Adult liver transplantation at UCL: update 2002.

The authors present the results of a single centre study of 587 liver transplants performed in 522 adults during the period 1984-2002. Results have improved significantly over time due to better pre-, peri- and post-transplant care. One, five, ten and fifteen year actuarial survivals for the whole patient group are 81.2; 69.8; 58.9 and 51.2%. The high incidence of de novo tumors (12.3%), of cardiovascular diseases (7.5%) and of end-stage renal function (3.6%) should be further incentives to tailor the immunosuppression to the individual patient and to direct the attention of the transplant physician to the long-term quality of life of the liver recipient.

ELISA D-dimer measurement for the clinical suspicion of pulmonary embolism in the emergency department: one-year observational study of the safety profile and physician's prescription.

OBJECTIVES: To validate the safety profile of a rapid ELISA D-dimer as the first diagnostic step in the clinical suspicion of pulmonary embolism (PE) in outpatients admitted to an emergency department (ED), and to retrospectively evaluate the appropriateness of the physician's prescription. DESIGN AND SETTING: An observational study of all patients admitted to the ED of an urban university teaching hospital with signs and symptoms justifying the prescription of a rapid ELISA D-dimer measurement (Vidas; Biomerieux; France) as the first line diagnostic test for PE. Acute PE was established or excluded according to an appropriate combination of the D-dimer concentration, the lung scintigraphy, the spiral computerized tomography (spiral CT), the venous ultrasonography, and the arteriography in case of uncertain results. All patients with D-dimer values under the cut-off point of 500 ng/ml were followed up after 6 months. RESULTS: 395 patients were studied. A normal D-dimer concentration < 500 ng/ml was found in 179 patients (45% of the cohort). The retrospective analysis showed that none of these patients were found to have a high pre-test clinical probability. None of these 179 patients received anticoagulation nor displayed a PE event during a 6-month period (negative predictive value 100%; 95% CI, 98.0 to 100%; sensitivity 100%; 95% CI, 90.3 to 100%). Among the 216 patients (55%) with D-dimer values above 500 ng/ml, PE was confirmed in 32 cases, for a prevalence of the disease of 8.1%. Eighty-six patients (22%) had no additional testing in spite of positive D dimer values > 500 ng/ml, pointing out a 22% rate of inappropriate use of the D-dimer measurement. CONCLUSION: This observational study confirms that a normal rapid ELISA D-dimer value (< 500 ng/ml) used as a first diagnostic step in ruling out the diagnosis of PE is a safe clinical practice when the pre-test clinical probability is low or intermediate. Nevertheless, the low prevalence rate of the disease (8.1%) suggests a potential overused and inappropriate prescription.

Early multi-system organ failure associated with acute pancreatitis: a plea for a conservative therapeutic strategy.

The mortality of severe acute pancreatitis still ranges between 10 and 20%. Nowadays, infected pancreatic necrosis is the leading cause of death. Despite advances in intensive care therapy, however, early and worsening multi-system organ failure remains a source of substantial morbidity and still accounts for 20 to 50% of the deaths. In recent years, the systemic inflammatory response syndrome and the relevant cascades of inflammatory mediators have been implicated as the key factor in the emergence of remote tissue damage. Early multi-system organ failure that supervenes in the first week is typically associated with a sterile necrotizing process. There are no pathophysiological, clinical or economical data to support the practice of debridement of sterile necrosis to prevent or to control early multi-system organ failure. This issue has never been addressed in a controlled study. Besides intensive care support, non-surgical therapeutic modalities including urgent endoscopic sphincterotomy for impacted stones, antibiotic prophylaxis for the prevention of pancreatic infection and early jejunal nutrition have been specifically developed hopefully to attenuate multiple organ failure, to obviate the need of surgical drainage and to improve survival. Fine needle aspiration of necrotic areas must be incorporated in any conservative therapeutic strategy in order to identify and not to jeopardize those with infected necrosis that remains an absolute indication for drainage. A specific treatment of acute pancreatitis is still lacking, so far. However, there is ample experimental and pathophysiological evidence in favour of immunomodulatory therapy in severe acute pancreatitis. The administration of one or several antagonists of inflammatory mediators possibly combined with a protease inhibitor may at last provide the opportunity to interfere with the two major determinants of prognosis: the severity of multiple organ failure and the extent of necrotic areas that creates the culture medium for bacterial superinfection. These benefits remain to be substantiated in a controlled study, however.

