[Is control fever mandatory in severe infections?] / Faut-il contrôler la fièvre dans les infections sévères ?

Temperature control during severe sepsis is currently used in intensive care and involves 66% and 70% of severe sepsis and septic shock, respectively. Nevertheless, the conclusive evidence of the benefit of such a strategy is still lacking.We might wonder, with regards to experimental works and recent noninterventional studies, about the risk of a control strategy on an ongoing infectious process, the patient's outcome, and the safety of the means implemented to obtain temperature control. On the other hand, it is also demonstrated that fever increases oxygen consumption, which may lead in some clinical situations to tissular ischemia and that fever may be associated with a deleterious focal inflammatory process. Methods to control the temperature include external and/or internal cooling and/or antipyretic medications such as paracetamol and nonsteroidal antiinflammatory drugs. In septic patients, external cooling and paracetamol are the mains means used to control temperature. Despite the uncertainties about the benefit to control or not the temperature, it could be stated that extreme temperature (hypo- or hyperthermia) should be avoided and that the benefit/risk of temperature control must be individually weighted.

Are enterococci playing a role in postoperative peritonitis in critically ill patients?

This prospective non-interventional study is aimed at evaluating the role of enterococci in the postoperative course of postoperative peritonitis (POP) and the predictive factors for isolating Enterococcus spp. All adult patients, hospitalized in intensive care, who had POP between September 2006 and February 2010 were analysed. The patients' baseline clinical characteristics and microbiological and surgical characteristics of the first episode of POP were recorded. The rates of surgical and non-surgical complications and mortality were studied. A total of 139 patients were analysed and Enterococcus spp. were recovered in 61 patients (43%). The presence of enterococci was associated with significantly more intra-abdominal abscesses (26% vs 12%, p=0.025), but did not affect the rate of reoperation or mortality. Antibiotic use before reoperation was the only independent predictive factor for isolating enterococci (OR=2.19, CI95%: 1.02-4.70, p<0.043). Although mortality was not affected by the presence of Enterococcus spp., a higher rate of intra-abdominal abscess was found, suggesting that enterococci play a significant role in postoperative peritonitis, but the need to treat them remains to be determined. Previous antibiotic use before reoperation was a key factor in predicting the subsequent recovery of enterococci.

Factors associated with multidrug-resistant bacteria in secondary peritonitis: impact on antibiotic therapy.

Secondary peritonitis includes community-acquired and nosocomial peritonitis. These intra-abdominal infections have a common pathogenesis but some microbiological differences, particularly with respect to the type of bacteria recovered and the level of antimicrobial susceptibility. This report describes a prospective observational study of 93 consecutive patients with secondary peritonitis during an 11-month period. Community-acquired peritonitis accounted for 44 cases and nosocomial peritonitis for 49 cases (post-operative in 35 cases). Fifteen multidrug-resistant (MDR) bacteria were recovered from 14 patients. In univariate analysis, the presence of MDR bacteria was associated significantly with pre-operative and total hospital lengths of stay, previous use of antimicrobial therapy, and post-operative antimicrobial therapy duration and modifications. A 5-day cut-off in length of hospital stay had the best specificity (58%) and sensitivity (93%) for predicting whether MDR bacteria were present. In multivariate analysis, only a composite variable associating pre-operative hospital length of stay and previous use of antimicrobial therapy was a significant independent risk-factor for infection with MDR bacteria. In conclusion, knowledge of these two factors may provide a more rational basis for selecting initial antimicrobial therapy for patients with secondary peritonitis.

[Cardiac arrest outside hospital: initial and subsequent cardiological management]. / Arrêt cardiaque extrahospitalier: prise en charge initiale puis en milieu cardiologique.

