Neuromuscular blockade during therapeutic hypothermia after cardiac arrest: Observational study of neurological and infectious outcomes

AbstractIntroductionNeuromuscular blockade (NMB) is widely used during therapeutic hypothermia (TH) after cardiac arrest but its effect on patient outcomes is unclear. We compared the effects of NMB on neurological outcomes and frequency of early-onset pneumonia in cardiac-arrest survivors managed with TH.MethodsWe retrospectively studied consecutive adult cardiac-arrest survivors managed with TH in a tertiary-level intensive care unit between January 2008 and July 2013. Patients given continuous NMB for persistent shivering were compared to those managed without NMB. Cases of early-onset pneumonia and vital status at ICU discharge were recorded. To avoid bias due to between-group baseline differences, we adjusted the analysis on a propensity score.ResultsOf 311 cardiac-arrest survivors, 144 received TH, including 117 with continuous NMB and 27 without NMBs. ICU mortality was lower with NMB (hazard ratio [HR], 0.54 [0.32; 0.89], p=0.016) but the difference was not significant after adjustment on the propensity score (HR, 0.70 [0.39; 1.25], p=0.22). The proportion of patients with good neurological outcomes was not significantly different (36% with and 22% without NMB, p=0.16). Early-onset pneumonia was more common with NMB (HR, 2.36 [1.24; 4.50], p=0.009) but the difference was not significant after adjustment on the propensity score (HR, 1.68 [0.90; 3.16], p=0.10).ConclusionsContinuous intravenous NMB during TH after cardiac arrest has potential owns effects on ICU survival with a trend increase in the frequency of early-onset pneumonia. Randomised controlled trials are needed to define the role for NMB among treatments for TH-induced shivering

Efficacy and safety of human soluble thrombomodulin (ART-123) for treatment of patients in France with sepsis-associated coagulopathy: post hoc analysis of SCARLET.

Background: The phase 3 multinational SCARLET study evaluated the efficacy and safety of a recombinant human soluble thrombomodulin (ART-123) for treatment of sepsis-associated coagulopathy (SAC), which correlates with increased mortality risk in patients with sepsis. Although no significant reduction in mortality was observed with ART-123 compared with placebo in the full analysis set (FAS), an efficacy signal of ART-123 was observed in subgroups of patients who sustained coagulopathy until the first treatment and those not administered concomitant heparin. Post hoc analysis was performed of patients treated in France, the country with the largest enrollment (19% of the FAS) and consistent patient enrollment throughout the study duration. Methods: Adult patients with SAC (international normalized ratio > 1.4; platelets > 30 × 109/L to 30% within 24 h) and evidence of bacterial infection were included. The primary efficacy outcome was 28-day all-cause mortality. Safety outcomes included adverse, serious adverse, and major bleeding events. This analysis assessed patient characteristics and efficacy and safety outcomes in France compared with the rest of the world (ROW; excluding France). Mortality rates were assessed in patients in France or the ROW with characteristics previously associated with ART-123 efficacy. Results: Baseline characteristics were similar between France and the ROW, but some measurements of disease severity were higher in patients in France. The 28-day all-cause mortality absolute risk reductions (ARRs) with ART-123 were 8.3% in France and 1.1% in the ROW. The greater ARR in France may be related to a higher rate of sustained coagulopathy and lower rate of heparin use. In France and the ROW, 84.6% and 78.0% of patients sustained coagulopathy from the time of initial SAC diagnosis to first treatment with the study drug, and 65.8% and 43.9% did not receive heparin, respectively. The ARRs for these subgroups of patients in France were 13.4% and 16.6%, respectively. Safety of ART-123 was comparable between France and the ROW. Conclusions: Results from this exploratory analysis suggest that patients with sustained SAC not receiving concomitant heparin may benefit from ART-123, a fact that should be confirmed in future studies with more restrictive inclusion criteria

Efficacy and safety of human soluble thrombomodulin (ART-123) for treatment of patients in France with sepsis-associated coagulopathy: post hoc analysis of SCARLET

