key: cord-0841601-aa5b2b8w
authors: Ziatkowski-Michaud, Julia; Mazard, Tessa; Delignette, Marie-Charlotte; Wallet, Florent; Aubrun, Frederic; Dziadzko, Mikhail
title: Neuromuscular monitoring and neuromuscular blocking agent shortages when treating critically ill COVID-19 patients
date: 2021-05-14
journal: Br J Anaesth
DOI: 10.1016/j.bja.2021.04.028
sha: 3fa96846dbf06cd28c2b9e0d7e0f0036252b1828
doc_id: 841601
cord_uid: aa5b2b8w

nan

academic hospitals during the first epidemic peak in France from 27 February to 21 April 2020. At that time use of qualitative (TOF-count) monitoring (TOFscan®, Draeger, city, Germany; applied to the adductor pollicis muscle) to adjust cisatracurium infusion rate was standardized (Supplement, Figure S1 ) and applied per physician discretion.

The primary endpoint was cisatracurium consumption in mg kg -1 day -1 . Baseline characteristics, severity of patients using SAPS II and SOFA scores, mechanical ventilation, arterial blood gas parameters at three time points (intubation, 48 h after intubation, 7 days after intubation), number of prone positionings, mechanical ventilation time, length of stay in ICU, and 90-day mortality were collected. Multiple logistic regression was employed to identify independent risk factors for higher cisatracurium consumption (≥4 mg kg -1 day -1 ). A post hoc power analysis based on the primary endpoint was calculated and yielded 72.7% accuracy for 5% alpha error. All calculations were performed using R software version 3.4.4 (R Core Team 2017, Vienna, Austria), and significance level was set at p<0.05. The study was approved by the local ethics committee; no written consent was required.

Out of 121 patients included, 86 were allocated to the TOF group (at least one qualitative TOF-count measurement reported in the electronic health record), otherwise they were allocated to the control group (n=35). Patient characteristics were comparable (Supplement , Table S1 ). No adjuncts (magnesium or alpha-adrenergic agonists) were used to reduce the dose of neuromuscular blocking drug administered. 1 Cisatracurium consumption was significantly lower in the TOF group (2.9 mg kg -1 day -1 [IQR 2.2-4.2] vs. 4.4 mg kg -1 day -1 [IQR 2.5-6.1], p = 0.02) ( Figure 1 ). The number of patients with higher cisatracurium consumption (> 4 mg kg -1 day -1 ) in the TOF group was 26 patients (30.2%), and was 18 (51.4%) in thecontrol group (p=0.02). The absence of monitoring was independently associated with higher cisatracurium consumption (OR = 2.77; 95% CI 1.18-6.66, p = 0.02). The number of prone positionings (OR = 1.46; 95% CI 1.11-1.46, p = 0.0007) was also independently associated with greater cisatracurium consumption. No clinically significant difference in ventilation-related parameters was found in the first 7 days of mechanical ventilation or duration of cisatracurium administration (Supplement , Table S2 ). In the TOF group, duration of mechanical ventilation and length of hospital stay were significantly longer, but there was no difference in 90-day mortality (Table 1) .

Although underpowered, our study demonstrated a clinically relevant (35%) decrease in cisatracurium consumption in patients with neuromuscular blockade for more than 48 J o u r n a l P r e -p r o o f h. These findings may inform decision-making during situations with acute or expected NMBA shortage.

Use of TOF monitoring has been shown to reduce NMBA use hourly and cumulatively with no impairment in quality of neuromuscular block, ventilator and blood gas parameters, or occurrence of adverse events. 5 Use of a bundle directed (sedation, clinical assessment and qualitative TOF-count monitoring) protocol was also beneficial in terms of NMBA dose reduction. 6 However, in the beginning of the COVID-19 pandemic, with limited time and material resources, little was known regarding the pathophysiology of SARS-COV-2-induced lung injury. 7, 8 Physicians may have used greater doses of NMBA because of the frequently observed high respiratory drive in COVID-19 ARDS patients. 9 The major limitation of our study is the retrospective case-control design and the absence of sample size calculation. Patients were hospitalized in different ICUs, including temporary units created on demand to increase ICU bed capacity during the COVID-19 outbreak. Train-of-four count may have been estimated but not recorded.

The NMBA-monitoring protocol implemented used a qualitative reading, only estimating TOF-count combined with clinical judgment. Poor agreement regarding neuromuscular blockade quality between solely used clinical assessment and qualitative TOF (number of twitches) alone has been reported. 10 However combined use of qualitative TOF-count monitoring and clinical assessment together may help modify the infusion rate of NMBA in a considerable proportion of paralyzed ICU patients, helping to reduce total NMBA dose administered. We did observe such saving in our study.

In conclusion, we observed a 35% reduction of weight-adjusted cisatracurium daily use in patients with TOF-count monitoring. No clinically relevant difference in ventilation related parameters were found in the first 7 days of mechanical ventilation, or in duration of neuromuscular block. Our support endorse the use of qualitative TOF monitoring in COVID19 ARDS patients as part of a strategy to reduce the dose of NMBA used in the context of limited supply. A larger randomised controlled trial is needed to study remote outcomes of mechanical ventilation guided with neuromuscular block in critically ill adult patients. 

The Croix Rousse University Hospital, Lyon, France.

The authors have no competing interests. 

Reducing the dose of neuromuscular blocking agents with adjuncts: a systematic review and meta-analysis

Neuromuscular blocking agents (NMBA) for COVID-19 acute respiratory distress syndrome: a multicenter observational study

Neuromuscular blocking drugs in the critically ill

Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient

How to reduce cisatracurium consumption in ARDS patients: the TOF-ARDS study

The Implementation of Protocol-Based Utilization of Neuromuscular Blocking Agent Using Clinical Variables in Acute Respiratory Distress Syndrome Patients

COVID-19 pneumonia: ARDS or not?

Respiratory Mechanics and Gas Exchange in COVID-19-associated Respiratory Failure

High Respiratory Drive and Excessive Respiratory Efforts Predict Relapse of Respiratory Failure in Critically Ill Patients with COVID-19

Clinical assessment and train-of-four measurements in critically ill patients treated with recommended doses of cisatracurium or atracurium for neuromuscular blockade: a prospective descriptive study