An Update on Management of Adult Patients with Acute Respiratory Distress Syndrome: An Official American Thoracic Society Clinical Practice Guideline.

Background: This document updates previously published Clinical Practice Guidelines for the management of patients with acute respiratory distress syndrome (ARDS), incorporating new evidence addressing the use of corticosteroids, venovenous extracorporeal membrane oxygenation, neuromuscular blocking agents, and positive end-expiratory pressure (PEEP). Methods: We summarized evidence addressing four "PICO questions" (patient, intervention, comparison, and outcome). A multidisciplinary panel with expertise in ARDS used the Grading of Recommendations, Assessment, Development, and Evaluation framework to develop clinical recommendations. Results: We suggest the use of: 1) corticosteroids for patients with ARDS (conditional recommendation, moderate certainty of evidence), 2) venovenous extracorporeal membrane oxygenation in selected patients with severe ARDS (conditional recommendation, low certainty of evidence), 3) neuromuscular blockers in patients with early severe ARDS (conditional recommendation, low certainty of evidence), and 4) higher PEEP without lung recruitment maneuvers as opposed to lower PEEP in patients with moderate to severe ARDS (conditional recommendation, low to moderate certainty), and 5) we recommend against using prolonged lung recruitment maneuvers in patients with moderate to severe ARDS (strong recommendation, moderate certainty). Conclusions: We provide updated evidence-based recommendations for the management of ARDS. Individual patient and illness characteristics should be factored into clinical decision making and implementation of these recommendations while additional evidence is generated from much-needed clinical trials.

Neuromuscular blocking agents during targeted temperature management for out-of-hospital cardiac arrest patients.

BACKGROUND: Neuromuscular blocking agents (NMBAs) can control shivering during targeted temperature management (TTM) of patients with cardiac arrest. However, the effectiveness of NMBA use during TTM on neurologic outcomes remains unclear. We aimed to evaluate the association between NMBA use during TTM and favorable neurologic outcomes after out-of-hospital cardiac arrest (OHCA). MATERIALS AND METHODS: A multicenter, prospective, observational cohort study from 2019 to 2021. It included OHCA patients who received TTM after hospitalization. We conducted overlap weight propensity-score analyses after multiple imputation to evaluate the effect of NMBAs during TTM. The primary outcome was a favorable neurological outcome, defined as a cerebral performance category of 1 or 2 at discharge. Subgroup analyses were conducted based on initial monitored rhythm and brain computed tomography findings. RESULTS: Of the 516 eligible patients, 337 received NMBAs during TTM. In crude analysis, the proportion of patients with favorable neurological outcome was significantly higher in the NMBA group (38.3% vs. 16.8%; risk difference (RD): 21.5%; 95% confidence interval (CI): 14.0% to 29.1%). In weighted analysis, a significantly higher proportion of patients in the NMBA group had a favorable neurological outcome compared to the non-NMBA group (32.7% vs. 20.9%; RD: 11.8%; 95% CI: 1.2% to 22.3%). In the subgroup with an initial shockable rhythm and no hypoxic encephalopathy, the NMBA group showed significantly higher proportions of favorable neurological outcomes. CONCLUSIONS: The use of NMBAs during TTM was significantly associated with favorable neurologic outcomes at discharge for OHCA patients. NMBAs may have benefits in selected patients with initial shockable rhythm and without poor prognostic computed tomography findings.

[Neuromuscular Blockade in Geriatric Patients]. / Muskelrelaxierung bei geriatrischen Patient*innen.

The administration of neuromuscular blocking agents has been used in anesthesia for decades and continues to play an important role in modern anesthesia. Special patient populations, such as very young or very old patients, require adapted use. The following article discusses the specifics of neuromuscular blocking agents administration in geriatric patients.

[Neuromuscular Blockade in the Critically Ill]. / Muskelrelaxanzien in der Intensivmedizin.

The management of sedation in intensive care medicine has changed substantially in the last few years. Neuromuscular blocking agents (NMBA) are only rarely indicated in modern intensive care medicine. In this review, the mechanism of action, potential side effects, and special considerations for the application of NMBA to critically ill patients will be discussed. We further present the rationale for the use of NMBA for the remaining indications, such as endotracheal intubation, selected cases of severe acute respiratory distress syndrome, and shivering during temperature control after cardiac arrest. The review will close with a description of potential side effects of NMBA use in the intensive care setting, such as awareness, acquired skeletal muscle weakness as well as corneal injuries, and how monitoring of sedation and peripheral muscle blockade may be handled.

