Adverse Effects Related to Corticosteroid Use in Sepsis, Acute Respiratory Distress Syndrome, and Community-Acquired Pneumonia: A Systematic Review and Meta-Analysis.

OBJECTIVES: We postulate that corticosteroid-related side effects in critically ill patients are similar across sepsis, acute respiratory distress syndrome (ARDS), and community-acquired pneumonia (CAP). By pooling data across all trials that have examined corticosteroids in these three acute conditions, we aim to examine the side effects of corticosteroid use in critical illness. DATA SOURCES: We performed a comprehensive search of MEDLINE, Embase, Centers for Disease Control and Prevention library of COVID research, CINAHL, and Cochrane center for trials. STUDY SELECTION: We included randomized controlled trials (RCTs) that compared corticosteroids to no corticosteroids or placebo in patients with sepsis, ARDS, and CAP. DATA EXTRACTION: We summarized data addressing the most described side effects of corticosteroid use in critical care: gastrointestinal bleeding, hyperglycemia, hypernatremia, superinfections/secondary infections, neuropsychiatric effects, and neuromuscular weakness. DATA SYNTHESIS: We included 47 RCTs (n = 13,893 patients). Corticosteroids probably have no effect on gastrointestinal bleeding (relative risk [RR], 1.08; 95% CI, 0.87-1.34; absolute risk increase [ARI], 0.3%; moderate certainty) or secondary infections (RR, 0.97; 95% CI, 0.89-1.05; absolute risk reduction, 0.5%; moderate certainty) and may have no effect on neuromuscular weakness (RR, 1.22; 95% CI, 1.03-1.45; ARI, 1.4%; low certainty) or neuropsychiatric events (RR, 1.19; 95% CI, 0.82-1.74; ARI, 0.5%; low certainty). Conversely, they increase the risk of hyperglycemia (RR, 1.21; 95% CI, 1.11-1.31; ARI, 5.4%; high certainty) and probably increase the risk of hypernatremia (RR, 1.59; 95% CI, 1.29-1.96; ARI, 2.3%; moderate certainty). CONCLUSIONS: In ARDS, sepsis, and CAP, corticosteroids are associated with hyperglycemia and probably with hypernatremia but likely have no effect on gastrointestinal bleeding or secondary infections. More data examining effects of corticosteroids, particularly on neuropsychiatric outcomes and neuromuscular weakness, would clarify the safety of this class of drugs in critical illness.

Home respiratory strategies in COPD patients with chronic hypercapnic respiratory failure: a systematic review and network meta-analysis.

Background: Home non-invasive positive pressure ventilation (NPPV) may improve chronic hypercarbia in COPD and patient important outcomes. The efficacy of home high flow nasal cannula (HFNC) as an alternative is unclear.Methods: We searched MEDLINE, EMBASE, Cochrane CENTRAL, SCOPUS, and Clinicaltrials.gov for randomized trials of patients from inception to March 31st and updated the search on July 14, 2023. We performed a frequentist network meta-analysis and assessed the certainty of the evidence using the GRADE approach. We analyzed randomized trials (RCTs) comparing NPPV, HFNC, or standard care in adult COPD patients with chronic hypercapnic respiratory failure. Outcomes included mortality, COPD exacerbations, hospitalizations, and quality of life (SGRQ).Results: We analyzed twenty-four RCTs (1850 patients). We found that NPPV may reduce death risk compared to standard care (relative risk [RR] 0.82 [95% CI 0.66 to 1.00]) and probably reduces acute exacerbations (RR 0.71 [95% CI 0.58 to 0.87]). HFNC probably reduces acute exacerbations compared to standard care (RR 0.77 [0.68 to 0.88]) but its effect on mortality is uncertain (RR 1.20 [95% CI 0.63 to 2.28]). HFNC probably improves SGRQ scores (mean difference [MD] -7.01 [95% CI -12.27 to -1.77]) and may reduce hospitalizations (RR 0.87 [0.69 to 1.09]) compared to standard care. No significant difference was observed between HFNC and NPPV in reducing exacerbations.Conclusion: Both NPPV and HFNC reduce exacerbation risks in COPD patients compared to standard care. HFNC may offer advantages in improving quality of life.

Exploring the Impact of Age, Frailty, and Multimorbidity on the Effect of ICU Interventions: A Systematic Review of Randomized Controlled Trials.

