The accuracy of various neuro-prognostication algorithms and the added value of neurofilament light chain dosage for patients resuscitated from shockable cardiac arrest: An ancillary analysis of the ISOCRATE study.

PURPOSE: In current guidelines, neurological prognostication after cardiopulmonary resuscitation is based on a multimodal approach bundled in algorithms. Biomarkers are of particular interest because they are unaffected by interpretation bias. We assessed the predictive value of serum neurofilament light chains (NF-L) in patients with a shockable rhythm who received cardiopulmonary resuscitation, and evaluated the predictive value of a modified algorithm where NF-L dosage is included. METHODS: All patients who were included participated in the randomized ISOCRATE trial. NF-L values 48 h after ROSC were compared for patients with a good (Cerebral Performance Category (CPC) 1 or 2) and a poor prognosis (CPC 3 to 5 or death). The benefit of adding NF-L dosage to the current guideline algorithm was then assessed for NF-L thresholds of 500 and 1,200 pg/ml as previously described. RESULTS: NF-L was assayed for 49 patients. In patients with good versus those with poor outcomes, median NF-L values at 48 h were 72 ± 78 and 7,755 ± 9,501 pg/ml respectively (P < 0.0001; AUC [95 %CI] = 0.87 [0.74;0.99]). The sensitivity of the modified ESICM/ERC 2021 algorithm after adding NF-L with thresholds of 500 and 1,200 pg/ml was 0.74 (CI 95% 0.51-0.88) and 0.68 (CI 95% 0.46-0.86), respectively, versus 0.53 (CI 95% 0.32-0.73) for the unmodified algorithm. In three instances the specificity was 1. CONCLUSION: High NF-L plasma levels 48 h after cardiac arrest was significantly associated with a poor outcome. Adjunction to the current guideline algorithm of an NF-L assay with a 500 pg/ml threshold 48 h after cardiac arrest provided the best sensitivity compared to the algorithm alone, while specificity remained excellent.

Impact of rewarming rate on interleukin-6 levels in patients with shockable cardiac arrest receiving targeted temperature management at 33 °C: the ISOCRATE pilot randomized controlled trial.

PURPOSE: While targeted temperature management (TTM) has been recommended in patients with shockable cardiac arrest (CA) and suggested in patients with non-shockable rhythms, few data exist regarding the impact of the rewarming rate on systemic inflammation. We compared serum levels of the proinflammatory cytokine interleukin-6 (IL6) measured with two rewarming rates after TTM at 33 °C in patients with shockable out-of-hospital cardiac arrest (OHCA). METHODS: ISOCRATE was a single-center randomized controlled trial comparing rewarming at 0.50 °C/h versus 0.25 °C/h in patients coma after shockable OHCA in 2016-2020. The primary outcome was serum IL6 level 24-48 h after reaching 33 °C. Secondary outcomes included the day-90 Cerebral Performance Category (CPC) and the 48-h serum neurofilament light-chain (NF-L) level. RESULTS: We randomized 50 patients. The median IL6 area-under-the-curve was similar between the two groups (12,389 [7256-37,200] vs. 8859 [6825-18,088] pg/mL h; P = 0.55). No significant difference was noted in proportions of patients with favorable day-90 CPC scores (13/25 patients at 0.25 °C/h (52.0%; 95% CI 31.3-72.2%) and 13/25 patients at 0.50 °C/h (52.0%; 95% CI 31.3-72.2%; P = 0.99)). Median NF-L levels were not significantly different between the 0.25 °C/h and 0.50 °C/h groups (76.0 pg mL, [25.5-3074.0] vs. 192 pg mL, [33.6-4199.0]; P = 0.43; respectively). CONCLUSION: In our RCT, rewarming from 33 °C at 0.25 °C/h, compared to 0.50 °C/h, did not decrease the serum IL6 level after shockable CA. Further RCTs are needed to better define the optimal TTM strategy for patients with CA. Trial registration ClinicalTrials.gov, NCT02555254 . Registered September 14, 2015. TAKE-HOME MESSAGE: Rewarming at a rate of 0.25 °C/h, compared to 0.50 °C, did not result in lower serum IL6 levels after achievement of hypothermia at 33 °C in patients who remained comatose after shockable cardiac arrest. No associations were found between the slower rewarming rate and day-90 functional outcomes or mortality. 140-character Tweet: Rewarming at 0.25 °C versus 0.50 °C did not decrease serum IL6 levels after hypothermia at 33 °C in patients comatose after shockable cardiac arrest.

