Richard Hall

Critically Ill Patients With 2009 Influenza A(H1N1) Infection in Canada

CONTEXTnBetween March and July 2009, the largest number of confirmed cases of 2009 influenza A(H1N1) infection occurred in North America.nnnOBJECTIVEnTo describe characteristics, treatment, and outcomes of critically ill patients in Canada with 2009 influenza A(H1N1) infection.nnnDESIGN, SETTING, AND PATIENTSnA prospective observational study of 168 critically ill patients with 2009 influenza A(H1N1) infection in 38 adult and pediatric intensive care units (ICUs) in Canada between April 16 and August 12, 2009.nnnMAIN OUTCOME MEASURESnThe primary outcome measures were 28-day and 90-day mortality. Secondary outcomes included frequency and duration of mechanical ventilation and duration of ICU stay.nnnRESULTSnCritical illness occurred in 215 patients with confirmed (n = 162), probable (n = 6), or suspected (n = 47) community-acquired 2009 influenza A(H1N1) infection. Among the 168 patients with confirmed or probable 2009 influenza A(H1N1), the mean (SD) age was 32.3 (21.4) years; 113 were female (67.3%) and 50 were children (29.8%). Overall mortality among critically ill patients at 28 days was 14.3% (95% confidence interval, 9.5%-20.7%). There were 43 patients who were aboriginal Canadians (25.6%). The median time from symptom onset to hospital admission was 4 days (interquartile range [IQR], 2-7 days) and from hospitalization to ICU admission was 1 day (IQR, 0-2 days). Shock and nonpulmonary acute organ dysfunction was common (Sequential Organ Failure Assessment mean [SD] score of 6.8 [3.6] on day 1). Neuraminidase inhibitors were administered to 152 patients (90.5%). All patients were severely hypoxemic (mean [SD] ratio of Pao(2) to fraction of inspired oxygen [Fio(2)] of 147 [128] mm Hg) at ICU admission. Mechanical ventilation was received by 136 patients (81.0%). The median duration of ventilation was 12 days (IQR, 6-20 days) and ICU stay was 12 days (IQR, 5-20 days). Lung rescue therapies included neuromuscular blockade (28% of patients), inhaled nitric oxide (13.7%), high-frequency oscillatory ventilation (11.9%), extracorporeal membrane oxygenation (4.2%), and prone positioning ventilation (3.0%). Overall mortality among critically ill patients at 90 days was 17.3% (95% confidence interval, 12.0%-24.0%; n = 29).nnnCONCLUSIONnCritical illness due to 2009 influenza A(H1N1) in Canada occurred rapidly after hospital admission, often in young adults, and was associated with severe hypoxemia, multisystem organ failure, a requirement for prolonged mechanical ventilation, and the frequent use of rescue therapies.

A Comparison of Sucralfate and Ranitidine for the Prevention of Upper Gastrointestinal Bleeding in Patients Requiring Mechanical Ventilation

BACKGROUNDnCritically ill patients who require mechanical ventilation are at increased risk for gastrointestinal bleeding from stress ulcers. There are conflicting data on the effect of histamine H2-receptor antagonists and the cytoprotective agent sucralfate on rates of gastrointestinal bleeding, ventilator-associated pneumonia, and mortality.nnnMETHODSnIn a multicenter, randomized, blinded, placebo-controlled trial, we compared sucralfate with the H2-receptor antagonist ranitidine for the prevention of upper gastrointestinal bleeding in 1200 patients who required mechanical ventilation. Patients received either nasogastric sucralfate suspension (1 g every six hours) and an intravenous placebo or intravenous ranitidine (50 mg every eight hours) and a nasogastric placebo.nnnRESULTSnThe patients in the two groups had similar base-line characteristics. Clinically important gastrointestinal bleeding developed in 10 of 596 (1.7 percent) of the patients receiving ranitidine, as compared with 23 of 604 (3.8 percent) of those receiving sucralfate (relative risk, 0.44; 95 percent confidence interval, 0.21 to 0.92; P=0.02). In the ranitidine group, 114 of 596 patients (19.1 percent) had ventilator-associated pneumonia, as compared with 98 of 604 (16.2 percent) in the sucralfate group (relative risk, 1.18; 95 percent confidence interval, 0.92 to 1.51; P=0.19). There was no significant difference between the groups in mortality in the intensive care unit (ICU) (23.5 percent in the ranitidine group and 22.9 percent in the sucralfate group) or the duration of the stay in the ICU (median, nine days in both groups).nnnCONCLUSIONSnAmong critically ill patients requiring mechanical ventilation, those receiving ranitidine had a significantly lower rate of clinically important gastrointestinal bleeding than those treated with sucralfate. There were no significant differences in the rates of ventilator-associated pneumonia, the duration of the stay in the ICU, or mortality.

