Pancuronium-phenytoin interaction: a case of decreased duration of neuromuscular blockade.

A 33-year-old female presented for elective excision of a posterior fossa tumour following two generalized seizures six months earlier. The patient had been asymptomatic on phenytoin 300 mg/day. Two h pre-operatively, a 300-mg dose of phenytoin was administered, general anesthesia induced and pancuronium bromide given to achieve neuro-muscular paralysis. Respiration was supported and anesthesia maintained with isoflurane and nitrous oxide in oxygen. Thirty min into the operation a further 2-mg dose of pancuronium bromide was administered. One h later, the patient coughed. A peripheral nerve stimulator was applied to the right common peroneal nerve with surface electrodes. Over the next 75 min a total of 15 mg of pancuronium bromide was required. With each dose there was a complete loss of response to peripheral nerve stimulation, followed by a rapid return of full train-of-four response, accompanied by coughing and cerebral engorgement. At this point, metocurine iodide was administered with full sustained paralysis for 45 min. Blood samples collected during a second operation indicated the patient had an extremely short pancuronium elimination half-life and a small volume of distribution. Several explanations are offered including phenytoin induction of hepatic microsomal enzymes responsible for the biotransformation of pancuronium, alterations in tissue or protein binding and/or alterations in myoneuronal junctional response.

Therapy-related leukemia and myelodysplasia in small-cell lung cancer. Report of a case and results of morphologic, cytogenetic, and bone marrow culture studies in long-term survivors.

The bone marrow of 11 patients with small-cell lung cancer, who survived more than two years following combined-modality therapy, was subjected to morphologic, cytogenetic, and bone marrow culture studies. One patient, after a prodrome of anemia and thrombocytopenia, developed acute leukemia 60 months after the start of chemotherapy. Four months before frank leukemia developed, bone marrow culture studies showed a marked inability to form colonies. Cytogenetic studies demonstrated an abnormal clone of cells that included the deletion of the long arm of chromosome 5. No morphologic abnormalities were noted in the bone marrow of any other long-term survivor; however, the mean corpuscular volume of peripheral red blood cells was greater than normal in three of four patients who remain alive and disease free. In one of these patients marrow culture studies also failed to grow colonies. The other patients showed a decreased ability to form multilineage colonies and colonies of the granulocyte-macrophage lineage in vitro compared with a control population. All patients showed some degree of aneuploidy on cytogenetic analysis; in two cases approximately 50% of cells were aneuploid. However, no clonal abnormality was detected in any patient. Follow-up for the development of secondary acute leukemia and other long-term complications continues in these patients.

Anaesthesia and amiodarone.

Two recent reports support and one report disputes the existence of dangerous interactions between the new benzofuran antiarrhythmic amiodarone and the anaesthetic state. We have reviewed our experience with 17 anaesthetics administered to 16 patients taking amiodarone. Haemodynamics and serum amiodarone levels were evaluated where available. Twelve cases involved cardio-pulmonary bypass; of these, three patients died. There were no deaths in the non-cardio-pulmonary bypass group. The charts of 30 patients with poor left ventricular function, who were not receiving amiodarone but who were undergoing coronary artery bypass surgery, were reviewed to establish a comparison group. Interactions were manifested in three forms: nodal rhythm and/or complete heart block developed in ten of 15 patients (one patient had a preoperative pacemaker inserted for the sick sinus syndrome), poor cardiac output requiring intra-aortic balloon pump augmentation developed in six of 12 cardio-pulmonary bypass patients, or, a state of alpha adrenergic blockade leading to a low systemic vascular resistance despite alpha agonist therapy developed in two of 16 patients. We conclude that dangerous, fatal interactions may occur in patients taking amiodarone who undergo general anaesthesia with cardio-pulmonary bypass. Anaesthesia for non-cardiac surgery may be associated with haemodynamically significant bradyarrhythmias. We recommend aggressive invasive monitoring, including pulmonary artery catheterization and consideration of an atrio-ventricular pacemaker in high risk patients.

Tuberous sclerosis with pulmonary involvement.

Pulmonary tuberous sclerosis produced interstitial disease in a woman with normal-sized lungs; numerous hemosiderin-laden macrophages were found in the fluid obtained through bronchoalveolar lavage. The pathological changes seen in the lungs were identical to those of pulmonary lymphangiomyomatosis, in which the constellation of clinical signs usually found in tuberous sclerosis is absent. The two conditions are sufficiently similar in clinical presentation, pathological changes and prognosis to be considered variants of the same disease. The recent findings of progestin receptors in lung tissue from patients with pulmonary lymphangiomyomatosis will likely direct future management towards hormonal manipulation.