Effect of Awake Prone Positioning on Endotracheal Intubation in Patients With COVID-19 and Acute Respiratory Failure: A Randomized Clinical Trial.

Importance: The efficacy and safety of prone positioning is unclear in nonintubated patients with acute hypoxemia and COVID-19. Objective: To evaluate the efficacy and adverse events of prone positioning in nonintubated adult patients with acute hypoxemia and COVID-19. Design, Setting, and Participants: Pragmatic, unblinded randomized clinical trial conducted at 21 hospitals in Canada, Kuwait, Saudi Arabia, and the US. Eligible adult patients with COVID-19 were not intubated and required oxygen (≥40%) or noninvasive ventilation. A total of 400 patients were enrolled between May 19, 2020, and May 18, 2021, and final follow-up was completed in July 2021. Intervention: Patients were randomized to awake prone positioning (n = 205) or usual care without prone positioning (control; n = 195). Main Outcomes and Measures: The primary outcome was endotracheal intubation within 30 days of randomization. The secondary outcomes included mortality at 60 days, days free from invasive mechanical ventilation or noninvasive ventilation at 30 days, days free from the intensive care unit or hospital at 60 days, adverse events, and serious adverse events. Results: Among the 400 patients who were randomized (mean age, 57.6 years [SD, 12.83 years]; 117 [29.3%] were women), all (100%) completed the trial. In the first 4 days after randomization, the median duration of prone positioning was 4.8 h/d (IQR, 1.8 to 8.0 h/d) in the awake prone positioning group vs 0 h/d (IQR, 0 to 0 h/d) in the control group. By day 30, 70 of 205 patients (34.1%) in the prone positioning group were intubated vs 79 of 195 patients (40.5%) in the control group (hazard ratio, 0.81 [95% CI, 0.59 to 1.12], P = .20; absolute difference, -6.37% [95% CI, -15.83% to 3.10%]). Prone positioning did not significantly reduce mortality at 60 days (hazard ratio, 0.93 [95% CI, 0.62 to 1.40], P = .54; absolute difference, -1.15% [95% CI, -9.40% to 7.10%]) and had no significant effect on days free from invasive mechanical ventilation or noninvasive ventilation at 30 days or on days free from the intensive care unit or hospital at 60 days. There were no serious adverse events in either group. In the awake prone positioning group, 21 patients (10%) experienced adverse events and the most frequently reported were musculoskeletal pain or discomfort from prone positioning (13 of 205 patients [6.34%]) and desaturation (2 of 205 patients [0.98%]). There were no reported adverse events in the control group. Conclusions and Relevance: In patients with acute hypoxemic respiratory failure from COVID-19, prone positioning, compared with usual care without prone positioning, did not significantly reduce endotracheal intubation at 30 days. However, the effect size for the primary study outcome was imprecise and does not exclude a clinically important benefit. Trial Registration: ClinicalTrials.gov Identifier: NCT04350723.

Tolerability and safety of awake prone positioning COVID-19 patients with severe hypoxemic respiratory failure.

PURPOSE: Prone positioning of non-intubated patients with coronavirus disease (COVID-19) and hypoxemic respiratory failure may prevent intubation and improve outcomes. Nevertheless, there are limited data on its feasibility, safety, and physiologic effects. The objective of our study was to assess the tolerability and safety of awake prone positioning in COVID-19 patients with hypoxemic respiratory failure. METHODS: This historical cohort study was performed across four hospitals in Calgary, Canada. Included patients had suspected COVID-19 and hypoxic respiratory failure requiring intensive care unit (ICU) consultation, and underwent awake prone positioning. The duration, frequency, tolerability, and adverse events from prone positioning were recorded. Respiratory parameters were assessed before, during, and after prone positioning. The primary outcome was the tolerability and safety of prone positioning. RESULTS: Seventeen patients (n = 12 ICU, n = 5 hospital ward) were included between April and May 2020. The median (range) number of prone positioning days was 1 (1-7) and the median number of sessions was 2 (1-6) per day. The duration of prone positioning was 75 (30-480) min, and the peripheral oxygen saturation was 91% (84-95) supine and 98% (92-100) prone. Limitations to prone position duration were pain/general discomfort (47%) and delirium (6%); 47% of patients had no limitations. Seven patients (41%) required intubation and two patients (12%) died. CONCLUSIONS: In a small sample, prone positioning non-intubated COVID-19 patients with severe hypoxemia was safe; however, many patients did not tolerate prolonged durations. Although patients had improved oxygenation and respiratory rate in the prone position, many still required intubation. Future studies are required to determine methods to improve the tolerability of awake prone positioning and whether there is an impact on clinical outcomes.

