S. Estanove

Inhaled Nitric Oxide after Mitral Valve Replacement in Patients with Chronic Pulmonary Artery Hypertension

Patients with mitral valve disease can develop pulmonary artery hypertension that persists after mitral valve replacement. In 1987, nitric oxide (NO) was reported to be an important factor accounting for the biologic activity of endothelium-derived relaxing factor. Inhaled NO was subsequently reported to be a selective pulmonary vasodilator in animals and patients. Therefore we investigated the vasodilating effect of inhaled NO in patients with mild pulmonary artery hypertension after mitral valve replacement. Six patients who underwent mitral valve replacement for mitral stenosis presented with a mean pulmonary artery pressure greater than 25 mmHg within 24 h after surgery. During mechanical ventilation at FIO2 0.5, NO (36.8-38.4 ppm) was breathed for 10 min. Hemodynamic data were recorded before NO, after 10 min of NO inhalation, and 30 min after the end of NO inhalation. Statistically significant (P < 0.05) hemodynamic response to inhaled NO included a transient decrease in systolic (-10%), diastolic (-8%), and mean (-10%) pulmonary artery pressures; a decrease in pulmonary vascular resistance (-22%); an increase in mixed venous hemoglobin O2 saturation (+6%); and a decrease in arteriovenous O2 content difference (-7%). During NO inhalation, there was no change in systemic arterial or pulmonary wedge pressures. Methemoglobin levels remained < 1%. Inhalation of this concentration of NO for 10 min causes transient pulmonary artery vasodilation and hemodynamic improvement in patients with mild chronic pulmonary artery hypertension after mitral valve replacement.

Hemodynamic and hormonal responses to hypothermic and normothermic cardiopulmonary bypass

Normothermic cardiopulmonary bypass (CPB) is used in cardiac surgery at some institutions. To compare hemodynamic and hormonal responses to hypothermic (29 degrees C) and normothermic nonpulsatile CPB, 20 adults undergoing coronary artery bypass graft and/or aortic valve replacement were studied. Hemodynamic measurements and plasma hormone concentrations were obtained from preinduction to the third postoperative hour. The two groups were given similar amounts of anesthetics and vasodilators. Systemic vascular resistance increased only during hypothermic CPB, and heart rate was higher at the end of hypothermic CPB. Postoperative central venous pressure and pulmonary capillary wedge pressure were lower after hypothermic CPB. Oxygen consumption decreased by 45% during hypothermic CPB, did not change during normothermic CPB, but increased similarly in the two groups after surgery; mixed venous oxygen saturation (SvO2) was significantly lower during normothermic CPB. Urine output and composition were similar in the two groups. In both groups, plasma epinephrine, norepinephrine, renin activity, and arginine vasopressin concentrations increased during and after CPB. However, epinephrine, norepinephrine, and dopamine were 200%, 202%, and 165% higher during normothermic CPB than during hypothermic CPB, respectively. Dopamine and prolactin increased significantly during normothermic but not hypothermic CPB. Atrial natriuretic peptide increased at the end of CPB and total thyroxine decreased during and after CPB, with no difference between groups. This study suggests that higher systemic vascular resistance during hypothermic CPB is not caused by hormonal changes, but might be caused by other factors such as greater blood viscosity. A higher perfusion index during normothermic CPB might have allowed higher SvO2.

Glucose and insulin supply before cardiopulmonary bypass in cardiac surgery: A double-blind study

A double-blind study versus placebo was carried out to evaluate the effects of a 500-mL infusion of 30% glucose containing 300 units of ordinary insulin and 5 g of potassium chloride administered at a rate of 1.66 mL.kg-1.h-1 for 1 hour before cardiopulmonary bypass. The hemodynamic parameters measured before and after administration of the solution, after cardiopulmonary bypass, after administration of protamine, and 3 hours after leaving the operating room showed the beneficial effect of the glucose-insulin-potassium infusion on cardiac index (+23.6% after protamine infusion) and left (+16.3% 3 hours postoperatively) and right (+47.3% after cardiopulmonary bypass) ventricular workload index with a decrease in systemic vascular resistance. For patients with a cardiac index of less than 2.5 L.min-1.m-2 before administration of the glucose-insulin-potassium solution, the beneficial effect on the cardiac index was further increased 3 hours postoperatively (+33%). During the postoperative period, the requirements in inotropic drugs and disturbances of rhythm were not significantly different between the two groups, although they were twofold lower in patients receiving glucose-insulin-potassium. Laboratory tests showed that postoperative hypoglycemia was more common in the glucose-insulin-potassium group but had no detrimental effects; it no longer occurs since we began administering the glucose infusion at 15 g/h over 8 hours. The data reflect the beneficial effect associated with the action of glucose-insulin-potassium on myocardial protection during heart operations and were confirmed by the hemodynamic results. This argues in favor of the routine use of this technique, especially in patients with poor ventricular function.