Background The phase 3 multinational SCARLET study evaluated the efficacy and safety of a recombinant human soluble thrombomodulin (ART-123) for treatment of sepsis-associated coagulopathy (SAC), which correlates with increased mortality risk in patients with sepsis. Although no significant reduction in mortality was observed with ART-123 compared with placebo in the full analysis set (FAS), an efficacy signal of ART-123 was observed in subgroups of patients who sustained coagulopathy until the first treatment and those not administered concomitant heparin. Post hoc analysis was performed of patients treated in France, the country with the largest enrollment (19% of the FAS) and consistent patient enrollment throughout the study duration. Methods Adult patients with SAC (international normalized ratio > 1.4; platelets > 30 x 10(9)/L to 30% within 24 h) and evidence of bacterial infection were included. The primary efficacy outcome was 28-day all-cause mortality. Safety outcomes included adverse, serious adverse, and major bleeding events. This analysis assessed patient characteristics and efficacy and safety outcomes in France compared with the rest of the world (ROW; excluding France). Mortality rates were assessed in patients in France or the ROW with characteristics previously associated with ART-123 efficacy. Results Baseline characteristics were similar between France and the ROW, but some measurements of disease severity were higher in patients in France. The 28-day all-cause mortality absolute risk reductions (ARRs) with ART-123 were 8.3% in France and 1.1% in the ROW. The greater ARR in France may be related to a higher rate of sustained coagulopathy and lower rate of heparin use. In France and the ROW, 84.6% and 78.0% of patients sustained coagulopathy from the time of initial SAC diagnosis to first treatment with the study drug, and 65.8% and 43.9% did not receive heparin, respectively. The ARRs for these subgroups of patients in France were 13.4% and 16.6%, respectively. Safety of ART-123 was comparable between France and the ROW. Conclusions Results from this exploratory analysis suggest that patients with sustained SAC not receiving concomitant heparin may benefit from ART-123, a fact that should be confirmed in future studies with more restrictive inclusion criteria

S'appuyer sur l'oxymétrie de pouls pour éviter l'hypoxémie et l'hyperoxie : une étude de cohorte prospective multicentrique chez des patients en insuffisance circulatoire

International audiencePurposeThe purpose of this study was to assess the predictive performance of pulse oximetry (SpO2) to rule out hypoxaemia and hyperoxia in critically ill patients.MethodsSpO2, arterial oxygenation (SaO2), and arterial partial pressure of oxygen (PaO2) were prospectively and simultaneously measured every 6 h during the first 24 h of intensive care unit admission in a multicentre cohort of critically ill patients suffering acute circulatory failure. Likelihood ratios associated with different cutoff values of SpO2 to rule out hypoxaemia (SaO2 95% or PaO2 > 100 mmHg) and post-test probabilities were calculated. Mean bias between SpO2 and SaO2 and agreement interval were calculated. Area under the receiver operating characteristics associated with SpO2 to predict different threshold values of SaO2 and PaO2 were calculated.ResultsFive hundred seventy-one patients (mean [standard deviation] Simplified Acute Physiology Score II: 58.7 [20.1]; mechanically ventilated 75.6%) with 2643 available SaO2 and PaO2 samples and corresponding 2643 SpO2 values were analysed. Mean bias between SpO2 and SaO2 was 1.1%, and its agreement interval ranged from −8.2 to +11.1%. SpO2 cutoff values of 88%, 90%, and 92% left the possibility that 8%–13% of patients had hypoxaemia. SpO2 < 95% left the possibility that 31% of patients had hyperoxia. All calculated areas under the receiver operating characteristics showed a lower limit of their 95% confidence interval below 0.85ConclusionIn this cohort of patients with circulatory failure, SpO2 had poor discriminative ability to rule out hypoxaemia and hyperoxia. Overconfidence upon SpO2 monitoring may be dangerous

Effect of a Recombinant Human Soluble Thrombomodulin on Mortality in Patients With Sepsis-Associated Coagulopathy The SCARLET Randomized Clinical Trial

