Supraglottic Airway Versus Tracheal Intubation for Airway Management in Out-of-Hospital Cardiac Arrest: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis of Randomized Controlled Trials.

OBJECTIVES: Given the uncertainty regarding the optimal approach for airway management for adult patients with out-of-hospital cardiac arrest (OHCA), we conducted a systematic review and meta-analysis to compare the use of supraglottic airways (SGAs) with tracheal intubation for initial airway management in OHCA. DATA SOURCES: We searched MEDLINE, PubMed, Embase, Cochrane Library, as well as unpublished sources, from inception to February 7, 2023. STUDY SELECTION: We included randomized controlled trials (RCTs) of adult OHCA patients randomized to SGA compared with tracheal intubation for initial prehospital airway management. DATA EXTRACTION: Reviewers screened abstracts, full texts, and extracted data independently and in duplicate. We pooled data using a random-effects model. We used the modified Cochrane risk of bias 2 tool and assessed certainty of evidence using the Grading Recommendations Assessment, Development, and Evaluation approach. We preregistered the protocol on PROSPERO (CRD42022342935). DATA SYNTHESIS: We included four RCTs ( n = 13,412 patients). Compared with tracheal intubation , SGA use probably increases return of spontaneous circulation (ROSC) (relative risk [RR] 1.09; 95% CI, 1.02-1.15; moderate certainty) and leads to a faster time to airway placement (mean difference 2.5 min less; 95% CI, 1.6-3.4 min less; high certainty). SGA use may have no effect on survival at longest follow-up (RR 1.06; 95% CI, 0.84-1.34; low certainty), has an uncertain effect on survival with good functional outcome (RR 1.11; 95% CI, 0.82-1.50; very low certainty), and may have no effect on risk of aspiration (RR 1.04; 95% CI, 0.94 to 1.16; low certainty). CONCLUSIONS: In adult patients with OHCA, compared with tracheal intubation, the use of SGA for initial airway management probably leads to more ROSC, and faster time to airway placement, but may have no effect on longer-term survival outcomes or aspiration events.

Intraoperative use of balanced crystalloids versus 0.9% saline: a systematic review and meta-analysis of randomised controlled studies.

BACKGROUND: The evidence regarding optimal crystalloid use in the perioperative period remains unclear. As the primary aim of this study, we sought to summarise the data from RCTs examining whether use of balanced crystalloids compared with 0.9% saline (saline) leads to differences in patient-important outcomes. METHODS: We searched Ovid MEDLINE, Embase, the Cochrane library, and Clinicaltrials.gov, from inception until December 15, 2022, and included RCTs that intraoperatively randomised adult participants to receive either balanced fluids or saline. We pooled data using a random-effects model and present risk ratios (RRs) or mean differences (MDs), along with 95% confidence intervals (CIs). We assessed individual study risk of bias using the modified Cochrane tool, and certainty of evidence using GRADE. RESULTS: Of 5959 citations, we included 38 RCTs (n=3776 patients). Pooled analysis showed that intraoperative use of balanced fluids compared with saline had an uncertain effect on postoperative mortality analysed at the longest point of follow-up (RR 1.51, 95% CI: 0.42-5.36) and postoperative need for renal replacement therapy (RR 0.95, 95% CI: 0.56-1.59), both very low certainty. Furthermore, use of balanced crystalloids probably leads to a higher postoperative serum pH (MD 0.05, 95% CI: 0.04-0.06), moderate certainty. CONCLUSIONS: Use of balanced crystalloids, compared with saline, in the perioperative setting has an uncertain effect on mortality and need for renal replacement therapy but probably improves postoperative acid-base status. Further research is needed to determine whether balanced crystalloid use affects patient-important outcomes. CLINICAL TRIAL REGISTRATION: CRD42022367593.

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.

End-of-Life Skills and Professionalism for Critical Care Residents in Training: The ESPRIT Survey.

