Effects of trimetaphan-induced deliberate hypotension on human cochlear blood flow.

In order to observe the reaction of cochlear blood flow (CBF) to trimetaphan (TMP)-induced hypotension, CBF was measured with laser-Doppler flowmetry in 7 human subjects during general anaesthesia for middle ear surgery. All subjects showed a decrease in mean arterial pressure (MAP) during intravenous infusion of TMP, followed by a gradual return to the baseline level after termination of the infusion. The CBF generally followed the MAP changes with the same pattern. Three of the seven subjects demonstrated a CBF change larger than the maximum MAP change, indicating the lack of a local autoregulatory mechanism in CBF. On the other hand, CBF changes were smaller in magnitude than the maximum change in MAP for the rest of the subjects, suggesting an autoregulatory mechanism in CBF. However, since the audiograms from these subjects indicated profound damage along the cochlear basal turn probably due to middle ear inflammation, concomitant vascular damage in this region offers another possible explanation for the inappropriate CBF changes. The present observations may also suggest that deliberately TMP-induced hypotension has a potentially harmful effect on CBF during otological surgery that attempts to preserve or improve hearing.

Trimetaphan may cause coronary artery spasm.

We describe a patient in whom possible coronary artery spasm occurred during the infusion of trimetaphan. A 55-year-old man with a meningioma was scheduled for surgical excision of the tumour. He denied any previous history of chest pain. Anaesthesia was maintained with nitrous oxide (67%) in oxygen. The blood pressure before commencement of the surgery was 114/70 mmHg, and the pulse rate was 60 beats min-1. The blood pressure rose to 152/94 mmHg (the pulse rate to 62 beats min-1) during incision of the scalp, and intravenous infusion of trimetaphan was initiated. The blood pressure gradually decreased to 113/58 mmHg (the pulse rate 64 beats min-1) 10 min after start of this infusion, and premature ventricular contractions were evident on the electrocardiogram. Trimetaphan was withheld, and lignocaine was given intravenously. The premature ventricular contractions disappeared but ST segments were elevated. Glyceryl trinitrate was then infused intravenously. The ST segments remained elevated for 5 min, were depressed for 2 min and finally became isoelectric. There were no wide swings in blood pressure or pulse rate during the event. Post-operative laboratory examination revealed no evidence of myocardial infarction. Recovery of the patient was uneventful.

Isoflurane prevents EEG depression during trimetaphan-induced hypotension in man.

We have studied the EEG analysed with the cerebral function analysing monitor (CFAM) during trimetaphan (TMP)-induced hypotension to a mean arterial pressure (MAP) of 40 mm Hg in 20 normocapnic patients anaesthetized with either 1% end-tidal isoflurane or 0.5% halothane. During the acute reduction in MAP, the average reduction in mean EEG amplitude with halothane was 14%, two patients showing short periods of EEG suppression; the decline in EEG amplitude correlated with declining MAP in four patients. In contrast, the average reduction in mean EEG amplitude with isoflurane was only 0.3% and there were neither periods of suppression nor any correlation between EEG amplitude and MAP. No significant changes in EEG frequency occurred in either group. Isoflurane prevented EEG amplitude depression during TMP-induced hypotension.

[Effect of induced hypotension on damage to renal tubular cells].

Urinary excretion of renal tubular cell enzymes, N-acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyl transpeptidase (gamma-GTP) was evaluated to elucidate the renal cell damage before, during and after the induced hypotension with trimetaphan (TMP), nitroglycerin (TNG) and prostaglandin E1 (PGE1) under halothane-nitrous oxide-oxygen anesthesia in patients undergoing neurosurgery. Significant increases in excretion of NAG and gamma-GTP were observed in TNG group. Urinary excretion of these two enzymes in TMP group tended to increase, but its increases were not statistically significant. In PGE1 treated group, there was no tendency for urinary NAG excretion, while gamma-GTP excretion tended to decrease compared with that observed before the induced hypotension. Among these three drugs, TNG exerted the most significant effect on urinary excretion of both enzymes and TMP ranked next. Effect of PGE1 on urinary enzyme excretion was weakest. According to the general opinions, degree in stray of renal tubular cell enzyme into urine is thought to parallel with the injury of renal tubular cells. Therefore, the finding obtained in this study suggests that the induced hypotension with PGE1 has a less harmful effect on renal tubular cells.

The effect of trimethaphan-induced hypotension on canine spinal cord blood flow. Measurement at different cord levels using radiolabelled microspheres.

Controlled hypotension which is used during scoliosis surgery to improve operating conditions and minimize transfusion requirements may decrease spinal cord blood flow (SCBF). Previous studies using hydrogen washout, an invasive technique, have shown that trimethaphan-induced hypotension is associated with a decrease in SCBF, whereas hypotension induced with sodium nitroprusside or nitroglycerin is not. To determine whether the decrease seen with trimethaphan represented a generalized rather than regional spinal cord phenomenon, SCBF was measured at three separate cord levels (T2-3, 7-8, L2-3) using a noninvasive radionuclide-labelled microsphere technique. When the mean arterial pressure was reduced by 50%, SCBF decreased 35 to 45% at all levels of the cord examined, and remained at this reduced level during the period of hypotension. The results confirm that trimethaphan-induced hypotension is associated with a significant reduction in SCBF and that this occurs throughout the spinal cord during the period of hypotension.

Severe electrocardiographic abnormalities during arfonad administration.

Severe and reversible electrocardiographic abnormalities (first degree atrioventricular block, left bundle branch block, ventricular fibrillation), were induced by the administration of Arfonad in a patient with type III acute aortic dissection previously chronically treated with alpha-methyl-dopa. Any other possible cause of the electrocardiographic changes was excluded on the basis of clinical findings and laboratory studies. The explanation of the electrocardiographic abnormalities induced by Arfonad are not readily apparent, also on careful review of the literature. We suggest a strict electrocardiographic monitoring during Arfonad administration especially in patients with cardiac conduction defects and previous administration of cardiac cathecholamines depleting drugs.

Prolonged neuromuscular blockade following trimetaphan infusion. A case report and in vitro study of cholinesterase inhibition.

This is a case report with postoperatively prolonged neuromuscular blockade of 17 hours duration suspected to be caused by trimetaphan. Inhibitory action of trimetaphan to true cholinesterase (human red cell cholinesterase) was estimated in vitro, and it is concluded that this action is too weak to cause neuromuscular disturbances by acetylcholine excess in clinical doses. Trimetaphan is considered to have a neuromuscular blocking action of a non-depolarising type.

Respiratory paralysis during treatment of hypertension with trimethaphan camsylate.

Four cases are reported in which respiratory arrest occured coincident with the intravenous administration of large doses of trimethaphan camsylate (Arfonad) to control hypertension. The mechanism of the respiratory depression is unknown, but it may have been related to a direct effect of trimethaphan on the respiratory center or to a curare-like effect of the drug. Close monitoring of ventilatory capacity should be maintained in all patients treated with trimethaphan.