Antagonism of Neuromuscular Blockage by Theophylline

Abstract

A 21-year-old comatose woman, weighing 45 kg, suffered smoke inhalation and hypoxic brain injury 4 days prior to admission to the intensive care unit. An endotracheal tube was in place and she was breathing spontaneously through a T-piece. A chest x-ray showed diffuse patchy infiltrates bilaterally. The electrocardiogram and serum sodium, potassium, chloride, calcium, and magnesium levels were within normal limits. The respiratory rate was 55 breaths per minute. The minute ventilation was 16.4 L. Arterial blood gases at F 1 0 2 0.4 were PO,, 167 torr; Pco,, 63 torr; pH 7.27. An infusion of aminophylline at a rate of 1.55 mg/kg/hr (69.9 mg/ hr) was being administered because of severe bronchospasm and this dose had been unchanged for the previous 48 hours. A blood theophylline level at this infusion rate was 35 mg/L (therapeutic range 10-20 ml/L). Other medications included hydrocortisone 100 mg every 6 hours IV and cimetidine 300 mg every 6 hours IV.Because of the patient's respiratory status, it was decided that controlled mechanical ventilation was necessary and muscular paralysis with pancuronium was planned. Six milligrams of pancuronium were given via a 16-g central intravenous line but after approximately 5 minutes the patient continued to hyperventilate and muscular paralysis did not occur. A peripheral nerve stimulator placed over the patient's left ulnar nerve showed sustained tetanus at a frequency of 50 Hz and sustained twitch height at a frequency of 0.5 Hz (train of 4). Two fresh ampules of pancuronium were Address reprint requests to Henry Rosenberg, MD. obtained from a refrigerated supply and an additional 16 mg of pancuronium were given over the next 20 minutes without change in respiratory status or response to nerve stimulation. The patient was then given succinylcholine, 100 mg IV; fasciculations were not observed and within 1 minute spontaneous ventilation ceased. Subsequent to the succinylcholine, no response to tetanic or twitch stimuli were observed for approximately 10 minutes. Spontaneous ventilation then returned and response to the nerve stimulator was similar to the presuccinylcholine period. The patient was then given d-tubocurarine in 3-mg increments to a total dose of 18 mg at which time muscular paralysis was clinically evident. At this time nonsustained tetanus, posttetanic facilitation, and evidence of twitch depression was seen upon nerve stimulation. She was then ventilated without difficulty by a Bennett MA-1 respirator. The patient subsequently required only 8 mg of pancuronium to be mechanically ventilated over the next 10 hours; however, during this time the aminophylline infusion had been decreased to 0.89 mg/kg/hr (40 mg/hr). Unfortunately, a theophylline blood level was not obtained at this infusion rate. DiscussionThis patient demonstrated marked resistance to the neuromuscular blocking effects of pancuronium. Potential causes of failure of drug action that were excluded were: (1) failure of the drug to enter the bloodstream-this is unlikely as pancuronium was injected ...

Pharmacodynamic drug-drug interactions in the intensive care unit – single-center experience and literature review

“…The median ICU stay was 12 (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25) days. The subjects were treated with a median number of 22 (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27) drugs. We identified 27 possible DDIs per patient, including 3 (1-7) DDI of a severe grade.…”

Analgesia, Sedation, and Therapeutic Paralysis in the Critically Ill

“…The potency and duration of paralytic agents are affected by concomitant medications and medical conditions (Table 5): burns, [160][161][162][163][164][165] edema, and use of corticosteroids, 166 methylxanthines, [167][168][169] phenytoin, 170,171 lithium, 172 and carbamazepine 173 all reduce or antagonize the effectiveness of paralytics. Tachyphylaxis may also be observed with chronic paralysis.…”

Neuromuscular Pharmacology

“…Then, when a larger dose of suxamethonium is used, the resultant paralysis may be somewhat prolonged. Azathioprine (Dretchen et al, 1976), theophylline (Doll and Rosenberg, 1979) and caffeine (personal observation) antagonize non-depolarizing neuromuscular block, probably by inhibition of phosphodiesterase in the motor nerve terminal, thereby increasing the output of transmitter.…”