We thank Drs. Kettler and Donati for their interest in our meta-analysis1and appreciate the opportunity to reply.
We agree with Dr. Kettler that pretreatment with a nondepolarizing neuromuscular blocker could be a confounder in the association between higher doses of succinylcholine and a reduced risk of fasciculation and myalgia. However, Dr. Kettler assumes that “It is a common practice for clinicians to use a larger dose of succinylcholine when they have provided pretreatment with a nondepolarizing neuromuscular blocker, making pretreatment a potential cointervention.” Currently, the literature does not provide any evidence for this statement. Unfortunately, the available data do not permit adjusting for this potential confounder. As suggested by Dr. Kettler, the association between the dose of succinylcholine and the risk of fasciculation and myalgia may thus serve as a hypothesis for future research.
Dr. Donati analyzed the increase of precurarization doses during the past years using a linear regression analysis. His very interesting analysis shows that equivalent doses of most of the neuromuscular blocking agents that have been used in precurarization studies were doubled on average during the past 30 yr. Because of this dose inflation, the incidence of precurarization-related side effects increased in more recent studies. Dr. Donati suggests that pretreatment with a nondepolarizing neuromuscular blocker is effective to avoid myalgia and fasciculation and is also safe when the dose does not exceed 10% of ED95. We agree with his comment that our conclusion on the risk of precurarization-related side effects should be more specific. However, there is some evidence in the literature that potentially serious side effects may occur even with the recommended dose of 0.1 × ED95. Engbaek and Viby-Mogensen2reported the case of a healthy 32-yr-old man who received a dose of 0.3 mg (0.005 mg/kg) vecuronium for precurarization. In the minutes after administration of the agent, the patient developed serious signs of partial paralysis with respiratory impairment and was not able to swallow or to move. Engbaek and Viby-Mogensen suggested an extreme sensitivity for neuromuscular blocking agents in this patient without a preexisting neuromuscular disease. As a conclusion, they recommended to inform patients about possible side effects of precurarization preoperatively. In addition, clinicians should be alert to a possible hypersensitivity to neuromuscular blocking agents even after precurarization.
In a clinical trial on the effect of precurarization with atracurium on pulmonary function and neuromuscular transmission, Howardy-Hansen et al. 3found a significant decrease in peak expiratory flow, vital capacity, and train-of-four-ratio after a dose of 0.02 mg/kg atracurium (0.08 × E95) compared with control. They concluded that careful observation of respiratory function should be mandatory after precurarization.
Based on the data of our meta-analysis, we agree with Dr. Donati that pretreatment with neuromuscular blocking agents is an effective method to avoid postoperative myalgia and fasciculation. Moreover, side effects from precurarization may occur less frequently when using a dose of 0.1 × ED95. However, in context of the cited reports, there is a finite risk of side effects related to the use of neuromuscular blocking agents even with a dose of 0.1 × ED95. Clinicians should be aware of this risk when using precurarization. To maximize patients’ safety, a close monitoring for precurarization-related side effects is strongly recommended.
*University Hospital of the Saarland, Homburg, Germany. firstname.lastname@example.org