OBJECTIVES: To date, age, frailty, and multimorbidity have been used primarily to inform prognosis in older adults. It remains uncertain, however, whether these patient factors may also predict response to critical care interventions or treatment outcomes. DATA SOURCES: We conducted a systematic search of top general medicine and critical care journals for randomized controlled trials (RCTs) examining critical care interventions published between January 1, 2011, and December 31, 2021. STUDY SELECTION: We included RCTs of critical care interventions that examined any one of three subgroups-age, frailty, or multimorbidity. We excluded cluster RCTs, studies that did not report interventions in an ICU, and studies that did not report data examining subgroups of age, frailty, or multimorbidity. DATA EXTRACTION: We collected study characteristics (single vs. multicountry enrollment, single vs. multicenter enrollment, funding, sample size, intervention, comparator, primary outcome and secondary outcomes, length of follow-up), study population (inclusion and exclusion criteria, average age in intervention and comparator groups), and subgroup data. We used the Instrument for assessing the Credibility of Effect Modification Analyses instrument to evaluate the credibility of subgroup findings. DATA SYNTHESIS: Of 2037 unique citations, we included 48 RCTs comprising 50,779 total participants. Seven (14.6%) RCTs found evidence of statistically significant effect modification based on age, whereas none of the multimorbidity or frailty subgroups found evidence of statistically significant subgroup effect. Subgroup credibility ranged from very low to moderate. CONCLUSIONS: Most critical care RCTs do not examine for subgroup effects by frailty or multimorbidity. Although age is more commonly considered, the cut-point is variable, and relative effect modification is rare. Although interventional effects are likely similar across age groups, shared decision-making based on individual patient preferences must remain a priority. RCTs focused specifically on critically ill older adults or those living with frailty and/or multimorbidity are crucial to further address this research question.

A Canadian survey of perceptions and practices related to ordering of blood tests in the intensive care unit.

PURPOSE: The ordering of routine blood test panels in advance is common in intensive care units (ICUs), with limited consideration of the pretest probability of finding abnormalities. This practice contributes to anemia, false positive results, and health care costs. We sought to understand practices and attitudes of Canadian adult intensivists regarding ordering of blood tests in critically ill patients. METHODS: We conducted a nationwide Canadian cross-sectional survey consisting of 15 questions assessing three domains (global perceptions, test ordering, daily practice), plus 11 demographic questions. The target sample was one intensivist per adult ICU in Canada. We summarized responses using descriptive statistics and present data as mean with standard deviation (SD) or count with percentage as appropriate. RESULTS: Over seven months, 80/131 (61%) physicians responded from 77 ICUs, 50% of which were from Ontario. Respondents had a mean (SD) clinical experience of 12 (9) years, and 61% worked in academic centres. When asked about their perceptions of how frequently unnecessary blood tests are ordered, 61% responded "sometimes" and 23% responded "almost always." Fifty-seven percent favoured ordering complete blood counts one day in advance. Only 24% of respondents believed that advanced blood test ordering frequently led to changes in management. The most common factors perceived to influence blood test ordering in the ICU were physician preferences, institutional patterns, and order sets. CONCLUSION: Most respondents to this survey perceived that unnecessary blood testing occurs in the ICU. The survey identified possible strategies to decrease the number of blood tests.

RéSUMé: OBJECTIF: La prescription à l'avance de tests sanguins de routine est courante dans les unités de soins intensifs (USI), avec une prise en compte limitée de la probabilité de découverte d'anomalies avant le test. Cette pratique contribue à l'anémie, aux résultats faussement positifs et aux coûts des soins de santé. Nous avons cherché à comprendre les pratiques et les attitudes des intensivistes pour adultes au Canada en ce qui concerne la prescription d'analyses sanguines chez la patientèle gravement malade. MéTHODE: Nous avons mené un sondage transversal à l'échelle nationale au Canada en posant 15 questions évaluant trois domaines (perceptions globales, commande de tests, pratique quotidienne), ainsi que 11 questions démographiques. L'échantillon cible était composé d'un·e intensiviste par unité de soins intensifs pour adultes au Canada. Nous avons résumé les réponses à l'aide de statistiques descriptives et présenté les données sous forme de moyennes avec écarts type (ET) ou de dénombrements avec pourcentages, selon le cas. RéSULTATS: Sur une période de sept mois, 80 médecins sur 131 (61%) ont répondu dans 77 unités de soins intensifs, dont 50% en Ontario. Les répondant·es avaient une expérience clinique moyenne (ET) de 12 (9) ans, et 61% travaillaient dans des centres universitaires. Lorsqu'on leur a demandé ce qu'ils ou elles pensaient de la fréquence à laquelle des tests sanguins inutiles étaient prescrits, 61% ont répondu « parfois ¼ et 23% ont répondu « presque toujours ¼. Cinquante-sept pour cent étaient en faveur de la réalisation d'une formule sanguine complète un jour à l'avance. Seulement 24% des personnes interrogées estimaient que la prescription de tests sanguins à l'avance entraînait fréquemment des changements dans la prise en charge. Les facteurs les plus souvent perçus comme influençant la prescription d'analyses sanguines à l'unité de soins intensifs étaient les préférences des médecins, les habitudes institutionnelles et les ensembles d'ordonnances. CONCLUSION: La plupart des répondant·es à ce sondage ont l'impression que des tests sanguins inutiles sont prescrits aux soins intensifs. L'enquête a permis d'identifier des stratégies possibles pour réduire le nombre de tests sanguins.