UNLABELLED: The prognosis of cardiac arrest outside hospital is directly related to the initial management. The aim of this work was to evaluate the characteristics of the initial and subsequent cardiological management of victims of cardiac arrest outside hospital with a retrospective analysis of data from the SAMU 35 (Emergency Medical Service, IIIe et Vilaine region) in the period April 1998 - April 2002. RESULTS: 533 non-traumatic cardiac arrests outside hospital were reported in 532 patients (average age 63 +/- 17, 73% male). The cardiac arrest occurred at home in 77% of cases. The initial cardiac rhythm documented was asystole in 63% of cases, ventricular fibrillation (VF) in 30% ventricular tachycardia (VT) in 1% and electromechanical dissociation in 6%. A cardiac aetiology was presumed in 294 (69%) of the 424 resuscitated patients. Among these, 22% (66/294) were admitted to coronary care units, 11% (31) left hospital alive, 8% (24) with no neurological sequelae. The survival rate for patients with cardiac arrest outside hospital in the presence of a witness and for whom the initial rhythm was VF or VT was 21%. The patient's age (<60 years)[OR: 1.05; CI 95%: 1.02-1.07; p < 0.001], rapid arrival of the SAMU (<10 min) [OR: 5.68; CI 95%: 1.42-22.7; p = 0.01] and resuscitation by the witness (OR: 8.26; CI 95%: 3.28-20.83; p < 0.001) were factors predictive of survival in a multivariate analysis. Coronary heart disease remains the principal cause of cardiac arrest in patients admitted to cardiology units (68%), with a recent coronary thrombosis shown in 40% of patients undergoing angiography (16/40). CONCLUSION: the prognosis of cardiac arrest outside hospital remains bleak, with a mortality of 90%. The survival rate is higher if the initial management is optimal, associated with bystander resuscitation and an immediate emergency service response allowing rapid defibrillation. Diagnosis and management of acute coronary syndrome in a cardiological setting must be integrated into the strategy.

[Activated protein C treatment: experience about 23 patients in the operative period]. / Traitement par la protéine C activée: expérience à propos de 23 patients dans un contexte périopératoire.

OBJECTIVE: To evaluate the use of activated C protein (ACP) in a Surgical Intensive Care Unit. STUDY DESIGN: A prospective observational study. PATIENTS AND METHODS: All patients receiving ACP during 20 months in the operative period. RESULTS: Twenty-three patients were treated by ACP. The origin of sepsis was peritonitis (n = 14), infected pancreatitis (n = 3), mediastinitis (n = 2), one urologic sepsis, one facial cellulitis, one catheter related infection, and one postoperative pneumonia. In two cases, the peritonitis was associated with a pleuretic infection, and in two other cases with parietal cellulites. Mean age was 69+/-13 years. Severities evaluated by SAPS II, LODS were 59+/-13 and 7+/-3, respectively. Mean number organ dysfunction was 3.3+/-1.0. Septic shock was present in 91% with concomitant use of catecholamines for a mean period of 87+/-64 hours. Bacteraemia was present in 43% of the patients. A treatment with hydrocortisone was associated in 52% of the patients. The ICU and hospital lengths of stay were 15+/-16 days, and 34+/-38 days, respectively. Mortality at day 28 was 35%. Two significant bleeding were observed, one requiring red blood cell transfusion and the other one a surgical control of the bleeding associated with red blood cell transfusion. CONCLUSION: With global management of severe sepsis, including the use of activated C Protein, this prospective observational study showed a 30% reduction of the predicted mortality by SAPS II scoring without significant increase of bleeding episodes in a surgical context.

[Testing nasogastric tube placement: evaluation of three different methods in intensive care unit]. / Evaluation prospective de trois méthodes de positionnement de la sonde nasogastrique en réanimation.

