Midazolam infusion for basal sedation in intensive care: absence of accumulation.

This study was designed to: (1) determine plasma midazolam concentrations producing adequate sedation in ICU patients; (2) establish an intravenous regimen to provide continuous sedation and rapid recovery after discontinuation of infusion. Initially, 13 ICU patients were given midazolam as a bolus injection, 0.20 mg.kg-1 over 30 s in order to define the midazolam plasma concentration corresponding to an adequate level of sedation. The optimal level was reached in a mean time of 61 +/- 26 min and the mean corresponding midazolam plasma concentration was 163 +/- 62 ng.ml-1. Estimations of the main pharmacokinetic parameters (elimination half life: 230 +/- 102 min, total body clearance: 520 +/- 283 ml.min-1, total volume of distribution: 2.23 +/- 1.15 l.kg-1) showed no marked differences with normal patients. From those variables, an infusion regimen (loading dose and maintenance rate) to provide long term (24 to 80 h) sedation was derived in 9 patients. The mean loading dose was 0.33 +/- 0.18 mg.kg-1 over 30 min and the mean continuous infusion dose was 0.06 +/- 0.02 mg.kg-1.h-1. The mean midazolam plasma concentration during infusion was 215 +/- 61 ng.ml-1, and the mean midazolam plasma concentration at the end of infusion was 199 +/- 93 ng.ml-1. The level of sedation was considered as optimal in most patients throughout the study. After discontinuation of infusion, the mean time for normalization of the mental state was 97 min.

[Analysis of factors related to early mortality in digestive hemorrhage caused by portal hypertension]. / Analyse des facteurs liés à la mortalité précoce au cours des hémorragies digestives dues à l'hypertension portale.

In order to determine immediate criteria of prognosis for patients with portal hypertension hospitalized for digestive hemorrhage, in an intensive care unit, 18 variables were recorded during the 24 hours following admission in 65 patients. Data related to death were age, ascites, hepatic encephalopathy, shock, active hemorrhage, acute pneumonia, decrease in prothrombin time, use of esophageal balloon tamponade, use of mechanical ventilation, number of red blood cell units transfused. Discriminant analysis yielded a linear combination of 4 variables which best separated survivors from non survivors with the following equation: F = 0.330 X hepatic encephalopathy + 0.433 X shock + 0.226 X active hemorrhage + 0.0097 X age - 0.396. The threshold decision of the hemorrhage prognosis index (HPI) was F = 0.57; 80 p 100 of all patients were correctly classified. In order to be validated, HPI was compared with a general (SAPS) and specific (Pugh's classification) scoring system, in a prospective study of 57 episodes of digestive hemorrhage. In this study, sensitivity was better with HPI than with SAPS (0.70 versus 0.45), specificity was higher with HPI than with Pugh's classification (0.86 versus 0.70). Percentage of correctly classified patients was higher using HPI (81 p. 100) than SAPS (77 p. 100) and Pugh's classification (68 p. 100). We suggest that the HPI, determined with 4 easily defined and recorded variables should be used prospectively to compare efficacy of different treatments.

[Budd-Chiari's syndrome with caval membranous web treated by liver transplantation]. / Syndrome de Budd-Chiari par membrane cave traité par transplantation hépatique.

In this paper, the case of a 30 year-old Asiatic man with a Budd-Chiari syndrome secondary to a caval membranous web, associated with cirrhosis is presented. After unsuccessful percutaneous dilatation, liver transplantation associated with membranotomy treated the venous obstacle and ensured satisfactory recovery. Orthotopic liver transplantation is the most effective treatment in this setting.

[Cytomegalovirus infections in patients after liver transplantation: determination of risk groups]. / Infections à cytomégalovirus chez les transplantés hépatiques: détermination de groupes à risque.

The goal of this study was to identify high-risk groups for cytomegalovirus infection after liver transplantation. Sixty-one patients were evaluated. Twenty-five patients (41 percent) had infection. Among the 16 patients who were seronegative for the virus before transplantation, 11 received a liver graft and blood products from seronegative donors and none of them developed infection. All seronegative recipients of a liver from seropositive donors (5/5) developed primary infection. Among the 45 patients seropositive before transplantation, 20 developed a cytomegalovirus infection, whatever the donor serologic status. The incidence of symptomatic reactivation or reinfection was high (14/20), and, for 12/14 of them, associated with early acute rejection. Two high-risk groups of patients, eligible for cytomegalovirus prophylaxis, were identified: seronegative recipients of seropositive donors and seropositive recipients with early acute rejection.

[Pathology of the inferior vena cava and liver transplantation]. / Pathologie de la veine cave inférieure et transplantation hépatique.

Pathology of the inferior vena cava is not frequently encountered in the context of liver transplantation. Such a pathology was observed in 7.9% of our recipients, in the pre- intra- and post-operative period. Pre-existing anomalies of the IVC consisted the absence of the retrohepatic vena cava in 7 children with biliary atresia; technical adjustments were quite simple. During the operative period, dissection of the supra-hepatic vena cava was made very difficult in 2 patients with hepatic alveolar echinococcosis complicated by secondary biliary cirrhosis it was necessary to make a trans-diaphragmatic approach to the inferior vena cava. Post-operative inferior vena cava thrombosis occurred in four recipients, in three cases, it was caused by the inadequate size of the graft and major anastomotic discrepancy between the inferior vena cava of donor and recipient and in one case IVC thrombosis occurred in a context of allergy to heparin. Six of the 13 recipients with pathology of inferior vena cava died directly of indirectly because of these problems. Analysis of the causes of this pathology and their possible correction will perhaps allow better results in these patients who undergo liver transplantation.