Neuromuscular Blocking Agent Use in Critical Care Transport Not Associated With Intubation.

OBJECTIVE: Variable indications exist for neuromuscular blocking agents (NMBAs) in the critical care transport setting beyond facilitation of intubation. METHODS: This retrospective cohort study included adult patients (≥ 18 years) who underwent critical care transport from July 1, 2020, to May 2, 2023, and received NMBAs during transport that was not associated with intubation. The primary outcome was the indication for NMBA administration. Secondary outcomes included the characterization of NMBA use, mean Richmond Agitation Sedation Scale score before NMBA administration, sedation strategy used, and continuation of NMBAs within 48 hours of hospital admission. RESULTS: One hundred twenty-six patients met the inclusion criteria. The most common indication for NMBA administration was ventilator dyssynchrony (n = 71, 56.4%). The majority of patients received rocuronium during transport (n = 113, 89.7%). The mean pre-NMBA Richmond Agitation Sedation Scale score was -3.7 ± 2.4. The most common sedation strategy was a combination of continuous infusion and bolus sedatives (76.2%). One hundred (79.4%) patients had sedation changes in response to NMBA administration. Seventy-two (57.1%) received NMBAs during the first 48 hours of their intensive care unit admission. CONCLUSION: NMBAs were frequently administered for ventilator dyssynchrony and continuation of prior therapy. Optimization opportunities exist to ensure adequate deep sedation and reassessment of NMBA indication.

Comparison of a Modern Digital Mechanomyograph to a Mechanomyograph Utilizing an Archival Grass Force Transducer.

BACKGROUND: Mechanomyography is the traditional gold standard research technique for quantitative assessment of neuromuscular blockade. Mechanomyography directly measures the isometric force generated by the thumb in response to ulnar nerve stimulation. Researchers must construct their own mechanomyographs since commercial instruments are no longer available. A mechanomyograph was constructed, and its performance was compared against an archival mechanomyography system from the 1970s that utilized an FT-10 Grass force transducer, hypothesizing that train-of-four ratios recorded on each device would be equivalent. METHODS: A mechanomyograph was constructed using 3D-printed components and modern electronics. An archival mechanomyography system was assembled from original components, including an FT-10 Grass force transducer. Signal digitization for computerized data collection was utilized instead of the original paper strip chart recorder. Both devices were calibrated with standard weights to demonstrate linear voltage response curves. The mechanomyographs were affixed to opposite arms of patients undergoing surgery, and the train-of-four ratio was measured during the onset and recovery from rocuronium neuromuscular blockade. RESULTS: Calibration measurements exhibited a positive linear association between voltage output and calibration weights with a linear correlation coefficient of 1.00 for both mechanomyography devices. The new mechanomyograph had better precision and measurement sensitivity than the archival system: 5.3 mV versus 15.5 mV and 1.6 mV versus 5.7 mV, respectively (P < 0.001 for both). A total of 767 pairs of train-of-four ratio measurements obtained from eight patients had positive linear association (R 2 = 0.94; P < 0.001). Bland-Altman analysis resulted in bias of 3.8% and limits of agreement of -13% and 21%. CONCLUSIONS: The new mechanomyograph resulted in similar train-of-four ratio measurements compared to an archival mechanomyography system utilizing an FT-10 Grass force transducer. These results demonstrated continuity of gold standard measurement of neuromuscular blockade spanning nearly 50 yr, despite significant changes in the instrumentation technology.

Critical Care Pharmacist Attitudes and Perceptions of Neuromuscular Blocker Infusions in ARDS.

