Recommendations for the evaluation and management of the anticipated and non-anticipated difficult airway of the Societat Catalana d'Anestesiologia, Reanimació i Terapèutica del Dolor, based on the adaptation of clinical practice guidelines and expert consensus. / Recomendaciones para la evaluación y manejo de la vía aérea difícil prevista y no prevista de la Societat Catalana d'Anestesiologia, Reanimació i Terapèutica del Dolor, basadas en la adaptación de guías de práctica clínica y consenso de expertos.

The Airway Division of the Catalan Society of Anaesthesiology, Intensive Care and Pain Management (SCARTD) presents its latest guidelines for the evaluation and management of the difficult airway. This update includes the technical advances and changes observed in clinical practice since publication of the first edition of the guidelines in 2008. The recommendations were defined by a consensus of experts from the 19 participating hospitals, and were adapted from 5 recently published international guidelines following an in-depth analysis and systematic comparison of their recommendations. The final document was sent to the members of SCARTD for evaluation, and was reviewed by 11 independent experts. The recommendations, therefore, are supported by the latest scientific evidence and endorsed by professionals in the field. This edition develops the definition of the difficult airway, including all airway management techniques, and places emphasis on evaluating and classifying the airway into 3 categories according to the anticipated degree of difficulty and additional safety considerations in order to plan the management strategy. Pre-management planning, in terms of preparing patients and resources and optimising communication and interaction between all professionals involved, plays a pivotal role in all the scenarios addressed. The guidelines reflect the increased presence of video laryngoscopes and second-generation devices in our setting, and promotes their routine use in intubation and their prompt use in cases of unanticipated difficult airway. They also address the increased use of ultrasound imaging as an aid to evaluation and decision-making. New scenarios have also been included, such as the risk of bronchoaspiration and difficult extubation Finally, the document outlines the training and continuing professional development programmes required to guarantee effective and safe implementation of the guidelines.

A new mass spectrometry-based method for the quantification of histones in plasma from septic shock patients.

The aim of this study was to develop a novel method to detect circulating histones H3 and H2B in plasma based on multiple reaction monitoring targeted mass spectrometry and a multiple reaction monitoring approach (MRM-MS) for its clinical application in critical bacteriaemic septic shock patients. Plasma samples from 17 septic shock patients with confirmed bacteraemia and 10 healthy controls were analysed by an MRM-MS method, which specifically detects presence of histones H3 and H2B. By an internal standard, it was possible to quantify the concentration of circulating histones in plasma, which were significantly higher in patients, and thus confirmed their potential as biomarkers for diagnosing septic shock. After comparing surviving patients and non-survivors, a correlation was found between higher levels of circulating histones and unfavourable outcome. Indeed, histone H3 proved a more efficient and sensitive biomarker for septic shock prognosis. In conclusion, these findings suggest the accuracy of the MRM-MS technique and stable isotope labelled peptides to detect and quantify circulating plasma histones H2B and H3. This method may be used for early septic shock diagnoses and for the prognosis of fatal outcomes.

CYP2C9*3 Loss-of-Function Allele Is Associated With Acute Upper Gastrointestinal Bleeding Related to the Use of NSAIDs Other Than Aspirin.

Nonsteroidal anti-inflammatory drugs (NSAIDs), other than aspirin, are to some extent metabolized by cytochrome P450 2C9 (CYP2C9). The CYP2C9 359Leu (CYP2C9*3) loss-of-function allele could be a risk factor for acute upper gastrointestinal bleeding (AUGIB) related to the use of NSAIDs other than aspirin. To test this hypothesis, we performed a prospective, multicenter, case-case study in patients hospitalized for AUGIB related to the use of NSAIDs. A total of 131 patients had been treated with aspirin and 57 patients had been treated with an NSAID other than aspirin (non-ASP). In the aspirin group, 12 patients (9.2%) had the CYP2C9 359Leu allele as compared with 19 (33.3%) in the non-ASP group (odds ratio (OR) = 5.0; 95% confidence interval 2.2-11.1, P < 0.0001). In a multivariate analysis, CYP2C9 359Leu remained associated with the non-ASP group (OR = 7.2 (2.6-20.3), P = 0.0002) even though 40% of these patients were under treatment with antiulcer drugs at the time of admission. Therefore the results of the study support the hypothesis that the CYP2C9 359Leu allele is a robust risk factor for AUGIB related to the use of NSAIDs other than aspirin.

HHV-6-related acute liver failure in two immunocompetent adults: favourable outcome after liver transplantation and/or ganciclovir therapy.