[Validation of a triage scale: first step in patient admission and in emergency service models]. / Validation d'une grille de tri: première étape dans l'analyse du flux des patients et dans la modélisation d'un service d'urgence.

INTRODUCTION: At present, most emergency services handle the multitude of various demands in the same unity of place and by the same team of nurses aides, with direct consequences on the waiting time and in the handling of problems of varying degrees of importance. Our service examines other administrative models based on a triage of time and of orientation. METHODS AND RESULTS: In a prospective study on 679 patients, we have validated a triage tool inspired from the ICEM model (International Cooperation of Emergency Medicine) allowing patients to receive, while they wait, information and training, based on the resources provided, in order to deal with their particular medical problem. CONCLUSION: The validation of this tool was carried out in terms of its utilization as well as its reliability. It appears that, with the type of triage offered, there is a theoretical reserve of waiting time for the patients in which the urgency is relative, and which could be better used in the handling of more vital cases.

Surveillance of hospital-acquired infections in an intensive care department-the benefit of the full-time presence of an infection control nurse.

In the 42-bed intensive care department of a teaching hospital, the creation of a full-time infection control nurse post was followed by a 42% reduction in device-related hospital-acquired infection rates over a period of three years, and 33% reduction over a period of five years. Permanent surveillance accompanied by revision of procedures and bedside teaching were key factors in the improvement of quality of care. In the specific setting of an intensive care department, this study validates the previous conclusions reached in the SENIC study and emphasizes the essential role played by the infection control nurse in the care of critically ill patients.

Noninvasive ventilation for acute respiratory failure: a prospective randomised placebo-controlled trial.

The aim of the present study was to clarify whether the known effects of noninvasive positive-pressure ventilation (NPPV) in patients with respiratory failure are real or due to placebo effects and whether early application of NPPV in the emergency department leads to rapid improvement of the patients condition and outcome. A prospective randomised placebo-controlled study was conducted in 20 patients with severe acute respiratory failure (ARF) secondary to an acute exacerbation of chronic obstructive pulmonary disease (COPD) or acute pulmonary oedema, not improving under conventional medical therapy and on the edge of intubation. Patients received either conventional medical therapy plus two-level NPPV (hi-level NPPV) or conventional medical therapy plus "placebo" NPPV. The main outcome measures involved the need for endotracheal intubation in the bi-level NPPV arm and in the placebo arm after crossing over to active NPPV. Morbidity, length of stay, mortality and the effect of the ventilatory mode on clinical, arterial-blood gas parameters, and the sternocleidomastoid muscles electromyogram (EMG) activity were also measured. The 10 patients in the active NPPV group rapidly improved and none needed intubation. Placebo NPPV resulted in no change in the clinical condition of patients that continued to worsen and the 10 patients were crossed over to active NPPV. Three patients were intubated. No differences in terms of morbidity, length of stay or mortality between the two groups were observed. Active NPPV (but not placebo NPPV) led to a rapid and significant improvement in the clinical parameters, pH and the carbon dioxide tension in arterial blood and to a decrease in respiratory frequency and sternocleidomastoid EMG activity. Early application of bi-level noninvasive positive-pressure ventilation in patients with severe acute respiratory failure, due to chronic obstructive pulmonary disease and acute pulmonary oedema, leads to a rapid improvement in clinical status and blood gases. Noninvasive positive-pressure ventilation had no placebo effect.

Skeletonizing en bloc esophagectomy for cancer.

