Prevention of postischaemic ventricular fibrillation by long term beta adrenoceptor blockade with acebutolol in the anaesthetised dog.

Acute occlusions of the proximal left circumflex coronary arteriovenous pedicle were performed in open chest anaesthetised dogs. Twenty eight dogs were randomly allocated to receive acebutolol (3 mg X kg-1 twice daily) or placebo given blindly by mouth for five days; a control group of 14 dogs without any pretreatment underwent the same procedure. Coronary ligations in the randomised study were performed during seven consecutive days, and four dogs were operated on each day. This schedule was chosen in order to measure acebutolol plasma concentrations just before ligation from 60 to 540 min after the last dose of the drug. Long term oral treatment with acebutolol protected against postischaemic ventricular fibrillation and significantly reduced the incidence of both early phase (0-10 min postocclusion) ventricular arrhythmias and ventricular fibrillation. As a result the outcome was significantly improved after 60 min of ischaemia in acebutolol compared with placebo treated animals. The results in the control animals were similar to those in the placebo treated dogs. The protective effect of long term oral treatment with acebutolol lasted for nine hours and was apparently independent of the plasma concentrations of the drug. These data show that improved outcome in this canine model is due to the prevention of ischaemia induced ventricular fibrillation by long term beta adrenoceptor blockade, which is able to overcome the effect, if any, of partial agonist activity of acebutolol. A direct myocardial anti-ischaemic effect might explain the effectiveness of long term oral treatment, which is independent of plasma concentrations of the drug.

Molsidomine prevents post-ischaemic ventricular fibrillation in dogs.

Forty anaesthetized dogs were subjected to left circumflex coronary artery ligation followed by reperfusion. Molsidomine was randomly administered to 20 dogs (50 micrograms kg-1 as an i.v. bolus - 15 min prior to coronary occlusion - followed by an infusion of 0.05 micrograms kg-1 min-1. Standard electrocardiographic leads 2 and 3 were continuously recorded to measure ST segment and delta R% changes and to document both the number of ventricular premature beats and the onset of ventricular fibrillation; aortic pressure and cardiac output were measured; thromboxane B2 plasma levels, platelet aggregation produced by ADP, and molsidomine plasma levels were determined before and at 10, 30 and 75 min after the start of the drug protocol. Molsidomine protected the treated animals from early (10 min) post-ischaemic ventricular fibrillation (0 of 20 vs 6 of 20, P = 0.0202), reduced the incidence of overall post-occlusion ventricular fibrillation (3 of 20 vs 10 of 20, P = 0.0407) and improved the total survival rate (P = 0.0067). In molsidomine treated dogs: mean aortic pressure and the rate-pressure product were lowered 10 min after the start of the drug; immediate post-occlusion (3 min) ST segment changes (0.82 +/- 0.52 vs 1.52 +/- 0.78 mV, P less than 0.025) and delta R% changes (37 +/- 50 vs 90 +/- 84%, P less than 0.025) were less marked; the number of ventricular premature beats was lowered and finally, a progressive decline of platelet aggregation produced by ADP was achieved after 75 min of drug infusion. These results were obtained in the presence of mean plasma levels of molsidomine ranging from 20 to 28 ng ml-1. The time-action curve of the antifibrillatory effect of molsidomine parallels those at the level of post-ischaemic electrocardiographic changes.

Is lung cancer surgery justified in patients with coronary artery disease?

