 (15-90) Days

Recommendations (Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021) (Crit Care Med, 2021) [MEDLINE]

• For Adult Survivors of Sepsis/Septic Shock and Their Families, Referral to Peer Support Groups is Recommended (Weak Recommendation, Very Low Quality of Evidence)
• For Adults with Sepsis/Septic Shock and Their Families, Written/Verbal Sepsis Education (Diagnosis, Treatment, and Post-Intensive Care Unit/Post-Sepsis Syndrome) Prior to Hospital Discharge and in the Follow-Up Setting is Recommended (Weak, very low quality of evidence)
• For Adults with Sepsis/Septic Shock and Their Families, Clinical Team Should Provide the Opportunity to Participate in Shared Decision Making in Post-Intensive Care Unit and Hospital Discharge Planning to Ensure Discharge Plans are Acceptable and Feasible (Best Practice)
• For Adults with Sepsis/Septic Shock and Their Families, Use of a Critical Care Transition Program on Transfer to the Floor is Recommended (Weak, very low quality of evidence)
• For Adults with Sepsis/Septic Shock, Reconciling Medications at Both Intensive Care Unit and Hospital Discharge is Recommended (Best Practice)
• For Adults with Sepsis/Septic Shock and Their Families, Including Information About the Intensive Care Unit Stay, Sepsis and Related Diagnoses, Treatments, and Common Impairments After Sepsis in the Written and Verbal Hospital Discharge Summary is Recommended (Best Practice)
• For Adults with Sepsis/Septic Shock Who Have Developed New Impairments, Hospital Discharge Plans Should Include Follow-Up with Clinicians Able to Support and Manage New and Long-Term Sequelae (Best Practice)
• For Adults with Sepsis/Septic Shock and Their Families, There is Insufficient Evidence to Make a Recommendation Regarding Early Post-Hospital Discharge Follow-Up, as Compared with Routine Post-Hospital Discharge Follow-Up (No Recommendation)
• For Adults with Sepsis/Septic Shock, There is Insufficient Evidence to Make a Recommendation Regarding Early Cognitive Therapy (No Recommendation)
• For Adult Survivors of Sepsis/Septic Shock, Assessment and Follow-Up for Physical, Cognitive, and Emotional Problems After Hospital Discharge is Recommended (Best Practice)
• For Adult Survivors of Sepsis/Septic Shock, Referral to a Post-Critical Illness Follow-Up Program is Recommended, if Available (Weak Recommendation, Very Low Quality of Evidence)
• For Adult Survivors of Sepsis/Septic Shock Receiving Mechanical Ventilation for >48 hrs or an Intensive Care Unit Stay of >72 hrs, Referral to a Post-Hospital Rehabilitation Program is Recommended (Weak Recommendation, Very Low Quality of Evidence)