OBJECTIVE: To evaluate the long-term outcome of patients with esophageal cancer after resection of the extraesophageal component of the neoplastic process en bloc with the esophageal tube. SUMMARY BACKGROUND DATA: Opinions are conflicting about the addition of extended resection of locoregional lymph nodes and soft tissue to removal of the esophageal tube. METHODS: Esophagectomy performed en bloc with locoregional lymph nodes and resulting in a real skeletonization of the nonresectable anatomical structures adjacent to the esophagus was attempted in 324 patients. The esophagus was removed using a right thoracic (n = 208), transdiaphragmatic (n = 39), or left thoracic (n = 77) approach. Lymphadenectomy was performed in the upper abdomen and lower mediastinum in all patients. It was extended over the upper mediastinum when a right thoracic approach was used and up to the neck in 17 patients. Esophagectomy was carried out flush with the esophageal wall as soon as it became obvious that a macroscopically complete resection was not feasible. Neoplastic processes were classified according to completeness of the resection, depth of wall penetration, and lymph node involvement. RESULTS: Skeletonizing en bloc esophagectomy was feasible in 235 of the 324 patients (73%). The 5-year survival rate, including in-hospital deaths (5%), was 35% (324 patients); it was 64% in the 117 patients with an intramural neoplastic process versus 19% in the 207 patients having neoplastic tissue outside the esophageal wall or surgical margins (P <.0001). The latter 19% represented 12% of the whole series. The 5-year survival rate after skeletonizing en bloc esophagectomy was 49% (235 patients), 49% for squamous cell versus 47% for glandular carcinomas (P =.4599), 64% for patients with an intramural tumor versus 34% for those with extraesophageal neoplastic tissue (P <.0001), and 43% for patients with fewer than five metastatic nodes versus 11% for those with involvement of five or more lymph nodes (P =.0001). CONCLUSIONS: The strategy of attempting skeletonizing en bloc esophagectomy in all patients offers long-term survival to one third of the patients with resectable extraesophageal neoplastic tissues. These patients represent 12% of the patients with esophageal cancer suitable for esophagectomy and 19% of those having neoplastic tissue outside the esophageal wall or surgical margins.

PaCO(2)/ETCO(2) gradient: early indicator of thrombolysis efficacy in a massive pulmonary embolism.

End tidal CO(2) measurement may be helpful in detecting the efficacy of thrombolysis after a massive pulmonary embolism. We report the case of a 76-year-old man with a massive pulmonary embolism, who required early intubation and mechanical ventilation. Thrombolysis with rtpA (total dosage: 60 mg) was initiated. During this procedure, clinical data, arterial blood gases and end-tidal CO(2) with a capnograph were recorded. Before thrombolysis the P(a-ET)CO(2) gradient was raised to 25 mmHg. During thrombolysis, the clinical data improved and the P(a-ET) gradient fell to 14 mmHg. We postulate that the P(a-ET)CO(2) gradient seems to be a reasonable indicator of efficacy of thrombolysis in this setting. However, the gradient did not return to normal values (4-5 mmHg). The possible reasons for this may be that during mechanical ventilation there was a large ventilation-perfusion ratio and the cardiac output may have still reduced. With these limitations, we conclude that the P(a-ET)CO(2) gradient should be evaluated as an indicator of pulmonary reperfusion in massive pulmonary embolism.

Lenercept (p55 tumor necrosis factor receptor fusion protein) in severe sepsis and early septic shock: a randomized, double-blind, placebo-controlled, multicenter phase III trial with 1,342 patients.