Between 1987 and 1992, 21 patients who presented with potentially resectable non-small cell lung cancer and coronary artery disease, underwent a preoperative cardiac catheterization in order to assess the coronary artery anatomy and left ventricular function. There were 20 men and 1 woman whose ages ranged from 57 to 77 years. Patients with triple-vessel disease and poor distal circulation or impaired ventricular function (n = 2) were excluded from myocardial revascularization and pulmonary surgery. Patients with a curable left-main or triple-vessel disease (group I) first underwent surgical (n = 3) or transluminal (n = 4) myocardial revascularization. The remaining patients presented with single- or double-vessel disease, and were operated on without prior myocardial revascularization (group II; n = 12). The thoracic procedures consisted of exploratory thoracotomy in two cases, lung-sparing resection in one, lobectomy in ten, bilobectomy in one and pneumonectomy in five. The overall mortality and morbidity rates were 5.3% and 31.6%, respectively. Four patients (21%) experienced postoperative cardiac complications: fatal myocardial infarction (n = 1) and dysrhythmia (n = 2) in three group II patients (25%), and transient myocardial ischemia in one group I patient (14.3%). The overall survival rate at 5 years was 57.4% for the 17 patients who underwent resection of their cancer. We conclude that 1) lung surgery in patients with non-small cell lung cancer and coronary artery disease is justified in selected cases, 2) previous myocardial revascularization appears to confer protection against the development of postoperative cardiac morbidity.

Effects of cicletanine in the left circumflex coronary artery occlusion-reperfusion canine model of sudden death: analysis of 107 experiments using Cox's proportional hazards model.

Multivariate analysis of survival using Cox's proportional hazards model demonstrates that several clinically measurable covariates are determinants of life-threatening arrhythmias following left circumflex coronary artery occlusion-reperfusion in 107 dogs. These are heart rate, ST segment elevation and mean aortic pressure immediately (3 min) following occlusion, and the presence of early (0-10 min) post-occlusion sustained ventricular tachycardia. The risk of occlusion-reperfusion ventricular fibrillation was determined according to Cox's solution based on ST segment elevation, thus enabling quantification of the role of cicletanine. Since cicletanine-treated dogs had reduced mean ST segment elevation at 3 min post-occlusion, lower incidence of early post-occlusion (0-10 min) sustained ventricular tachycardia, and increased endogenous production of prostacyclin, and the latter was inversely correlated with the level of ST segment elevation, it is concluded that such favourable effects on the ischaemic myocardium were contributory to the improved outcome in these experiments. These effects on the ischaemic myocardium obtained in spite of a hypotensive action in the experimental setting might be regarded as desirable and it is therefore suggested that they should be further investigated by pharmacodynamic studies in human subjects.

Is it a medical error if we do not screen cirrhotic patients for minimal hepatic encephalopathy?

Minimal hepatic encephalopathy (MHE) refers to subtle neurocognitive and neurophysiological defects in patients with liver cirrhosis without clinical signs of hepatic encephalopathy. Using appropriate diagnostic methods the prevalence of MHE is approximately 25-30%. MHE has clinical significance as it results in a diminished daily functioning, precedes overt hepatic encephalopathy and is associated with a poor prognosis. Treatment with non-absorbable disaccharides can reverse the neurocognitive and neurophysiological defects found in MHE. The failure to diagnose MHE in apparently normal cirrhotic patients could, therefore, be considered a medical error. However, whether treatment also improves patients' quality of life and prognosis remains to be determined.

Hepatic encephalopathy: nomenclature, pathogenesis and treatment.

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome in patients with liver failure and/or a portal-systemic bypass. Since 2002 a new nomenclature of HE exists, that classifies HE in encephalopathy type A (associated with acute liver failure), type B (associated with portal-systemic bypass), and type C (associated with liver cirrhosis). HE type A is characterized by a rapid development to coma, cerebral edema, and a poor short-term prognosis. Therefore, these patients should be referred to a liver transplantation center. Standard treatment of HE consists of non absorbable disaccharides, non absorbable antibiotics, and a diet with an appropriate amount of proteins. In addition, the possibility of performing a liver transplantation should be evaluated. In patients with intractable HE other alternative treatments adjunct to standard treatment, like zinc, sodium benzoate, ornithine aspartate, branched chain amino acids, flumazenil, and bromocriptine should be considered.