A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group.

BACKGROUNDnCritically ill patients who require mechanical ventilation are at increased risk for gastrointestinal bleeding from stress ulcers. There are conflicting data on the effect of histamine H2-receptor antagonists and the cytoprotective agent sucralfate on rates of gastrointestinal bleeding, ventilator-associated pneumonia, and mortality.nnnMETHODSnIn a multicenter, randomized, blinded, placebo-controlled trial, we compared sucralfate with the H2-receptor antagonist ranitidine for the prevention of upper gastrointestinal bleeding in 1200 patients who required mechanical ventilation. Patients received either nasogastric sucralfate suspension (1 g every six hours) and an intravenous placebo or intravenous ranitidine (50 mg every eight hours) and a nasogastric placebo.nnnRESULTSnThe patients in the two groups had similar base-line characteristics. Clinically important gastrointestinal bleeding developed in 10 of 596 (1.7 percent) of the patients receiving ranitidine, as compared with 23 of 604 (3.8 percent) of those receiving sucralfate (relative risk, 0.44; 95 percent confidence interval, 0.21 to 0.92; P=0.02). In the ranitidine group, 114 of 596 patients (19.1 percent) had ventilator-associated pneumonia, as compared with 98 of 604 (16.2 percent) in the sucralfate group (relative risk, 1.18; 95 percent confidence interval, 0.92 to 1.51; P=0.19). There was no significant difference between the groups in mortality in the intensive care unit (ICU) (23.5 percent in the ranitidine group and 22.9 percent in the sucralfate group) or the duration of the stay in the ICU (median, nine days in both groups).nnnCONCLUSIONSnAmong critically ill patients requiring mechanical ventilation, those receiving ranitidine had a significantly lower rate of clinically important gastrointestinal bleeding than those treated with sucralfate. There were no significant differences in the rates of ventilator-associated pneumonia, the duration of the stay in the ICU, or mortality.

Evidence-based clinical practice guideline for the prevention of ventilator-associated pneumonia.