Measures and Impact of Caseload Surge During the COVID-19 Pandemic: A Systematic Review.

OBJECTIVES: COVID-19 pandemic surges strained hospitals globally. We performed a systematic review to examine measures of pandemic caseload surge and its impact on mortality of hospitalized patients. DATA SOURCES: PubMed, Embase, and Web of Science. STUDY SELECTION: English-language studies published between December 1, 2019, and November 22, 2023, which reported the association between pandemic "surge"-related measures and mortality in hospitalized patients. DATA EXTRACTION: Three authors independently screened studies, extracted data, and assessed individual study risk of bias. We assessed measures of surge qualitatively across included studies. Given multidomain heterogeneity, we semiquantitatively aggregated surge-mortality associations. DATA SYNTHESIS: Of 17,831 citations, we included 39 studies, 17 of which specifically described surge effects in ICU settings. The majority of studies were from high-income countries (n = 35 studies) and included patients with COVID-19 (n = 31). There were 37 different surge metrics which were mapped into four broad themes, incorporating caseloads either directly as unadjusted counts (n = 11), nested in occupancy (n = 14), including additional factors (e.g., resource needs, speed of occupancy; n = 10), or using indirect proxies (e.g., altered staffing ratios, alternative care settings; n = 4). Notwithstanding metric heterogeneity, 32 of 39 studies (82%) reported detrimental adjusted odds/hazard ratio for caseload surge-mortality outcomes, reporting point estimates of up to four-fold increased risk of mortality. This signal persisted among study subgroups categorized by publication year, patient types, clinical settings, and country income status. CONCLUSIONS: Pandemic caseload surge was associated with lower survival across most studies regardless of jurisdiction, timing, and population. Markedly variable surge strain measures precluded meta-analysis and findings have uncertain generalizability to lower-middle-income countries (LMICs). These findings underscore the need for establishing a consensus surge metric that is sensitive to capturing harms in everyday fluctuations and future pandemics and is scalable to LMICs.

Use of Intravenous Albumin: A Guideline From the International Collaboration for Transfusion Medicine Guidelines.

BACKGROUND: Albumin is used commonly across a wide range of clinical settings to improve hemodynamics, to facilitate fluid removal, and to manage complications of cirrhosis. The International Collaboration for Transfusion Medicine Guidelines developed guidelines for the use of albumin in patients requiring critical care, undergoing cardiovascular surgery, undergoing kidney replacement therapy, or experiencing complications of cirrhosis. METHODS: Cochairs oversaw the guideline development process and the panel included researchers, clinicians, methodologists, and a patient representative. The evidence informing this guideline arises from a systematic review of randomized clinical trials and systematic reviews, in which multiple databases were searched (inception through November 23, 2022). The panel reviewed the data and formulated the guideline recommendations using Grading of Recommendations Assessment, Development and Evaluation methodology. The guidelines were revised after public consultation. RESULTS: The panel made 14 recommendations on albumin use in adult critical care (three recommendations), pediatric critical care (one recommendation), neonatal critical care (two recommendations), cardiovascular surgery (two recommendations), kidney replacement therapy (one recommendation), and complications of cirrhosis (five recommendations). Of the 14 recommendations, two recommendations had moderate certainty of evidence, five recommendations had low certainty of evidence, and seven recommendations had very low certainty of evidence. Two of the 14 recommendations suggested conditional use of albumin for patients with cirrhosis undergoing large-volume paracentesis or with spontaneous bacterial peritonitis. Twelve of 14 recommendations did not suggest albumin use in a wide variety of clinical situations where albumin commonly is transfused. CONCLUSIONS: Currently, few evidence-based indications support the routine use of albumin in clinical practice to improve patient outcomes. These guidelines provide clinicians with actionable recommendations on the use of albumin.