BACKGROUND: Current critical care pharmacist (CCP) practices and perceptions related to neuromuscular infusion (NMBI) use for acute respiratory distress syndrome (ARDS) maybe different with the COVID-19 pandemic and the publication of 2020 NMBI practice guidelines. OBJECTIVE: To evaluate CCP practices and perceptions regarding NMBI use for patients with moderate-severe ARDS. METHODS: We developed, tested, and electronically administered a questionnaire (7 parent-, 42 sub-questions) to 409 American College of Clinical Pharmacy (ACCP) Critical Care Practice and Research Network members in 12 geographically diverse states. The questionnaire focused on adults with moderate-severe ARDS (PaO2:FiO2<150) whose causes of dyssynchrony were addressed. Two reminders were sent at 10-day intervals. RESULTS: Respondents [131/409 (32%)] primarily worked in a medical intensive care unit (ICU) 102 (78%). Compared to COVID-negative(-) ARDS patients, COVID positive(+) ARDS patients were twice as likely to receive a NMBI (34 ± 18 vs.16 ± 17%; P < 0.01). Respondents somewhat/strongly agreed a NMBI should be reserved until after trials of deep sedation (112, 86%) or proning (92, 81%) and that NMBI reduced barotrauma (88, 67%), dyssynchrony (87, 66%), and plateau pressure (79, 60%). Few respondents somewhat/strongly agreed that a NMBI should be initiated at ARDS onset (23, 18%) or that NMBI reduced 90-day mortality (12, 10%). Only 2/14 potential NMBI risks [paralysis awareness (101, 82%) and prolonged muscle weakness (84, 68%)] were frequently reported to be of high/very high concern. Multiple NMBI titration targets were assessed as very/extremely important including arterial pH (109, 88%), dyssynchrony (107, 86%), and PaO2: FiO2 ratio (82, 66%). Train-of-four (55, 44%) and BIS monitoring (36, 29%) were deemed less important. Preferred NMBI discontinuation criteria included absence of dysschrony (84, 69%) and use ≥48 hour (72, 59%). CONCLUSIONS AND RELEVANCE: Current critical care pharmacists believe NMBI for ARDS patients are best reserved until after trials of deep sedation or proning; unique considerations exist in COVID+ patients. Our results should be considered when ICU NMBI protocols are being developed and bedside decisions regarding NMBI use in ARDS are being formulated.

Pharmacotherapy optimization for rapid sequence intubation in the emergency department.

PURPOSE: Rapid-sequence intubation (RSI) is the process of administering a sedative and neuromuscular blocking agent (NMBA) in rapid succession to facilitate endotracheal intubation. It is the most common and preferred method for intubation of patients presenting to the emergency department (ED). The selection and use of medications to facilitate RSI is critical for success. The purpose of this review is to describe pharmacotherapies used during the RSI process, discuss current clinical controversies in RSI medication selection, and review pharmacotherapy considerations for alternative intubation methods. SUMMARY: There are several steps to the intubation process requiring medication considerations, including pretreatment, induction, paralysis, and post-intubation sedation and analgesia. Pretreatment medications include atropine, lidocaine, and fentanyl; but use of these agents in clinical practice has fallen out of favor as there is limited evidence for their use outside of select clinical scenarios. There are several options for induction agents, though etomidate and ketamine are the most used due to their more favorable hemodynamic profiles. Currently there is retrospective evidence that etomidate may produce less hypotension than ketamine in patients presenting with shock or sepsis. Succinylcholine and rocuronium are the preferred neuromuscular blocking agents, and the literature suggests minimal differences between succinylcholine and high dose rocuronium in first-pass success rates. Selection between the two is based on patient specific factors, half-life and adverse effect profiles. Finally, medication-assisted preoxygenation and awake intubation are less common methods for intubation in the ED but require different considerations for medication use. AREAS FOR FUTURE RESEARCH: The optimal selection, dosing, and administration of RSI medications is complicated, and further research is needed in several areas. Additional prospective studies are needed to determine optimal induction agent selection and dosing in patients presenting with shock or sepsis. Controversy exists over optimal medication administration order (paralytic first vs induction first) and medication dosing in obese patients, but there is insufficient evidence to significantly alter current practices regarding medication dosing and administration. Further research examining awareness with paralysis during RSI is needed before definitive and widespread practice changes to medication use during RSI can be made.

Effect of Remifentanil vs Neuromuscular Blockers During Rapid Sequence Intubation on Successful Intubation Without Major Complications Among Patients at Risk of Aspiration: A Randomized Clinical Trial.