[Video-assisted pulmonary resection surgery. Technique, indications and first results]. / La chirurgie d'exérèse pulmonaire vidéo-assistée. Technique, indications et premiers résultats.

Video-assisted thoracic surgery (VATS) is a compromise between conventional thoracic surgery performed via a thoracotomy of variable dimensions and surgical videothoracoscopy, which, using only small operating channels, requires the use of specific instruments, gives a field of vision exclusively by video camera and raises the delicate problem of extraction of the resection specimen. VATS is performed via a minithoracotomy, 3.5 to 5 cm long, using a video camera. In this way, the operator has two forms of vision throughout the operation: direct vision through the orifice of the minithoracotomy and visualization of the video screen. This technique also allows extraction of the resection specimen at the end of the operation. Between February and May 1993, 20 patients (14 males and 6 females with a mean age of 56 years) underwent lung resection by VATS (18 lobectomies and 2 pneumonectomies). Eighty-eight patients had a malignant tumour and 2 had a benign disease. Lymph node dissection was routinely performed in patients with a malignant lesion. The mean size of the tumours was 3.2 cm. The operative mortality was nil. The mean operating time was 154 minutes. The postoperative course was uneventful in 14 patients, but two cases of atelectasis on DO, one bronchial infection and one chylothorax, treated medically, were observed. The authors report the current criteria of their indications as the feasibility and reliability of this new technique. Results on pain and patient comfort, postoperative analgesia requirements, recovery of respiratory function and possible long-term sequelae remain to be demonstrated, which is the objective of a current prospective study.

[Prolonged epidural analgesia following thoracotomy. Clinical study and serum levels over five days]. / Analgésie péridurale prolongée après thoracotomie. Etude clinique et taux sériques pendant cinq jours.

Prolonged continuous epidural analgesia allows perithecal infusion with fentanyl and bupivacaine for 5 postoperative days after thoracic surgery. This study included 27 thoracotomized patients randomised into two groups: group X consisted of 15 subjects, group Y consisted of 12 subjects. Each patient received 33 micrograms/hr or fentanyl for 48 hours, associated with 0.25% bupivacaine in group X, and 0.125% bupivacaine in group Y. Over the three last days, the infusion rate of both drugs was decreased in the two groups. No significant clinical difference appeared between X and Y. No clinical respiratory depression occurred. In group Y, mean plasma bupivacaine concentrations remained significantly lower (p less than 0.05). Mean fentanyl levels did not increase beyond 0.8 ng/ml. The use of 0.125% bupivacaine improved the margin of safety but did not impair clinical analgesia in the study. This method provides good analgesia for thoracotomized patients.

[Video-assisted pulmonary excision surgery. Technique, indications and initial results]. / La chirurgie d'exérese pulmonaire vidéo-assistée. Technique, indications et premiers résultats.

Video-assisted thoracic surgery (VATS) is a compromise between conventional thoracic surgery performed via a thoracotomy of variable dimensions and surgical videothoracoscopy, which, using only small operating channels, requires the use of specific instruments, gives a field of vision exclusively by video camera and raises the delicate problem of extraction of the resection specimen. VATS is performed via a minithoracotomy, 3.5 to 5 cm long, using a video camera. In this way, the operator has two forms of vision throughout the operation: direct vision through the orifice of the minithoracotomy and visualization of the video screen. This technique also allows extraction of the resection specimen at the end of the operation. Between February and May 1993, 20 patients (14 males and 6 females with a mean age of 56 years) underwent lung resection by VATS (18 lobectomies and 2 pneumonectomies). Eighty-eight patients had a malignant tumour and 2 had a benign disease. Lymph node dissection was routinely performed in patients with a malignant lesion. The mean size of the tumours was 3.2 cm. The operative mortality was nil. The mean operating time was 154 minutes. The postoperative course was uneventful in 14 patients, but two cases of atelectasis on DO, one bronchial infection and one chylothorax, treated medically, were observed. The authors report the current criteria of their indications as the feasibility and reliability of this new technique. Results on pain and patient comfort, postoperative analgesia requirements, recovery of respiratory function and possible long-term sequelae remain to be demonstrated, which is the objective of a current prospective study.