Fulminant hepatitis of unknown origin remain a significant cause of mortality, for which liver transplantation is often considered as the only therapeutic option. In retrospective studies, human herpesvirus 6 (HHV-6) infections have been associated with such diseases, but the diagnosis of HHV-6 infection of the liver is rarely established during the acute phase of liver failure. Using real-time polymerase chain reaction (PCR), we diagnosed two cases of severe acute liver failure (ALF) related to HHV-6 occurring in immunocompetent young adults. Both cases had a favourable outcome, one after valganciclovir therapy, one after liver transplantation associated with ganciclovir. Viral origin was evidenced in each case by the detection of high amounts of HHV-6 DNA in liver tissue by the PCR assay. The decrease of intrahepatic viral load after therapeutic intervention was also monitored by quantitative PCR and paralleled in the two cases the clinical improvement. Diagnosis of HHV-6 infection must be systematically evoked in case of unexplained ALF, since it might lead to specific therapeutic interventions, in addition of liver transplantation.

Sepsis and SOFA score: related outcome for critically ill renal patients.

AIMS: To evaluate the influence of sepsis in critically ill patients with acute renal failure (ARF), and to analyze the value of the sequential organ failure assessment (SOFA) score for assessing the morbidity and related mortality of these patients. MATERIAL AND METHODS: A prospective observational study developed in a medical intensive care unit (ICU) of a tertiary care university hospital. Data were collected from January 1, 2001 - July 31, 2002. The inclusion criterion was either a creatinine plasma level > or = 2 mg/dl on ICU admission or increases > or = 30% from its initial value. Sepsis was evaluated at the time of study inclusion, and patients were distributed into 2 groups (septic and nonseptic patients). RESULTS: Two hundred patients with ARF were prospectively enrolled in the study (91 (45.5%) septic and 109 (54.5%) nonseptic patients). Median age was 68 years in septic patients and 72 in nonseptic ones while the percentage of males in both groups was 66% vs 69%, respectively. Septic patients showed more organ failures and more respiratory, cardiovascular and coagulation failures at the time of study admission as well as a worse mean SOFA score during the first 4 days after inclusion (p < 0.01). Mortality rate at the ICU was significantly higher in the septic group when compared to the nonseptic one (55% vs 19.3%, OR = 2.21 (1.65 - 2.97)). Using stepwise logistic regression, acute tubular necrosis and oliguria in septic patients as well as cardiovascular failure (evaluated by SOFA score) in nonseptic patients were identified as independent risk factors for mortality. CONCLUSIONS: Septic and nonseptic ICU patients with ARF have an increased risk of ICU mortality depending on the type of organ failure. Although SOFA score does not predict outcome, it is a useful tool to categorize these patients and to describe a sequence of complications in critically ill patients.

[Acute renal failure in critically ill patients. A prospective epidemiological study]. / Fracaso renal agudo en la unidad de cuidados intensivos. Estudio observacional prospectivo.

AIMS: To determine factors which may predict mortality in patients admitted to intensive care unit who present acute renal failure. METHODS: Prospective observational study of the patients admitted to a multidisciplinary intensive care unit over a year. The inclusion criteria were a creatinine plasmatic value > or = 2 mg/dl (177 micromol/l) or an increase (30% or higher) of its basal value on admittance. RESULTS: One hundred and twenty-seven patients (age = 65.83 +/- 15.06 years; 38% male) with acute renal failure, were prospectively enrolled in the study (13% of intensive care unit admissions). The univariate analysis showed that hospital origin, acute tubular necrosis, late ARF, oliguria, maintained hypotension, sedation or coma, oncological disease and need of mechanical ventilation were significantly associated with mortality (p < 0.05). This association was also found for sepsis (OR: 41.5), multiorganic failure (OR: 3.58) and respiratory, cardiovascular or haematological failure according to the SOFA score. The multivariate analysis found that four clinical variables had an independent predictive value for mortality risk: acute tubular necrosis [OR: 4.57 (2.32-9.00)], use of vasoactive drugs [OR: 2.32 (1.22-4.40)], oliguria [OR: 2.15 (1.12-4.13)] and the acute renal failure starting during admission [OR: 2.06 (1.09-3.88)]. CONCLUSION: Data related to renal failure have worse prognosis than other demographic or clinical data in critically ill patients with acute renal failure. Multicentric studies with unified criteria are needed to analyse the most important prognostic factors.

[Complications due to peripheral venous catheterization. Prospective study]. / Complications liées au cathétérisme veineux périphérique. Etude prospective.

