Myopathy from Steroids/Neuromuscular Blockers (paralytics) ========================================================== The combination of steroids and NMBs has been known for awhile to cause a myopathy. This myopathy may cause prolonged paralysis and is associated with evidence of rhabdomyolysis. As a result some have recommended not paralyzing intubated asthmatics since they will invariably be receiving steroids. This syndrome has been described with pancuronium (1), atracurium (2) and vecuronium (3). Some patients have exhibited a neuropathic component (4). Regrettably they may require prolonged mechanical ventilation as a consequence of this paralysis (5). --H. Louzon, M.D. (1) Picado C; Montserrat J; Agusti-Vidal A Muscle atrophy in severe exacerbation of asthma requiring mechanical ventilation. Respiration, 53: 3, 1988, 201-3 An unusual case of acute muscular atrophy in a patient with a severe exacerbation of asthma requiring mechanical ventilation is reported. High doses of pancuronium bromide and 6-methylprednisolone were administered. It is suggested that the conditions of mechanical ventilation increase in some way the potential of corticosteroids to cause myopathy. The possible implication of myorelaxant drugs in the development of this complication is also suggested. (2) Hoey LL; Joslin SM; Nahum A; Vance-Bryan K Prolonged neuromuscular blockade in two critically ill patients treated with atracurium. Pharmacotherapy, 15: 2, 1995 Mar-Apr, 254-9 Recent literature suggests that the risk of prolonged neuromuscular blockade associated with atracurium compared with other nondepolarizing neuromuscular blocking agents may be minimal. Two patients experienced prolonged weakness associated with the administration of atracurium. Both received atracurium 0.5-0.7 mg/kg/hour in combination with methylprednisolone 500-600 mg/day. Electromyographic results and creatine kinase levels were suggestive of muscular weakness in both patients. Despite high-dose corticosteroid therapy, the electromyographic evidence supporting prolonged weakness did not suggest typical corticosteroid myopathy. Although some clinicians advocate routine administration of atracurium in critically ill patients due to the relative lack of reports of prolonged weakness, this may be premature. Although there are fewer reports of atracurium-associated prolonged weakness compared with pancuronium and vecuronium, the patients we describe suggest that it may occur. (3) Douglass JA; Tuxen DV; Horne M; Scheinkestel CD; Weinmann M; Czarny D; Bowes G Myopathy in severe asthma. Am Rev Respir Dis, 146: 2, 1992 Aug, 517-9 Myopathy complicating the therapy of severe asthma has been recently described in several case reports. Twenty-five consecutive patients admitted to the intensive care unit (ICU) at this hospital for mechanical ventilation for severe asthma were studied for the incidence of creatine kinase (CK) enzyme rise and for the development of clinical myopathy. Pharmacologic therapy was standardized, every patient receiving corticosteroids and aminophylline intravenously and salbutamol both nebulized and intravenously. Twenty-two patients received muscle relaxant therapy with vecuronium. In 19 of 25 (76%) of patients there was elevation of CK levels to a median of 1,575 U/L (range, 66 to 7,430) occurring 3.6 +/- 1.5 days after admission. In nine patients there was clinically detectable myopathy. The presence of either myopathy or CK enzyme rise was associated with a significant prolongation of ventilation time. Arterial blood gas measurements on admission to the ICU revealed a pH (mean +/- SD) of 7.07 +/- 0.21, a PaCO2 of 87.2 +/- 32.7, and a PaO2 (with a high FIO2) of 129 +/- 97 mm Hg; however, no correlation was found between the severity of initial metabolic disturbance and the subsequent development of myopathy. There was no association between the type of corticosteroid administered and the subsequent development of myopathy. Patients with myopathy had received a significantly higher total dose of vecuronium when compared with those who did not develop myopathy (p < 0.001, Kruskal Wallis test). We have therefore found a surprisingly high incidence of CK enzyme rise and myopathy in this group of mechanically ventilated patients with severe asthma. (4) Blackie JD; Gibson P; Murree-Allen K; Saul WP Acute myopathy in status asthmaticus. Clin Exp Neurol, 30:1993, 72-81 An acute myopathy complicating life-threatening asthma has been reported with increasing frequency. We present a