Reduction in blood loss and blood use after cardiopulmonary bypass with high-dose aprotinin versus autologous fresh whole blood transfusion

Ninety patients undergoing cardiac surgery were randomly divided into three groups of 30 patients to compare the effects on bleeding and transfusion requirements of either intraoperative infusion of high-dose aprotinin (GpI) or reinfusion of autologous fresh whole blood (GpII) versus a control group (GpIII). Standardized anesthetic, perfusion, and surgical techniques were used. Platelet counts, hemoglobin concentration, hematocrit, fibrinogen, and Ivy-Nelson bleeding times determined at fixed times perioperatively did not differ among the three groups. The total loss from the chest drains was significantly reduced in GpI (328 +/- 28 mL; mean +/- SEM) as compared with the loss in GpII and GpIII (775 +/- 75 mL and 834 +/- 68 mL, respectively). There was a threefold difference in the total hemoglobin loss (GpI, 14.2 +/- 1.7 g; GpII, 50.1 +/- 5.0 g; GpIII, 45.0 +/- 5.2 g). GpI patients also received less banked blood: 250 +/- 53 mL versus 507 +/- 95 mL in GpII and 557 +/- 75 mL in GpIII. No GpI patient required transfusion of platelets or fresh frozen plasma. Fresh whole autologous blood transfusions had no significant hemostatic effect and failed to reduce the homologous blood requirement. Conversely, high-dose aprotinin reduced blood loss and transfusion requirements.

Cefazolin and netilmicin serum levels during and after cardiac surgery with cardiopulmonary bypass.

The kinetics of cefazolin and netilmicin were studied in 10 patients undergoing elective cardiac surgery with hemodilution and cardiopulmonary bypass (CPB). During surgery, but before CPB, cefazolin, 25 mg/kg, and netilmicin, 2 mg/kg, were administered intravenously over 30 minutes. For the 48-hour period following CPB, cefazolin, 25 mg/kg, and netilmicin, 1 mg/kg, were administered intravenously every 8 hours. Initiation of CPB was accompanied by a 28% to 30% decrease in hematocrit and serum antibiotic levels. At the conclusion of surgery, cefazolin and netilmicin serum levels were 41 +/- 12 micrograms/L and 2.5 +/- 0.6 micrograms/mL (mean +/- SD), respectively. During the postoperative period, cefazolin levels were consistently greater than the minimum inhibitory concentration (MIC) for sensitive bacteria (4 micrograms/mL); average netilmicin levels were greater than MIC of sensitive bacteria (2 micrograms/mL) for 2 hours after antibiotic infusion. The netilmicin trough levels were 0.6 +/- 0.5 micrograms/mL. Pharmacokinetic parameters were determined using a model-independent method, and gave the following results during surgery: cefazolin--elimination half-life, 231 minutes, total body clearance, 1.05 mL/kg/min, and steady-state volume of distribution, 243 mL/kg. The values for netilmicin were 249 minutes, 1.18 mL/kg/min, and 353 mL/kg, respectively. Postoperatively there were no significant changes in the disposition of cefazolin, but the elimination half-life of netilmicin was shorter (124 minutes, P less than 0.01) and the total body clearance greater (3.58 mL/kg/min, P less than 0.01) than during surgery.