[Hyperammonemia in hydronephrosis]. / Hyperammoniëmie bij hydronefrose.

A man aged 81 with bilateral hydronephrosis presented with lethargy deepening into coma caused by hyperammonaemia. The hyperammonaemia was most likely caused by excessive absorption of ammonia produced by Proteus mirabilis in the obstructed and dilated urinary tract. The patient died within a few hours.

Perioperative cerebral ischaemia in cardiac surgery and BIS.

A 46-year-old woman was monitored by bispectral index monitoring (BIS) during redo aortic and mitral valve replacement. On release of the aortic cross clamp there was a sudden, severe, unexplained, and sustained fall in the BIS value. Postoperatively, a CT scan was consistent with multiple ischaemic lesions. The lesions were presumed to be due to air embolism. This case suggests that a sudden unexplained and persistent fall in BIS may indicate cerebral ischaemia.

[Anesthesia for esophageal surgery]. / Anesthésie en chirurgie oesophagienne.

At the present time, it is rarely necessary to operate after a digestive perforation complicating the ingestion of a caustic fluid. By contrast, cancer surgery progresses. Anaesthesia requires protection with a high degree of analgesia and curarisation. The use of a Carlens tube during oesophagectomy via a thoracic approach facilitates the surgeon's task. Compensation for blood and water losses should be generous. Insertion of a gastric tube through the plasty makes it possible to avoid gastrostomy. Finally, postoperative artificial ventilation is necessary in these individuals who often suffer from some form of respiratory pathology.

The circumflex coronary artery occlusion canine model of sudden death: methodology and electrocardiographic observations.

This study deals with a left circumflex coronary artery occlusion-reperfusion canine model of sudden death using multiple electrocardiographic leads to define a subgroup of animals at high risk of ventricular fibrillation. Occlusion was followed by ventricular fibrillation in 15 of 30 animals (50%). In the 15 dogs surviving 60 min postocclusion, reperfusion gave rise to ten cases of ventricular fibrillation (66.7%). Thus, the total incidence of occlusion-reperfusion ventricular fibrillation was 25 of 30 (83.3%). Electrocardiographic delta R% changes greater than or equal to 25% in leads 2 and 3 at both 3 and 5 min postocclusion predicted the occurrence of postocclusion ventricular fibrillation with 80% specificity and 56% sensitivity. However, ST segment elevation greater than or equal to 0.5 mV in the same leads at the same times predicted postocclusion ventricular fibrillation with 67% specificity and 100% sensitivity. When only dogs with ST segment elevation greater than or equal to 0.5 mV in leads 2 and 3 at both 3 and 5 min postocclusion were considered, ventricular fibrillation postocclusion was seen in 15 of 20 dogs (75%) and ventricular fibrillation after reperfusion occurred in four of the remaining five animals (80%). Thus, in the subgroup of animals presenting with ST segment elevation greater than or equal to 0.5 mV in leads 2 and 3 at both 3 and 5 min postocclusion, the overall incidence of occlusion-reperfusion ventricular fibrillation was 19 of 20 (95%). These data may be useful in studies aimed at testing the effectiveness of drugs or other interventions in a canine model of sudden death.

[Value of Soludactone in cardiac surgery in adults]. / Intérêt de la Soludactone en chirurgie cardiaque de l'adulte

The use of potassium canrenoate (Soludactone) in the post-operative period in 31 patients who had undergone open-heart surgery, in comparison with a control batch of patients, led to a more rapid and easier regression of myocardial hyperexcitability, the maintenance of kaliemia at values near normal, a reduction in kaliuresis, a rapid elevation of the urinary Na/K ratio and the maintenance of satisfactory diuresis. But the majority of these effects appear progressively during the first 3 days of treatment, so potassium canrenoate should be prescribed 3 days before the intervention so that the beneficial effects may be manifested from the day of the intervention itself.