OBJECTIVE: Evaluation of three methods (aspiration of gastric fluid, pH measurement of gastric fluid, and insufflation of air) in order to determine the right position of the nasogastric (NG) tube. STUDY DESIGN: Prospective, observational study in an intensive care unit. PATIENTS AND METHODS: All patients requiring a NG tube were included. Since the NG tube was inserted three tests were successively performed: aspiration of gastric fluid, pH measurement of the gastric fluid, and auscultation over the epigastrium of air injected through the NG tube. The feasibility and the results obtained for each test were noted and compared to chest X-ray, considered as the reference. Chest X-ray classified the complications as major or minor. RESULTS: A total of 419 NG tube (202 decompressive NG tube and 217 gastric feeding tube) were analysed in 280 patients. Malpositions of the NG tube were observed in 10% (majors, n=11 and minors, n=31). Aspiration of gastric fluid and pH measurement were not sensible (77% and 49%, respectively) and not specific (38% and 74%, respectively). Insufflation of air was sensible (96%) but not specific (17%). The combination of the three methods did not improve the sensibility and specificity. Two complications were only detected by chest X-ray (one insertion in the intrapleural space, and one pneumothorax). CONCLUSION: None of the test evaluated, alone or associated, was sufficient to avoid chest X-ray. Moreover the occurrence of two potential and serious complications only detected by chest X-ray increase this assertion.

Modulation of the functional properties of human thyrocytes in monolayer or follicle culture: effects of some anaesthetic drugs.

It is well known that some volatile anaesthetic drugs, such as halothane and isoflurane, alter the functions of the human thyroid gland, but the action of other anaesthetic drugs, such as thiopental, midazolam and ketamine, on thyroid function is still unknown. We have investigated the effects of these three drugs on the functional properties of human thyrocytes cultured in monolayers or follicles and stimulated by TSH. Thiopental, midazolam and ketamine induced total suppression or a partial reduction, depending on the dose administered, of cyclic AMP (cAMP), follicular thyroglobulin (Tg) and free tri-iodothyronine (FT3) production. In contrast, free thyroxine levels increased in the medium of thyrocytes cultured as follicles. Small doses of the drugs did not affect thyrocyte production. The inhibiting effect of thiopental, midazolam and ketamine on Tg and FT3 production seems to result from the inhibition of cAMP production and 5'-deiodinase.

Survival, proliferation, and functions of porcine hepatocytes encapsulated in coated alginate beads: a step toward a reliable bioartificial liver.

Orthotopic liver transplantation is the most effective treatment for fulminant hepatic failure. As an alternative treatment, an efficient extracorporeal bioartificial liver should contain a large yield of functional hepatocytes with an immunoprotective barrier, for providing temporary adequate metabolic support to allow spontaneous liver regeneration or for acting as a bridge toward transplantation. Survival, proliferation, and functions of porcine hepatocytes were evaluated in primary cultures and after embedding in alginate beads, which were subsequently coated with a membrane made by a transacylation reaction between propylene glycol alginate and human serum albumin. Disruption of total pig livers by collagenase perfusion/recirculation allowed the obtention of up to 10(11) hepatocytes with a viability greater than 95%. Hepatocytes in conventional cultures or embedded in coated alginate beads survived for about 10 days, secreted proteins, particularly albumin, and maintained several phase I and II enzymatic activities, namely ethoxyresorufin-O-deethylase, oxidation of nifedipine to pyridine, phenacetin deethylation to paracetamol, glucuroconjugation of paracetamol, and N-acetylation of procainamide. Typical features of mitosis and [3H]thymidine incorporation indicated that porcine hepatocytes proliferated in both conventional cultures and alginate beads. The efficacy of the membrane surrounding alginate beads for protecting cells from immunoglobulins was tested by embedding HLA-typed human lymphocytes, which were subsequently incubated with specific anti-HLA immunoglobulin G and complement. These data show that large yields of porcine hepatocytes that are embedded in coated alginate beads remain functional and are isolated from large molecular weight molecules, such as immunoglobulins. This system represents a promising tool for the design of an extracorporeal bioartificial liver, containing xenogeneic hepatocytes, to treat acute liver disease in humans.

Human hepatocytes express trifluoroacetylated neoantigens after in vitro exposure to halothane.

