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A prospective, randomized, controlled evaluation of peripheral nerve stimulation versus standard clinical dosing of neuromuscular blocking agents in critically ill patients

Rudis, Maria I. PharmD, BCPS; Sikora, Caryl Ann MD; Angus, Elizabeth MD; Peterson, Edward PhD; Popovich, John Jr, MD; Hyzy, Robert MD; Zarowitz, Barbara J. PharmD, FCCM

Feature Article

Objectives  To determine if vecuronium doses individualized by peripheral nerve stimulation are lower than those doses chosen by standard clinical techniques; and to determine whether patients monitored by peripheral nerve stimulation exhibit shorter recovery times and less prolonged neuromuscular blockade after discontinuation of vecuronium than control patients.

Design  A prospective, randomized, controlled, single-blind trial.

Setting  Two ten-bed medical intensive care units of a 937-bed tertiary care, not-for-profit, teaching hospital and health system.

Patients  Mechanically ventilated patients requiring continuous neuromuscular blockade as part of their therapy.

Interventions  After obtaining written, informed consent and baseline neurologic examinations, patients were randomized to treatment, where dosing was individualized by peripheral nerve stimulation or standard clinical assessment. Doses in the peripheral nerve stimulation group were adjusted to 90% blockade (Train-of-Four of 1/4). The standard clinical dosing group received doses individualized to clinical response by the medical team (blinded to Train-of-Four). Differences between groups were evaluated by Wilcoxon matched-pairs signed rank test.

Measurements and Main Results  A total of 77 patients (35 standard clinical patients vs. 42 peripheral nerve stimulation patients) were enrolled in the study. Despite no difference in initial doses and time to reach 90% blockade or clinical response between groups, the peripheral nerve stimulation group used less drug than the standard clinical group (0.040 +/- 0.028 vs. 0.070 +/- 0.030 mg/kg/hr, respectively, p = .001). The total cumulative amount of vecuronium for the episode of paralysis was greater in the control group (285.8 +/- 246.6 vs. 137.1 +/- 106.4 mg, p = .001). The peripheral nerve stimulation group recovered neuromuscular function (relative risk of 1.85, with 95% confidence interval [CI] of 1.02-3.35, p = .039) and spontaneous ventilation (relative risk of 1.86, 95% CI 1.00-3.45, p = .047) faster than the control group. In patients, adjusting for renal dysfunction, the likelihood of a faster recovery in the peripheral nerve stimulation group increased for neuromuscular function (relative risk of 1.89, 95% CI of 1.07-3.32, p = .018) and spontaneous ventilation (relative risk of 2.27, 95% CI of 1.23-4.21, p = .019). Patients with combined renal and liver failure similarly demonstrated a faster recovery in the peripheral nerve stimulation group. The recovery was affected to a lesser extent by adjusting for concurrent aminoglycoside and corticosteroid administration.

Conclusions  Use of peripheral nerve stimulation for monitoring the degree of blockade and adjusting drug doses in continuously paralyzed critically ill medical patients results in lower doses of vecuronium to maintain a desired depth of paralysis, and allows a faster recovery of neuromuscular function and spontaneous ventilation. (Crit Care Med 1997; 25:575-583)

From the Departments of Pharmacy Services (Drs. Rudis and Zarowitz), Pulmonary and Critical Care Medicine (Drs. Sikora, Popovich, and Hyzy), and Neurology (Dr. Angus), and the Division of Epidemiology and Biostatistics (Dr. Peterson), Henry Ford Health System, Detroit, MI.

Supported, in part, by the Small Projects Funding Committee, Henry Ford Health System ($10,000). A partial supply of vecuronium (Norcuron[R]) was provided by Organon Pharmaceuticals (equivalent to $10,000), along with a grant of $5,000.

Address requests for reprints to: Dr. Barbara J. Zarowitz, Henry Ford Health System, 30100 Telegraph Road, Suite 200, Bingham Farms, MI 48025.

© Williams & Wilkins 1997. All Rights Reserved.