OBJECTIVE: Phase III study to confirm a trend observed in a previous phase II study showing that a single dose of lenercept, human recombinant p55 tumor necrosis factor receptor-immunoglobulin G1 (TNFR55-IgG1) fusion protein, decreased mortality in patients with severe sepsis or early septic shock. DESIGN: Multicenter, double-blind, phase III, placebo-controlled, randomized study. SETTING: A total of 108 community and university-affiliated hospitals in the United States (60), Canada (6) and Europe (42). PATIENTS: A total of 1,342 patients were recruited who fulfilled the entry criteria within the 12-hr period preceding the study drug administration. INTERVENTION: After randomization, an intravenous dose of 0.125 mg/kg lenercept or placebo was given. The patient was monitored for up to 28 days, during which standard diagnostic, supportive, and therapeutic care was provided. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was 28-day all-cause mortality. Baseline characteristics were as follows: a total of 1,342 patients were randomized; 662 received lenercept and 680 received placebo. The mean age was 60.5 yrs (range, 17-96 yrs); 39% were female; 65% had medical admissions, 8% had scheduled surgical admissions, and 27% had unscheduled surgical admissions; 73% had severe sepsis without shock, and 27% had severe sepsis with early septic shock. Lenercept and placebo groups were similar at baseline with respect to demographic characteristics, simplified acute physiology score II-predicted mortality, profiles of clinical site of infection and microbiological documentation, number of dysfunctioning organs, and interleukin-6 (IL-6) plasma concentration. Lenercept pharmacokinetics were similar in severe sepsis and early septic shock patients. Tumor necrosis factor was bound in a stable manner to lenercept as reflected by the accumulation of total serum tumor necrosis factor alpha concentrations. There were 369 deaths, 177 on lenercept (27% mortality) and 192 on placebo (28% mortality). A one-sided Cochran-Armitage test, stratified by geographic region and baseline, predicted 28-day all-cause mortality (simplified acute physiology score II), gave a p value of .141 (one-sided). Lenercept treatment had no effect on incidence or resolution of organ dysfunctions. There was no evidence that lenercept was detrimental in the overall population. CONCLUSION: Lenercept had no significant effect on mortality in the study population.

Conservative treatment of postsurgical lymphatic leaks with somatostatin-14.

Successful management of lymphatic leaks by continuous IV administration of somatostatin was first reported by Ulibarri and coworkers in Spain,(1) and more recently by authors from Italy(2) and Switzerland.(3) The present article reports the clinical history of two patients in whom postsurgical lymphatic leak was successfully treated after the administration of either somatostatin-14 alone (case 1) or combined somatostatin-14 and total parenteral nutrition (TPN; case 2). Although further pathophysiologic studies are needed for the elucidation of its mechanisms of action, somatostatin-14 seems to be an intriguing therapy against postsurgical lymphatic leaks that may make potentially risky transthoracic reoperation unnecessary.

Chylous ascites: diagnosis, causes and treatment.

Chylous ascites is a rare form of ascites and generally associated with a poor outcome since it is often secondary to neoplasms. Its true incidence is not well established in the general medico-surgical population. Any source of lymph vessels obstruction or leakage can potentially cause chylous effusions in the peritoneal or retroperitoneal cavities. Any type of cancer and lymph node involvement may be associated with this uncommon type of ascites. Traumatic, and mainly surgical, vessels leakage is the second most common source of chylous effusions. Other even more rare underlying conditions have been described as leading to chyloperitoneum. Large fluid volume losses together with proteins, and lymphocytes can induce additional morbidity in a previously debilitated population or severely ill patients. This includes organ dysfunction related to volume and electrolytes losses, but mainly secondary infections due to impaired immunity by antibodies and lymphocytes depletion. Even if a vast majority of chylous effusions shall heal spontaneously, early and full treatment has to be initiated in order to reduce morbidity and mortality associated with this condition. Adapted oral diet is to be introduced to reduce lymph flow. Low lipid, high medium-chain triglycerides alimentation is the first measure to implement. Total parenteral nutrition is to be reserved to failures of oral diet. In addition, paracentesis is indicated to improve patient comfort, reduce intra-adbominal pressure and secondary renal dysfunction. Somatostatin analogues have been demonstrated to be effective in reducing lymphorragia and may be proposed prior to consider the surgical approach. Direct lymph vessels ligation can be indicated for large lymph vessels leakage demonstrated by radiologic techniques and when medical treatment has failed. Peritoneo-venous shunt becomes a less common technique in refractory chylous effusion because of its high morbidity. Herein, the other causes of chylous effusions are reviewed as the diagnostic procedures. A treatment algorythm is proposed.

Ascites fluid in severe acute pancreatitis: from pathophysiology to therapy.