End-of-life (EOL) care is a key aspect of critical care medicine (CCM) training. The goal of this study was to survey CCM residents and program directors (PDs) across Canada to describe current EOL care education. Using a literature review, we created a self-administered survey encompassing 10 CCM national objectives of training to address: (1) curricular content and evaluation methods, (2) residents' preparedness to meet these objectives, and (3) opportunities for educational improvement. We performed pilot testing and clinical sensibility testing, then distributed it to all residents and PDs across the 13 Canadian CCM programs. Our response rate was 84.3% overall (77 [81.1%] for residents and 13 [100%] for PDs). Residents rated direct observation, informal advice, and self-reflection as both the top 3 most utilized and perceived most effective teaching modalities. Residents most commonly reported comfort with skills related to pain and symptom management (n = 67, 94.3%; score > 3 on 5-point Likert scale), and least commonly reported comfort with donation after cardiac death skills (n = 26-38; 44.8%-65.5%). Base specialty and time in CCM training were independently associated with comfort ratings for some, but not all, EOL skills. With respect to family meetings, residents infrequently received feedback; however, most PDs believed feedback on 6 to 10 meetings is required for competence. When PD perceptions of teaching effectiveness were compared with resident comfort ratings, differences were most apparent for skills related to pain and symptom management, cultural awareness, and ethical principles. By the end of their first subspecialty training year, PDs expect residents to be competent at most, but not all, EOL skills. In summary, trainees and programs rely on clinical activities to develop competency in EOL care, resulting in some educational gaps. Transitioning to competency-based medical education presents an opportunity to address some of these gaps, while other gaps will require more specific curricular intervention.

Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19).

BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. METHODS: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. RESULTS: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which four are best practice statements, nine are strong recommendations, and 35 are weak recommendations. No recommendation was provided for six questions. The topics were: 1) infection control, 2) laboratory diagnosis and specimens, 3) hemodynamic support, 4) ventilatory support, and 5) COVID-19 therapy. CONCLUSION: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new evidence in further releases of these guidelines.

A mixed-methods study of organ donation in the intensive care unit: 22 actionable practices to improve organ donation.

PURPOSE: Rates of organ donation vary between otherwise comparable intensive care units (ICUs) suggesting that the process of donation must vary between ICUs. The purpose of this study was to describe the process of organ donation from the perspective of ICU staff, identify important drivers of successful donation, and develop strategies to improve the process of donation. METHODS: We conducted qualitative interviews with 32 ICU staff, including physicians, nurses, and respiratory therapists, using an interview guide developed from previous studies on organ donation. Using a qualitative descriptive approach, we coded interviews using qualitative content analysis. We integrated findings from the interviews in a mixed-methods analysis with previously published data from a document analysis and cross-sectional survey to identify practices that may enhance organ donation in the ICU. RESULTS: Five major themes important to the organ donation process emerged from the interviews: i) staff relationship with organ donation coordinators; ii) standardized processes; iii) ICU staff beliefs; iv) integration of donation and high quality end-of-life care; v) feedback and staff support. In the mixed-methods analysis, we identified 22 actionable practices to enhance the process of organ donation in the ICU. CONCLUSION: Incorporating the perspectives of ICU staff, we were able to identify 22 practice changes that may have a significant cumulative impact on donation outcomes. Future research is required to evaluate whether these findings account for the variability of donation rates between otherwise comparable ICUs.

Methodologic Innovation in Creating Clinical Practice Guidelines: Insights From the 2018 Society of Critical Care Medicine Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption Guideline Effort.

OBJECTIVES: To describe novel guideline development strategies created and implemented as part of the Society of Critical Care Medicine's 2018 clinical practice guidelines for pain, agitation (sedation), delirium, immobility (rehabilitation/mobility), and sleep (disruption) in critically ill adults. DESIGN: We involved critical illness survivors from start to finish, used and expanded upon Grading of Recommendations, Assessment, Development and Evaluation methodology for making recommendations, identified evidence gaps, and developed communication strategies to mitigate challenges. SETTING/SUBJECTS: Thirty-two experts from five countries, across five topic-specific sections; four methodologists, two medical librarians, four critical illness survivors, and two Society of Critical Care Medicine support staff. INTERVENTIONS: Unique approaches included the following: 1) critical illness survivor involvement to help ensure patient-centered questions and recommendations; 2) qualitative and semiquantitative approaches for developing descriptive statements; 3) operationalizing a three-step approach to generating final recommendations; and 4) systematic identification of evidence gaps. MEASUREMENTS AND MAIN RESULTS: Critical illness survivors contributed to prioritizing topics, questions, and outcomes, evidence interpretation, recommendation formulation, and article review to ensure that their values and preferences were considered in the guidelines. Qualitative and semiquantitative approaches supported formulating descriptive statements using comprehensive literature reviews, summaries, and large-group discussion. Experts (including the methodologists and guideline chairs) developed and refined guideline recommendations through monthly topic-specific section conference calls. Recommendations were precirculated to all members, presented to, and vetted by, most members at a live meeting. Final electronic voting provided links to all forest plots, evidence summaries, and "evidence to decision" frameworks. Written comments during voting captured dissenting views and were integrated into evidence to decision frameworks and the guideline article. Evidence gaps, reflecting clinical uncertainty in the literature, were identified during the evidence to decision process, live meeting, and voting and formally incorporated into all written recommendation rationales. Frequent scheduled "check-ins" mitigated communication gaps. CONCLUSIONS: Our multifaceted, interdisciplinary approach and novel methodologic strategies can help inform the development of future critical care clinical practice guidelines.

Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU.

OBJECTIVE: To update and expand the 2013 Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the ICU. DESIGN: Thirty-two international experts, four methodologists, and four critical illness survivors met virtually at least monthly. All section groups gathered face-to-face at annual Society of Critical Care Medicine congresses; virtual connections included those unable to attend. A formal conflict of interest policy was developed a priori and enforced throughout the process. Teleconferences and electronic discussions among subgroups and whole panel were part of the guidelines' development. A general content review was completed face-to-face by all panel members in January 2017. METHODS: Content experts, methodologists, and ICU survivors were represented in each of the five sections of the guidelines: Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption). Each section created Population, Intervention, Comparison, and Outcome, and nonactionable, descriptive questions based on perceived clinical relevance. The guideline group then voted their ranking, and patients prioritized their importance. For each Population, Intervention, Comparison, and Outcome question, sections searched the best available evidence, determined its quality, and formulated recommendations as "strong," "conditional," or "good" practice statements based on Grading of Recommendations Assessment, Development and Evaluation principles. In addition, evidence gaps and clinical caveats were explicitly identified. RESULTS: The Pain, Agitation/Sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) panel issued 37 recommendations (three strong and 34 conditional), two good practice statements, and 32 ungraded, nonactionable statements. Three questions from the patient-centered prioritized question list remained without recommendation. CONCLUSIONS: We found substantial agreement among a large, interdisciplinary cohort of international experts regarding evidence supporting recommendations, and the remaining literature gaps in the assessment, prevention, and treatment of Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) in critically ill adults. Highlighting this evidence and the research needs will improve Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) management and provide the foundation for improved outcomes and science in this vulnerable population.

Use of a daily goals checklist for morning ICU rounds: a mixed-methods study.

OBJECTIVE: To understand the perspectives and attitudes of ICU clinicians about use of a daily goals checklist on rounds. DESIGN: Our three data collection methods were as follows: (1) Field observations: two investigators conducted field observations to understand how and by whom the daily goals checklist was used for 80 ICU patient rounds over 6 days. (2) Document analysis: The 72 completed daily goals checklists from observed rounds were analyzed using mixed methods. (3) Interviews: With 56 clinicians, we conducted semistructured individual and focus-group interviews, analyzing transcripts using a qualitative descriptive approach and content analysis. Triangulation was achieved by a multidisciplinary investigative team using two research methods and three data sources. SETTING: Fifteen bed closed ICU in a tertiary care, university-affiliated hospital. PATIENTS: Medical-surgical ICU patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Field observations: The daily goals checklist was completed for 93% of observed rounds, largely by residents (86%). The champion of the verbal review was commonly a resident (83%) or medical student (9%). Document analysis: Domains with high completion rates included ventilation, sedation, central venous access, nutrition, and various prophylactic interventions. Interviews: The daily goals checklist enhanced communication, patient care, and education. Nurses, physicians, and pharmacists endorsed its enhancement of interdisciplinary communication. It facilitated a structured, thorough, and individualized approach to patient care. The daily goals checklist helped to identify new patient care issues and sparked management discussions, especially for sedation, weaning, and medications. Residents were prominent users, finding served as a multipurpose teaching tool. CONCLUSIONS: The daily goals checklist was perceived to improve the management of critically ill patients by creating a systematic, comprehensive approach to patient care and by setting individualized daily goals. Reportedly improving interprofessional communication and practice, the daily goals checklist also enhanced patient safety and daily progress, encouraging momentum in recovery from critical illness. Daily goals checklist review prompted teaching opportunities for multidisciplinary learners on morning rounds.

