The profound augmentation of the oculocardiac reflex by fast acting opioids.

BACKGROUND: Trigemino-vagal bradycardia elicited by tension on an extraocular muscles (oculocardiac reflex; OCR) is a hazard for strabismus surgery patients. OCR can be reduced by anticholinergic medications and regulating the depth of anesthesia. We investigated the influence of narcotic agents as a routine part of general anesthesia for strabismus surgery in adults and children. METHOD: From August, 1992 through September, 2000, 1275 patients undergoing extraocular muscle surgery were prospectively studied during 10 second, 200 gram square wave tension on gently isolated rectus muscles. The anesthetic agents, gas concentrations, and patient age were recorded. Patients receiving an anticholinergic agent and reoperated cases were excluded, yielding 1029 study cases. 849 received no narcotic as a part of induction. Two groups of patients were given no opiate before the first inferior rectus muscle was pulled. A narcotic was administered IV 5 minutes before the second inferior rectus was pulled. One group of 49 received fentanyl 0.15 uL/Kg and the second group of 12 received meperidine 1 mg/kg. RESULTS: Faster acting intravenous induction opioids had a profound augmenting effect on the degree of oculocardiac reflex. Compared to no narcotic, the OCR was increased most by remifentanyl (p less than .0001), then sufenta (p=.02), and fentanyl (p less than .0001). Induction morphine had no appreciable effect on the OCR (p=.9). For the 49 patients with IV fentanyl delivered between the first OCR and second OCR, a significant increase occurred (p=.003). This increase in %OCR was not correlated with a change in inhalational gas concentration (p=.9), CO2 concentration (p=.6) or age (p=.12). For the 12 patients given demerol between the first and second rectus tension, no significant OCR change occurred (p=.7). The OCR was greatest for inferior rectus, then superior rectus, then medial rectus, and least for lateral rectus. (See text for details.) CONCLUSION: In the absence of anticholinergic blockade, rapidly acting narcotics enhance the degree of bradycardia due to the OCR elicited by controlled extraocular muscle tension during strabismus surgery. Some opioids had the same augmenting magnitude as the blocking effect of IV anticholinergic medication. Meperidine, which has some anticholinergic characteristics, neither blocked nor augmented the OCR.

Preclinical pharmacology of GW280430A (AV430A) in the rhesus monkey and in the cat: a comparison with mivacurium.

BACKGROUND: No replacement for succinylcholine is yet available. GW280430A (AV430A) is a representative of a new class of nondepolarizing neuromuscular blocking drugs called asymmetric mixed-onium chlorofumarates. It undergoes rapid degradation in plasma by chemical hydrolysis and inactivation by cysteine adduction, resulting in a very short duration of effect. The neuromuscular, cardiovascular, and autonomic pharmacology of GW280430A is compared herein with that of mivacurium. METHODS: Adult male rhesus monkeys and adult male cats were anesthetized with nitrous oxide-oxygen-halothane and chloralose-pentobarbital, respectively. The neuromuscular blocking properties of GW280430A and mivacurium were compared at a stimulation rate of 0.15 Hz in the extensor digitorum of the foot (monkey) and the tibialis anterior (cat). Sympathetic responses were assayed in the cat in the nictitating membrane preparation, and vagal effects were evaluated in the cat via observation of bradycardic responses after stimulation of the cervical right vagus nerve. RESULTS: GW280430A and mivacurium were equipotent in the monkey (ED95 was 0.06 mg/kg in each case). GW280430A was half as potent as mivacurium in the cat. The total duration of action of GW280430A was less than half that of mivacurium in the monkey; recovery slopes were more than twice as rapid. The 25-75% recovery index of GW280430A did not vary significantly after various bolus doses or infusions, averaging 1.4-1.8 min in the monkey, significantly shorter than the same time interval (4.8-5.7 min) for mivacurium. Dose ratios for autonomic versus neuromuscular blocking properties in the cat were greater than 25 for both GW280430A and mivacurium. The ratio ED Hist:ED95 Neuromuscular Block in the monkey was significantly greater (approximately 53 vs. 13) for GW280430A, indicating approximately four times less relative prominence of the side effects of skin flushing and decrease of blood pressure, which are associated with release of histamine. CONCLUSIONS: These experiments show a much shorter neuromuscular blocking effect and much-reduced side effects in the case of GW280430A vis-à-vis mivacurium. These results, together with the novel chemical degradation of GW280430A, suggest further evaluation in human subjects.