Patient-important upper gastrointestinal bleeding in the ICU: A mixed-methods study of patient and family perspectives.

INTRODUCTION: The objective of this study was to create a definition of patient-important upper gastrointestinal bleeding during critical illness as an outcome for a randomized trial. DESIGN: This was a sequential mixed-methods qualitative-dominant multi-center study with an instrument-building aim. In semi-structured individual interviews or focus groups we elicited views from survivors of critical illness and family members of patients in the intensive care unit (ICU) regarding which features indicate important gastrointestinal bleeding. Quantitative demographic characteristics were collected. We analyzed qualitative data using inductive content analysis to develop a definition for patient-important upper gastrointestinal bleeding. SETTING: Canada and the United States. PARTICIPANTS: 51 ICU survivors and family members of ICU patients. RESULTS: Participants considered gastrointestinal bleeding to be important if it resulted in death, disability, or prolonged hospitalization. The following also signaled patient-important upper gastrointestinal bleeding: blood transfusion, vasopressors, endoscopy, CT-angiography, or surgery. Whether an intervention evinced concern depended on its effectiveness, side-effects, invasiveness and accessibility; contextual influences included participant familiarity and knowledge of interventions and trust in the clinical team. CONCLUSIONS: Survivors of critical illness and family members described patient-important upper gastrointestinal bleeding differently than current definitions of clinically-important upper gastrointestinal bleeding.

Prognostic Factors Associated with Venous Thromboembolism Following Traumatic Injury: A Systematic Review and Meta-Analysis.

INTRODUCTION: Trauma patients are at increased risk of venous thromboembolism (VTE), including deep venous thrombosis (DVT) and/or pulmonary embolism (PE). We conducted a systematic review and meta-analysis summarizing the association between prognostic factors and the occurrence of VTE following traumatic injury. METHODS: We searched the EMBASE and MEDLINE databases from inception to August 2023. We identified studies reporting confounding adjusted associations between patient, injury or post-injury care factors and risk of VTE. We performed meta-analyses of odds ratios (ORs) using the random effects method and assessed individual study risk of bias using the QUIPS tool. RESULTS: We included 31 studies involving 1,981,946 patients. Studies were predominantly observational cohorts from North America. Factors with moderate or higher certainty of association with increased risk of VTE include older age, obesity, male sex, higher injury severity score, pelvic injury, lower extremity injury, spinal injury, delayed VTE prophylaxis, need for surgery and tranexamic acid use. After accounting for other important contributing prognostic variables, a delay in the delivery of appropriate pharmacologic prophylaxis for as little as 24 to 48 hours independently confers a clinically meaningful two-fold increase in incidence of VTE. CONCLUSION: These findings highlight the contribution of patient predisposition, the importance of injury pattern, and the impact of potentially modifiable post-injury care on risk of VTE after traumatic injury. These factors should be incorporated into a risk stratification framework to individualize VTE risk assessment and support clinical and academic efforts reduce thromboembolic events among trauma patients.Study TypeSystematic Review & Meta-Analysis. LEVEL OF EVIDENCE: Level II.

Long-term survival and functional outcomes of critically ill patients with hematologic malignancies: a Canadian multicenter prospective study.

PURPOSE: Patients with hematologic malignancy (HM) commonly develop critical illness. Their long-term survival and functional outcomes have not been well described. METHODS: We conducted a prospective, observational study of HM patients admitted to seven Canadian intensive care units (ICUs) (2018-2020). We followed survivors at 7 days, 6 months and 12 months following ICU discharge. The primary outcome was 12-month survival. We evaluated functional outcomes at 6 and 12 months using the functional independent measure (FIM) and short form (SF)-36 as well as variables associated with 12-month survival. RESULTS: We enrolled 414 patients including 35% women. The median age was 61 (interquartile range, IQR: 52-69), median Sequential Organ Failure Assessment (SOFA) score was 9 (IQR: 6-12), and 22% had moderate-severe frailty (clinical frailty scale [CFS] ≥ 6). 51% had acute leukemia, 38% lymphoma/multiple myeloma, and 40% had received a hematopoietic stem cell transplant (HCT). The most common reasons for ICU admission were acute respiratory failure (50%) and sepsis (40%). Overall, 203 (49%) were alive 7 days post-ICU discharge (ICU survivors). Twelve-month survival of the entire cohort was 21% (43% across ICU survivors). The proportion of survivors with moderate-severe frailty was 42% (at 7 days), 14% (6 months), and 8% (12 months). Median FIM at 7 days was 80 (IQR: 50-109). Physical function, pain, social function, mental health, and emotional well-being were below age- and sex-matched population scores at 6 and 12 months. Frailty, allogeneic HCT, kidney injury, and cardiac complications during ICU were associated with lower 12- month survival. CONCLUSIONS: 49% of all HM patients were alive at 7 days post-ICU discharge, and 21% at 12 months. Survival varied based upon hematologic diagnosis and frailty status. Survivors had important functional disability and impairment in emotional, physical, and general well-being.