[P50 and stored blood (+4 degrees C and -80 degrees C). In vitro studies]. / P50 et sangs conservés (+4 degrees C et -80 degrees C). Etudes in vitro.

The authors studied the hemoglobin oxygen affinity (P50) and the 2,3 diphospho-glycerate (2,3-DPG) level in: 33 samples of total stored blood (ACD medium); 14 samples of the same blood after mixing with a solution including inosine, pyruvate, phosphate (I.P.P.); 9 samples of freezed erythrocytes. The increase of the hemoglobin oxygen affinity, associated with a decrease of the 2,3-DPG level appears to be very fast in the samples of ACD stored blood since two hours after sampling, the P50 decrease was of 4 torr. Exposure to the I.P.P. solution (1 H at 37 degrees C), caused the hemoglobin oxygen affinity and the 2,3-DPG concentration to return to their normal values (P50 = 25.4 torr +/- 0.4 torr); 2,3-DPG = 15.6 +/- 0.9 muM.gHb-1). When freezed red blood cells, were defreezed the P50 was found to be 4 torr lower than that of fresh blood and the 2,3-DPG level was also decreased (-4.1 muM.gHb-1). These decreases are probably related to the delay which occurred between blood sampling and freezing.

Lower oesophageal reflux during priming with vecuronium.

We have studied the effects of vecuronium given in divided doses (priming principle) on the frequency of acid reflux into the oesophagus. Two groups of 16 patients were studied. After induction with thiopentone 6 mg kg-1 and fentanyl 3 micrograms kg-1, patients in one group were given vecuronium 0.01 mg kg-1 as a priming dose, followed by an intubation dose of 0.1 mg kg-1 4 min later. Patients in the other group were given no priming dose. Lower oesophageal pH was monitored continuously and acid reflux was defined as a decrease in pH to less than 4.0. One patient in each group had acid reflux during the time course of the induction. This study suggests that vecuronium 0.01 mg kg-1 given as a priming dose does not increase the risk of acid reflux into the oesophagus.

Prevention of postischemic ventricular fibrillation late after right or left stellate ganglionectomy in dogs.

To gain insight into the differences in antiarrhythmic potential of right vs left stellate ganglionectomy, 72 dogs were randomized to either unilateral stellectomy or second intercostal space thoracotomy and left circumflex coronary arteriovenous pedicle occlusion was performed, without vagotomy, a mean of 8 weeks later under anesthesia. The type and timing of ventricular ectopic beats, including both nonsustained and sustained ventricular tachycardia and ventricular fibrillation, were investigated. Several covariates, including postischemic electrocardiographic changes, were considered. Both right and left stellate ganglionectomy reduced the incidence of early (0 to 10 min) (p = .004 and p = .001, respectively) and total (0 to 60 min) (p = .009 and p = .008, respectively) ischemia-induced ventricular fibrillation, and improved outcome (p = .0013 and p = .0012, respectively). Early sustained ventricular tachycardia was similarly reduced (p = .02) in both stellectomized groups. By contrast, neither the type nor the time distribution of the other forms of ventricular arrhythmias differed significantly among the randomized groups. The multivariate Cox's regression model showed that ST segment elevation at 3 min postocclusion, unilateral stellate ganglionectomy (either right or left), sex, and weight were significant independent predictors of the incidence of ventricular fibrillation during the occlusion period. Lower ST segment elevation and reduced incidence of sustained ventricular tachycardia in the early postischemic period might explain improved outcome in stellectomized dogs by Cox analysis. The side of intervention (either stellectomy or sham operation) did not influence survival; however, left-sided interventions were more effective than right-sided ones. These results confirm the previously reported antifibrillatory effect of left and indicate like effects of right stellate ganglionectomy in a randomized experimental study.