[Inhaled nitric oxide: therapeutic applications in cardiac surgery]. / Le monoxyde d'azote inhalé: applications thérapeutiques en chirurgie cardiaque.

The occurrence of right ventricular failure secondary to pulmonary arterial hypertension is a major postoperative complication of cardiac surgery in children and adults. The selective pulmonary vasodilation produced by inhaled nitric oxide (NO) constitutes a fundamental therapeutic advance in the management of this pathology. NO binds immediately with haemoglobin, resulting in its immediate inactivation. This results in perfect maintenance of systemic and coronary blood pressures. A first study performed in 1989 after mitral valve replacement for mitral stenosis with pulmonary hypertension and clinical trials after surgical correction for congenital heart disease and heart transplantation with pulmonary hypertension suggested the efficacy and safety of 20 to 40 ppm NO concentrations in these indications. Potential toxicity of NO (NO2 production by oxidation, methaemoglobin formation) leads to caution with its use. Monitoring of NO concentration and methaemoglobin production is recommended, especially in new-borns.

[Inhaled nitric oxide in anesthesia and intensive care]. / Monoxyde d'azote inhalé en anesthésie-réanimation.

The role of endothelium in vascular relaxation is linked to the existence of endothelium derived relaxing factors (EDRF) known since 1980. In 1987, nitric oxide (NO) was identified as one of these factors. NO acts in many physiologic and pathophysiologic events. Atmospheric NO is a pollutant. Inhaled NO allows selective pulmonary vasodilation and is used to treat pulmonary artery hypertension (PAH). As inhaled NO is inactivated immediately in the blood by linking to haemoglobin, systemic vasodilation does not occur and right ventricular coronary perfusion pressure does not decrease. This is particularly important in the treatment of right ventricular failure due to PAH following cardiothoracic surgery. In patients with an acute respiratory distress syndrome (ARDS), inhaled NO improves the perfusion of adequately ventilated pulmonary territories. Very low concentrations of NO, such as two parts per million, decrease intrapulmonary venous admixture and may reverse hypoxaemia. However its long term benefits in ARDS must be assessed more accurately with multicentre controlled studies. Inhaled NO also improves refractory hypoxaemia in neonates. Its bronchodilatory effect, demonstrated experimentally, does not occur in acute obstructive bronchopulmonatory disease. The toxicity of NO, and overall of its oxidated derivative NO2 requires precise conditions of administration and close monitoring of inhaled fractions. In that case, the risk of NO toxicity seems very low when compared to its therapeutic benefits in selected patients.

Transesophageal echocardiographic assessment of left ventricular function in brain-dead patients: are marginally acceptable hearts suitable for transplantation?

BACKGROUND: The brain-dead donor supply has become one of the criteria limiting the performance of heart transplantation. Conventional screening criteria are too limiting and exclude suitable heart donors. Echocardiography is now widely available and is a reliable tool to assess left ventricular dysfunction in brain-dead donors. Yet few data are available on the degree of left ventricular dysfunction where a transplantation is possible. METHODS: Fifty-five potential brain-dead heart donors (age 38 +/- 11 years) were prospectively evaluated by transesophageal echocardiography (TEE) before harvesting. Fractional area change (FAC) was used to assess left ventricular function in potential brain-dead donors. Transplanted hearts were evaluated on the fifth postoperative day. The transplantation was considered a success if the recipient was alive, not retransplanted, without an assistance device or an epinephrine infusion of more than 1 mg/h and showed an ejection fraction above 40%. RESULTS: Of the 55 potential heart donors, 20 exhibited an FAC of less than 50%. Forty hearts were harvested, 36 of which were successfully transplanted. Nine patients had an FAC below 50% (group H2) and 27 had an FAC over 50% (group H1). Four patients died: 2 from hemorrhage (FAC > 50% in donors); 1 from right and one from left ventricular dysfunction (FAC < 50% in donors). The FAC increased significantly from 51 +/- 15% to 57 +/- 11% in 18 hearts that underwent TEE in donors and afterwards in recipients. Overall actuarial survival was 86.2% versus 64.6% at 1 and 2 years in group H1 and group H2, respectively (p = NS). CONCLUSIONS: TEE is useful to assess left ventricular function in potential brain-dead donors. An FAC less than 50% is present in 36% of potential heart donors. Because left ventricular dysfunction is often reversible shortly after transplantation, an FAC below 50% may not necessarily preclude the use of hearts for transplantation.

Relationship between oxygen uptake and mixed venous oxygen saturation in the immediate postoperative period.