Venous congestion in septic shock quantified with point-of-care ultrasound: a pilot prospective multicentre cohort study.

PURPOSE: Venous congestion is a pathophysiologic state that can result in organ dysfunction, particularly acute kidney injury (AKI). We sought to evaluate the feasibility of performing a definitive observational study to determine the impact of venous congestion quantified using point-of-care ultrasound (POCUS) in patients with septic shock. METHODS: We conducted a prospective observational feasibility study at two intensive care units (ICUs). We recruited adult patients with septic shock within 12 hr of ICU admission. Using the validated Venous Excess Ultrasound Score (VEXUS), we quantified venous congestion on day 1 and day 3 of ICU admission. The primary feasibility outcome was successful completion rate of the two VEXUS scores. We performed a survival analysis to quantify the hazard of renal replacement therapy (RRT). RESULTS: We enrolled 75 patients from January 2022 to January 2023. The success rate of completion for VEXUS scans was 94.5% (95% confidence interval [CI], 89.5 to 97.6). Severe venous congestion was present in 19% (14/75) of patients on ICU admission day 1 and in 16% (10/61) of patients on day 3. Venous congestion on ICU admission may be associated with a higher risk of requiring RRT (unadjusted hazard ratio, 3.35; 95% CI, 0.94 to 11.88; P = 0.06). CONCLUSIONS: It is feasible to conduct a definitive observational study exploring the association between venous congestion quantified with POCUS and clinical outcomes in patients with septic shock. We hypothesize that venous congestion may be associated with an increased hazard of receiving RRT.

RéSUMé: OBJECTIF: La congestion veineuse est un état physiopathologique qui peut entraîner un dysfonctionnement des organes, en particulier une insuffisance rénale aiguë (IRA). Nous avons cherché à évaluer la faisabilité de la réalisation d'une étude observationnelle définitive pour déterminer l'impact de la congestion veineuse quantifiée à l'aide de l'échographie ciblée (POCUS) chez des patient·es en choc septique. MéTHODE: Nous avons réalisé une étude de faisabilité observationnelle prospective dans deux unités de soins intensifs (USI). Nous avons recruté des patient·es adultes souffrant d'un choc septique dans les 12 heures suivant leur admission aux soins intensifs. À l'aide du score VEXUS (score d'échographie de l'excès veineux) validé, nous avons quantifié la congestion veineuse au jour 1 et au jour 3 de leur admission aux soins intensifs. Le principal critère de faisabilité était le taux de réussite des deux scores VEXUS. Nous avons réalisé une analyse de survie pour quantifier le risque de thérapie de substitution rénale (TSR). RéSULTATS: Nous avons recruté 75 patient·es de janvier 2022 à janvier 2023. Le taux de réussite des scores VEXUS était de 94,5 % (intervalle de confiance [IC] à 95 %, 89,5 à 97,6). Une congestion veineuse sévère était présente chez 19 % (14/75) des patient·es au jour 1 d'admission aux soins intensifs et chez 16 % (10/61) des patient·es au jour 3. La congestion veineuse lors de l'admission aux soins intensifs peut être associée à un risque plus élevé de nécessiter une TSR (rapport de risque non ajusté, 3,35; IC 95 %, 0,94 à 11,88; P = 0,06). CONCLUSION: Il est possible de mener une étude observationnelle définitive explorant l'association entre la congestion veineuse quantifiée par POCUS et les devenirs cliniques chez les patient·es en choc septique. Nous émettons l'hypothèse que la congestion veineuse peut être associée à un risque accru de recevoir une thérapie de substitution rénale.

Ventilator Weaning and Extubation.

