Cefazolin kinetics was studied in 8 patients the day before (PREOP), during (SURG), and the day after (POSTOP) cardiopulmonary bypass (CPB) surgery. PREOP (48.6 ml/min) and POSTOP (46.6 ml/min) total body clearances were of the same order and both were greater than the SURG (27.4 ml/min) total body clearance. Since cefazolin is almost entirely eliminated by the kidney, the lower SURG clearance is a result of reduced renal elimination, as confirmed by measuring cefazolin SURG (28.7 ml/min) and POSTOP (52.9 ml/min) renal clearance. The reduction in cefazolin renal elimination was the same throughout the surgical procedure, including the period of extracorporeal circulation. Cefazolin distribution was altered by the operative procedure as evidence by a higher SURG steady-state volume of distribution. This increase in apparent cefazolin distribution volume brought about by surgery was not seen with cephalothin, which was investigated by us in a similar group of patients. The different effect of CPB surgery on cefazolin and cephalothin distribution may be due to differences in plasma protein binding.

Cephalothin kinetics was studied in 5 patients the day before (PREOP), during (SURG), and the day after (POSTOP) cardiopulmonary bypass surgery. The PREOP (114 ml/min) and SURG (94 ml/min) renal clearances were of the same order but both were less than POSTOP renal clearance (248 ml/min). Cephalothin total body clearance during operation was lower (p less than 0.01) than PREOP or POSTOP clearance, with decreased metabolic clearance the primary cause. There was reduction in cephalothin elimination throughout the surgical procedure, not only in the period of extracorporeal circulation, indicating that general anesthesia had a significant influence on drug disposition. The metabolite deacetylcephalothin was rapidly formed on all 3 days and its kinetic behavior paralleled that of the parent drug.

No abstract

We undertook a retrospective study of 36 victims of high-voltage electrical contact injuries to determine the incidence and possible source of elevated creatine kinase (CK)-MB enzyme in their serum. Only two sustained myocardial infarctions (one late) according to history, electrocardiographic findings, and clinical course. Serum lactate dehydrogenase isoenzyme levels were abnormal but revealed no myocardial infarction patterns. Creatine kinase total activity, however, reached 1.5 to 1,140 times normal in 92% and the CK-MB level was abnormal in 50% despite the low incidence of myocardial damage. Skeletal muscle CK and CK-MB levels in four nonelectrically injured patients were comparable to those in normal muscle while CK and CK-MB activity was elevated in six such electrical injuries. There was a gradient in CK-MB activity with greatest CK-MB activity in "normal" muscle near the injury site, lesser amounts in border tissue, and least in the worst-injured site. We conclude that myocardial injury is uncommon in high-voltage electrical injury and skeletal muscle injured by high electrical voltage is stimulated to produce, as well as release, CK-MB.