Importance: It is uncertain whether a rapid-onset opioid is noninferior to a rapid-onset neuromuscular blocker during rapid sequence intubation when used in conjunction with a hypnotic agent. Objective: To determine whether remifentanil is noninferior to rapid-onset neuromuscular blockers for rapid sequence intubation. Design, Setting, and Participants: Multicenter, randomized, open-label, noninferiority trial among 1150 adults at risk of aspiration (fasting for <6 hours, bowel occlusion, recent trauma, or severe gastroesophageal reflux) who underwent tracheal intubation in the operating room at 15 hospitals in France from October 2019 to April 2021. Follow-up was completed on May 15, 2021. Interventions: Patients were randomized to receive neuromuscular blockers (1 mg/kg of succinylcholine or rocuronium; n = 575) or remifentanil (3 to 4 µg/kg; n = 575) immediately after injection of a hypnotic. Main Outcomes and Measures: The primary outcome was assessed in all randomized patients (as-randomized population) and in all eligible patients who received assigned treatment (per-protocol population). The primary outcome was successful tracheal intubation on the first attempt without major complications, defined as lung aspiration of digestive content, oxygen desaturation, major hemodynamic instability, sustained arrhythmia, cardiac arrest, and severe anaphylactic reaction. The prespecified noninferiority margin was 7.0%. Results: Among 1150 randomized patients (mean age, 50.7 [SD, 17.4] years; 573 [50%] women), 1130 (98.3%) completed the trial. In the as-randomized population, tracheal intubation on the first attempt without major complications occurred in 374 of 575 patients (66.1%) in the remifentanil group and 408 of 575 (71.6%) in the neuromuscular blocker group (between-group difference adjusted for randomization strata and center, -6.1%; 95% CI, -11.6% to -0.5%; P = .37 for noninferiority), demonstrating inferiority. In the per-protocol population, 374 of 565 patients (66.2%) in the remifentanil group and 403 of 565 (71.3%) in the neuromuscular blocker group had successful intubation without major complications (adjusted difference, -5.7%; 2-sided 95% CI, -11.3% to -0.1%; P = .32 for noninferiority). An adverse event of hemodynamic instability was recorded in 19 of 575 patients (3.3%) with remifentanil and 3 of 575 (0.5%) with neuromuscular blockers (adjusted difference, 2.8%; 95% CI, 1.2%-4.4%). Conclusions and Relevance: Among adults at risk of aspiration during rapid sequence intubation in the operating room, remifentanil, compared with neuromuscular blockers, did not meet the criterion for noninferiority with regard to successful intubation on first attempt without major complications. Although remifentanil was statistically inferior to neuromuscular blockers, the wide confidence interval around the effect estimate remains compatible with noninferiority and limits conclusions about the clinical relevance of the difference. Trial Registration: ClinicalTrials.gov Identifier: NCT03960801.

Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome.

BACKGROUND: The benefits of early continuous neuromuscular blockade in patients with acute respiratory distress syndrome (ARDS) who are receiving mechanical ventilation remain unclear. METHODS: We randomly assigned patients with moderate-to-severe ARDS (defined by a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of <150 mm Hg with a positive end-expiratory pressure [PEEP] of ≥8 cm of water) to a 48-hour continuous infusion of cisatracurium with concomitant deep sedation (intervention group) or to a usual-care approach without routine neuromuscular blockade and with lighter sedation targets (control group). The same mechanical-ventilation strategies were used in both groups, including a strategy involving a high PEEP. The primary end point was in-hospital death from any cause at 90 days. RESULTS: The trial was stopped at the second interim analysis for futility. We enrolled 1006 patients early after the onset of moderate-to-severe ARDS (median, 7.6 hours after onset). During the first 48 hours after randomization, 488 of the 501 patients (97.4%) in the intervention group started a continuous infusion of cisatracurium (median duration of infusion, 47.8 hours; median dose, 1807 mg), and 86 of the 505 patients (17.0%) in the control group received a neuromuscular blocking agent (median dose, 38 mg). At 90 days, 213 patients (42.5%) in the intervention group and 216 (42.8%) in the control group had died before hospital discharge (between-group difference, -0.3 percentage points; 95% confidence interval, -6.4 to 5.9; P = 0.93). While in the hospital, patients in the intervention group were less physically active and had more adverse cardiovascular events than patients in the control group. There were no consistent between-group differences in end points assessed at 3, 6, and 12 months. CONCLUSIONS: Among patients with moderate-to-severe ARDS who were treated with a strategy involving a high PEEP, there was no significant difference in mortality at 90 days between patients who received an early and continuous cisatracurium infusion and those who were treated with a usual-care approach with lighter sedation targets. (Funded by the National Heart, Lung, and Blood Institute; ROSE ClinicalTrials.gov number, NCT02509078.).

Neuromuscular Blocker Use in Critically Ill Children: Assessing Mortality Risk by Propensity Score-Weighted Analysis.