Increasing evidence supports specific approaches to liberate patients from invasive ventilation including the use of liberation protocols, inspiratory assistance during spontaneous breathing trials (SBTs), early extubation of patients with chronic obstructive pulmonary disease to noninvasive ventilation, and prophylactic use of noninvasive support strategies after extubation. Additional research is needed to elucidate the best criteria to identify patients who are ready to undergo an SBT and to inform optimal screening frequency, the best SBT technique and duration, extubation assessments, and extubation decision-making. Additional clarity is also needed regarding the optimal timing to measure and report extubation success.

Extracorporeal cardiopulmonary resuscitation versus conventional CPR in cardiac arrest: an updated meta-analysis and trial sequential analysis.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) may reduce mortality and improve neurological outcomes in patients with cardiac arrest. We updated our existing meta-analysis and trial sequential analysis to further evaluate ECPR compared to conventional CPR (CCPR). METHODS: We searched three international databases from 1 January 2000 through 1 November 2023, for randomised controlled trials or propensity score matched studies (PSMs) comparing ECPR to CCPR in both out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA). We conducted an updated random-effects meta-analysis, with the primary outcome being in-hospital mortality. Secondary outcomes included short- and long-term favourable neurological outcome and survival (30 days-1 year). We also conducted a trial sequential analysis to evaluate the required information size in the meta-analysis to detect a clinically relevant reduction in mortality. RESULTS: We included 13 studies with 14 pairwise comparisons (6336 ECPR and 7712 CCPR) in our updated meta-analysis. ECPR was associated with greater precision in reducing overall in-hospital mortality (OR 0.63, 95% CI 0.50-0.79, high certainty), to which the trial sequential analysis was concordant. The addition of recent studies revealed a newly significant decrease in mortality in OHCA (OR 0.62, 95% CI 0.45-0.84). Re-analysis of relevant secondary outcomes reaffirmed our initial findings of favourable short-term neurological outcomes and survival up to 30 days. Estimates for long-term neurological outcome and 90-day-1-year survival remained unchanged. CONCLUSIONS: We found that ECPR reduces in-hospital mortality, improves neurological outcome, and 30-day survival. We additionally found a newly significant benefit in OHCA, suggesting that ECPR may be considered in both IHCA and OHCA.

Corticosteroids in Sepsis and Septic Shock: A Systematic Review, Pairwise, and Dose-Response Meta-Analysis.

OBJECTIVES: To perform a systematic review and meta-analysis to assess the efficacy and safety of corticosteroids in patients with sepsis. DATA SOURCES: We searched PubMed, Embase, and the Cochrane Library, up to January 10, 2023. STUDY SELECTION: We included randomized controlled trials (RCTs) comparing corticosteroids with placebo or standard care with sepsis. DATA EXTRACTION: The critical outcomes of interest included mortality, shock reversal, length of stay in the ICU, and adverse events. DATA ANALYSIS: We performed both a pairwise and dose-response meta-analysis to evaluate the effect of different corticosteroid doses on outcomes. We used Grading of Recommendations Assessment, Development and Evaluation to assess certainty in pooled estimates. DATA SYNTHESIS: We included 45 RCTs involving 9563 patients. Corticosteroids probably reduce short-term mortality (risk ratio [RR], 0.93; 95% CI, 0.88-0.99; moderate certainty) and increase shock reversal at 7 days (RR, 1.24; 95% CI, 1.11-1.38; high certainty). Corticosteroids may have no important effect on duration of ICU stay (mean difference, -0.6 fewer days; 95% CI, 1.48 fewer to 0.27 more; low certainty); however, probably increase the risk of hyperglycemia (RR, 1.13; 95% CI, 1.08-1.18; moderate certainty) and hypernatremia (RR, 1.64; 95% CI, 1.32-2.03; moderate certainty) and may increase the risk of neuromuscular weakness (RR, 1.21; 95% CI, 1.01-1.45; low certainty). The dose-response analysis showed a reduction in mortality with corticosteroids with optimal dosing of approximately 260 mg/d of hydrocortisone (RR, 0.90; 95% CI, 0.83-0.98) or equivalent. CONCLUSIONS: We found that corticosteroids may reduce mortality and increase shock reversal but they may also increase the risk of hyperglycemia, hypernatremia, and neuromuscular weakness. The dose-response analysis indicates optimal dosing is around 260 mg/d of hydrocortisone or equivalent.

Mechanical circulatory support for cardiogenic shock: a network meta-analysis of randomized controlled trials and propensity score-matched studies.