RéSUMé: OBJECTIF: Le positionnement ventral des patients non intubés atteints de coronavirus (COVID-19) et d'insuffisance respiratoire hypoxémique pourrait éviter de devoir les intuber et améliorer leurs pronostics. Nous ne disposons toutefois que de peu de données concernant la faisabilité, la sécurité et les effets physiologiques d'un tel positionnement. L'objectif de notre étude était d'évaluer la tolérabilité et la sécurité du positionnement ventral éveillé chez des patients atteints de la COVID-19 et d'insuffisance respiratoire hypoxémique. MéTHODE: Cette étude de cohorte historique a été réalisée dans 4 hôpitaux de Calgary, au Canada. Les patients inclus avaient une suspicion de COVID-19, souffraient d'insuffisance respiratoire hypoxique nécessitant une consultation à l'unité de soins intensifs (USI), et ont été positionnés sur le ventre éveillés. La durée, la fréquence, la tolérabilité et les événements indésirables liés au positionnement ventral ont été enregistrés. Les paramètres respiratoires étaient évalués avant, pendant et après le positionnement ventral. Les critères d'évaluation principaux étaient la tolérabilité et la sécurité du positionnement ventral. RéSULTATS: Dix-sept patients (n = 12 USI, n = 5 à l'étage) ont été inclus entre avril et mai 2020. Le nombre médian de jours de positionnement ventral était de 1 (fourchette 1-7) et de 2 sessions (fourchette 1-6) par jour. La durée médiane du positionnement ventral était de 75 min (fourchette, 30-480). La saturation en oxygène périphérique médiane en position dorsale était de 91 % (fourchette, 84-95) et de 98 % (fourchette 92-100) en position ventrale. Les obstacles à une durée prolongée de la position ventrale étaient la douleur / l'inconfort général (47%) et le delirium (6%). Au total, 47 % des patients n'ont fait état d'aucun obstacle. Sept patients (41 %) ont nécessité une intubation, et deux patients (12 %) sont décédés. CONCLUSION: Dans un petit échantillon, le positionnement ventral de patients non intubés atteints de COVID-19 et d'hypoxémie grave était sécuritaire, mais plusieurs patients n'ont pas toléré cette position pour une durée prolongée. Bien que l'oxygénation et la fréquence respiratoire des patients étaient améliorées en position ventrale, bon nombre ont tout de même nécessité une intubation. Des études futures sont nécessaires afin de déterminer quelles méthodes amélioreraient la tolérabilité du positionnement ventral éveillé et si cette position a un impact sur les devenirs cliniques.

Methods for determination of optimal positive end-expiratory pressure: a protocol for a scoping review.

INTRODUCTION: Titrated application of positive end-expiratory pressure (PEEP) is an important part of any mechanical ventilation strategy. However, the method by which the optimal PEEP is determined and titrated varies widely. Methods for determining optimal PEEP have been assessed using a variety of different study designs and patient populations. We will conduct a scoping review to systematically identify all methods for determining optimal PEEP, and to identify the patient populations, outcomes measured and study designs used for each method. The goal will be to identify gaps in the optimal PEEP literature and identify areas where there may be an opportunity to further systematically synthesise and meta-analyse existing literature. METHODS AND ANALYSIS: Using scoping review methodology, we will generate a comprehensive search strategy based on inclusion and exclusion criteria generated using the population, concept, context framework. Five different databases will be searched (MEDLINE, EMBASE, CENTRAL, Web of Science and Scopus). Three investigators will independently screen titles and abstracts, and two investigators will independently complete full-text review and data extraction. Included citations will be categorised in terms of PEEP method, study design, patient population and outcomes measured. The methods for PEEP titration will be described in detail, including strengths and limitations. ETHICS AND DISSEMINATION: Given this is a synthesis of existing literature, ethics approval is not required. The results will be disseminated to stakeholders via presentation at local, regional and national levels, as well as publication in a high-impact critical care journal. There is also the potential to impact local clinical care protocols and inform broader clinical practice guidelines undertaken by societies.

Prognostic value of echocardiography-derived right ventricular dysfunction in haemodynamically stable pulmonary embolism: a systematic review and meta-analysis.