Importance: Previous research suggested that soluble human recombinant thrombomodulin may reduce mortality among patients with sepsis-associated coagulopathy. Objective: To determine the effect of human recombinant thrombomodulin vs placebo on 28-day all-cause mortality among patients with sepsis-associated coagulopathy. Design, Setting, and Participants: The SCARLET trial was a randomized, double-blind, placebo-controlled, multinational, multicenter phase 3 study conducted in intensive care units at 159 sites in 26 countries. All adult patients admitted to one of the participating intensive care units between October 2012 and March 2018 with sepsis-associated coagulopathy and concomitant cardiovascular and/or respiratory failure, defined as an international normalized ratio greater than 1.40 without other known etiology and a platelet count in the range of 30 to 150 × 10 9/L or a greater than 30% decrease in platelet count within 24 hours, were considered for inclusion. The final date of follow-up was February 28, 2019. Interventions: Patients with sepsis-associated coagulopathy were randomized and treated with an intravenous bolus or a 15-minute infusion of thrombomodulin (0.06 mg/kg/d [maximum, 6 mg/d]; n = 395) or matching placebo (n = 405) once daily for 6 days. Main Outcome and Measures: The primary end point was 28-day all-cause mortality. Results: Among 816 randomized patients, 800 (mean age, 60.7 years; 437 [54.6%] men) completed the study and were included in the full analysis set. In these patients, the 28-day all-cause mortality rate was not statistically significantly different between the thrombomodulin group and the placebo group (106 of 395 patients [26.8%] vs 119 of 405 patients [29.4%], respectively; P =.32). The absolute risk difference was 2.55% (95% CI, -3.68% to 8.77%). The incidence of serious major bleeding adverse events (defined as any intracranial hemorrhage; life-threatening bleeding; or bleeding event classified as serious by the investigator, with administration of at least 1440 mL [typically 6 units] of packed red blood cells over 2 consecutive days) was 23 of 396 patients (5.8%) in the thrombomodulin group and 16 of 404 (4.0%) in the placebo group. Conclusions and Relevance: Among patients with sepsis-associated coagulopathy, administration of a human recombinant thrombomodulin, compared with placebo, did not significantly reduce 28-day all-cause mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT01598831

Effect of a Recombinant Human Soluble Thrombomodulin on Mortality in Patients With Sepsis-Associated Coagulopathy The SCARLET Randomized Clinical Trial

Importance: Previous research suggested that soluble human recombinant thrombomodulin may reduce mortality among patients with sepsis-associated coagulopathy. Objective: To determine the effect of human recombinant thrombomodulin vs placebo on 28-day all-cause mortality among patients with sepsis-associated coagulopathy. Design, Setting, and Participants: The SCARLET trial was a randomized, double-blind, placebo-controlled, multinational, multicenter phase 3 study conducted in intensive care units at 159 sites in 26 countries. All adult patients admitted to one of the participating intensive care units between October 2012 and March 2018 with sepsis-associated coagulopathy and concomitant cardiovascular and/or respiratory failure, defined as an international normalized ratio greater than 1.40 without other known etiology and a platelet count in the range of 30 to 150 × 10 9/L or a greater than 30% decrease in platelet count within 24 hours, were considered for inclusion. The final date of follow-up was February 28, 2019. Interventions: Patients with sepsis-associated coagulopathy were randomized and treated with an intravenous bolus or a 15-minute infusion of thrombomodulin (0.06 mg/kg/d [maximum, 6 mg/d]; n = 395) or matching placebo (n = 405) once daily for 6 days. Main Outcome and Measures: The primary end point was 28-day all-cause mortality. Results: Among 816 randomized patients, 800 (mean age, 60.7 years; 437 [54.6%] men) completed the study and were included in the full analysis set. In these patients, the 28-day all-cause mortality rate was not statistically significantly different between the thrombomodulin group and the placebo group (106 of 395 patients [26.8%] vs 119 of 405 patients [29.4%], respectively; P =.32). The absolute risk difference was 2.55% (95% CI, -3.68% to 8.77%). The incidence of serious major bleeding adverse events (defined as any intracranial hemorrhage; life-threatening bleeding; or bleeding event classified as serious by the investigator, with administration of at least 1440 mL [typically 6 units] of packed red blood cells over 2 consecutive days) was 23 of 396 patients (5.8%) in the thrombomodulin group and 16 of 404 (4.0%) in the placebo group. Conclusions and Relevance: Among patients with sepsis-associated coagulopathy, administration of a human recombinant thrombomodulin, compared with placebo, did not significantly reduce 28-day all-cause mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT01598831