Critically ill patients in the intensive care unit (ICU) are at high risk for infections associated with increased morbidity, mortality, and health care costs (1-3). The overall infection rate in critically ill patients approaches 40% and may be as high as 50% or 60% in patients who remain in the ICU for more than 5 days (4, 5). Respiratory tract infections account for 30% to 60% of all such infections. The incidence of pneumonia acquired in the ICU ranges from 10% to 65% (6-11). Among patients at high risk for ventilator-associated pneumonia (VAP) are those who have chronic obstructive pulmonary disease, burns, neurosurgical conditions, the acute respiratory distress syndrome, and witnessed aspiration; those who are reintubated; and those who receive paralytic agents or enteral nutrition (12, 13). The attributable morbidity and mortality of VAP are clinically important. In a prospective, matched cohort study, patients with VAP remained in the ICU 4.3 days (95% CI, 1.5 to 7.0 days) longer than patients who did not have VAP and had a trend toward an increased risk for death (absolute risk increase, 5.8% [CI, 2.4% to 14.0%]) (14). Six other studies using a matching strategy found a prolonged length of ICU stay associated with VAP (range, 5 to 13 days) and attributable mortality ranging from an absolute risk increase of 0% to 50% (15-20). Therefore, strategies to decrease the incidence of VAP could decrease morbidity, mortality, and health care costs and improve patient safety. A survey of the use of VAP prevention strategies identified differences across countries (21). For example, changing the ventilator circuit for each new patient was reported more frequently by French ICU directors than those in Canada (21). This survey also showed that some effective strategies were used infrequently, suggesting inadequate translation of randomized trial results into practice. One potential catalyst for knowledge translation is an evidence-based clinical practice guideline. Therefore, a Joint Planning Group of the Canadian Critical Care Society and Canadian Critical Care Trials Group commissioned the development of an evidence-based clinical practice guideline for the prevention of VAP. In this paper, we describe the methods used to create the guideline and the recommendations generated. Methods The Joint Planning Group selected an 11-member VAP Prevention Guideline Panel made up of 9 intensivists from university-affiliated and community hospitals, an ICU nurse, and an ICU respiratory therapist. Panel members were experts in critical care medicine (n= 9), VAP (n= 4), evidence-based medicine (n= 4), and guideline development (n= 3). The context was mechanically ventilated adult patients cared for in the ICU. The target audience was ICU clinicians in university-affiliated and community hospitals. To identify potentially relevant evidence, we searched 3 bibliographic databases (MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews) to 1 April 2003 for randomized trials that evaluated interventions influencing VAP (Appendix). We had no language restrictions. We also reviewed personal files and practice guidelines on this subject previously published by the Centers for Disease Control and Prevention (22) and the American Thoracic Society (23). We included randomized trials and systematic reviews of randomized trials that 1) studied adult critically ill patients; 2) had VAP as an outcome; and 3) evaluated any of the following interventions: physical strategies (route of endotracheal intubation, systematic search for maxillary sinusitis, frequency of ventilator circuit changes, type of airway humidification, frequency of humidifier changes, endotracheal suctioning system, subglottic secretion drainage, chest physiotherapy, and tracheostomy timing), positional strategies (kinetic beds, semi-recumbent positioning, and prone positioning), and pharmacologic strategies (stress ulcer prophylaxis and prophylactic antibiotics, including selective decontamination of the digestive tract). Since study authors used various definitions of VAP, we used the definitions they provided. The most common definition was a new or persistent radiographic infiltrate plus fever, leukocytosis, change in the volume or color of sputum, or isolation of a pathogen. If available, histologic evidence of pneumonia was also used. A priori, we decided to review only systematic reviews of randomized clinical trials for antibiotic prophylaxis and only randomized clinical trials for all other topics. We excluded crossover and beforeafter studies. We also excluded randomized trials of ventilator weaning, including noninvasive mechanical ventilation, and nutritional interventions evaluating VAP because guidelines addressing these topics have recently been published (24, 25). In duplicate and independently, 3 pairs of panel members critically appraised each trial (26, 27) and systematic review (28). Each member of a pair compared his or her independent appraisal of a given trial or systematic review with that of the other member of the pair. For each randomized trial, we abstracted sample, allocation, intervention, co-interventions, exclusions after randomization, blinding of outcome assessment, definition of VAP, crude VAP events, relative risk for VAP, and other outcomes. For each intervention, we summarized the risk differences and calculated a pooled risk difference. For each systematic review, we abstracted number of trials, population, intervention, selection criteria, search strategy, validity assessment, method of pooling results, homogeneity assessment, VAP definition, pooled event rates, and other outcomes. Before the panel meeting, each pair of appraisers achieved consensus on the validity and results of the trials they reviewed. One month before the panel meeting, panel members received the evidence tables for review prepared by the 3 pairs of appraisers. A priori, panel members agreed to read all circulated documents and evidence tables in advance, to use levels of evidence to generate a status statement for each item, and to abide by the group process and consensus methods. The Canadian Critical Care Society appointed a chair to ensure that the panel achieved its objectives through group process (29). At the panel meeting, each member recorded any potential conflicts of interest (30). The pair of panel members responsible for critical appraisal of each intervention provided a structured written and oral presentation of the evidence. After the panel discussion, the initial evidence summary was revised if necessary. The panel members assigned levels of evidence, semi-quantitative scores to summarize the evidence and describe the intervention, and a status statement. We classified trials as level 1 if they had all of the following: concealed randomization, blinded outcome adjudication, an intention-to-treat analysis, and an explicit definition of VAP. Trials were classified as level 2 if any one of these characteristics was unfulfilled and as level 3 if allocation was not strictly randomized. We used a semi-quantitative score (0, 1, 2, or 3) to evaluate each intervention with respect to the validity of the randomized trials; the effect size of each intervention; the confidence intervals around the estimate of effect; the homogeneity of the trial results; and the safety, feasibility, and economic consequences of the intervention. The language of the status statement for each item was keyed to the levels of evidence and the semi-quantitative scores. We used the term recommended if there were no reservations about endorsing an intervention and the term considered if the evidence supported an intervention but there were minor uncertainties about the benefits, harms, or costs. No recommendation was made if evidence regarding an intervention was inadequate or if there were major uncertainties about the benefits, harms, or costs. After the panel meeting, the chair compiled the summaries and status statements and sent them to all panel members to check accuracy and clarity. In addition, the pairs of evidence appraisers wrote background documents for the interventions they appraised, including the rationale for each intervention, appraisal of randomized trials and systematic reviews, and harms and costs of the interventions. The chair and the writing committee organized the background documents, the evidence summaries, a table of the semi-quantitative scores, and the status statement for each item. We formatted the document with a structured abstract (31), a summary of the evidentiary basis for each recommendation, and a status statement for each item. We also created a quick reference guide. The draft guideline document was submitted for structured external review by the executives of the Canadian Critical Care Society and the Canadian Critical Care Trials Group and the respective executives of the Canadian Association of Critical Care Nurses, Canadian Society of Respiratory Therapists, Canadian Infectious Disease Society, and Canadian Thoracic Society. External reviewers were asked to critique whether the guideline was logical, clear, and practical and to critique the guideline development process. The panel revised the document on the basis of this feedback. The final guideline was returned to the external reviewers for further comments and official endorsement by their respective organizations. The final guideline was then piloted in 2 institutions. To record the agreement of each panel member with the final status statement for each item, we sent the final document to all panel members. Independently, blinded to each others ratings, panel members used a Likert scale from 1 to 9 that was anchored by disagree completely at the low end and agree completely at the high end. The panel will formally review and update this guideline every 2 years (32). The funding source played no role in study selection for this guideline and had no role in its development

