Argatroban, bivalirudin, and lepirudin do not decrease clot propagation and strength as effectively as heparin-activated antithrombin in vitro.

BACKGROUND: Heparin-induced thrombocytopenia is a potentially limb- and life-threatening response to heparin exposure. Direct thrombin inhibitors (DTIs) have been reported to provide anti-coagulation for cardiopulmonary bypass; however, clot formation within the cardiopulmonary bypass circuit has been reported after the administration of DTIs. We present a case of thrombosis of the cardiopulmonary bypass circuit and, ultimately, death after argatroban administration. An in vitro thrombelastographic assessment of the effects of DTIs on clot kinetics was consequently performed to determine potential causes for this complication. METHODS: Normal human plasma was unmodified or exposed to heparin (1, 2, 3 U/ml), argatroban (5, 10, 50 microg/ml), bivalirudin (12, 20, 120 microg/ml), or lepirudin (3, 6, 10 microg/ml) before activation with tissue factor/kaolin in a thrombelastograph. Clot initiation (R, reaction time), propagation (MTG, maximum thrombus generation), and strength (MG, maximum elastic modulus) were determined. Analysis of variance was performed, with p < 0.05 considered significant. RESULTS: Compared with unmodified plasma, heparin significantly prolonged R and essentially reduced MTG and MG to the limits of detection in an activity-dependent fashion. In general, the DTIs tested prolonged R in a concentration-dependent fashion but did not diminish MTG or MG nearly as well as heparin. The only exception was 10 microg/ml lepirudin, which eliminated coagulation. CONCLUSIONS: DTIs demonstrated a significant prolongation of clot initiation but poor attenuation of propagation and strength. Further in vitro and clinical investigations to design a heparin-equivalent regimen to provide anti-coagulation for patients with heparin-induced thrombocytopenia are indicated.

Intraoperative solumedrol helps prevent postpneumonectomy pulmonary edema.

BACKGROUND: Postpneumonectomy pulmonary edema and pneumonia are life threatening and seemingly unavoidable complications after pneumonectomy. We theorized that an intraoperative dose of intravenous steroids (as a prophylactic measure to reduce pulmonary injury to the remaining lung) just before pulmonary artery ligation might decrease this problem. METHODS: Seventy-two patients (52 men) who had pneumonectomy during two time periods were studied prospectively. Thirty-five patients received 250 mg of methylprednisolone sodium succinate (Solumedrol; Upjohn, Kalamazoo, MI) just before pulmonary artery ligation (S group) and 37 did not (non-S group). Groups were matched for known or suspected preoperative, intraoperative, and postoperative risk factors for postpneumonectomy pulmonary edema. RESULTS: The incidence of postpneumonectomy pulmonary edema or adult respiratory distress syndrome was less in the S group (0 of 35, 0% versus 5 of 37, 13.5%, p = 0.049), the overall major complication rate was less in the S group (7 of 35, 20% versus 16 of 37, 43%, p = 0.04), and the length of hospital stay was shorter in the S group (6.1 days versus 11.9 days, p = 0.02). In addition, there were no bronchopleural fistulas in the S group compared with two (both right-sided) in the non-S group. CONCLUSIONS: The intraoperative intravenous administration of 250 mg of methylprednisolone sodium succinate just before pulmonary artery ligation during pneumonectomy may reduce the incidence of postpneumonectomy pulmonary edema and adult respiratory distress syndrome as well as decrease other major complications and shorten the hospital stay. It does not seem to increase the incidence of bronchopleural fistula. Further randomized trials are needed.

Nitric oxide: lifesaving measure for pulmonary vasospasm after modified Blalock-Taussig shunt.

Pulmonary vasospasm and hypertension may occur after repair or palliation of congenital cardiac defects, and can be fatal in spite of conventional treatment. Nitric oxide has been shown to improve pulmonary hypertension unresponsive to conventional measures after a variety of repairs, but use has infrequently been reported after palliative systemic to pulmonary artery shunts. We report a case of pulmonary hypertension and life threatening desaturation after a modified Blalock-Taussig shunt that responded rapidly to inhaled nitric oxide. Clinical use, further study, and prospective analysis of prophylactic use of nitric oxide appear warranted.

Glucose-insulin-potassium infusion for myocardial protection during off-pump coronary artery surgery.

BACKGROUND: The purpose of this randomized, double-blind, placebo-controlled pilot study was to determine the effectiveness of an intravenous glucose-insulin-potassium (GIK) infusion in preventing myocardial damage and maintaining cardiac performance in patients undergoing "off-pump" myocardial revascularization. METHODS: Forty-six adult patients undergoing elective off-pump coronary artery bypass received either normal saline or a GIK infusion immediately after the induction of anesthesia through the first 12 hours of intensive care unit convalescence. Measurements of blood glucose, circulating creatine kinase MB and troponin I concentrations, as well as cardiac index (CI) and mixed venous oxygen saturation (SvO2), were obtained immediately before starting the infusion (baseline) and at 6, 12, and 24 hours post-initial coronary artery occlusion. RESULTS: Five patients (8%) requiring cardiopulmonary bypass were excluded from data analysis. Twenty patients received saline. Twenty-one received GIK. Blood glucose was significantly higher in the GIK group. The concentration of circulating creatine kinase MB and troponin I significantly increased over time after off-pump coronary artery bypass, with no significant intergroup differences. Cardiac index and SvO2 did not differ significantly between groups. CONCLUSIONS: A GIK infusion protocol commonly used as an adjunct to reperfusion therapy for acute myocardial infarction causes insulin-resistant hyperglycemia in elective off-pump coronary artery bypass patients with no demonstrable benefit. The finding of significant release of cardio-specific enzymes in individual patients implies an ongoing need to develop more effective strategies for myocardial protection during off-pump coronary artery bypass.