BACKGROUND: We sought to determine the prognostic value of transthoracic echocardiography (TTE)-derived right ventricular dysfunction (RVD) in haemodynamically stable and intermediate-risk patients with acute pulmonary embolism (PE), evaluate continuous RVD parameters, and assess the literature quality. METHODS: We searched MEDLINE, Embase and the Cochrane Central Register of Controlled Trials for studies assessing TTE-derived RVD in haemodynamically stable PE that reported in-hospital adverse events within 30 days. We determined pooled odds ratios (ORs) using a random-effects model, created funnel plots, evaluated the Newcastle-Ottawa scale and performed Grading of Recommendations, Assessment, Development and Evaluation. RESULTS: Based on 55 studies (17 090 patients, 37.8% RVD), RVD was associated with combined adverse events (AEs) (OR 3.29, 95% confidence interval (CI) 2.59-4.18), mortality (OR 2.00, CI 1.66-2.40) and PE-related mortality (OR 4.01, CI 2.79-5.78). In intermediate-risk patients, RVD was associated with AEs (OR 1.99, CI 1.17-3.37) and PE-related mortality (OR 6.16, CI 1.33-28.40), but not mortality (OR 1.63, CI 0.76-3.48). Continuous RVD parameters provide a greater spectrum of risk compared to categorical RVD. We identified publication bias, poor methodological quality in 34/55 studies and overall low certainty of evidence. CONCLUSIONS: RVD is frequent in PE and associated with adverse outcomes. However, data quality and publication bias are limitations of existing evidence.

Ventricular-arterial decoupling is associated with in-hospital adverse events in normotensive pulmonary embolism.

During acute pulmonary embolism (PE) a compensatory increase in right ventricular (RV) contractility is required to match increased afterload to maintain right ventricular-pulmonary arterial (RV-PA) coupling. The aim of this study was to assess the prognostic utility of RV-PA decoupling in acute PE. We assessed the association between measures of transthoracic echocardiography (TTE)-derived RV-PA coupling including tricuspid annular plane systolic excursion (TAPSE)/right ventricular systolic pressure (RVSP) and right ventricular fractional area change (FAC)/RVSP as well as stroke volume index (SVI)/RVSP (a measure of pulmonary artery capacitance) with adverse PE-related events (in-hospital PE-related mortality or cardiopulmonary decompensation) using logistic regression analysis. In 820 normotensive patients TTE-derived markers of RV-PA coupling were associated with PE-related adverse events. For each 0.1 mm/mmHg decrease in TAPSE/RVSP the odds of an adverse event increased by 2.5-fold [adjusted OR (aOR) 2.49, 95% confidence interval (CI) 1.46-4.24, p = 0.001], for every 0.1%/mmHg decrease in FAC/RVSP the odds of an adverse event increased by 1.4-fold (aOR 1.42, CI 1.09-1.86, p = 0.010), and for every 0.1 mL/mmHg m2 decrease in SVI/RVSP the odds of an event increased by 2.75-fold (aOR 2.78, CI 1.72-4.50, p < 0.001). In multivariable analysis, TAPSE/RVSP and SVI/RVSP were independent of other risk stratification methods including computed tomography-derived right ventricular dysfunction (RVD), the Bova score, and subjective assessment of TTE-derived RVD. In patients with normotensive acute PE, TTE-derived measures of RV-PA coupling are associated with adverse in-hospital PE-related events and provide incremental value in the risk assessment beyond computed tomography-derived RVD, the Bova score, or subjective TTE-derived RVD.

Efficacy of awake prone positioning in patients with covid-19 related hypoxemic respiratory failure: systematic review and meta-analysis of randomized trials.