Several pathophysiological mechanisms are involved in the development of the inflammatory necrotizing process that takes place in the retroperitoneal area during the early phase of acute pancreatitis. They include premature intraglandular activation of pancreatic proenzymes (zymogens) and in particular trypsin, early microcirculatory impairment with subsequent ischaemia/reperfusion and overstimulation of immune effector cells. Although intra-acinar or interstitial activation of trypsinogen is most probably the trigger of acute pancreatitis, in recent years much emphasis has been put on the role of leukocytes. Based on numerous experimental and human data several pro-inflammatory mediators including cytokines, arachidonic acid derivatives, activated oxygen species and proteases are released locally by overactivated neutrophils and monocytes/macrophages among other cells. They are now believed to play a central role in the development of pancreatic necrosis and, once they gain access to the systemic circulation, in the emergence of early multisystem organ failure. However the sequential and relative contribution of each of these 3 pathophysiological mechanisms remain controversial and the precise identification of the mediators incriminated in local and remote tissue injury is still awaited. Severe acute pancreatitis still carries a mortality of 20% to 30%. With advances in intensive care management 80% of the deaths occur somewhat late in the attack due to infected pancreatic necrosis. Nevertheless early remote organ failures still remain a lifethreatening condition for most of these patients. A peritoneal exudate rich in activated lipolytic and proteolytic enzymes, vasoactive substances and several other pro-inflammatory mediators collect in over 60% of the patients with severe acute pancreatitis. On the basis of favourable animal experiments early percutaneous or surgical peritoneal lavage with or without the addition of antiproteases has been carried out in human acute pancreatitis. The rationale behind this procedure was the washout of potential toxic mediators from the peritoneal cavity before they gain access to the systemic circulation. Contrary to animal and uncontrolled human data no prospective randomized study could ever demonstrated a significant effect of peritoneal lavage neither in the prevention and control of remote organ failures or in early mortality and ultimate survival after severe acute pancreatitis in humans. Differences between experimentally-induced pancreatitis, difference in the timing of the initiation of lavage and a type II error in controlled human studies may account for the discrepancy in the outcome between these studies. Anyway, this disparity should raise the question as whether the peritoneal cavity acts simply as a reservoir or as a route of transfer of toxic mediators to the systemic circulation. Although data are scarce, conflicting and limited to animal experiments and to a few molecules, peripancreatic veins and lymphatics seem to be the major routes of transfer whereas transperitoneal absorption is trivial. Nevertheless early peritoneal aspiration of ascitic fluid in acute pancreatitis and measurement of trypsinogen activation peptides may be used as a means of severity assessment and identification of pancreatic necrosis. This implies that even if not taking part actively in the emergence of remote organ failures ascitic fluid may reflect the peripancreatic necrotizing process. So careful comparative analysis of peritoneal exudate, plasma and lymph with regards to putative mediators of local and remote injury may provide essential pathophysiological clues. At the time of trials of antimediator therapy early in the attack this kind of insight is essential.

Adult liver transplantation: the Université Catholique de Louvain experience.

Liver transplantation remains a formidable surgical and medical procedure. The larger single centre experience confirms that standardization of perioperative care and simplification of the surgical procedure markedly improve results. Further efforts must be made in relation to immunosuppressive therapy in order to minimize late morbidity and mortality.

[Radiology and emergency medicine: state of the art]. / Radiologie et medecine d'urgence: etat de la question.

Emergency medicine has emerged as a specific medical specialty for 30 years. To be efficient, the emergency clinician frequently needs the contribution of radiological examinations. This is the reason why emergency radiology has emerged as a new radiologic subspecialty. The aim of this paper is to review the recent history of emergency medicine and to summarize the present state of the radiological organisation for emergency care in the Western countries.

Two-level non-invasive positive pressure ventilation in the initial treatment of acute respiratory failure in an emergency department.

There are few data on the use of two-level non-invasive positive pressure ventilation (two-level nIPPV) in the initial treatment of severe acute respiratory failure in emergency departments (ED). In a prospective, non-randomized, pilot study, we assessed (1) the feasability of this method in an ED, (2) its effect on clinical and laboratory data, and (3) its effect on the need of intubation and the final outcome of patients. During a 1-year period all eligible patients admitted for acute respiratory failure, with absence of improvement after periods of specific classic treatments, were included in the study. Each patient received a specific classic treatment and two-level nIPPV with a two-level positive pressure ventilator through a face mask. We recorded parameters on admission, after 15 and 45 minutes of nIPPV and at the end of nIPPV. Sixty-two patients were included: 29 with acute pulmonary oedema (APO), 16 with acute exacerbation of chronic obstructive pulmonary disease (COPD), four with asthma, and 13 with various diseases. In the APO-group, we observed a statistically significant improvement of respiratory and pulse rates, diastolic blood pressure, pH, PaCO2 and SaO2. In acute exacerbation of COPD, we observed only a statistical improvement of respiratory and pulse rates without any significant change of PaCO2 and pH. In the two other groups, there was a clinical, gasometric and haemodynamic improvement in all patients. Four patients were intubated and 10 died, but none in the ED or in the first 24 hours after hospital admission. We were able to institute two-level nIPPV for severe acute respiratory failure in an ED without complications. Its addition to the rest of classic specific treatment seems to bring about a rapid improvement of various clinical and laboratory parameters in most patients. We found no deleterious effect of nIPPV when implemented for short periods of time in the emergency department setting.