PURPOSE: Cardiogenic shock is associated with high mortality. In refractory shock, it is unclear if mechanical circulatory support (MCS) devices improve survival. We conducted a network meta-analysis to determine which MCS devices confers greatest benefit. METHODS: We searched MEDLINE, Embase, and Scopus databases through 27 August 2023 for relevant randomized controlled trials (RCTs) and propensity score-matched studies (PSMs). We conducted frequentist network meta-analysis, investigating mortality (either 30 days or in-hospital) as the primary outcome. We assessed risk of bias (Cochrane risk of bias 2.0 tool/Newcastle-Ottawa Scale) and as sensitivity analysis reconstructed survival data from published survival curves for a one-stage unadjusted individual patient data (IPD) meta-analysis using a stratified Cox model. RESULTS: We included 38 studies (48,749 patients), mostly reporting on patients with Society for Cardiovascular Angiography and Intervention shock stages C-E cardiogenic shock. Compared with no MCS, extracorporeal membrane oxygenation with intra-aortic balloon pump (ECMO-IABP; network odds ratio [OR]: 0.54, 95% confidence interval (CI): 0.33-0.86, moderate certainty) was associated with lower mortality. There were no differences in mortality between ECMO, IABP, microaxial ventricular assist device (mVAD), ECMO-mVAD, centrifugal VAD, or mVAD-IABP and no MCS (all very low certainty). Our one-stage IPD survival meta-analysis based on the stratified Cox model found only ECMO-IABP was associated with lower mortality (hazard ratio, HR, 0.55, 95% CI 0.46-0.66). CONCLUSION: In patients with cardiogenic shock, ECMO-IABP may reduce mortality, while other MCS devices did not reduce mortality. However, this must be interpreted within the context of inter-study heterogeneity and limited certainty of evidence.

Pharmacological agents for procedural sedation and analgesia in the emergency department and intensive care unit: a systematic review and network meta-analysis of randomised trials.

BACKGROUND: We aimed to evaluate the comparative effectiveness and safety of various i.v. pharmacologic agents used for procedural sedation and analgesia (PSA) in the emergency department (ED) and ICU. We performed a systematic review and network meta-analysis to enable direct and indirect comparisons between available medications. METHODS: We searched Medline, EMBASE, Cochrane, and PubMed from inception to 2 March 2023 for RCTs comparing two or more procedural sedation and analgesia medications in all patients (adults and children >30 days of age) requiring emergent procedures in the ED or ICU. We focused on the outcomes of sedation recovery time, patient satisfaction, and adverse events (AEs). We performed frequentist random-effects model network meta-analysis and used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to rate certainty in estimates. RESULTS: We included 82 RCTs (8105 patients, 78 conducted in the ED and four in the ICU) of which 52 studies included adults, 23 included children, and seven included both. Compared with midazolam-opioids, recovery time was shorter with propofol (mean difference 16.3 min, 95% confidence interval [CI] 8.4-24.3 fewer minutes; high certainty), and patient satisfaction was better with ketamine-propofol (mean difference 1.5 points, 95% CI 0.3-2.6 points, high certainty). Regarding AEs, compared with midazolam-opioids, respiratory AEs were less frequent with ketamine (relative risk [RR] 0.55, 95% CI 0.32-0.96; high certainty), gastrointestinal AEs were more common with ketamine-midazolam (RR 3.08, 95% CI 1.15-8.27; high certainty), and neurological AEs were more common with ketamine-propofol (RR 3.68, 95% CI 1.08-12.53; high certainty). CONCLUSION: When considering procedural sedation and analgesia in the ED and ICU, compared with midazolam-opioids, sedation recovery time is shorter with propofol, patient satisfaction is better with ketamine-propofol, and respiratory adverse events are less common with ketamine.

2024 Focused Update: Guidelines on Use of Corticosteroids in Sepsis, Acute Respiratory Distress Syndrome, and Community-Acquired Pneumonia.