BACKGROUND: During muscular exercise, a negative correlation has been demonstrated between the value of mixed venous oxygen saturation (SvO2) and the level of muscular work, expressed at each level as the ratio of oxygen uptake (VO2) to each subject's maximal oxygen uptake (VO2max). Because the immediate postoperative period is associated with an increase in whole body oxygen demand, and in this regard resembles the effects of muscular exercise, a similar correlation may exist during this period. METHODS: VO2max was determined in 11 patients 3-5 days before coronary artery bypass surgery. During the first 2 postoperative h, VO2 and SvO2 were monitored. VO2 was measured by indirect calorimetry and SvO2 by a fiberoptic pulmonary arterial catheter. RESULTS: The highest postoperative value of VO2 was most often associated with visible shivering and ranged among patients from 19% to 53% of preoperatively measured VO2max. There was a highly significant negative correlation between SvO2 and the ratio VO2/VO2max. This correlation was observed when data were examined collectively (136 simultaneous determinations of the two variables) and at the individual level (10-18 determinations for each patient). The slopes and the y intercepts of individual lines of correlation were within a narrow range. CONCLUSIONS: During the first 2 postoperative h after coronary artery bypass surgery, VO2 rarely exceeds 50% of preoperative VO2max. Assuming a stable state of myocardial function, SvO2 measurement may provide an indirect means of assessment of the "exercise test" imposed on patients recovering from general anesthesia.

[Traumatic rupture of the isthmic aorta: analysis of 22 recent cases]. / Ruptures traumatiques de l'isthme de l'aorte: analyse de 22 cas récents.

This study is an analysis of the cases of acute traumatic rupture of the aorta treated in our hospital between 1987 and 1993. Recent progress concern especially the role of computed tomography and transoesophageal echocardiography in the diagnosis and the confirmation of the benefit of mechanical circulatory support in the treatment. Immediate surgery in all the cases is not yet the rule. Delayed surgical repair can be feasible in cases of severe and multiple associated lesions.

[Antibiotic prophylaxis in heart surgery]. / Antibioprophylaxie en chirurgie cardiaque.

Cardiac surgery enters mainly into the class I of Altemeier ("clean surgery"). However, many factors may explain an intraoperative contamination: surgery of long duration, extra-corporeal circulation, aspiration of blood and air, immunodepression...). In fact, the infectious risk decreases from about 25% with placebo to 5% with prophylactic antibiotics. The staphylococcal infections are the most frequent (mediastinitis, endocarditis, parietal infections...). Cephalosporins, particularly of second-generation type (cefamandole, cefuroxime), perform better than antistaphylococcal penicillins. The combination with an amino-side may be used when Gram negative bacilli infection prevalence is high. Vancomycin is efficient but hypotension and renal impairment have been reported. Therefore, vancomycin is used in patients allergic to cephalosporins, when a high prevalence of methicillin-resistant Staphylococcus or enterococci infections is reported, or when the patient has recently received broad-spectrum antimicrobial therapy. The antibiotic doses must take into account the haemodilution due to extracorporeal circulation and the necessity to obtain sufficient serum concentrations throughout surgery. A prophylaxis of more than 48 hours is not associated with an improved outcome. In cardiac transplantation a prophylaxis is essential, but is still questioned during the insertion of pace-markers. In any case, the antibiotic prophylaxis must take into account the bacterial prevalence of each institution.

Clinical use of ganciclovir during renal failure and continuous hemodialysis.

OBJECTIVE: Data is scarce concerning ganciclovir, used in CMV-related diseases in transplant patient with renal failure, especially when dialysis is necessary. DESIGN: Prospective trial. SETTING: Intensive care unit in a university hospital, and pharmacy laboratory. PATIENTS: pharmacokinetics were obtained in 3 patients undergoing continuous veno-venous hemodialysis (CVVHD) (PAN 69). INTERVENTIONS: HPLC measurements of plasmatic and ultrafiltrated ganciclovir were determined at 17 times intervals after a 5 mg/kg every 48 h dosage. RESULTS: Peak and trough concentrations were respectively 16.1 +/- 2.4 and 5.5 +/- 0.5 mg/l, sieving coefficient 0.75-0.95, and volume of distribution at steady state 0.64 +/- 0.09 l/kg, half life (beta phase) 18.6 +/- 1.8 h. No direct toxicity, or CMV-related death occurred. CONCLUSION: Plasma concentrations were higher than the ID 90. A dosage of 5 mg/kg/48 h of ganciclovir could be used during CVVHD, and ideally adjusted to monitoring of plasma drug levels.