further 3 patients with this complication. Each patient had nerve conduction studies, electromyography and muscle biopsy performed. The records of a cohort of 12 patients, ventilated in an intensive care unit over a 16 month period, were reviewed. Eleven out of the 12 patients developed an elevated creatine kinase level (median 1311 U/L, range 185-9973 U/L) and 4 developed symptomatic weakness. The myopathy of status asthmaticus is not a homogeneous clinicopathological entity. Although myopathy is the predominant feature, there is a neuropathic component in some patients. Full recovery is usual. The combination of corticosteroids and neuromuscular blocking agents has been proposed as the possible cause of the complication. (5) Coakley JH; Nagendran K; Ormerod IE; Ferguson CN; Hinds CJ Prolonged neurogenic weakness in patients requiring mechanical ventilation for acute airflow limitation. Chest, 101: 5, 1992 May, 1413-6 We describe three patients who required mechanical ventilation for severe acute exacerbations of obstructive airways disease. When treatment with sedatives and muscle relaxants was withdrawn, they exhibited profound generalized weakness and consequently required prolonged ventilation despite resolution of the airway obstruction. Clinical features were variable, but none of the patients developed failure of other organs and infection was confined to the lungs. All had electrophysiologic evidence of a predominantly motor axonal syndrome. One patient in whom sensory action potentials were abnormal may represent an unusually severe case of critical illness neuropathy occurring in the absence of systemic sepsis and multiple organ failure. In the other two cases, this diagnosis is made less likely by the complete absence of sensory involvement and in these patients the lesion appeared to be either in the most distal portion of the motor neuron or at the neuromuscular junction. In all three patients, resolution was slow but eventually complete. The etiology of the condition is not clear, but it seems to be distinct from the acute myopathy previously described in asthmatics who had received mechanical ventilation. It is important to recognize this phenomenon to avoid erroneous conclusions about the likelihood of the patient recovering from ventilator dependence. A prolonged weaning period is to be expected in such cases. --------------------------------- Looking further into the problems evoked by the use steroids/NMBs in paralyzed ventilated asthmatics I came across a prospective study that measured CK levels and followed patients for the development of myopathy (1). Out of 25 patients on this combination of drugs, 19 (76%) had elevations of CK to a mean of 1575. Clinically, myopathy occurred in 9 (36%) of these cases all of whom had elevated CK levels. The average duration of myopathy was 27 days. No correlation between total dose or nature of steroid used was found. However, there was a striking association between the total dose of vecuronium administered and the occurrence of either CK elevation or myopathy: All CK rise No CK rise Myopathy CK rise w/o myopathy Total 492 626 68 1065 231 Dose Vec Days 2.5 3.1 0.5 5.4 1.3 Paralyzed Total number of days on ventilator was significantly prolonged in those who developed myopathy (12) compared to those who did not (3). The authors did not specify, other than noting average total doses, what the smallest cumulative dose of vecuronium was that resulted in myopathy but a dose-response effect seems to be clearly operative here. Of interest is that although all of these patients were paralyzed with vec on the ventilator, the initial drug used for RSI in all these cases was sux. Obviously they, like myself, are not concerned about the histamine releasing effects of sux in asthmatics. We now know that it is not only vec, but also other NMBs of the aminosteroid class such as pancuronium, that can cause this syndrome. Vec may be implicated more often simply because it appears to be used more commonly. As far as the pulmonologist who lost his cool when a single dose of vec was administered in the ED I would write him a letter challenging him to demonstrate that this has ever been shown to be detrimental. I would also cc a copy this study showing a dose-response effect and a copy of other abstracts that I previously posted concerning the occurrence of a myopathy with other NMBs and ask for his comments. H. Louzon MD (1) Douglass et. al. Myopathy in Severe Asthma. Am Rev Respir Dis 1992;146:517-519