Definitions, rates and associated mortality of ICU-acquired pneumonia: A multicenter cohort study.

INTRODUCTION: We aimed to analyze intensive care unit (ICU)-acquired pneumonia according to 7 definitions, estimating associated hospital mortality. METHODS: This cohort study was nested within an international randomized trial, evaluating the effect of probiotics on ICU-acquired pneumonia in 2650 mechanically ventilated adults. Each clinically suspected pneumonia was adjudicated by two physicians blinded to allocation and center. The primary outcome was ventilator-associated pneumonia (VAP) informed by ventilation for ≥2 days, new, progressive or persistent infiltrate plus 2 of: temperature > 38 °C or < 36 °C; leukopenia (<3 × 10(Fernando et al., 20206)/L) or leukocytosis (>10 × 10(Fernando et al., 20206)/L); and purulent sputum. We also used 6 other definitions estimating the risk of hospital mortality. RESULTS: The frequency of ICU-acquired pneumonia varied by definition: the trial primary outcome VAP (21.6%), Clinical Pulmonary Infection Score (CPIS) (24.9%), American College Chest Physicians (ACCP) (25.0%), International Sepsis Forum (ISF) (24.4%), Reducing Oxidative Stress Study (REDOXS) (17.6%), Centers for Disease Control (CDC) (7.8%), and invasively microbiologically confirmed (1.9%). The trial primary outcome VAP (HR 1.31 [1.08, 1.60]), ISF (HR 1.32 [1.09,1.60]), CPIS (HR 1.30 [1.08,1.58]) and ACCP definitions (HR 1.22 [1.00,1.47]) were associated with hospital mortality. CONCLUSIONS: Rates of ICU-acquired pneumonia vary by definition and are associated with differential increased risk of death.

Surviving Sepsis Campaign Guidelines 2021: highlights for the practicing clinician.

The 2021 Surviving Sepsis Campaign Guidelines provided evidence-based recommendations for adult patients with sepsis and septic shock. This iteration of the guidelines placed increased emphasis on a diverse, global perspective, as well as on the long-term sequelae of sepsis experienced by patients and their families. The guidelines encompassed the following sections: 1) screening and early treatment; 2) infection; 3) hemodynamic management; 4) ventilation; 5) additional therapies; and 6) goals of care and long-term outcomes. In this review, we provide a summary of key recommendations of interest to the practicing clinician, which are either novel or require a change in practice, as well as those for which the evidence has substantially evolved in the 5 years since the 2016 iteration of the Guidelines. Rather than reviewing the underlying evidence, we emphasize the practical aspects of interpretation, dissemination, and implementation of these recommendations in the clinical setting.

Dexmedetomidine vs other sedatives in critically ill mechanically ventilated adults: a systematic review and meta-analysis of randomized trials.

Conventional gabaminergic sedatives such as benzodiazepines and propofol are commonly used in mechanically ventilated patients in the intensive care unit (ICU). Dexmedetomidine is an alternative sedative that may achieve lighter sedation, reduce delirium, and provide analgesia. Our objective was to perform a comprehensive systematic review summarizing the large body of evidence, determining if dexmedetomidine reduces delirium compared to conventional sedatives. We searched MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov and the WHO ICTRP from inception to October 2021. Independent pairs of reviewers identified randomized clinical trials comparing dexmedetomidine to other sedatives for mechanically ventilated adults in the ICU. We conducted meta-analyses using random-effects models. The results were reported as relative risks (RRs) for binary outcomes and mean differences (MDs) for continuous outcomes, with corresponding 95% confidence intervals (CIs). In total, 77 randomized trials (n = 11,997) were included. Compared to other sedatives, dexmedetomidine reduced the risk of delirium (RR 0.67, 95% CI 0.55 to 0.81; moderate certainty), the duration of mechanical ventilation (MD - 1.8 h, 95% CI - 2.89 to - 0.71; low certainty), and ICU length of stay (MD - 0.32 days, 95% CI - 0.42 to - 0.22; low certainty). Dexmedetomidine use increased the risk of bradycardia (RR 2.39, 95% CI 1.82 to 3.13; moderate certainty) and hypotension (RR 1.32, 95% CI 1.07 to 1.63; low certainty). In mechanically ventilated adults, the use of dexmedetomidine compared to other sedatives, resulted in a lower risk of delirium, and a modest reduction in duration of mechanical ventilation and ICU stay, but increased the risks of bradycardia and hypotension.