OBJECTIVES: We aim to describe the use of continuous infusion of neuromuscular blocking agents in mechanically ventilated critically ill children and to test its association with in-hospital mortality. DESIGN: Multicenter, registry-based, observational, two-cohort-comparison retrospective study using prospectively collected data from a web-based national registry. SETTING: Seventeen PICUs in Italy. PATIENTS: We included children less than 18 years who received mechanical ventilation and a neuromuscular blocking agent infusion from January 2010 to October 2017. A propensity score-weighted Cox regression analysis was used to assess the relationship between the use of neuromuscular blocking agents and in-hospital mortality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 23,227 patients admitted to the PICUs during the study period, 3,823 patients were included. Patients who received a continuous infusion of neuromuscular blocking agent were more likely to be younger (p < 0.001), ex-premature (p < 0.001), and presenting with less chronic respiratory insufficiency requiring home mechanical ventilation (p < 0.001). Reasons for mechanical ventilation significantly differed between patients who received a continuous infusion of neuromuscular blocking agent and patients who did not receive a continuous infusion of neuromuscular blocking agent, with a higher frequency of respiratory and cardiac diagnosis among patients who received neuromuscular blocking agents compared with other diagnoses (all p < 0.001). The covariates were well balanced in the propensity-weighted cohort. The mortality rate significantly differed among the two cohorts (patients who received a continuous infusion of neuromuscular blocking agent 21% vs patients who did not receive a continuous infusion of neuromuscular blocking agent 11%; p < 0.001 by weighted logistic regression). Patients who received a continuous infusion of neuromuscular blocking agent experienced longer mechanical ventilation and PICU stay (both p < 0.001 by weighted logistic regression). A weighted Cox regression analysis found the use of neuromuscular blocking agents to be a significant predictor of in-hospital mortality both in the unadjusted analysis (hazard ratio, 1.7; 95% CI, 1.3-2.2) and in the adjusted one (hazard ratio, 1.6; 95% CI, 1.2-2.1). CONCLUSIONS: Thirteen percent of mechanically ventilated children in PICUs received neuromuscular blocking agents. When adjusting for selection bias with a propensity score approach, the use of neuromuscular blocking agent was found to be a significant predictor of in-hospital mortality.

Early short course of neuromuscular blocking agents in patients with COVID-19 ARDS: a propensity score analysis.

BACKGROUND: The role of neuromuscular blocking agents (NMBAs) in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) is not fully elucidated. Therefore, we aimed to investigate in COVID-19 patients with moderate-to-severe ARDS the impact of early use of NMBAs on 90-day mortality, through propensity score (PS) matching analysis. METHODS: We analyzed a convenience sample of patients with COVID-19 and moderate-to-severe ARDS, admitted to 244 intensive care units within the COVID-19 Critical Care Consortium, from February 1, 2020, through October 31, 2021. Patients undergoing at least 2 days and up to 3 consecutive days of NMBAs (NMBA treatment), within 48 h from commencement of IMV were compared with subjects who did not receive NMBAs or only upon commencement of IMV (control). The primary objective in the PS-matched cohort was comparison between groups in 90-day in-hospital mortality, assessed through Cox proportional hazard modeling. Secondary objectives were comparisons in the numbers of ventilator-free days (VFD) between day 1 and day 28 and between day 1 and 90 through competing risk regression. RESULTS: Data from 1953 patients were included. After propensity score matching, 210 cases from each group were well matched. In the PS-matched cohort, mean (± SD) age was 60.3 ± 13.2 years and 296 (70.5%) were male and the most common comorbidities were hypertension (56.9%), obesity (41.1%), and diabetes (30.0%). The unadjusted hazard ratio (HR) for death at 90 days in the NMBA treatment vs control group was 1.12 (95% CI 0.79, 1.59, p = 0.534). After adjustment for smoking habit and critical therapeutic covariates, the HR was 1.07 (95% CI 0.72, 1.61, p = 0.729). At 28 days, VFD were 16 (IQR 0-25) and 25 (IQR 7-26) in the NMBA treatment and control groups, respectively (sub-hazard ratio 0.82, 95% CI 0.67, 1.00, p = 0.055). At 90 days, VFD were 77 (IQR 0-87) and 87 (IQR 0-88) (sub-hazard ratio 0.86 (95% CI 0.69, 1.07; p = 0.177). CONCLUSIONS: In patients with COVID-19 and moderate-to-severe ARDS, short course of NMBA treatment, applied early, did not significantly improve 90-day mortality and VFD. In the absence of definitive data from clinical trials, NMBAs should be indicated cautiously in this setting.