Relationship between preoperative amiodarone treatment and complications observed during anaesthesia for valvular cardiac surgery

Two groups of ASA physical status class III and IV patients undergoing cardiac surgery were reviewed in an attempt to obtain more conclusive data concerning dangerous interactions between amiodarone and anaesthesia. The amiodarone group (Group 1, ten patients, cumulative dose 10 g) was compared with a control group (nine patients, Group 2). Amiodarone (A) and desethylamiodarone (NA) concentrations in plasma and myocardium were measured and haemodynamic and antiarrhythmic effects were analysed. Throughout anaesthesia haemodynamic status was similar in both groups. No correlation was found between A/NA and cardiac index changes. No patients needed intraaortic blood pressure augmentation or developed low systemic vascular resistances. Pacemaker dependency was similar in both groups and there was no evidence of increased anaesthetic risk. An excellent antiarrhythmic effect was obtained during the postoperative period. We conclude that preoperative treatment with amiodarone is effective against postoperative arrhythmias.RésuméDans le but d’éclaircir l’interaction dangereuse décrite entre l’amiodarone et l’anesthésie générate, nous avons comparé deux groupes de patients ASA III ou IV subissant une intervention à coeur ouvert soit un groupe amiodarone (Groupe 1: dix patients, dose cumulative 10 g) et un groupe contrôle (Groupe 2: neuf patients). Nous avons mesuré les concentrations myocardiques et plasmatiques d’amiodarone et de déséthylamiodarone ainsi que leurs effets antiarythmiques et hémodynamiques. Les profils hémodynamiques des deux groupes étaient comparables sauf pour une plus faible augmentation de l’index cardiaque dans le Groupe I. Nous n’avons pas trouvé de corrélation entre A,NA et les variations d’index cardiaque. Aucun patient n’a eu besoin de contrepulsion aortique ou n’a présente de résistances vasculaires périphériques trop basses. L’usage de pacemaker etait comparable dans les deux groupes et l’amiodarone n’a pas augmenté le risque anesthésique. L’effet antiarythmique obtenu pendant la période postopératoire était excellent. Nous concluons done que l’amiodarone en préopératoire prévient efficacement les arythmies postopératoires.

Oxacillin and tobramycin serum levels during cardiopulmonary bypass

Antibiotic prophylaxis in cardiac surgery is recommended to combat acquired infections caused by staphylococci and gram-negative bacilli. Prophylaxis seems effective provided blood levels are greater than minimal inhibitory concentrations (MIC). In this study, two doses of antibiotics were compared in 45 patients with normal renal function during cardiopulmonary bypass (CPB). All patients received 50 mg/kg of oxacillin. Group 1 (30 patients) also received 1 mg/kg of tobramycin, while group 2 (15 patients) received 2 mg/kg of tobramycin. Blood samples were taken after the administration of antibiotics, as well as at the onset and conclusion of CPB. Additional samples were taken before and after heparin injection before CPB, and from the arterial and venous cannulae of the bubble oxygenator during CPB. In both groups, oxacillin serum levels were constantly greater than MIC for susceptible bacteria. In group 1, tobramycin levels less than 2 micrograms/mL (MIC for most susceptible bacteria) occurred in four patients before CPB, in 14 patients at the onset of CPB, and in 19 patients at the conclusion of CPB. These low levels were not explained by heparin administration or absorption onto the CPB circuit, but were the result of hemodilution. In group 2, in which all the tobramycin levels were higher than 2 micrograms/mL, serum levels decreased from 9.9 +/- 3.4 (mean +/- SD) to 3.7 +/- 0.7 micrograms/mL throughout the procedure. Plasma creatinine did not change significantly in either group. It is concluded that in patients with normal renal function, doses as high as 50 mg/kg of oxacillin and 2 mg/kg of tobramycin may be necessary before CPB to provide adequate serum levels throughout CPB.