Use of dexmedetomidine for sedation in mechanically ventilated adult ICU patients: a rapid practice guideline.

PURPOSE: The aim of this Intensive Care Medicine Rapid Practice Guideline (ICM­RPG) was to formulate evidence­based guidance for the use of dexmedetomidine for sedation in invasively mechanically ventilated adults in the intensive care unit (ICU). METHODS: We adhered to the methodology for trustworthy clinical practice guidelines, including use of the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty of evidence, and the Evidence-to-Decision framework to generate recommendations. The guideline panel comprised 28 international panelists, including content experts, ICU clinicians, methodologists, and patient representatives. Through teleconferences and web­based discussions, the panel provided input on the balance and magnitude of the desirable and undesirable effects, the certainty of evidence, patients' values and preferences, costs and resources, feasibility, acceptability, and research priorities. RESULTS: The ICM­RPG panel issued one weak recommendation (suggestion) based on overall moderate certainty of evidence: "In invasively mechanically ventilated adult ICU patients, we suggest using dexmedetomidine over other sedative agents, if the desirable effects including a reduction in delirium are valued over the undesirable effects including an increase in hypotension and bradycardia". CONCLUSION: This ICM-RPG provides updated evidence-based guidance on the use of dexmedetomidine for sedation in mechanically ventilated adults, and outlines uncertainties and research priorities.

Pain management in post-craniotomy patients: a survey of canadian neurosurgeons.

INTRODUCTION: Despite the growing recognition for analgesic needs in post-craniotomy patients, this remains a poorly studied area in neurological surgery. The class and regimen of analgesia that is most suitable for these patients remains controversial. The objective of this study is to examine the current beliefs and practices of Canadian neurosurgeons when managing post-craniotomy pain. METHODS: A survey was sent to all practicing Canadian neurosurgeons to examine the following aspects of analgesia in craniotomy patients: type of analgesics used, common side effects encountered, satisfaction with current regimen and the rationale for their practice. RESULTS: Of 156 potential respondents, 103 neurosurgeons (66%) completed the survey. Codeine (59%) was the most prescribed first line analgesic followed by morphine (38%). The use of a second-line opioid was significantly higher among codeine prescribers compared to morphine, 53% compared to 28% (p < 0.001). Nausea, constipation and neurologic depression were reported as common side effects by 76%, 66% and 27% of respondents respectively. Of the respondents, 90% reported a high level of satisfaction with their current choice of analgesia; nonetheless, they predominantly described their practice as personal preference or protocol driven rather than evidence-based. CONCLUSIONS: Codeine - a weak opioid - is the most common first-line analgesic prescribed to craniotomy patients. This practice is associated with substantially increased reliance on potent opioids for rescue analgesia. Whether novel regimens can provide optimal pain control while minimizing neurologic and gastrointestinal side effects remains to be addressed by future trials.

Neuromuscular blocking agents in acute respiratory distress syndrome: updated systematic review and meta-analysis of randomized trials.

