F. M. Ramsey

Twitch, tetanus and train-of-four as indices of recovery from nondepolarizing neuromuscular blockade

This study was undertaken to compare the sensitivities of the train-of-four response (2 Hz for 2 s), the single twitch (0.15 Hz), and the tetanic response (50 Hz for 5 s) as indices of residual nondepolarizing block. Spontaneous or induced recovery of evoked thumb adduction in response to ulnar nerve stimulation was studied. One hundred and seven adult surgical patients were divided according to the relaxant used, into six groups. We found that when the single twitch recovered to control height, the train-of-four ratio was well below 1.0. This ratio was significantly lower during spontaneous recovery than following neostigmine antagonism of the block (P < 0.01). The tetanic response was fully sustained when the train-of-four ratio was above 0.7. When the ratio was less than 0.7, variable degrees of fade of tetanus were evident. Analysis of variance indicated similar train-of-four ratios among the six groups at complete recovery of the single twitch irrespective of the relaxant technique used (P < 0.1). It is concluded that a train-of-four ratio of 0.7 or higher reliably indicates the recovery of the single twitch to control height and a sustained response to tetanic stimulation at 50 Hz for 5 s. The clinical significance of this study is as follows: the train-of-four response provides the same indication of clinical recovery from nondepolarizing block as obtained from tetanic stimulation at a physiological frequency; and reliance on the recovery of the single twitch to control height as a criterion of spontaneous return to normal clinical neuromuscular function may be misleading.

Potentiation of neuromuscular blockade in man produced by combinations of pancuronium and metocurine or pancuronium and d-tubocurarine

Simultaneous administration of combinations of pancuronium, metocurine, and d-tubocurarine (dTc) were given to A.S.A. class l-ll surgical patients during N2O-narcotic-thiopental anesthesia to determine the degree of neuromuscular blockade produced. The pancuronium-metocu-rine and the pancuronium-dTc combinations were each significantly more potent (p < 0.05) than the additive effects of each of the individual drugs given alone. This greater than additive neuromuscular blocking effect was not seen with the metocurine-dTc combination. Despite the potentiation of neuromuscular blocking intensity by the pancuronium-metocurine and the pancuronium-dTc combination, the duration of blockade was not prolonged. Possibly, such potentiation of neuromuscular blockade might be attributed to simultaneous pre- and postjunctional receptor inhibition. Additional mechanisms might involve augmented conformational attachment to pre- and postjunctional cholinergic receptors or altered protein binding such that a greater than expected proportion of unbound drug reaches its neuromuscular site of activity. Regardless of mechanism, combining pancuronium with dTc or with metocurine can provide surgical relaxation or ideal conditions for endotracheal intubation with smaller amounts of each drug than would be anticipated if their effects were simply additive.

Rapid administration of a narcotic and neuromuscular blocker: a hemodynamic comparison of fentanyl, sufentanil, pancuronium, and vecuronium

High-dose narcotic anesthetic inductions usually avoid circulatory depression bettrthan do other techniques; however, the selection of a narcotic and neuromuscular blocker influences subsequent hemodynamic responses. One hundred-one patients having aortocoronary bypass graft (CABG) surgery were investigated using four combinations of a narcotic and neuromuscular blocker: group FP (fentanyl 50 μg/kg, pancuronium 100 μg/kg); group FV (fentanyl 50 μg/kg, vecuronium 80 μg/kg); group SP (sufentanil 10 μg/kg, pancuronium 100 μg/kg); and group SV (sufentanil 10 μg/kg, vecuronium 80 μg/kg), each combination being administered over 2 minutes. Hemodynamic functions were then monitored for 10 minutes before tracheal intubation. Significant changes included increases in heart rate in the groups receiving pancuronium and decreases in those receiving vecuronium. In all groups mean arterial pressure initially decreased; systemic vascular resistance index decreased significantly in all groups except SV. Cardiac index decreased significantly only in group SV. Circulatory depression requiring treatment with vasopressor or anticholinergic drugs was more common in patients given vecuronium. Cardiac arrhythmia occurred most often in group SP; only in group FP were there no arrhythmias, ischemic changes, or hemodynamic disturbances requiring intervention. Time to onset of neuromuscular blockade did not differ among the four groups, but transient chest wall rigidity occurred significantly more often with sufentanil than with fentanyl. Overall, the fentanyl/pancuronium combination afforded the greatest hemodynamic stability, whereas the sufentanil/vecuronium combination proved least satisfactory because of bradycardia and hypotension, requiring treatment in 35% of group SV patients. Differences in anesthetic premedication, social habits, preoperative medications, narcotic and muscle relaxant doses, and speed of anesthetic drug administration may also influence hemodynamicresponses and may explain differing results reported by others using the same drug combinations.

Combination of pancuronium and metocurine: neuromuscular and hemodynamic advantages over pancuronium alone.

Combination of pancuronium and metocurine or pancuronium and d-tubocurarine produces potentiation of neuromuscular blocking effects such that administration of relatively small doses of these drugs can yield clinically effective neuromuscular blockade. The clinical characteristics of the block produced in A. S. A. class I-II patients during N2O-narcotic-thiopental anesthesia by the pancuronium-metocurine combination at the calculated ED95 (N = 8) and at twice the ED95 (N = 9) were compared with the block produced by pancuronium alone at its ED95 (N = 20) and at twice the ED95 (N = 6). Onset time (from drug injection to 95% twitch suppression) and the maximum twitch depression achieved were comparable between corresponding groups, but the 25% recovery time (from drug injection to 25% recovery of twitch height) was significantly shorter in the groups that received the pancuronium-metocurine combination. Furthermore, at twice the ED95, heart rate increased significantly more in the pancuronium group than in the pancuronium-metocurine combination group. Mean systemic blood pressure did not change significantly in either group. We conclude that patients given a combination of pancuronium and metocurine in large doses experience less hemodynamic change and more rapid recovery of neuromuscular function than do patients given equivalent doses of pancuronium alone.

Clinical characteristics of long-term succinylcholine neuromuscular blockade during balanced anesthesia

Thumb adductor twitch response to train-of-four (2 Hz for 2 seconds) stimulation of the ulnar nerve was used to assess the clinical characteristics of long-term neuromuscular blockade induced with continuous infusion of succinylcholine during balanced (N2O-O2-narcotic-thiopental) anesthesia. Twitch depression of 80 to 90% was maintained for 86 to 365 minutes by continuous infusion of succinylcholine at 86 ± 5(SEM) μg/kg/min. Of 32 patients, 24 developed phase II block, defined as a train-of-four ratio of less than 50%. There was a large degree of individual variability in sensitivity to development of phase II block. This precluded defining a narrow dose range where transition from phase I to phase II occurred. Tachyphylaxis occurred in 25% of patients and was independent of the type of block. Neither dose nor duration of infusion was predictive of spontaneous recovery rate from phase II block. Of 24 patients who developed phase II block, 50% recovered spontaneously at a rate comparable to the recovery rate from a phase I block. The other 50% manifested prolonged recovery of neuromuscular function. After observing spontaneous recovery in these patients for 31 ± 5(SEM) minutes, successful antagonism of residual phase II block with anticholinesterase agents was achieved.