Biotransformation of anaesthetic halothane by cytochrome P450-dependent monooxygenases resulted in the production of reactive intermediate trifluoroacetyl (TFA) halide, capable of covalently binding to hepatocyte proteins. TFA-modified liver proteins can act as antigens and are implicated in the pathogenesis of halothane hepatitis in humans. The aim of this study was to investigate the formation of TFA-neoantigens in halothane-treated primary cultures of adult human hepatocytes and to evaluate the usefulness of this in vitro model for studying immune-mediated halothane hepatotoxicity. Cultured human hepatocytes were incubated with halothane under constant temperature, atmosphere and anaesthetic concentration conditions. The results obtained show that halothane-treated hepatocytes isolated from seven different donors produced TFA-antigens as detected by immunocytochemical and western immunoblot analysis using rabbit anti-TFA antiserum. TFA-adducts were localized mainly in the endoplasmic reticulum and in small amounts on the plasma membrane of parenchymal cells. By immunoblotting, several neoantigens, with molecular masses from 42 to 100 kDa, were detected in halothane-exposed hepatocytes. These observations are consistent with the formation of TFA-adducts through metabolism of the anaesthetic and suggest that primary cultures of human hepatocytes represent a suitable in vitro model to study the pathogenesis of immune-mediated halothane hepatotoxicity.

Retrosternal bypass operation for unresectable squamous cell cancer of the esophagus.

BACKGROUND: A palliative bypass operation may be beneficial when severe dysphagia or tracheoesophageal fistula occurs after radiochemotherapy for unresectable tumor of the esophagus. METHODS: Thirty-two patients with an unresectable tumor of the esophagus underwent a palliative retrosternal gastric (29) or colonic (3) bypass operation with ligature of the lower esophagus (3) or drainage (27). Tracheoesophageal fistula was present at operation in 20 (62.5%), including 8 after radiochemotherapy. RESULTS: The overall operative mortality rate was 34.4%: 45% with tracheoesophageal fistula and 16.6% without (p < 0.01). Median intensive care and hospitalization times were 5 and 19 days, respectively. Median postoperative survival was 6 months (range, 53 to 492 days). Complications in 21 survivors were lung infections (seven), cervical fistulas (eight), and failure of the esophageal suture (two); 19 patients resumed oral nutrition, and quality of life was excellent in 6. All eight cervical fistulas regressed favorably. Postoperative radiotherapy or chemotherapy did not improve survival. CONCLUSIONS: Despite the high operative mortality rate, bypass operation can provide good palliation and allow subsequent radiochemotherapy in selected patients with an unresectable tumor of the esophagus.

Modulation of airway remodeling-associated mediators by the antifibrotic compound, pirfenidone, and the matrix metalloproteinase inhibitor, batimastat, during acute lung injury in mice.

Matrix metalloproteinases (MMPs) are potent to degrade basement membrane collagen associated with acute lung injury in inflammatory processes. We have investigated effects of pirfenidone, antifibrotic agent, and batimastat, inhibitor of MMPs, on gelatinase activities, on release of tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta), as well as on recruitment of inflammatory cells in bronchoalveolar lavage (BAL) fluid after aerosol administration of lipopolysaccharide (LPS) in mice. Pretreatment with pirfenidone reduced neutrophil recruitment, TNF-alpha and TGF-beta levels, and MMP-9 secretion. In contrast, pretreatment with batimastat (30 or 60 mg/kg, i.p.) only reduced TNF-alpha and TGF-beta levels. Batimastat did not reduce MMP secretion in BAL fluid but inhibited MMP-9 activity. The increase in tissue inhibitor of matrix metalloproteinase (TIMP)-1 induced by LPS was not modified by the two drugs. These findings demonstrate that the two drugs can inhibit the in vivo increase in MMP induced by LPS, batimastat with a direct inhibitor effect on MMP activity and pirfenidone as a consequence of its antiinflammatory effect.

Labeled granulocyte scanning for the diagnosis of infected necrosis in acute pancreatitis: what kind of labeling should be used?