OBJECTIVE: Peripheral venous catheter (PVC)-associated complications were prospectively evaluated in a 2 month-study performed in 3 different wards. METHODS: For each inserted PVC, the following complications were observed daily by an external investigator: tenderness, erythema, swelling or induration, palpable cord and purulence. PVC that were removed were systematically sent to the Microbiology department and analysed according to the semi-quantitative method described by Brun-Buisson et al. RESULTS: A total of 525 PVC (corresponding to 1,036 catheterisation-days) were included. Main clinical complications were erythema (22.1%), tenderness (21.9%), swelling or induration (20.9%), palpable cord (2.7%) and purulence (0.2%). Phlebitis, defined by 2 or more of the following signs: tenderness, erythema, swelling or induration and palpable cord, was observed in 22%. Catheter colonization (> or = 103 CFU/ml) occurred in 13%. Bacteria isolated from colonized catheters were coagulase-negative staphylococci (88.1%), Staphylococcus aureus (7.1%) and Candida sp. (4.8%). Multivariate risk factor analysis showed that age > or = 55 y. (OR = 3.16, p = 0.003), insertion on articulation site (OR = 2.94, p = 0.01) or in jugular vein (OR = 8.18, p = 0.01) and > 72 hour-catheterisation (OR = 4.74, p = 0.0003) were significantly associated with PVC colonization. Risk factors for phlebitis were skin lesions (OR = 1.88, p < 0.016), active infection unrelated to PVC (OR = 2.8, p = 0.001), "poor quality" peripheral vein (OR = 2.46, p < 0.02) and > 72 hour-catherisation (OR = 2.38, p = 0.009). CONCLUSION: Complications associated with peripheral venous catheters are frequent but remain benign. They could probably be reduced by a systematic change every 72-96 hours as recommended by different guidelines.

[Cholestatic icterus induced by the administration of fusidic acid in a cirrhotic patient]. / Ictère cholestatique induit par la prise d'acide fucidique chez un patient cirrhotique.

INTRODUCTION: Fucidic acid is an antibiotic essentially used to treat staphylococcal infections. Its chemical structure is very similar to that of bilary acids and hence implies competitive mechanisms between their elimination and metabolization. OBSERVATION: A patient with a past history of alcohol-induced cirrhosis was treated with fucidic acid for a Staphylococci aureus urinary infection. On day 2 of treatment a conjugate bilirubine icterus appeared. There was no argument to suggest a decompensation of the icterus. The icterus disappeared on suspension of fucidic acid. COMMENTS: The occurrence of an icterus in a cirrhotic patient may evoke decompensation of the hepatopathy and an extensive exploration must be made. A thorough survey of all drug administration must be made. Notably, the possibility of the occurrence of a connective bilirubin icterus during treatment with fucidic acid must be known. The icterus always regresses on withdrawal of treatment and this etiology must be evoked before conducting invasive examinations.

Acute liver failure as initial manifestation of low-grade non-Hodgkin's lymphoma transformation into large-cell lymphoma.

Acute liver failure as an initial manifestation of primary non-Hodgkin's lymphoma is a rare phenomenon with a grim prognosis. We report for the first time on a patient with a history of follicular lymphoma in complete remission, presenting fulminant liver failure due to massive liver infiltration by transformed lymphoma cells and portal vein thrombosis, as an initial manifestation of transformation into large-cell lymphoma.

Sequential treatment with lamivudine and interferon monotherapies in patients with chronic hepatitis B not responding to interferon alone: results of a pilot study.

Sustained viral suppression using monotherapy with interferon alfa (IFN-alpha) or lamivudine can only be achieved in a small percentage of patients with chronic hepatitis B. The concomitant administration of lamivudine and IFN-alpha does not enhance efficacy. We postulated that the optimal timing of therapy might be sequential treatment with lamivudine and IFN-alpha. The aim of this study was therefore to assess the efficacy of sequential treatment in patients resistant to IFN-alpha alone. Fourteen male patients, with a median age of 40 years, nonresponders to IFN-alpha with hepatitis B virus (HBV) DNA > 100 pg/mL (branched DNA [bDNA] Chiron) and positive hepatitis B e antigen (HBeAg) in 11 of 14 patients, were treated with lamivudine 100 mg/d alone for 20 weeks, then with both IFN-alpha2b 5 MU 3 times per week and lamivudine for 4 weeks, and lastly with IFN-alpha alone for 24 weeks. At the end of lamivudine therapy, all patients had undetectable serum HBV DNA, and none exhibited an emergence of HBV polymerase mutant or breakthrough. Sustained serum HBV-DNA clearance 6 months after the end of sequential treatment was achieved in 8 of 14 patients, HBeAg-to-anti-HBe seroconversion in 5 of 11 patients, and HBeAg and hepatitis B surface antigen (HBsAg) seroconversions in 3 of 14 patients (anti-HBs > 100 IU/mL). All sustained responders had normalized their alanine transaminase (ALT) values and exhibited histologic improvements. In conclusion, the results of this pilot study suggest that sequential treatment with lamivudine and IFN-alpha can induce a sustained virologic response, including HBs seroconversion, in patients with chronic hepatitis B not responding to IFN-alpha alone, without the selection of drug-resistant mutants. This therapeutic schedule warrants further evaluation in clinical trials.

