Functional Recovery Following Neuromuscular Blockade in Critically Ill Adults
Introduction: Neuromuscular blocking agents (NMBAs) are drugs that paralyze all skeletal muscles and are commonly administered to critically ill individuals, primarily to facilitate mechanical ventilation. An estimated 24 to 70% of individuals suffer persistent weakness or paralysis after receiving the drugs, leading to sustained immobility, multiple systemic complications, and exponential increases in the cost of care. Monitoring neuromuscular twitch response with a peripheral nerve stimulator (PNS) for medication titration and prevention of prolonged drug effects results in lower doses of NMBAs and faster recovery of neuromuscular transmission (NMT), however, no improvement in functional muscle activity has been reported. Objective: The purposes of this study were to: evaluate the relationship between recovery of NMT and functional muscle activity when peripheral nerve monitoring is performed during NMBA administration; identify characteristics of individuals who demonstrated delayed recovery; and examine the relationship between delayed recovery of NMT, muscle activity, functional performance and persistent weakness and paralysis. In addition, the efficacy of peripheral nerve monitoring to facilitate recovery from drug-induced paralysis in critically ill patients was determined. Design: This was a multi-center study using a prospective, nonexperimental design. Convenience sampling techniques were used. Sample, Setting, Years: Data collection took place over a 20-month period. Thirty-seven subjects comprised the sample and were hospitalized in one of four intensive care units (ICU) in a large metropolitan area in the southwest. There were 27 males and 10 females with ages ranging from 18 to 87 years (median 34). Severity of illness was assessed using Acute Physiology and Chronic Health Evaluation (APACHE) scores (M=55, SD=20). Subjects had 1 to 6 medical diagnoses. Outcome variables: The primary outcome variables studied included recovery of NMT and muscle activity within 24 hours of neuromuscular blockade termination, time to recover mobility, and time to return of unassisted breathing. Length of ICU and hospital stay were secondary variables of interest, along with the associated costs. Methods: Neuromuscular transmission was measured with a PNS. Muscle activity was measured with actigraphy and a standardized, five-point muscle activity scoring system. Functional performance was measured by direct observation. Findings: Neuromuscular transmission returned promptly after NMBAs were discontinued in all subjects (median=1hour, M=4.5, SD=7.9). Muscle activity remained depressed by all measures. Muscle activity scores ranged from 0 to 5, with 10 out of 31 subjects scoring 0 (no movement) and only 3 of the subjects scoring 5 (normal movement). Median recovery time for best scores was 12 hours (M=12.9, SD=9.6). Actigraphy counts were low at 3 intervals after NMBAs were discontinued: within 4 hours (median=7.7 counts per minute, M=18, SD=36.7); 20-24 hours (median=5.5, M=13, SD=28.6); and over the 24 hour period (median=8, M=9, SD=4.7). These values represent sharply depressed activity compared with counts reported in the literature (35-80, M=66). Only 2 subjects (5%) recovered functional performance within 24 hours. Median time to initial mobility and extubation was 12.9 and 11days, respectively. Predictors of delayed recovery included cumulative dose of aminosteroid NMBAs (R2=.261, F=6.309, p=.025), age (R2=.509, F=16.594, p=.001), and renal function (R2=.313, F=5.93, p=.030). Concomitant propofol administration, severity of illness, and hepatic function were associated with prolonged weakness. Return of unassisted breathing and ambulation was associated with failure to recover muscle activity (X2=5.98, df=2, p=.014; X2=5.07, df=2, p=.024, respectively) within 24 hours following neuromuscular blockade. Length of hospital stay ranged from 9 to 120 days (median 37). Range of ICU length of stay was 7 to 60 days (median 26). Conclusions: The findings suggest that prolonged recovery of NMT and muscle weakness are two different phenomenon, as NMT recovered quickly whereas extreme muscle weakness persisted. Monitoring level of neuromuscular blockade with a PNS and titrating NMBA dosage during therapy can effectively prevent prolonged blockade when NMBAs are stopped but is ineffective in preventing persistent muscle weakness. Persistent weakness contributes to delayed return of ambulation and prolonged ventilator dependency, necessitating continued intensive and acute care. Extended ICU and hospital stays are costly and consume disproportionate health care resources. Implications: NMBAs should be titrated according to PNS response to facilitate rapid recovery of NMT as this is antecedent to return of muscle activity. Vigilant assessment of renal and hepatic function, particularly in the elderly, is necessary to prevent persistent weakness, facilitate mobility and hasten ventilator weaning.
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