Effect of inorganic ions on the oxyhemoglobin dissociation curve of severely ill patients.

We have shown that administration of inorganic potassium phosphates (Pi) to patients with severe diabetic ketoacidosis was able to increase the P50 (the PO2 necessary to achieve a hemoglobin saturation of 50%) by a non diphosphoglycerate (DPG) mediated effect. This suggests that the oxyhemoglobin dissociation curve (ODC) may be determined not only by pH, temperature, CO2 content and DPG but also by plasmatic ions. In order to test this hypothesis we have determined the ODC on whole blood in two groups of subjects, 49 control subjects with matching age and sex and 49 patients suffering from liver cirrhosis, acute pancreatitis, septic shock and acute respiratory distress syndrome. The patients had many ionic disorders induced either by their diseases or by the applied treatment. The mean ODC of the patients did not differ from the normal values. In contrast, the dispersion of PO2 around the saturations values was increased from 5 to 80% saturation. A forward regression analysis showed that the DPG level and the levels of inorganic phosphates and natrium (Na+) played a significant role in determining the position of the ODC according to the following equation: P50 (mmHg) = 34.5 + 0.225 DPG + 0.62 Pi-0.09 Na+, where DPG is in micromol.gHb-1 and Pi and Na+ in mEq.l-1. In separate experiments we showed that the Bohr effect as expressed in d (log PO2)/dpH amounted to -0.53, -0.46 and -0.42 for SO2 equal to 5%, 50% and 95%, respectively. The corresponding values for the temperature effect was expressed in d (log PO2)/dT amounted to 0.028, 0.024, and 0.020 respectively. The fact that ions play an role in regulating the position of the ODC of patients with ionic disorders may have therapeutical implications, preventive or curative.

Is early enteral nutrition in acute pancreatitis dangerous? About 20 patients fed by an endoscopically placed nasogastrojejunal tube.

Bowel rest during treatment of acute pancreatitis deprives the gut of nutrients and affects its structure and function. Enteral feeding is usually performed late in the course of acute pancreatitis and therefore cannot prevent intestinal barrier dysfunction and possible bacterial translocation. To assess the effect of early enteral nutrition we performed a prospective study on 21 patients (11 males/10 females) presenting with severe acute pancreatitis (13 biliary, 6 alcoholic, and 2 miscellaneous). Severity was established by a mean Ranson score of 3.57. All but one patient could be fed through a double-lumen nasogastrojejunal tube within 60 h after admission. No significant complication of the technique was observed. We conclude that early jejunal feeding can be used safely in severe acute pancreatitis. Further comparative studies are necessary to demonstrate any superiority to total parenteral nutrition.

Rapid and specific molecular identification of methicillin-resistant Staphylococcus aureus in endotracheal aspirates from mechanically ventilated patients.

Multiplex amplification of femA and mecA genetic determinants allowed an early and rapid identification of methicillin-resistant Staphylococcus aureus (MRSA) in endotracheal aspirates of mechanically ventilated patients. femA and/or mecA amplification and bacteriological results were concordant in 57 of 60 samples. In all three discrepant cases, complementary bacteriological tests confirmed the presence of MRSA first identified by molecular analysis. These results underline the value and rapidity of this molecular diagnosis for MRSA infection and control surveillance in intensive care units. Rapid MRSA detection is expected to have a significant clinical impact not only on patient outcome but also on the costs for isolation and treatment.