Comparison of two pharmacokinetic-pharmacodynamic models of rocuronium bromide during profound neuromuscular block: analysis of estimated and measured post-tetanic count effect.

BACKGROUND: Profound neuromuscular block (NMB) is important in surgeries where complete immobility is considered essential to improve tracheal intubation and surgical conditions. Rocuronium bromide is a commonly used NMB agent. This work describes a noninvasive approach for estimation of post-tetanic count (PTC) based on two pharmacokinetic (PK) models, the Saldien and the De Haes models. The aim was to investigate the rocuronium bromide PK-pharmacodynamic (PD) relationship in estimating the PTC effect during profound NMB. METHODS: In this prospective, non-randomised, observational study, an induction bolus of rocuronium bromide was administered followed by continuous infusion for maintenance of a PTC of 1-2. measured every 3 min. Measurements were analysed as discrete categorical data and by applying the nonlinear mixed-effect modelling approach. Performance of the selected models was evaluated through simulation model-based diagnostics, further assessing the precision of the parameter estimates and the performance of the models at the individual level. RESULTS: Data from 30 adult patients undergoing elective abdominal or neurosurgical procedures were included. Post-tetanic count response profiles during rocuronium bromide infusion were successfully characterised using the population PD analysis. The models showed a good performance for all PTC categories, albeit with a moderate over-prediction of PTC >6. CONCLUSIONS: Our findings indicate that using plasma concentrations of rocuronium bromide estimated with either of the two models, combined with a PD model, provides equal model performance when predicting PTC. These promising results may provide an important advance in guiding rocuronium bromide administration when profound NMB in routine clinical practice is desired.

Prone Positioning and Neuromuscular Blocking Agents as Adjunctive Therapies in Mechanically Ventilated Patients with Acute Respiratory Distress Syndrome.

Neuromuscular blocking agents (NMBAs) and prone position (PP) are two major adjunctive therapies that can improve outcome in moderate-to-severe acute respiratory distress syndrome. NMBA should be used once lung-protective mechanical ventilation has been set, for 48 hours or less and as a continuous intravenous infusion. PP should be used as early as possible for long sessions; in COVID-19 its use has exploded. In nonintubated patients, PP might reduce the rate of intubation but not mortality. The goal of this article is to perform a narrative review on the pathophysiological rationale, the clinical effects, and the clinical use and recommendations of both NMBA and PP.

[A meta-analysis of the effect of neuromuscular blocking agents on oxygenation in patients with acute respiratory distress syndrome].

Objective: To evaluate the effects of neuromuscular blocking agents (NMBA) on oxygenation and respiratory conditions in patients with acute respiratory distress syndrome(ARDS). Methods: English databases such as MEDLINE, Embase and Web of Science were searched online, as well as Chinese databases such as China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database and Wanfang Database. Randomized controlled trials (RCTs) of NMBA therapy for ARDS with publication date up to May 2020 were retrieved. Literature was screened according to inclusion and exclusion criteria, and the main analysis indicators were oxygenation index. Results: A total of 5 RCTs were included, and 1 462 ARDS patients were enrolled. Compared with the control group, the ratio of partial arterial oxygen pressure to fraction of inspired (PaO2)/(FiO2) significantly improved in the intervention group after 72 hours MD=14.39, (95%CI 6.40-22.38, P=0.000 4) and 96 hours of NMBA, but there was no difference between PaO2/FiO2 at 24 and 48 hours (P>0.05).Positive end expiratory pressure (PEEP) significantly decreased at 72 hours (MD=-0.45, 95%CI -0.87--0.03, P=0.04) and 96 hours (MD=-0.82, 95%CI -1.39--0.26, P=0.004) treatment with NMBA, while there was no significant difference in PEEP between 24 and 48 hours after treatment (P>0.05). At 96 h, plateau pressure (Pplat) in the intervention group was significantly lower (MD=-1.69, 95%CI -2.64--0.75, P=0.000 4), and there was no significant difference in Pplat between 24, 48 and 72 h after treatment (P>0.05). Conclusion: The early use of NMBA within 48 hours has a delayed improvement effect on oxygenation and ventilator conditions in ARDS patients.

Optimal Sedation in Patients Who Receive Neuromuscular Blocking Agent Infusions for Treatment of Acute Respiratory Distress Syndrome-A Retrospective Cohort Study From a New England Health Care Network.