[Liver transplantation in adults: postoperative management and development during the first months]. / Transplantation hépatique chez l'adulte: prise en charge postopératoire et évolution au cours des premiers mois.

Recent improvements in the results of orthotopic liver transplantation (OLT) have made this a well-accepted treatment for patients with severe hepatic failure. Current problems encountered following OLT are discussed. Immediate complications comprise surgical bleeding, primary graft non-function, and graft failure due to hepatic artery occlusion. Secondary complications are frequent. Surgical ones include biliary and vascular (hepatic artery thrombosis most often) problems, as well as intra-abdominal abscesses associated with gastrointestinal perforation, biliary leak, graft ischaemia or an infected haematoma. 40% of patients having undergone OLT will be reoperated on, 2/3 of them within 3 months. Non-surgical complications are mostly pulmonary. The risk of pneumonitis is increased by prolonged mechanical ventilation; it is always potentially disastrous in the immunosuppressed, transplanted patient. Hypertension is also often seen in the early postoperative period; it requires prompt treatment. Early renal impairment after OLT is common, and of better prognosis than late onset renal failure, which is generally associated with shock, graft failure, sepsis or use of nephrotoxic agents. Seizures, usually only one, occur in about 10% of patients; recovery is complete. Encephalopathy with intracranial oedema related to fulminant hepatitis has a worse prognosis, but survival figures are quite encouraging. Three type of rejection are described after OLT: 1) severe accelerated rejection (very rare), 2) acute rejection encountered in about 70% of patients over the first 3 months, and 3) late rejection, which can lead to the vanishing bile duct syndrome (VBDS). Diagnosis of rejection is made by liver biopsy. Prophylactic immunosuppression includes cyclosporin, methylprednisolone and azathioprine. Cyclosporin toxicity and drug interactions are reviewed. Treatment of acute rejection episodes comprises an initial bolus of high doses of corticoid drugs; if there is no response, antilymphocyte globulin or monoclonal antibodies may have to be used. Infection is the main cause of death following OLT. Early infections, mostly intra-abdominal and pulmonary, are bacterial or fungal. Vital (especially CMV) and other opportunistic infections occur generally after the second week. Retransplantation, carried out in 10 to 25% of patients, may be urgent in case of primary graft failure, or hepatic artery thrombosis associated with graft failure, or hepatic artery thrombosis associated with graft failure. Other indications are early graft rejection with severe hepatic dysfunction, chronic rejection with severe VBDS, and recurrence of the initial disease.

[Evaluation of the population received and cared for in France in the "Doctors of the World" Health Centers]. / Présentation de la population accueillie et soignée en France dans les Centres de soins de "Médecins du Monde".

For 11 years now, Médecins du Monde's Mission to France has tried to respond to the needs of a part of marginalized population, which has no access to health care. In 1996, 72,000 consultations have been given throughout the 31 free Health centers based in 31 cities in France. Who is this population? Basically young people (more than half are under the age of 30 and 10% are underaged), men in 213 of the cases, living alone, in 80% of the cases. How do they live? Almost 65% live with less than 20 francs per day (given by social care); 54% are officially jobless. As far as housing is concerned, only 1/4 have a home (women in particular). The others live in hostels, self-made shelters, hotels, or with relatives; 13% admit living on the street. Why do they come to health centers? Almost all diseases observed are identical to the ones detected in regular Health care centers, i.e., Ear--Nose and Throat, respiratory and gynecological infections. What makes them particular is the fact they are diagnosed later than usual, which makes them more serious than usual. The living conditions of this marginalized population explain the high frequency of skin problems (12%) and neuropsychologic disorders. Why do they come to Médecins du Monde? 1/4 of the patients do benefit from social welfare, but are unable to advance the payment of medical costs, or support the difference between the actual cost and the reimbursement by the Social security. 40% have no social coverage whatsoever. However, other motives (1 to 7%) such as administrative problems, rights outside their district, refusal to start the administrative procedures, ignorance of their rights ... are rarely put forward. The population with no access to health care is still unknown. This is why the information gathered is so important. It allows a better qualification of the patients' requests and, consequently, a better comprehension of the social exclusion phenomenon, particularly in the area of health.

[Infectious complications after liver transplantation]. / Complications infectieuses après transplantation hépatique.

Infections after liver transplantation are frequent and represent the first cause of mortality. Bacterial and fungal infections are favourized by preoperative clinical status, surgical conditions, degree of immunosuppression, and surgical complications. Perioperative antibiotics and, for patients at risk, antifungal prophylaxis, reduce their indicidence. Viral infections are attributed principally to CMV. Prophylaxis against CMV with immunoglobulins can be suggested for patients at risk. Curative antiviral treatment is always effective.