Effect of High-Dose Baclofen on Agitation-Related Events Among Patients With Unhealthy Alcohol Use Receiving Mechanical Ventilation: A Randomized Clinical Trial.

Importance: Unhealthy alcohol use can lead to agitation in the intensive care unit (ICU). Objective: To assess whether high-dose baclofen reduces agitation-related events compared with placebo in patients with unhealthy alcohol use receiving mechanical ventilation. Design, Settings, and Participants: This phase 3, double-blind, placebo-controlled, randomized clinical trial conducted in 18 ICUs in France recruited adults receiving mechanical ventilation who met criteria for unhealthy alcohol use. Patients were enrolled from June 2016 to February 2018; the last follow-up was in May 2019. Interventions: Baclofen (n = 159), adjusted from 50 to 150 mg per day based on estimated glomerular filtration rate, or placebo (n = 155) during mechanical ventilation up to a maximum of 15 days before gradual dose reduction over 3 to 6 days. Main Outcomes and Measures: The primary end point was the percentage of patients with at least 1 agitation-related event over the treatment period. Secondary outcomes included duration of mechanical ventilation, length of ICU stay, and 28-day mortality. Results: Among 314 patients who were randomized (mean age, 57 years; 60 [17.2%] women), 313 (99.7%) completed the trial. There was a statistically significant decrease in the percentage of patients who experienced at least 1 agitation-related event in the baclofen group vs the placebo group (31 [19.7%] vs 46 [29.7%]; difference, -9.93% [95% CI, -19.45% to -0.42%]; adjusted odds ratio, 0.59 [95% CI, 0.35-0.99]). Of 18 prespecified secondary end points, 14 were not significantly different. Compared with the placebo group, the baclofen group had a significantly longer median length of mechanical ventilation (9 vs 8 days; difference, 2.00 [95% CI, 0.00-3.00]; hazard ratio [HR] for extubation, 0.76 [95% CI, 0.60-0.97]) and stay in the ICU (14 vs 11 days; difference, 2.00 [95% CI, 0.00-4.00]; HR for discharge, 0.70 [95% CI, 0.54-0.90]). At 28 days, there was no significant difference in mortality in the baclofen vs placebo group (25.3% vs 21.6%; adjusted odds ratio, 1.24 [95% CI, 0.72-2.13]). Delayed awakening (no eye opening at 72 hours after cessation of sedatives and analgesics) occurred in 14 patients (8.9%) in the baclofen group vs 3 (1.9%) in the placebo group. Conclusions and Relevance: Among patients with unhealthy alcohol use receiving mechanical ventilation, treatment with high-dose baclofen, compared with placebo, resulted in a statistically significant reduction in agitation-related events. However, considering the modest effect and the totality of findings for the secondary end points and adverse events, further research is needed to determine the possible role of baclofen in this setting and to potentially optimize dosing. Trial Registration: ClinicalTrials.gov Identifier: NCT02723383.

Subglottic secretion drainage for ventilator-associated pneumonia prevention: an underused efficient measure.

Subglottic secretion drainage (SSD) is one of the recommended strategies to prevent ventilator-associated pneumonia (VAP) with a high level of evidence, especially regarding early-onset pneumonia. All meta-analysis found that the use of SSD reduces VAP occurrence with a relative risk (RR) reduction of 45%. In some of them, SSD reduces the duration of mechanical ventilation (MV) but without beneficial effect on intensive care unit (ICU) or hospital mortality. In spite of the edited recommendations, SSD has not been widely implemented in ICUs and remains underused. Several factors could account for this: doubts on the innocuousness of using SSD, persisting reservations on the SSD effect on other outcomes than VAP, a high variability in the volume of secretions suctioned between patients and, for each individual patient, during the period of MV and the initial increased expense of the specific endotracheal tubes (ETs) allowing SSD which limits the availability of these devices.