Cefamandole pharmacokinetics during standard and pulsatile cardiopulmonary bypass.

The pharmacokinetics of cefamandole during standard or pulsatile cardiopulmonary bypass were studied in 13 adult cardiac surgery patients. All patients received 20 mg/kg of cefamandole intravenously at midnight before surgery, 6 AM on the morning of surgery and just prior to the initiation of cardiopulmonary bypass (CPB) surgery. Serum, skeletal muscle, and fat samples were taken at the beginning of CPB and at 30-minute intervals thereafter and assayed for cefamandole concentration. The average elimination rate constant and elimination half-life for cefamandole in patients undergoing standard CPB were 0.73 +/- 0.09 hour-1 and 0.94 +/- 0.11 hour, respectively. In contrast patients undergoing pulsatile CPB had significantly slower elimination rate constants (0.50 +/- 0.1 hour-1 and 1.4 +/- 0.28 hours, respectively; P less than or equal to .05). Area under the curve (AUC) values for cefamandole in fat and muscle tissue were higher in patients undergoing pulsatile CPB, but the differences were not statistically significant. Prolonged elimination from the serum, skeletal muscle, and adipose tissue, as compared with normal subjects, is seen with both pulsatile and standard CPB but is greater for the pulsatile method. Intraoperative dosing of cefamandole is required to maintain adequate serum and tissue levels for operations lasting longer than 4 or 6 hours in which standard or pulsatile CPB, respectively, are used.

Use of nitroprusside for control of pulmonary hypertension in repair of ventricular septal defect.

After repair of ventricular septal defect (VSD) in a 3-year-old child with markedly elevated pulmonary vascular resistance (PVR), sodium nitroprusside was administered by intravenous infusion at 3.0 microgram per kilogram of body weight per minute. Nitroprusside was effective in reducing pulmonary artery pressure and increasing systemic blood pressure in the intraoperative and early post-operative periods. It is suggested that nitroprusside may facilitate the perioperative management and enhance the early survival in patients with increased PVR secondary to a VSD.

An improved technique for coronary vascular anastomosis.

A vein holder is described that is used for anastomosis of both ends of aortocoronary bypass grafts. It minimizes handling of the graft, ensures precision in placing sutures with excellent visualization, and provides maximum patency at the anastomotic sites.

Transverse femoral arteriotomy for intraaortic balloon insertion.

A technique for intraaortic balloon placement employing a transverse femoral arteriotomy is described. After balloon removal, the arteriotomy can be closed primarily. Avoidance of retained graft material or use of a vein patch reduces the likelihood of vascular complications.

Warfarin dosage following prosthetic valve replacement: effect of smoking history.

Warfarin currently is the most widely used agent in the prevention of thrombosis and embolism after prosthetic cardiac valve replacement. Since smoking has been shown to increase the requirement for medications undergoing hepatic metabolism, this study was designed to determine if a correlation exists between smoking history and warfarin daily maintenance dose (DMD) in patients undergoing cardiac valve replacement. Of 200 charts retrospectively reviewed at the New England Medical Center, 174 satisfied the criteria for inclusion in the study (normal hepatic, renal, and hematologic function, and absence of complicating medications). The study population included aortic, mitral, and combined valve replacement. Study groups consisted of 117 nonsmokers (Group A), 23 light smokers (Group B), and 34 heavy smokers (Group C). Thirty-three percent of patients required a low DMD of warfarin (less than or equal to 2.5 mg), 43 percent required a moderate DMD (greater than 2.5-7.5 mg), and 24 percent required a high DMD (greater than 7.5 mg). Each of the subgroups followed a similar pattern. In Group A, there were 31 percent low, 44 percent moderate, and 25 percent high-dose requiring patients. In Group B, there were 48 percent low, 39 percent moderate, and 13 percent high-dose requiring patients and in Group C there were 29.5 percent low, 41 percent moderate, and 29.5 percent high-dose requiring patients. Chi-square analysis did not demonstrate any statistically significant difference between smokers and nonsmokers in regard to daily maintenance warfarin dose (p = 0.5). The study population followed a normal pattern of distribution in regard to warfarin dosage. On the basis of these data we conclude that smoking history does not affect warfarin dose requirement.

Warfarin induced necrosis of the skin.

Necrosis of the skin is a rare complication of oral anticoagulation therapy by coumarin congeners. Three males receiving prophylactic warfarin anticoagulation therapy following cardiac valve replacement and one female similarly receiving anticoagulation drugs because of bilateral deep thrombophlebitis associated with carcinoma of the pancreas had typical skin necrosis develop. The lesions passed rapidly through stages beginning with pain, edema, erythema and petechiae. Ecchymoses followed in the localized area with a large bullae containing deep red fluid. Biopsy of the skin revealed involvement of the dermovascular loops with localized necrosis from extensive occlusion of dermal capillaries and venulae by fibrin thrombi. There was red cell extravasation, but inflammatory changes were inconstant. In the patients, in our study, the involvement ranged from small localized lesions of the trunk to extreme extensive skin involvement of both legs with full thickness necrosis in areas. This condition is not dose related nor the result of simple hypoprothrombinemia. It appears to be a conditioned and localized toxicity, although hypersensitivity has not been excluded. Once the diagnosis is made, orally administered anticoagulant drugs must be stopped immediately, and heparinization may be beneficial in confining the process.