Enoximone and acute left ventricular failure during weaning from mechanical ventilation after cardiac surgery.

OBJECTIVE: To evaluate enoximone, a phosphodiesterase III inhibitor, in the treatment of left ventricular failure during the weaning of patients from mechanical ventilation after heart surgery. DESIGN: Open label, prospective, weaning trial. SETTING: Cardiothoracic surgical intensive care unit (ICU) in a university hospital. PATIENTS: Nine patients were studied after one or more unsuccessful attempts at weaning from mechanical ventilation due to left ventricular dysfunction. INTERVENTION: For each patient, two respiratory weaning attempts were studied: the first one as a control and the second one with enoximone infused at a rate of 30 micrograms/kg/min for 30 mins, then at a rate of 10 micrograms/kg/min. MEASUREMENTS AND MAIN RESULTS: Hemodynamic measurements were performed at the following interval times: baseline during mechanical ventilation; during spontaneous ventilation with a T-piece for a minimum of 10 mins; during mechanical ventilation after the enoximone infusion for 30 mins; during spontaneous ventilation for a minimum of 10 mins with an enoximone infusion running. During spontaneous ventilation, enoximone increased cardiac index by 34% but mean artery, right atrial, and pulmonary artery occlusion pressures did not change. Despite an increase in venous admixture due to augmented cardiac index and inhibition of hypoxic vasoconstriction, no oxygen debt occurred because oxygen delivery increased. Seven of nine patients were weaned successfully from mechanical ventilation. CONCLUSION: Because of its positive inotropic and vasodilatory properties, enoximone is helpful for respiratory weaning of patients with left ventricular failure after cardiac surgery.

Immunization by bovine thrombin used with fibrin glue during cardiovascular operations. Development of thrombin and factor V inhibitors.

Brief case histories of three patients aged 58, 38, and 44 years are reported. All underwent cardiovascular operations. Subsequently hemostasis test abnormalities developed between the seventh and eighth postoperative days after exposure to bovine thrombin used with fibrin glue. These were characterized by an increased activated partial thromboplastin time (64 to 147 seconds), prothrombin time (19 to 24 seconds), bovine thrombin time (> 120 seconds) and a markedly reduced factor V level (< 10% in two patients and 16% in the third patient). A patient plasma dilution of 1 in 200 with a normal plasma pool was necessary to correct bovine thrombin time. No fast-acting or progressive inhibitor against factor V could be detected by coagulation tests, and fresh frozen plasma perfusion had no effect. Plasmapheresis was performed preventatively to avoid bleeding, and factor V levels stabilized at around 50% after two to four exchanges. Immunologic studies showed that the inhibitors were directed not only against bovine factors but also against human ones. Therefore factor V decrease could have been the result of rapid clearance from the circulation of complexes formed with a nonneutralizing inhibitor that is not detected by clotting tests. These antibodies were purified by standard methods and immunoaffinity. Fast immunization could be explained by a prior sensitization to bovine thrombin exposure during previous operations. It is suggested that bovine thrombin used with fibrin glue contains small amounts of factor V and may be responsible for these abnormalities. This is in agreement with previous literature reports. However, these described neutralizing factor V inhibitors, which were easily detected.

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.

[Plasma concentrations of diltiazem and its metabolites in coronary surgery: relation with preoperative treatment]. / Concentrations plasmatiques du diltiazem et de ses métabolites en chirugie coronarienne: relation avec le traitement préopératoire.

Preoperative oral administration of calcium channel blocking agents has been found ineffective to prevent perioperative myocardial ischaemia. Our hypothesis was that low plasma concentrations may account for this inefficiency. Twenty-three male patients, scheduled for surgical myocardial revascularisation, were administered their usual anti-anginal treatment, including 180 to 360 mg of diltiazem since more than one week. The usual dosage was given at 8.00 p.m. on the day before surgery. On the morning of surgery, after withdrawal of a first blood sample, 60 mg of diltiazem were administered per month before the induction of anaesthesia. The anaesthesia was obtained with fentanyl, midazolam or flunitrazepam, pancuronium and isoflurane as required. The cardiopulmonary bypass (CPB) was associated with total haemodilution with Ringer's Lactate and a membrane oxygenator. A second blood sample was withdrawn after CPB. Plasma concentrations of diltiazem and its two active metabolites, N-monodemethyldiltiazem (MA) and desacetyldiltiazem (M1), were assessed by HPLC. Plasma diltiazem concentrations decreased from 78 +/- 66 (mean +/- SD) to 51 +/- 42 micrograms.l-1 (p < 0.05) with wide individual variations. These concentrations were under therapeutic levels in 18 out of 23 patients before (p < 0.05) with wide individual variations. These concentrations were under therapeutic levels in 18 out of 23 patients before induction and in 22 patients after CPB. The metabolite/diltiazem ratios remained constant. A dosage-plasma concentration relationship was observed preoperatively with diltiazem and MA. It is concluded that plasma concentrations of diltiazem should be optimized preoperatively in order to prevent myocardial ischaemia.