Clinical and laboratory data or imaging results cannot provide a positive diagnosis of septic complications of pancreatic and peripancreatic necrosis in patients with acute pancreatitis. Confirmation can be obtained only after percutaneous computed tomography (CT)-guided aspiration of the necrotic tissues or fluid collection; although the important role of 99Tc(m)-HMPAO-labeled granulocyte scintigraphy has been recently emphasized. The aim of this study was to determine the sensitivity and specificity of 99m-technetium-hexamethylpropyleneamine oxime (99Tc(m)-HMPAO)- or 111In-oxine-labeled granulocyte scintigraphy for the diagnosis of infection in pancreatic or peripancreatic necrosis to define the ideal label for diagnosis. Thirty-six scintigraphic examinations were performed in 34 consecutive patients (mean age, 58 +/- 2 years) 20 +/- 2 days after the onset of acute pancreatitis (Balthazar classes A-C, n = 7; classes D and E, n = 29). The scintigraphic study included scintigraphic tomography and static acquisition 1 and 3 h, respectively, after reinjection of the autologous 99Tc(m)-labeled granulocytes and static images 3-4 and 24 h after the simultaneous reinjection of 111In-oxine-labeled autologous granulocytes. The diagnosis of infected pancreatic or peripancreatic necrosis was confirmed with percutaneous CT-guided aspiration (14 positive aspirates among 20 performed) and sterile necrosis after negative aspiration (6 negative aspirates) or after a 6 +/- 1-month follow-up free of clinical or biological signs of ongoing sepsis. The sensitivity and specificity were 86 and 73%, respectively, for scintigraphic tomography, 100 and 55% for 3-h 111In images, 93 and 68% for 3-4-h 111In images, and 100 and 64% for 24-h 111In images. The fall in splenic activity between the 3-4 and the 24-h 111In images was 26 +/- 3% in patients with septic pancreatic and peripancreatic necrosis (n = 14) and 16 +/- 3% in those with sterile necrosis (n = 22) (p < 0.01). Labeled granulocyte scintigraphy was thus shown to be an effective tool for the diagnosis of infection in pancreatic and/or peripancreatic necrosis due to acute pancreatitis, especially when the scintiscans are performed early after injection of 99Tc(m) or when the fall in splenic activity over the 24 h following reinjection of 111In is measured in particularly difficult cases. These promising preliminary results should be confirmed by a prospective study.

Spinal controlled delivery of bupivacaine from DL-lactic acid oligomer microspheres.

Bupivacaine-loaded microspheres made from DL-polylactic acid oligomers of different molecular weights (MW 2000 and 9000 g/mol, named PLA 2000 and PLA 9000, respectively) which displayed different in vitro release profiles were administered via the spinal route to rabbits. In comparison to the drug administered as a solution (2 mg as equivalent base), PLA 2000 and PLA 9000 microspheres (10 mg as equivalent base) led to a slower uptake of the drug in the systemic circulation, as suggested by the mean maximal plasma concentrations: 326 +/- 81, 321 +/- 57 and 64 +/- 54 ng/mL, respectively. Pharmacodynamic evaluation of the anesthetic action, by means of intensity and time course of motor blockade, indicated a sustained release. In comparison to the drug solution, the PLA 2000 microspheres led to an increase duration of median maximal blockade (172 min versus 44.5 min). The PLA 9000 microspheres failed to reach maximal blockade as a result of a too low release rate.

Use of adult human hepatocytes in primary culture for the study of clometacin-induced immunoallergic hepatitis.

To determine whether specific circulating antibodies from patients with drug-induced immunoallergic hepatitis could be involved in antibody-dependent cell-mediated cytotoxicity, an in vitro model system was set up. Normal human hepatocytes from male kidney transplantation donors were cultured and incubated with clometacin, a drug known to induce immunoallergic hepatitis in humans. After drug exposure and in the presence of lymphoid cells autologous to hepatocytes, addition of sera from patients with clometacin-induced hepatitis consistently resulted in hepatocyte injury characterized by morphological alterations and a decrease in intracellular lactate dehydrogenase and aspartate aminotransferase activities. Sera from patients with hepatitis induced by other drugs, such as cimetidine, halothane or methyldopa, were ineffective and no cytotoxicity occurred in the absence of lymphoid cells or without pre-incubation with clometacin. These results are consistent with the view that clometacin-induced hepatitis has an immunological basis and suggest that human hepatocytes co-cultured with autologous lymphoid cells represent a suitable model to study antibody-dependent cell-mediated cytotoxicity.