Should We Inhibit Gastric Acid Secretion Before Cardiac Surgery

Stress can decrease intragastric pH and cause erosion of gastric mucosa. Because cardiac surgery and cardiopulmonary bypass represent a major stress, the effects on intragastric pH of an H2-receptor antagonist, ranitidine, and an M1-muscarinic antagonist, pirenzepine, were evaluated. Intragastric pH was measured throughout elective cardiac surgery in 60 patients by a digital pH-meter during fentanyl-diazepam-nitrous oxide (50%) anesthesia. The gastric content was sampled at closure of the chest for bacterial count. Oral preoperative medication given randomly included (n = 20 in each group) 0.3 mg/kg diazepam 1 h before induction (group 1); diazepam plus ranitidine (150 mg) 1 h before induction (group 2); and diazepam plus pirenzepine (50 mg) on the evening before surgery and 1 h before induction of anesthesia (group 3).At induction intragastric pH was higher in group 2 (mean ± SD = 7.42 ± 1.07) than in group 1 (5.28 ± 2.14) (P < 0.01) but was not significantly different in group 3 (5.78 ± 1.89) than in group 1. In no group did intragastric pH change significantly during surgery. Gastric juice was sterile in 92% of group 1, in 25% of group 2, and in 71% of group 3 patients (P < 0.01). Postoperatively no gastrointestinal complications occurred, but there was a trend toward more patients developing nosocomial pneumonias in groups 2 and 3 (15%) than in group 1 (0%) (P = 0.06). Intraoperative intragastric pH is relatively high after diazepam premedication, thus the preoperative addition of ranitidine or pirenzepine would not be necessary and may possibly be hazardous.

Comparison of the pharmacokinetics of methohexital during cardiac surgery with cardiopulmonary bypass and vascular surgery

The aim of this study was to assess the pharmacokinetics of methohexital (ME) in major vascular surgery (VASC) and to compare these data with the pharmacokinetics of ME during hypothermic cardiopulmonary bypass (HCPB) (temperature: 28 degrees C) and normothermic cardiopulmonary bypass (NCPB) (temperature: 37 degrees C). An ME bolus (2 mg/kg) was administered to 8 VASC patients at the start of surgery and to 11 HCPB patients and 11 NCPB patients at the start of cardiopulmonary bypass (CPB). Twenty-one arterial blood samples were withdrawn over the following 24 hours for ME assays. All of the patients were given similar anesthesia (fentanyl, diazepam) and muscle relaxation (pancuronium). In the VASC group, ME total body clearance (TBC) was 6 +/- 2 mL/kg/min (mean +/- SD), which is less than in previous studies. When comparing HCPB and NCPB groups, elimination half-life (T1/2), TBC, volume of distribution (VD), area under the curve (AUC), and mean residence time (MRT) were similar. When comparing VASC and CPB patients, TBC and VD were greater in CPB patients than in VASC patients; thus, T1/2 (equal to 0.693 x VD/TBC) was similar. AUC was smaller in CPB patients because of hemodilution, but MRT was similar. It is concluded that ME clearance is lower in patients undergoing major vascular surgery than in healthy patients. The temperature and the duration of CPB do not seem to substantially influence the pharmacokinetics of ME when a bolus is administered. Parameters such as AUC, TBC, and VD appear modified by hemodilution during CPB; however, T1/2 and MRT, which allow comparisons between CPB and non-CPB patients, were similar in these patients.

Effets vasculaires de la kétamine en présence d'une anesthésie par diazépam et fentanyl

Twenty-six adults undergoing elective cardiac surgery were anaesthetized with diazepam and fentanyl (induction with 200 μg · kg−1 and 30 μg · kg−1 respectively, maintenance with incremental doses). Normothermic constant perfusion output cardiopulmonary bypass was carried out with a membrane oxygenator, haemodilution with Ringers lactate solution, and cardioplegia with St. Thomass Hospital solution. The patients were randomly assigned to two groups. They were given either 2 mg · kg−1 of ketamine (group 1) or placebo (5 ml of normal saline) (group 2) via the venous line of the oxygenator. The non pulsatile flow was then kept at a steady rate of 2.41 · min−1 · m−2, and no other infusion or treatment was started during the study period (ten minutes). The mean arterial pressure and blood reservoir level were measured every min during this period. The systemic vascular resistances did not change significantly in either group, but remained 27 % lower in the ketamine group than in the placebo group (p < 0.01). The blood reservoir level was 37 % higher in the ketamine group (p < 0.01), suggesting a decreased venous capacitance. It is therefore concluded that ketamine leads to venous constriction, and probably arterial dilation, during fentanyl-diazepam anaesthesia and normothermic cardiopulmonary bypass. The venous effects of ketamine could explain why it is usually well tolerated in hypovolaemic states.