OBJECTIVE: To determine the efficacy and safety of awake prone positioning versus usual care in non-intubated adults with hypoxemic respiratory failure due to covid-19. DESIGN: Systematic review with frequentist and bayesian meta-analyses. STUDY ELIGIBILITY: Randomized trials comparing awake prone positioning versus usual care in adults with covid-19 related hypoxemic respiratory failure. Information sources were Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to 4 March 2022. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently extracted data and assessed risk of bias. Random effects meta-analyses were performed for the primary and secondary outcomes. Bayesian meta-analyses were performed for endotracheal intubation and mortality outcomes. GRADE certainty of evidence was assessed for outcomes. MAIN OUTCOME MEASURES: The primary outcome was endotracheal intubation. Secondary outcomes were mortality, ventilator-free days, intensive care unit (ICU) and hospital length of stay, escalation of oxygen modality, change in oxygenation and respiratory rate, and adverse events. RESULTS: 17 trials (2931 patients) met the eligibility criteria. 12 trials were at low risk of bias, three had some concerns, and two were at high risk. Awake prone positioning reduced the risk of endotracheal intubation compared with usual care (crude average 24.2% v 29.8%, relative risk 0.83, 95% confidence interval 0.73 to 0.94; high certainty). This translates to 55 fewer intubations per 1000 patients (95% confidence interval 87 to 19 fewer intubations). Awake prone positioning did not significantly affect secondary outcomes, including mortality (15.6% v 17.2%, relative risk 0.90, 0.76 to 1.07; high certainty), ventilator-free days (mean difference 0.97 days, 95% confidence interval -0.5 to 3.4; low certainty), ICU length of stay (-2.1 days, -4.5 to 0.4; low certainty), hospital length of stay (-0.09 days, -0.69 to 0.51; moderate certainty), and escalation of oxygen modality (21.4% v 23.0%, relative risk 1.04, 0.74 to 1.44; low certainty). Adverse events related to awake prone positioning were uncommon. Bayesian meta-analysis showed a high probability of benefit with awake prone positioning for endotracheal intubation (non-informative prior, mean relative risk 0.83, 95% credible interval 0.70 to 0.97; posterior probability for relative risk <0.95=96%) but lower probability for mortality (0.90, 0.73 to 1.13; <0.95=68%). CONCLUSIONS: Awake prone positioning compared with usual care reduces the risk of endotracheal intubation in adults with hypoxemic respiratory failure due to covid-19 but probably has little to no effect on mortality or other outcomes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022314856.

Rapid prediction of adverse outcomes for acute normotensive pulmonary embolism: derivation of the Calgary Acute Pulmonary Embolism score.

BACKGROUND: Acute pulmonary embolism (PE) has a wide spectrum of outcomes, but the best method to risk-stratify normotensive patients for adverse outcomes remains unclear. METHODS: A multicentre retrospective cohort study of acute PE patients admitted from emergency departments in Calgary, Canada, between 2012 and 2017 was used to develop a refined acute PE risk score. The composite primary outcome of in-hospital PE-related death or haemodynamic decompensation. The model was internally validated using bootstrapping and the prognostic value of the derived risk score was compared to the Bova score. RESULTS: Of 2067 patients with normotensive acute PE, the primary outcome (haemodynamic decompensation or PE-related death) occurred in 32 (1.5%) patients. In simplified Pulmonary Embolism Severity Index high-risk patients (n=1498, 78%), a multivariable model used to predict the primary outcome retained computed tomography (CT) right-left ventricular diameter ratio ≥1.5, systolic blood pressure 90-100 mmHg, central pulmonary artery clot and heart rate ≥100 beats·min-1 with a C-statistic of 0.89 (95% CI 0.82-0.93). Three risk groups were derived using a weighted score (score, prevalence, primary outcome event rate): group 1 (0-3, 73.8%, 0.34%), group 2 (4-6, 17.6%, 5.8%), group 3 (7-9, 8.7%, 12.8%) with a C-statistic 0.85 (95% CI 0.78-0.91). In comparison the prevalence (primary outcome) by Bova risk stages (n=1179) were stage I 49.8% (0.2%); stage II 31.9% (2.7%); and stage III 18.4% (7.8%) with a C-statistic 0.80 (95% CI 0.74-0.86). CONCLUSIONS: A simple four-variable risk score using clinical data immediately available after CT diagnosis of acute PE predicts in-hospital adverse outcomes. External validation of the Calgary Acute Pulmonary Embolism score is required.

Wanting to Forget: Intrusive and Delusional Memories from Critical Illness.

Introduction. Delusional and fearful memories after critical illness are observed in up to 70% of patients post critical illness. However, they often go unrecognized after patients leave the intensive care unit (ICU). Case Presentation. A 40-year-old male was admitted to the ICU with community-acquired pneumonia and multiorgan failure requiring mechanical ventilation and renal replacement therapy. He developed protracted delirium and severe ICU-acquired weakness but was eventually discharged home. The patient returned to a follow-up clinic two months post-ICU discharge and revealed that he was suffering anxiety from memories in the ICU of different staff trying to harm and kill him, including being repeatedly suffocated. By providing context to the memories, the patient had significant relief in his anxiety. Conclusions. Intrusive memories contribute to psychological morbidity post critical illness, including posttraumatic stress disorder (PTSD) and reduced health-related quality of life. The majority of critical illness survivors do not share their intrusive or frightening memories, and therefore, most healthcare professionals are unaware of the problems they can pose. Assessment of patients' memories from the ICU is essential and may create the opportunity to help patients place memories into context and improve psychological morbidities.