Sedation for critically ill adults with severe traumatic brain injury: a systematic review of randomized controlled trials.

Objectives:To summarize randomized controlled trials on the effects of sedative agents on neurologic outcome, mortality, intracranial pressure, cerebral perfusion pressure, and adverse drug events in critically ill adults with severe traumatic brain injury. Data Sources:PubMed, MEDLINE, EMBASE, the Cochrane Database, Google Scholar, two clinical trials registries, personal files, and reference lists of included articles. Study Selection:Randomized controlled trials of propofol, ketamine, etomidate, and agents from the opioid, benzodiazepine, &agr;-2 agonist, and antipsychotic drug classes for management of adult intensive care unit patients with severe traumatic brain injury. Data Extraction:In duplicate and independently, two investigators extracted data and evaluated methodologic quality and results. Data Synthesis:Among 1,892 citations, 13 randomized controlled trials enrolling 380 patients met inclusion criteria. Long-term sedation (≥24 hrs) was addressed in six studies, whereas a bolus dose, short infusion, or doubling of plasma drug concentration was investigated in remaining trials. Most trials did not describe baseline traumatic brain injury prognostic factors or important cointerventions. Eight trials possibly or definitely concealed allocation and six were blinded. Insufficient data exist regarding the effects of sedative agents on neurologic outcome or mortality. Although their effects are likely transient, bolus doses of opioids may increase intracranial pressure and decrease cerebral perfusion pressure. In one study, a long-term infusion of propofol vs. morphine was associated with a reduced requirement for intracranial pressure-lowering cointerventions and a lower intracranial pressure on the third day. Trials of propofol vs. midazolam and ketamine vs. sufentanil found no difference between agents in intracranial pressure and cerebral perfusion pressure. Conclusions:This systematic review found no convincing evidence that one sedative agent is more efficacious than another for improvement of patient-centered outcomes, intracranial pressure, or cerebral perfusion pressure in critically ill adults with severe traumatic brain injury. High bolus doses of opioids, however, have potentially deleterious effects on intracranial pressure and cerebral perfusion pressure. Adequately powered, high-quality, randomized controlled trials are urgently warranted.