PURPOSE: Existing clinical practice guidelines support the use of neuromuscular blocking agents (NMBA) in acute respiratory distress syndrome (ARDS); however, a recent large randomized clinical trial (RCT) has questioned this practice. Therefore, we updated a previous systematic review to determine the efficacy and safety of NMBAs in ARDS. METHODS: We searched MEDLINE, EMBASE (October 2012 to July 2019), the Cochrane (Central) database, and clinical trial registries ( ClinicalTrials.gov , ISRCTN Register, and WHO ICTRP) for RCTs comparing the effects of NMBA as a continuous infusion versus placebo or no NMBA infusion (but allowing intermittent NMBA boluses) on patient-important outcomes for adults with ARDS. Two independent reviewers assessed the methodologic quality of the primary studies and abstracted data. RESULTS: Seven RCTs, including four new RCTs, met eligibility criteria for this review. These trials enrolled 1598 patients with moderate to severe ARDS at centers in the USA, France, and China. All trials assessed short-term continuous infusions of cisatracurium or vecuronium. The pooled estimate for mortality outcomes showed significant statistical heterogeneity, which was only explained by a subgroup analysis by depth of sedation in the control arm. A continuous NMBA infusion did not improve mortality when compared to a light sedation strategy with no NMBA infusion (relative risk [RR] 0.99; 95% CI 0.86-1.15; moderate certainty; P = 0.93). On the other hand, continuous NMBA infusion reduced mortality when compared to deep sedation with as needed NMBA boluses (RR 0.71; 95% CI 0.57-0.89; low certainty; P = 0.003). Continuous NMBA infusion reduced the rate of barotrauma (RR 0.55; 95% CI 0.35-0.85, moderate certainty; P = 0.008) across eligible trials, but the effect on ventilator-free days, duration of mechanical ventilation, and ICU-acquired weakness was uncertain. CONCLUSIONS: Inconsistency in study methods and findings precluded the pooling of all trials for mortality. In a pre-planned sensitivity analysis, the impact of NMBA infusion on mortality depends on the strategy used in the control arm, showing reduced mortality when compared to deep sedation, but no effect on mortality when compared to lighter sedation. In both situations, a continuous NMBA infusion may reduce the risk of barotrauma, but the effects on other patient-important outcomes remain unclear. Future research, including an individual patient data meta-analysis, could help clarify some of the observed findings in this updated systematic review.

Adjuvant Analgesic Use in the Critically Ill: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis addresses the efficacy and safety of nonopioid adjunctive analgesics for patients in the ICU. DATA SOURCES: We searched PubMed, Embase, the Cochrane Library, CINAHL Plus, and Web of Science. STUDY SELECTION: Two independent reviewers screened citations. Eligible studies included randomized controlled trials comparing efficacy and safety of an adjuvant-plus-opioid regimen to opioids alone in adult ICU patients. DATA EXTRACTION: We conducted duplicate screening of citations and data abstraction. DATA SYNTHESIS: Of 10,949 initial citations, we identified 34 eligible trials. These trials examined acetaminophen, carbamazepine, clonidine, dexmedetomidine, gabapentin, ketamine, magnesium sulfate, nefopam, nonsteroidal anti-inflammatory drugs (including diclofenac, indomethacin, and ketoprofen), pregabalin, and tramadol as adjunctive analgesics. Use of any adjuvant in addition to an opioid as compared to an opioid alone led to reductions in patient-reported pain scores at 24 hours (standard mean difference, -0.88; 95% CI, -1.29 to -0.47; low certainty) and decreased opioid consumption (in oral morphine equivalents over 24 hr; mean difference, 25.89 mg less; 95% CI, 19.97-31.81 mg less; low certainty). In terms of individual medications, reductions in opioid use were demonstrated with acetaminophen (mean difference, 36.17 mg less; 95% CI, 7.86-64.47 mg less; low certainty), carbamazepine (mean difference, 54.69 mg less; 95% CI, 40.39-to 68.99 mg less; moderate certainty), dexmedetomidine (mean difference, 10.21 mg less; 95% CI, 1.06-19.37 mg less; low certainty), ketamine (mean difference, 36.81 mg less; 95% CI, 27.32-46.30 mg less; low certainty), nefopam (mean difference, 70.89 mg less; 95% CI, 64.46-77.32 mg less; low certainty), nonsteroidal anti-inflammatory drugs (mean difference, 11.07 mg less; 95% CI, 2.7-19.44 mg less; low certainty), and tramadol (mean difference, 22.14 mg less; 95% CI, 6.67-37.61 mg less; moderate certainty). CONCLUSIONS: Clinicians should consider using adjunct agents to limit opioid exposure and improve pain scores in critically ill patients.

Surviving Sepsis Campaign: guidelines on the management of critically ill adults with Coronavirus Disease 2019 (COVID-19).

BACKGROUND: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed. METHODS: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations. RESULTS: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which 4 are best practice statements, 9 are strong recommendations, and 35 are weak recommendations. No recommendation was provided for 6 questions. The topics were: (1) infection control, (2) laboratory diagnosis and specimens, (3) hemodynamic support, (4) ventilatory support, and (5) COVID-19 therapy. CONCLUSION: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new recommendations in further releases of these guidelines.