Hepatitis C virus induced hypobetalipoproteinemia: a possible mechanism for steatosis in chronic hepatitis C.

BACKGROUND/AIMS: Steatosis could be the result of HCV (hepatitis C virus)-induced hypobetalipoproteinemia in patients with chronic hepatitis C. The aim of this study was to assess serum levels of main constituents of betalipoproteins and their relationship with steatosis in patients with chronic hepatitis C without known risk factors for steatosis. PATIENTS: One-hundred male patients with untreated biopsy proven non-cirrhotic chronic hepatitis C were included. Twenty-nine of these patients were further treated with interferon. RESULTS: Cholesterol concentration was significantly lower in patients compared to three control groups: reference male population, patients with chronic hepatitis B or with non-alcoholic fatty liver. In multivariate analysis, low apolipoprotein B concentration was an independent factor related with the degree of steatosis. Hypobetalipoproteinemia and degree of steatosis were significantly associated with infection with genotype 3. Among treated patients, only sustained virological responders had a significant increase of cholesterol (5.6 +/- 1 vs. 4.7 +/- 1.3 mmol/l; P = 0.03) and apolipoprotein B concentrations (113 +/- 19 vs. 75 +/- 14 mg/dl; P = 0.05). CONCLUSION: In chronic hepatitis C, hypobetalipoproteinemia is prevalent and associated with steatosis, especially in patients infected with genotype 3. The correction of hypobetalipoproteinemia following HCV eradication suggests that HCV itself could induce hypobetalipoproteinemia and steatosis.

Review article: Overview of medical treatments in unresectable hepatocellular carcinoma--an impossible meta-analysis?

BACKGROUND: Controversies surrounding medical treatment in patients with unresectable hepatocellular carcinoma continue to persist. AIM: To perform a meta-analysis of therapeutic modalities which had been evaluated in two or more randomized trials. METHODS: Fifty-two randomized trials were studied; only 30 were included. This overview identified seven therapeutic modalities which had been evaluated in two or more trials: adriamycin, 5-fluorouracil, interferon, percutaneous ethanol injection, transarterial chemotherapy, the combination of lipiodol with transarterial chemotherapy, and tamoxifen. RESULTS: Comparisons of survival between control groups showed substantial heterogeneity. There was no survival benefit at 1 year with adriamycin (mean difference 4%), 5-fluorouracil (mean difference -3%), percutaneous ethanol injection (mean difference 6%) or transarterial chemotherapy (mean difference -2%). For interferon, the survival benefit was significant with the Der Simonian & Laird method (mean difference 9%, 95% CI = 1-18%, P = 0.04) but not with the Peto et al. method (2.4 mean odds ratio, 95% CI = 0.9-6.8). The meta-analysis of tamoxifen showed a borderline survival benefit (mean difference 25%, 95% CI = 0-49%, P = 0.05). However, in sensitivity analyses, the survival benefit of tamoxifen was no longer significant. CONCLUSIONS: No treatment has clearly proven efficacy in survival. 5-Fluorouracil, adriamycin and transarterial chemotherapy were not associated with survival benefit at 1 year. The number of randomized controlled trials was insufficient to enable a conclusion to be reached for interferon and percutaneous ethanol injection. Controversy persists concerning tamoxifen efficacy. Interferon and tamoxifen require new randomized controlled trials on a larger population of patients.

Sickle cell anemia and beta-gene cluster haplotypes in Cuba.

We have studied 91 patients with SS genotype, 44 children and 47 adults. Excluding the Cameroon and atypical haplotypes, the distribution in the children's sample exhibited 43% Benin, 38% Bantu, and 3% Senegal. In adults, the sample exhibited 46% Benin, 30% Bantu, and 9% Senegal (chi 2: 13.511, 2 df, P = 0.001). When the whole sample of 198 chromosomes (SS, SC, and S/beta thal) is considered, we find that the beta s chromosome is linked 51% to the Benin haplotype, 41% with the Bantu, and 8% with the Senegal. After adjusting for the different frequencies of beta s in Africa, these numbers would predict the port of origin to be 16% from Atlantic West Africa, 37.3% from Central West Africa, and 46% from Bantu-speaking Africa. This is in direct contradiction with the historical record that establishes a higher percentage from Bantu-speaking Africa (55%) and a much lower percentage from Senegal (3.4%). The overall conclusions from these findings is that there is a loss of Bantu haplotypes in sickle cell syndromes in Cuba, particularly among adults, and that there is an excess of Senegal haplotype, also among adults. These differences might reflect the differential survival and severity of the sickle cell disease linked to these haplotypes.