RATIONALE: New evidence is available examining the use of corticosteroids in sepsis, acute respiratory distress syndrome (ARDS) and community-acquired pneumonia (CAP), warranting a focused update of the 2017 guideline on critical illness-related corticosteroid insufficiency. OBJECTIVES: To develop evidence-based recommendations for use of corticosteroids in hospitalized adults and children with sepsis, ARDS, and CAP. PANEL DESIGN: The 22-member panel included diverse representation from medicine, including adult and pediatric intensivists, pulmonologists, endocrinologists, nurses, pharmacists, and clinician-methodologists with expertise in developing evidence-based Clinical Practice Guidelines. We followed Society of Critical Care Medicine conflict of interest policies in all phases of the guideline development, including task force selection and voting. METHODS: After development of five focused Population, Intervention, Control, and Outcomes (PICO) questions, we conducted systematic reviews to identify the best available evidence addressing each question. We evaluated the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach and formulated recommendations using the evidence-to-decision framework. RESULTS: In response to the five PICOs, the panel issued four recommendations addressing the use of corticosteroids in patients with sepsis, ARDS, and CAP. These included a conditional recommendation to administer corticosteroids for patients with septic shock and critically ill patients with ARDS and a strong recommendation for use in hospitalized patients with severe CAP. The panel also recommended against high dose/short duration administration of corticosteroids for septic shock. In response to the final PICO regarding type of corticosteroid molecule in ARDS, the panel was unable to provide specific recommendations addressing corticosteroid molecule, dose, and duration of therapy, based on currently available evidence. CONCLUSIONS: The panel provided updated recommendations based on current evidence to inform clinicians, patients, and other stakeholders on the use of corticosteroids for sepsis, ARDS, and CAP.

Glycemic Variability As a Prognostic Factor for Mortality in Patients With Critical Illness: A Systematic Review and Meta-Analysis.

OBJECTIVES: To perform a systematic review and meta-analysis to evaluate the association of various measures of glycemic variability, including time-domain and complexity-domain, with short-term mortality in patients with critical illness. DATA SOURCES: We searched Embase Classic +, MEDLINE, and the Cochrane Database of Systematic Reviews from inception to November 3, 2023. STUDY SELECTION: We included English language studies that assessed metrics of glycemic variation or complexity and short-term mortality in patients admitted to the ICU. DATA EXTRACTION: Two authors performed independent data abstraction and risk-of-bias assessments. We used a random-effects model to pool binary and continuous data and summarized estimates of effect using odds ratios and mean difference. We used the Quality in Prognosis Studies tool to assess risk of bias and the Grading of Recommendations, Assessment, Development and Evaluations to assess certainty of pooled estimates. DATA SYNTHESIS: We included 41 studies (n = 162,259). We demonstrate that increased sd, coefficient of variance, glycemic lability index, and decreased time in range are probably associated with increased mortality in critically ill patients (moderate certainty) and that increased mean absolute glucose, mean amplitude of glycemic excursion, and detrended fluctuation analysis may be associated with increased mortality (low certainty). CONCLUSIONS: We found a consistent association between increased measures of glycemic variability and higher short-term mortality in patient with critical illness. Further research should focus on standardized measurements of glycemic variation and complexity, along with their utility as therapeutic targets and prognostic markers.

Society of Critical Care Medicine Guidelines on Recognizing and Responding to Clinical Deterioration Outside the ICU: 2023.

RATIONALE: Clinical deterioration of patients hospitalized outside the ICU is a source of potentially reversible morbidity and mortality. To address this, some acute care hospitals have implemented systems aimed at detecting and responding to such patients. OBJECTIVES: To provide evidence-based recommendations for hospital clinicians and administrators to optimize recognition and response to clinical deterioration in non-ICU patients. PANEL DESIGN: The 25-member panel included representatives from medicine, nursing, respiratory therapy, pharmacy, patient/family partners, and clinician-methodologists with expertise in developing evidence-based Clinical Practice Guidelines. METHODS: We generated actionable questions using the Population, Intervention, Control, and Outcomes (PICO) format and performed a systematic review of the literature to identify and synthesize the best available evidence. We used the Grading of Recommendations Assessment, Development, and Evaluation Approach to determine certainty in the evidence and to formulate recommendations and good practice statements (GPSs). RESULTS: The panel issued 10 statements on recognizing and responding to non-ICU patients with critical illness. Healthcare personnel and institutions should ensure that all vital sign acquisition is timely and accurate (GPS). We make no recommendation on the use of continuous vital sign monitoring among unselected patients. We suggest focused education for bedside clinicians in signs of clinical deterioration, and we also suggest that patient/family/care partners' concerns be included in decisions to obtain additional opinions and help (both conditional recommendations). We recommend hospital-wide deployment of a rapid response team or medical emergency team (RRT/MET) with explicit activation criteria (strong recommendation). We make no recommendation about RRT/MET professional composition or inclusion of palliative care members on the responding team but suggest that the skill set of responders should include eliciting patients' goals of care (conditional recommendation). Finally, quality improvement processes should be part of a rapid response system. CONCLUSIONS: The panel provided guidance to inform clinicians and administrators on effective processes to improve the care of patients at-risk for developing critical illness outside the ICU.