Faculty Bibliography

BACKGROUND AND PURPOSE: Cerebral injury after cardiac surgery is now recognized as a serious and costly healthcare problem mandating immediate attention. To effect solution, those subgroups of patients at greatest risk must be identified, thereby allowing efficient implementation of new clinical strategies. No such subgroup has been identified; however, patients undergoing intracardiac surgery are thought to be at high risk, but comprehensive data regarding specific risk, impact on cost, and discharge disposition are not available. METHODS: We prospectively studied 273 patients enrolled from 24 diverse US medical centers, who were undergoing intracardiac and coronary artery surgery. Patient data were collected using standardized methods and included clinical, historical, specialized testing, neurological outcome and autopsy data, and measures of resource utilization. Adverse outcomes were defined a priori and determined after database closure by a blinded independent panel. Stepwise logistic regression models were developed to estimate the relative risks associated with clinical history and intraoperative and postoperative events. RESULTS: Adverse cerebral outcomes occurred in 16% of patients (43/273), being nearly equally divided between type I outcomes (8.4%; 5 cerebral deaths, 16 nonfatal strokes, and 2 new TIAs) and type II outcomes (7.3%; 17 new intellectual deterioration persisting at hospital discharge and 3 newly diagnosed seizures). Associated resource utilization was significantly increased--prolonging median intensive care unit stay from 3 days (no adverse cerebral outcome) to 8 days (type I; P<0.001) and from 3 to 6 days (type II; P<0.001), and increasing hospitalization by 50% (type II, P=0.04) to 100% (type I, P<0.001). Furthermore, specialized care after hospital discharge was frequently necessary in those with type I outcomes, in that only 31% returned home compared with 85% of patients without cerebral complications (P<0.001). Significant risk factors for type I outcomes related primarily to embolic phenomena, including proximal aortic atherosclerosis, intracardiac thrombus, and intermittent clamping of the aorta during surgery. For type II outcomes, risk factors again included proximal aortic atherosclerosis, as well as a preoperative history of endocarditis, alcohol abuse, perioperative dysrhythmia or poorly controlled hypertension, and the development of a low-output state after cardiopulmonary bypass. CONCLUSIONS: These prospective multicenter findings demonstrate that patients undergoing intracardiac surgery combined with coronary revascularization are at formidable risk, in that 1 in 6 will develop cerebral complications that are frequently costly and devastating. Thus, new strategies for perioperative management--including technical and pharmacological interventions--are now mandated for this subgroup of cardiac surgery patients

THAM (trometamol; tris-hydroxymethyl aminomethane) is a biologically inert amino alcohol of low toxicity, which buffers carbon dioxide and acids in vitro and in vivo. At 37 degrees C, the pK (the pH at which the weak conjugate acid or base in the solution is 50% ionised) of THAM is 7.8, making it a more effective buffer than bicarbonate in the physiological range of blood pH. THAM is a proton acceptor with a stoichiometric equivalence of titrating 1 proton per molecule. In vivo, THAM supplements the buffering capacity of the blood bicarbonate system, accepting a proton, generating bicarbonate and decreasing the partial pressure of carbon dioxide in arterial blood (paCO2). It rapidly distributes through the extracellular space and slowly penetrates the intracellular space, except for erythrocytes and hepatocytes, and it is excreted by the kidney in its protonated form at a rate that slightly exceeds creatinine clearance. Unlike bicarbonate, which requires an open system for carbon dioxide elimination in order to exert its buffering effect, THAM is effective in a closed or semiclosed system, and maintains its buffering power in the presence of hypothermia. THAM rapidly restores pH and acid-base regulation in acidaemia caused by carbon dioxide retention or metabolic acid accumulation, which have the potential to impair organ function. Tissue irritation and venous thrombosis at the site of administration occurs with THAM base (pH 10.4) administered through a peripheral or umbilical vein: THAM acetate 0.3 mol/L (pH 8.6) is well tolerated, does not cause tissue or venous irritation and is the only formulation available in the US. In large doses, THAM may induce respiratory depression and hypoglycaemia, which will require ventilatory assistance and glucose administration. The initial loading dose of THAM acetate 0.3 mol/L in the treatment of acidaemia may be estimated as follows: THAM (ml of 0.3 mol/L solution) = lean body-weight (kg) x base deficit (mmol/L). The maximum daily dose is 15 mmol/kg for an adult (3.5L of a 0.3 mol/L solution in a 70kg patient). When disturbances result in severe hypercapnic or metabolic acidaemia, which overwhelms the capacity of normal pH homeostatic mechanisms (pH < or = 7.20), the use of THAM within a 'therapeutic window' is an effective therapy. It may restore the pH of the internal milieu, thus permitting the homeostatic mechanisms of acid-base regulation to assume their normal function. In the treatment of respiratory failure, THAM has been used in conjunction with hypothermia and controlled hypercapnia. Other indications are diabetic or renal acidosis, salicylate or barbiturate intoxication, and increased intracranial pressure associated with cerebral trauma. THAM is also used in cardioplegic solutions, during liver transplantation and for chemolysis of renal calculi. THAM administration must follow established guidelines, along with concurrent monitoring of acid-base status (blood gas analysis), ventilation, and plasma electrolytes and glucose

A sensitive high performance liquid chromatographic (HPLC) assay was developed to quantitate the organic amine proton-acceptor, tris(hydroxymethyl)aminomethane (THAM) in human plasma, erythrocytes, and whole blood. An aliquot of the sample was heat evaporated (200 degrees C for 2 h), derivatized, extracted, and then injected onto a symmetry Cs column. The UV absorbance of the effluent was monitored at 237 mn. 2-Amino-2-methyl-1,3-propanediol was found to be an appropriate internal standard. The method has been applied to quantitate the samples from patients undergoing orthotopic liver transplantation. The assay has also been employed to assess the in vitro time of THAM-uptake into the erythrocytes from blood samples incubated at 37 degrees C