Monitoring neuromuscular blockade in the ICU
The practice of controlling life-threatening symptoms in critically ill patients with neuromuscular blocking agents (NMBAs) has grown in the last decade, despite limitations in knowledge about safety, dosing, and monitoring during extended use.Prolonged paralysis and weakness related to extended NMBA use have been
reported.
These reports prompted the Food and Drug Administration and pharmaceutical
manufacturers to recommend the use of peripheral nerve stimulation (PNS)
to monitor NMBA intervention in ICU patients.
This recommendation was based on current practice in surgical anesthesia and on case reports or uncontrolled studies in the ICU setting.
The aim of this study was to determine whether using a peripheral nerve stimulator to guide the depth of paralysis would affect the amount of the drug given and subsequently the amount of time to recovery of neuromuscular function and spontaneous ventilation. Medical and respiratory ICU patients were eligible if their primary physicians planned to use NMBA to optimize mechanical ventilation, decrease oxygen consumption, or control agitation when conventional measures had failed.
Patients younger than 18, those with known neuromuscular abnormalities, or those with allergy to vecuronium, were excluded. Patients were randomized to either the treatment arm, with NMBA dose-adjusted by the investigators using PNS, or to the control arm, with NMBA dose-adjusted by standard clinical assessment by the ICU team. The ICU team was blinded to the results of all peripheral nerve testing.
A baseline neurologic exam was performed. Supramaximal stimulation was determined at ulnar and facial nerve sites. All patients were dosed with vecuronium according to the study protocol, and they received a loading dose based on renal function and body weight, followed by a maintenance infusion. Patients in the treatment arm had dose adjustments to attain 90% blockade or one twitch out of four from train-of-four (TOF) stimulation.
A total of 77 patients were randomized; 42 to the PNS group and 35 to standard clinical assessment. There were no differences in the initial doses or the time to reach 90% blockade, or clinical response between the groups. The PNS group used significantly less drug (0.04 vs. 0.07 mg/kg/hr) than the control group to maintain this state, which resulted in lower mean infusion rates and cumulative drug totals. During the period of clinical response in the control group, 28% of the patients were at 90% blockade, 56% were at 100% blockade, and 11% were lightly paralyzed with TOF responses of two out of four twitches.
Recovery from pharmacologic paralysis was evaluated in 65 patients; 11 patients died while receiving NMBA (eight from the PNS group and three from the control group). Overall, the PNS group had quicker recovery of neuromuscular function and return of spontaneous ventilation. Median length of time for 50% of the control patients to recover neuromuscular function and breathe spontaneously was more than twice as long as for the PNS group (3.5 hrs vs. 1.7 hrs and 4.8 hrs vs. 2 hrs, respectively).
Risk analysis of other clinical factors that could contribute to prolonged paralysis (concomitant use of aminoglycosides, corticosteroids, and kidney and/or liver impairment) showed that standard clinical dosing of NMBA, by itself, increases the risk of prolonged neuromuscular recovery. Renal impairment increased the risk of prolonged neuromuscular recovery, but PNS increased the chance of a quicker recovery from NMBA for patients with renal and/or liver impairment. PNS reduced the incidence of prolonged blockade even when adjusting for concomitant use of aminoglycosides and corticosteroids.
Post-paralysis neurologic exams were performed on 42 patients, 22 from the PNS group and 20 from the control group. More than 70% of the patients (13 PNS patients and 17 control patients) had abnormal exams. Electrodiagnostic studies in 13 of the patients revealed post-synaptic neuromuscular transmission defects and axonal denervation in four patients (one of the eight PNS patients and three of the five control patients). Three of the four patients received very large cumulative doses of vecuronium and were paralyzed for more than 48 hours; two patients had received corticosteroids, and none of the four had received aminoglycosides. In these four individuals, muscle weakness persisted until death (one patient) or hospital discharge (three patients) (Rudis MI, et al. Crit Care Med1997; 25:575-583).
Comment by Doreen M. Anardi RN, critical care research coordinator, department of surgery, Harborview Medical Center, Seattle:
hese findings support the notion that peripheral nerve stimulation is superior to clinical assessment alone in adjusting NMBA therapy.
Rudis and colleagues found that because of PNS monitoring, the treatment group needed less than the manufacturer’s recommended dose of vecuronium to maintain the desired level of blockade. Further, patients at high risk of prolonged recovery from NMBA treatment — those with renal and/or liver impairment — had shorter-than-predicted recovery times related to PNS monitoring. This method of monitoring can result in cost savings by using drugs less and decreasing the incidence of muscle weakness and need for supportive therapies after NMBA use.
TOF may not be the perfect monitoring method. It did not decrease the variability of recovery time of neuromuscular function. It is not always easy to perform, and interpretation of the results may be problematic. It may not accurately reflect the function of the respiratory muscles, since the sensitivities to neuromuscular blockade of the diaphragm and ulnar nerve are quite different. PNS, coupled with other clinical assessments of neuromuscular function, may improve dosing as well as assessment of recovery preventing prolonged paralysis. This study has taken a well-organized first step. n
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