OBJECTIVES: Two previously published trials (ARDS et Curarisation Systematique [ACURASYS] and Reevaluation of Systemic Early Neuromuscular Blockade [ROSE]) presented equivocal evidence on the effect of neuromuscular blocking agent infusions in patients with acute respiratory distress syndrome (acute respiratory distress syndrome). The sedation regimen differed between these trials and also within the ROSE trial between treatment and control groups. We hypothesized that the proportion of deeper sedation is a mediator of the effect of neuromuscular blocking agent infusions on mortality. DESIGN: Retrospective cohort study. SETTING: Seven ICUs in an academic hospital network, Beth Israel Deaconess Medical Center (Boston, MA). PATIENTS: Intubated and mechanically ventilated ICU patients with acute respiratory distress syndrome (Berlin definition) admitted between January 2008 until June 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The proportion of deeper sedation was defined as days with nonlight sedation as a fraction of mechanical ventilation days in the ICU after acute respiratory distress syndrome diagnosis. Using clinical data obtained from a hospital network registry, 3,419 patients with acute respiratory distress syndrome were included, of whom 577 (16.9%) were treated with neuromuscular blocking agent infusions, for a mean (sd) duration of 1.8 (±1.9) days. The duration of deeper sedation was prolonged in patients receiving neuromuscular blocking agent infusions (4.6 ± 2.2 d) compared with patients without neuromuscular blocking agent infusions (2.4 ± 2.2 d; p < 0.001). The proportion of deeper sedation completely mediated the negative effect of neuromuscular blocking agent infusions on in-hospital mortality (p < 0.001). Exploratory analysis in patients who received deeper sedation revealed a beneficial effect of neuromuscular blocking agent infusions on mortality (49% vs 51%; adjusted odds ratio, 0.80; 95% CI, 0.63-0.99, adjusted absolute risk difference, -0.05; p = 0.048). CONCLUSIONS: In acute respiratory distress syndrome patients who receive neuromuscular blocking agent infusions, a prolonged, high proportion of deeper sedation is associated with increased mortality. Our data support the view that clinicians should minimize the duration of deeper sedation after recovery from neuromuscular blocking agent infusion.

Association of Sedation, Coma, and In-Hospital Mortality in Mechanically Ventilated Patients With Coronavirus Disease 2019-Related Acute Respiratory Distress Syndrome: A Retrospective Cohort Study.

OBJECTIVES: In patients with coronavirus disease 2019-associated acute respiratory distress syndrome, sedatives and opioids are commonly administered which may lead to increased vulnerability to neurologic dysfunction. We tested the hypothesis that patients with coronavirus disease 2019-associated acute respiratory distress syndrome are at higher risk of in-hospital mortality due to prolonged coma compared with other patients with acute respiratory distress syndrome matched for disease severity. DESIGN: Propensity-matched cohort study. SETTING: Seven ICUs in an academic hospital network, Beth Israel Deaconess Medical Center (Boston, MA). PATIENTS: All mechanically ventilated coronavirus disease 2019 patients between March and May 2020 were identified and matched with patients with acute respiratory distress syndrome of other etiology. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Using clinical data obtained from a hospital registry, we matched 114 coronavirus disease 2019 patients to 228 noncoronavirus disease 2019-related acute respiratory distress syndrome patients based on baseline disease severity. Coma was identified using the Richmond Agitation Sedation Scale less than or equal to -3. Multivariable logistic regression and mediation analyses were used to assess the percentage of comatose days, sedative medications used, and the association between coronavirus disease 2019 and in-hospital mortality. In-hospital mortality (48.3% vs 31.6%, adjusted odds ratio, 2.15; 95% CI, 1.34-3.44; p = 0.002), the percentage of comatose days (66.0% ± 31.3% vs 36.0% ± 36.9%, adjusted difference, 29.35; 95% CI, 21.45-37.24; p < 0.001), and the hypnotic agent dose (51.3% vs 17.1% of maximum hypnotic agent dose given in the cohort; p < 0.001) were higher among patients with coronavirus disease 2019. Brain imaging did not show a higher frequency of structural brain lesions in patients with coronavirus disease 2019 (6.1% vs 7.0%; p = 0.76). Hypnotic agent dose was associated with coma (adjusted coefficient, 0.61; 95% CI, 0.45-0.78; p < 0.001) and mediated (p = 0.001) coma. Coma was associated with in-hospital mortality (adjusted odds ratio, 5.84; 95% CI, 3.58-9.58; p < 0.001) and mediated 59% of in-hospital mortality (p < 0.001). CONCLUSIONS: Compared with matched patients with acute respiratory distress syndrome of other etiology, patients with coronavirus disease 2019 received higher doses of hypnotics, which was associated with prolonged coma and higher mortality.