Latissimus dorsi cardiomyoplasty. Perioperative management and postoperative evolution.

Twelve men aged 45 to 69 years, NYHA class 3 or 4 with low isotopic ejection fraction (18 +/- 7 percent), underwent cardiomyoplasty. Eight required cardiopulmonary bypass to treat an associated cardiac lesion. Preoperatively, all patients needed inotropic support with dobutamine and half of them vasodilators, increasing cardiac index by nearly 100 percent. The SvO2 remained over 67 percent during the different stages of the surgical procedure. The mean operating time was 438 +/- 75 min. None of the patients required intra-aortic balloon counterpulsation. Inotropic and vasodilator support was continued in the ICU and appeared especially important during weaning from mechanical ventilation. The average stay in ICU was 6.8 +/- 4.0 days. Three patients died of cardiac failure respectively 8, 11 and 15 months after CMP. One patient underwent transplantation. The eight other surviving patients showed clinical improvement from the third month, but objective criteria for hemodynamic improvement were noted only after one year. Cardiomyoplasty can be an alternative treatment for selected cases of cardiomyopathy.

[A comparison of 3.5% dextran 40 and 4% albumin used as volume expansion solutions following heart surgery. Effects on the hemodynamic parameters and the oncotic colloidal pressure]. / Comparaison dextran 40 à 3.5% versus albumine à 4% utilisés comme solutés d'expansion volémique après chirurgie cardiaque. Effets sur les paramètres hémodynamiques et la pression oncotique colloïdale.

Dextran 40 (3.5%), a synthetic colloid solution used as a volaemic expander was compared to albumin 4% in 30 patients (15 in each group) during the first twenty hours after cardiac surgery. The patients were administered 500-600 ml.m-2 either dextran 40 or albumin at a rate of 10-12 ml.kg-1 x h-1 between 2nd and 4th postoperative hour. In the two groups, heart rate and mean arterial pressure did not change significantly but left and right filling pressures and cardiac index increased similarly. Colloid oncotic pressure and haemoglobin varied in the same way in the two groups. Proteinemia and albuminaemia were increased significantly in the albumin group during all the study. Diuresis was not different in the two groups. No side effect was observed. Dextran 40 was efficient and could be used as a volaemic expander after cardiac surgery.

[Current role of intra-aortic diastolic balloon counterpulsation in heart surgery]. / Place actuelle de la contrepulsion diastolique par ballonnet intra-aortique en chirurgie cardiaque.

Intra-aortic balloon counterpulsation (IABP) is a relatively non-invasive method of circulating assistance, easy to use and which has benefitted from a number of technological improvements in recent years. This retrospective study over 4 years was undertaken to analyse the results of IABP and to determine its role in therapeutic arsenal against cardiac failure. Sixty five patients, 57 coronary and 8 valvular cases, with an average age of 61 +/- 10 years were included. The indications of IABP were: a bridge to transplantation (3 cases), complications of coronary angioplasty (4 cases), and low cardiac output after cardiopulmonary bypass (58 cases), where IABP was curative in 85% of cases and prophylactic in 15% of cases (patients with risk factors of low output state after CPB). Beforehand, 65% of patients had poor left ventricular function (LVEF < 40% and/or CI < 2.2 l/mn/m2). An Aries Medical M700 console was used. The percutaneous femoral approach was feasible in 87% of cases. The results were: improvement with discharge from intensive care unit in 60% of cases, transient improvement in 7% of cases, no improvement in 15% of cases and cardiac transplantation in 8% of cases. The outcome was worse when the preoperative LV function was poor and when high dose inotropic agents had to be used. Survival was 100% in those patients in whom IABP was a prophylactic measure. The average duration of IABP was 72 hours, survival being significantly lower in those in whom IABP was continued for over 3 days. The complications (12.7%) were thromboembolic.(ABSTRACT TRUNCATED AT 250 WORDS)

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.