The Problem with Long-Acting Muscle Relaxants? They Cost More!

The introduction of neuromuscular blocking drugs (muscle relaxants) with an intermediate duration of action had a significant positive impact on the practice of anesthesia. Despite the fact that vecuronium and atracurium cost significantly more to purchase than the preexisting long-acting relaxants, their greater safety and ease of use made them first-line drugs in most clinical situations [1]. In recent years, arguments have been made for a return, whenever possible, to the use of the inexpensive long-acting relaxants [2-4]. The stimulus behind the return to the use of the long-acting drugs has been pressure to cut costs and the promise of savings of tens to hundreds of thousands of dollars per annum in drug acquisition costs by replacing intermediate-acting with long-acting drugs [5,6]. However, the savings quoted in such studies take no account of the potential for increased costs incurred by replacing intermediate-acting with long-acting relaxants. In this issue, the study by Ballantyne and Chang [7] examines the relative costs of intermediate- versus long-acting drugs from a broader perspective than just drug acquisition cost. Ballantyne and Chang [7] performed a retrospective study and examined the hypothesis that the inherent duration of action of the muscle relaxant influences the length of patient stay in the postanesthesia care unit (PACU). They found that a consequence of the use of long- versus intermediate-acting relaxants was a longer patient stay in the PACU, and they have estimated the cost associated with this effect. They examined pancuronium, d-tubocurarine, vecuronium, and atracurium, and their findings comparing pancuronium with vecuronium are representative of their overall results. They found that the use of pancuronium compared with vecuronium resulted in the patient spending an extra 41 min in the PACU, which was associated with an increased cost of more than $90. This cost penalty is in contrast to the acquisition cost savings of only $22 with the use of pancuronium in preference to vecuronium. Because of the significance of these findings for anesthesia practice, patient care, and health care costs, this study deserves our careful attention. We must examine the methodology and critically assess the plausibility of the results. A criticism of this study might be that it was retrospective, not prospective. As a result, data collection may have been incomplete, and there could have been factors contributing to the time of patient discharge from the PACU that were not considered. However, the authors have been careful to account for possible confounding factors, such as the length and type of surgery, and to exclude from analysis patients whose discharge from the PACU was delayed for reasons unrelated to their readiness to leave, e.g., no transportation available. Because the investigators have made reasonable assumptions as to the likely confounding factors and have made allowance for such factors in their data analysis and statistical comparisons, the economic model they propose, although based on retrospective data, is a plausible one [8]. The authors identified a drug acquisition cost saving of $22 per patient for pancuronium versus vecuronium, and this is an obvious and easily verifiable figure. In contrast, the cost penalty of approximately $90 for the increased length of stay in the PACU is less obvious in its derivation, and its accuracy is dependent on a number of assumptions. The most important assumption in relation to the accuracy of this cost penalty estimate is that a proportion of the cost of a patient being in the PACU is variable cost that would be decreased by a reduction in patient load. If PACU costs are fixed regardless of patient load, then there is little or no cost penalty to increased length of stay. However, if a significant proportion of PACU costs are variable, i.e., dependent on patient load, then significant costs will be incurred by increased length of stay. A study by Macario et al. [9] estimated that the PACU accounted for 3.7% of the total hospital costs for surgical patients, and that variable direct costs accounted for 44% of this total. Thus, it is a reasonable assumption that factors that increase length of stay in the PACU increase the costs to the hospital. The authors put a Figure ofapproximately $90 per patient as the cost of the increased PACU time in their institution. Even if this Figure of$90 is overestimated by a factor of 4, it is still sufficient to negate the savings in drug acquisition costs made by the use of pancuronium over vecuronium. Another factor that adds to the plausibility of Ballantyne and Chang's study [7] is that their results make sense in relation to what we are beginning to appreciate about the effects of minor-degree residual neuromuscular block. In 1979, Viby-Mogensen et al. [10] identified a high incidence of residual neuromuscular block in the PACU. These results have since been confirmed, and it has been demonstrated that residual weakness is much more common after long-acting drugs than after intermediate-acting drugs [11]. The reason for this observation is that reversal of the neuromuscular block induced by long-acting relaxants takes longer than reversal of blocks induced by intermediate-acting drugs [12]. Of particular importance is the observation that the use of a nerve stimulator to monitor neuromuscular function intraoperatively did not preclude the occurrence of residual weakness with pancuronium [11]. Thus, the use of long-acting relaxants carries an inherent, significant risk of inadequate neuromuscular function in the PACU. Is it possible that interrelaxant differences in recovery of neuromuscular function could be manifest after almost 2 h in the PACU and explain Ballantyne and Chang's results? Traditionally, because of the work of Ali et al. [13] and Brand et al. [14], adequate recovery of neuromuscular function has been defined as a train-of-four (TOF) ratio of 0.7. However, recent evidence suggests that at a TOF ratio of 0.7, significant impairment of neuromuscular function may persist [15-18]. Work by Pavlin et al. [18] demonstrated that the muscles of airway protection are very sensitive to residual effects of muscle relaxants, and Engbaek et al. [15] suggested that recovery is not adequate until a TOF ratio of 0.8 is achieved. More recently, there is evidence that significant residual effects of neuromuscular block may persist until the TOF ratio is 0.9 or greater [16,17]. In a group of healthy, awake, volunteers, Eriksson et al. [16] showed, with vecuronium-induced block, that the coordination of swallowing was disordered and aspiration possible until the TOF ratio was >or=to0.9. In another group of volunteers, Kopman et al. [17] studied the effects of minimal degrees of neuromuscular block induced by mivacurium and found that at a TOF ratio of 0.85-0.90, subjects complained of generalized fatigue, were unable to hold a tongue depressor tightly between their teeth, and had a grip strength reduced to 83% of normal. Thus, even minor degrees of residual neuromuscular block, which before were thought insignificant, can produce adverse clinical effects that may be sufficient to prevent discharge from the PACU. Because of the slow rate of spontaneous recovery of long-acting relaxants, minor-degree residual neuromuscular block may persist for a considerable time postoperatively and may result in delayed discharge from the PACU. By the same token, the effects of residual block with shorter-acting relaxants persist for a shorter period of time and may allow for an earlier discharge from the PACU. In their study, Ballantyne and Chang [7] have made reasonable assumptions in the construction of their economic model, and we have good indirect evidence from our knowledge of the persistence of residual effects of muscle relaxants to explain the difference they found between relaxants with long versus intermediate durations of action. Consequently, their study provides compelling evidence in favor of retaining intermediate-duration relaxants as the first-line drugs for the production of neuromuscular block in our clinical practice.