Non linear disposition of thiopentone following long-term infusion.

The pharmacokinetics of thiopentone administered at infusion rates ranging 4.5-11.5 mg.kg-1.h-1 for 50-130 h was studied in 6 patients with neurologic evidence of severe cerebral damage. Arterial plasma concentrations of thiopentone were measured during and after discontinuation of the infusion. The postinfusion plasma concentrations were fitted to the one compartment Michaelis-Menten model. At the end of the infusion, the level of saturation of the enzymatic systems ranged 67.0-95.7%. Vm was on average 0.93 +/- 0.57 mg.l-1.h-1. The mean plasma clearance was 2.0 +/- 1.4 ml.min-1.kg-1. The apparent half-life of the terminal phase was 5.5 +/- 3.9 h.

[Bilateral phrenic nerve paralysis after heart surgery]. / Paralysie phrénique bilatérale après chirurgie cardiaque.

A bilateral phrenic nerve paralysis after open heart surgery with cold cardioplegia in a 78-year-old patient is reported. This injury is observed after aortic valve replacement without use of an ice slush around the pericardium and no surgical or other direct nerve trauma. The diagnosis of clinical and radiologic abnormalities suggestive of phrenic dysfunction is assisted by portable sonography and measurement of the diaphragmatic compound muscle action potential after cervical transcutaneous phrenic nerve stimulation. This bilateral phrenic nerve paralysis required prolonged mechanical ventilation for 68 days with incomplete regression of the neuropathy five months after surgery.

[Mesenteric vein infarction associated with congenital antithrombin III (ATIII) deficiency]. / Infarctus veineux mésentérique associé à un déficit congénital en antithrombine III (ATIII).

A venous mesenteric infarction in a 27-year-old patient is reported. This patient presented a genetic quantitative AT-III deficiency without anticoagulation therapy. Ultrasonography revealed portal vein thrombosis and laparoscopy showed mesenteric vein infarction. Laparotomy was performed mmediately and revealed segmental infarction of 60 cm of the jejunum which was resected; the portal vein was considered to be partially occluded on palpation. No strangulation or mechanical factors were identified. Immediately postoperatively the patient received therapeutic doses of heparin with AT-III concentrates to increase AT-III levels; no recurrent thrombotic episode was observed. A systematic second-look operation 24 hours postoperatively showed good bowel viability. Five days later, long-term anticoagulation with acenocoumarol was decided. Twelve days later, ultrasonography showed complete portal revascularization which was confirmed by a third surgical operation on D60.

-Curative and preventive antibiotic therapy in infective endocarditis-. / Antibiothérapie curative et prophylactique des endocardites infectieuses.

Durack's criteria, including echocardiographic manifestations, are the current standard for the diagnosis of infective endocarditis (IE). The most common microorganisms known to cause IE are streptococci and staphylococci, and therapeutic principles are based on an association of parenteral antibiotics, as far as possible bactericidal and prolonged. Treatment also includes the search for the source of infection and its eradication. IE with negative blood cultures requires special techniques to obtain the causal microorganisms. In about half of the cases, a nosocomial bacteriaemia results in IE in patients with a prosthetic valve. Surgery is mandatory in IE with complications and/or caused by particular microorganisms; surgery is essential in most patients with a prosthetic valve. Although the presence of specific links between some procedures and the occurrence of IE has not been clearly proven, a prevention policy is nevertheless justified, considering the morbidity and mortality. Prophylaxis is indicated in patients with the cardiac conditions at risk for IE. IE prophylaxis prevails over prophylactic antibiotics usually administered for surgery.