Neuromuscular and Clinical Recovery in Thoracic Surgical Patients Reversed With Neostigmine or Sugammadex.

BACKGROUND: Patients undergoing thoracoscopic procedures may be at high-risk for incomplete neuromuscular recovery and associated complications. The aim of this clinical investigation was to assess the incidence of postoperative residual neuromuscular blockade in adult thoracic surgical patients administered neostigmine or sugammadex when optimal dosing and reversal strategies for these agents were used. The effect of choice of reversal agent on hypoxemic events and signs and symptoms of muscle weakness were also determined. Additionally, operative conditions in each group were graded by surgeons performing the procedures. METHODS: Two hundred patients undergoing thoracoscopic surgical procedures were enrolled in this nonrandomized controlled trial. One hundred consecutive patients maintained at moderate levels of neuromuscular blockade were reversed with neostigmine (neostigmine group) followed by 100 consecutive patients given sugammadex to antagonize deeper levels of neuromuscular blockade (sugammadex group). Anesthetic and neuromuscular management were standardized. Surgeons rated operative conditions at the conclusion of the procedure on a 4-point scale (grade 1 = excellent to grade 4 = poor). Train-of-four ratios were measured immediately before extubation and at PACU admission (primary outcomes). Postoperatively, patients were assessed for adverse respiratory events and 11 signs and 16 symptoms of muscle weakness. RESULTS: The 2 groups were similar in intraoperative management characteristics. The percentage of patients with residual neuromuscular blockade, defined as a normalized train-of-four ratio <0.9, was significantly greater in the neostigmine group than the sugammadex group at both tracheal extubation (80% vs 6%, respectively, P < .0001) and PACU admission (61% vs 1%, respectively, P < .0001). Patients in the neostigmine group had less optimal operative conditions (median score 2 [good] versus 1 [excellent] in the sugammadex group; P < .0001), and more symptoms of muscle weakness were present in these subjects (median number [interquartile range] 4 [1-8] vs 1 [0-2] in the sugammadex group, P < .0001). No differences between groups in adverse airway events were observed. CONCLUSIONS: Despite the application of strategies documented to reduce the risk of residual neuromuscular blockade, a high percentage of thoracoscopic patients whose neuromuscular blockade was reversed with neostigmine were admitted to the PACU with clinical evidence of residual paralysis. In contrast, muscle weakness was rarely observed in patients whose neuromuscular blockade was antagonized with sugammadex.

BET 2: Is the use of long-acting neuromuscular blocking agents for intubation associated with reduced provision of postintubation sedation?

A short cut review was conducted to assess if the use of rocuronium in the ED was associated with a decrease in the provision of postintubation sedation. Four papers were identified that presented the best evidence to answer the question. Again the studies, relevant outcomes, results and weaknesses are tabulated. All the identified studies were retrospective and there was a plethora of outcome measures used. When compared with suxamethonium, rocuronium was associated with a delayed initiation and reduced dose of postintubation sedation.

Pediatric Post-Cardiac Arrest Care: A Scientific Statement From the American Heart Association.

Successful resuscitation from cardiac arrest results in a post-cardiac arrest syndrome, which can evolve in the days to weeks after return of sustained circulation. The components of post-cardiac arrest syndrome are brain injury, myocardial dysfunction, systemic ischemia/reperfusion response, and persistent precipitating pathophysiology. Pediatric post-cardiac arrest care focuses on anticipating, identifying, and treating this complex physiology to improve survival and neurological outcomes. This scientific statement on post-cardiac arrest care is the result of a consensus process that included pediatric and adult emergency medicine, critical care, cardiac critical care, cardiology, neurology, and nursing specialists who analyzed the past 20 years of pediatric cardiac arrest, adult cardiac arrest, and pediatric critical illness peer-reviewed published literature. The statement summarizes the epidemiology, pathophysiology, management, and prognostication after return of sustained circulation after cardiac arrest, and it provides consensus on the current evidence supporting elements of pediatric post-cardiac arrest care.