Echocardiography-Derived Stroke Volume Index Is Associated With Adverse In-Hospital Outcomes in Intermediate-Risk Acute Pulmonary Embolism: A Retrospective Cohort Study.

BACKGROUND: There remains uncertainty in the optimal prognostication and management of patients with intermediate-risk pulmonary embolism (PE). Transthoracic echocardiography can identify right ventricular dysfunction to recognize intermediate-high-risk patients. RESEARCH QUESTION: Is echocardiographic-derived stroke volume index (SVI) associated with death or cardiopulmonary decompensation in intermediate-risk patients with PE? STUDY DESIGN AND METHODS: and Methods: We retrospectively evaluated echocardiographic-derived variables that included SVI in normotensive patients with acute PE who were admitted between January 2012 and March 2017. SVI was determined with the use of the Doppler velocity-time integral in the left or right ventricular outflow tract. The primary outcome was in-hospital PE-related death or cardiopulmonary decompensation. We used logistic regression to determine the association between SVI and outcomes and receiver operating characteristic analysis to compare the performance of SVI and other echocardiographic measures. RESULTS: The primary outcome occurred in 26 of the 665 intermediate-risk patients (3.9%) with PE. Univariate logistic regression showed an OR of 1.37 (95% CI, 1.23-1.52; P < .001) per 1-mL/m2 decrease in SVI for the primary outcome. Bivariate logistic regression showed that SVI was independent of age, sex, heart rate, tricuspid regurgitation velocity, tricuspid annular plane systolic excursion, troponin, and Bova score. SVI had the highest C-statistic of 0.88 (95% CI, 0.81-0.96) of all echocardiographic variables with a Youden's J-statistic that identifies an optimal cut-point of 20.0 mL/m2, which corresponds to positive and negative likelihood ratios of 6.5 (95% CI, 5.0-8.6) and 0.2 (95% CI, 0.1-0.5) for the primary outcomes, respectively. INTERPRETATION: Low SVI was associated with in-hospital death or cardiopulmonary decompensation in acute PE. SVI had excellent performance compared with other clinical and echocardiographic variables.

A Prospective Evaluation of the Diagnostic Accuracy of the Physical Examination for Pulmonary Hypertension.

BACKGROUND: The usefulness of physical examination findings for pulmonary hypertension (PH) is not well established. The purpose of this study was to evaluate prospectively the diagnostic performance of the physical examination for detecting PH. METHODS: Consecutive patients undergoing right-sided heart catheterization (n = 116) were examined by an attending physician, medical resident, and medical student in a blinded fashion. Sensitivity, specificity, and positive and negative likelihood ratios (LRs) were calculated for each physical finding. Jugular venous pulsation (JVP) height was compared with right atrial pressure (RAP) by using linear regression. The association between physical findings and PH was assessed using univariate and multivariate logistic regression. RESULTS: The prevalence of PH was 87%. Only a JVP > 3 cm (positive LR, 2.5; 95% CI, 1.2-5.4) and pulmonic regurgitation murmur (specificity, 100%; 95% CI, 79%-100%) helped rule in PH. The absence of JVP > 3 cm (negative LR, 0.4; 95% CI, 0.3-0.6) and absence of loud pulmonic component of the second heart sound (negative LR, 0.5; 95% CI, 0.3-0.9) had modest usefulness in excluding PH. JVP correlated with RAP (r = 0.59; P < .001) but tended to lead to underestimation of RAP (mean bias, -3.4 cm H2O; 95% limits of agreement, -14.0 to 7.2). The presence of JVP > 3 cm and a parasternal heave discriminated PH (area under the curve [AUC] = 0.75). The combination of JVP > 3 cm, heave, and peripheral edema discriminated severe PH (mean pulmonary arterial pressure ≥ 45 mm Hg; AUC = 0.82). CONCLUSIONS: Individual physical examination findings have inadequate diagnostic usefulness for PH. No combination of findings can be used to exclude PH, but the presence of high JVP, peripheral edema, and parasternal heave suggests severe PH.

Intentional overdose of liraglutide in a non-diabetic patient causing severe hypoglycemia.

ABSTRACTCases of liraglutide overdose are rare in the literature. Prior reports have not found hypoglycemia related to the medication overdose. We describe a case of a non-diabetic patient who intentionally overdosed on liraglutide leading to severe hypoglycemia. The patient required admission to the intensive care unit for a dextrose infusion and close monitoring. Glucagon-like protein-1 agonists are recognized for their safety and rarely causing hypoglycemia in diabetic patients. However, in this case the patient's non-diabetic status may have put him at risk for hypoglycemia in contrast to prior cases showing no hypoglycemia in diabetic patients. The case highlights the possible dangers of liraglutide overdose and need for blood glucose monitoring in the acute presentation.

Assessment of sleep quality post-hospital discharge in survivors of critical illness.

BACKGROUND: Sleep quality is impaired during critical illness and may remain abnormal after discharge from hospital. Sleep dysfunction in patients after critical illness may impair recovery and health related quality of life. The purpose of this study was to use objective and subjective measures to evaluate sleep quality in critical illness survivors 3 months after hospital discharge. METHODS: This was a prospective cohort study of 55 patients admitted to a multidisciplinary intensive care unit (ICU) between April 1st, 2009 and March 31, 2010. Patients enrolled were over 17 years of age and stayed a minimum of 4 days in the ICU. Patients were assessed in an outpatient clinic 3-months after hospital discharge. Sleep quality was measured using multi-night sleep actigraphy and the Pittsburgh Sleep Quality Index (PSQI). RESULTS: A total of 62% of patients had poor sleep quality measured with the PSQI. The average (SD) sleep time, sleep efficiency and number of sleep disruptions per night was 6.15 h (3.4), 78% (18), and 11 disruptions (5) respectively. The APACHE II score was correlated with total sleep time (ß = -12.6, P = 0.019) and sleep efficiency (ß = -1.18, P = 0.042). The PSQI score was associated with anxiety (ß = 4.00, p = 0.001), reduced mobility (ß = 3.39, p = 0.002) and EuroQol-5D visual analogue scale score (ß = -0.85, p = 0.003) and low Physical Composite Scores (ß = -0.13, p = 0.004) and Mental Composite Scores (ß = -0.15, p = 0.002) of the Short-Form 36 survey. CONCLUSIONS: Reduced sleep quality following critical illness is common and associated with reduced health related quality of life. Critical illness severity is a predictor of reduced sleep duration and sleep disruption 3 months after hospital discharge. This cohort study highlights the important role sleep may contribute to the long-term recovery from critical illness.

Assessment and predictors of physical functioning post-hospital discharge in survivors of critical illness.

BACKGROUND: Prior studies of physical functioning after critical illness have been mostly limited to survivors of acute respiratory distress syndrome. The purpose of this study was to objectively assess muscle strength and physical functioning in survivors of critical illness from a general ICU and the associations of these measures to health-related quality of life (HRQL), mental health and critical illness variables. METHODS: This was a prospective cohort study of 56 patients admitted to a medical ICU (length of stay ≥4 days) from April 1, 2009, and March 31, 2010. Patients were assessed in clinic at 3 months post-hospital discharge. Muscle strength and physical functioning were measured using hand-held dynamometry and the 6-min walk test. HRQL was assessed using the short-form 36 (SF-36) and EuroQol-5D (EQ-5D) questionnaires. RESULTS: Three months post-hospital discharge, median age- and sex-matched muscle strength was reduced across all muscle groups. The median 6-min walk distance was 72 % of predicted. Physical functioning was associated with reductions in self-reported HRQL (SF-36, EQ-5D) and increased anxiety. Univariate regression modeling showed that reduced muscle strength and 6-min walk distance were associated with sepsis but not ICU length of stay. Multivariate regression modeling showed that sepsis and corticosteroid use were associated with a reduced 6-min walk distance, but again ICU length of stay was not. CONCLUSIONS: Survivors of critical illness have reduced strength in multiple muscle groups and impaired exercise tolerance impacting both HRQL and mental health. These outcomes were worsened by sepsis and corticosteroid use in the ICU but not ICU length of stay. Interventions to minimizing the burden of sepsis in critically ill patients may improve long-term outcomes.