The role of recombinant factor VIIa in on-pump cardiac surgery : Proceedings of the Canadian Consensus Conference

PurposeRecombinant activated factor VII (rFVIIa) is currently not approved by Health Canada or the Food and Drug Administration for treating excessive blood loss in nonhemophiliac patients undergoing on-pump cardiac surgery, but is increasingly being used “off-label” for this indication. A Canadian Consensus Conference was convened to generate recommendations for rFVIIa use in on-pump cardiac surgery.Methods: The panel undertook a literature review of the use of rFVIIa in both cardiac and non-cardiac surgery. Appropriateness, timing, and dosage considerations were addressed for three cardiac surgery indications: prophylactic, routine, and rescue uses. Recommendationswere based on evidencefromtheliterature and derived by consensus following recognized grading procedures.ResultsThe panel recommended against prophylactic or routine use of rFVIIa, as there is no evidence at this time that the benefits of rFVIIa outweigh its potential risks compared with standard hemostatic therapies. On the other hand, the panel made a weak recommendation (grade 2C) for the use of rFVIIa (one to two doses of 35–70 μg·kg-1) as rescue therapy for blood loss that is refractory to standard hemostatic therapies, despite the lack of randomized controlled trial data for this indication.ConclusionsIn cardiac surgery, the risks and benefits of rFVIIa are unclear, but current evidence suggests that its benefits may outweigh its risks for rescue therapy in selected patients. Methodologically rigorous studies are needed to clarify its risk-benefit profile in cardiac surgery patients.ObjectifLe facteur VII activé recombinant (rFVIIa) n’est actuellement approuvé ni par Santé Canada ni par la Food and Drug Administration (FDA) pour le traitement du saignement excessif chez les patients non-hémophiles subissant une chirurgie cardiaque avec circulation extra-corporelle (CEC); néanmoins, il est de plus en plus utilisé de manière ‘non conforme’ pour cette indication. Une Conférence canadienne de consensus s’est réunie afin de rédiger des recommandations quant à l’utilisation du rFVIIa lors de la chirurgie cardiaque avec CEC.MéthodeLe panel a entrepris une revue de la littérature traitant de l’utilisation du rFVIIa en chirurgies cardiaque et non cardiaque. Des considérations quant à la justification, au moment de l’administration et à la posologie ont été évaluées pour trois indications en chirurgie cardiaque: les utilisations prophylactique, de routine ou de sauvetage. Les recommandations, basées sur des données probantes tirées de la littérature, ont été interprétées par un consensus suivant des procédures de gradation reconnues.RésultatsLe panel s’est prononcé contre une utilisation prophylactique ou de routine du rFVIIa, étant donné qu’il n’existe actuellement pas de preuve que les bienfaits du rFVIIa l’emportent sur les risques potentiels encourus en comparaison des thérapies hémostatiques standard. En revanche, le panel a énoncé une recommandation faible (note 2C) en faveur de l’utilisation du rFVIIa (une à deux doses de 35–70 μg·kg-1) comme thérapie de sauvetage en cas de saignement réfractaire aux thérapies hémostatiques standard et ce, malgré le manque de données d’études randomisées contrôlées concernant cette indication.ConclusionEn chirurgie cardiaque, les risques et bienfaits du rFVIIa ne sont pas clairs; toutefois, les données actuelles suggèrent que ses bienfaits pourraient contrebalancer ses risques dans les cas de thérapie de sauvetage chez certains patients. Des études méthodologiquement rigoureuses sont nécessaires afin de clarifier le profil risque/bénéfice du rFVIIa pour les patients de chirurgie cardiaque.

Effect of acute inflammatory brain injury on accumulation of morphine and morphine 3- and 6-glucuronide in the human brain.

Objective: In animals, central nervous system inflammation increases drug accumulation in the brain partly due to a loss of central nervous system drug efflux transporter function at the blood‐brain barrier. To determine whether a similar loss of active drug efflux occurs in humans after acute inflammatory brain injury. Design: Observational human pharmacokinetic study. Setting: Medical‐surgical‐neurosurgical intensive care unit at a university‐affiliated, Canadian tertiary care center. Patients: Patients with acute inflammatory brain injury, including subarachnoid hemorrhage (n = 10), intracerebral and/or intraventricular hemorrhage (n = 4), or closed head trauma (n = 2) who received morphine intravenously after being fitted with cerebrospinal fluid ventriculostomy and peripheral arterial catheters. Interventions: We correlated the cerebrospinal fluid distribution of morphine, morphine‐3‐glucuronide, and morphine‐6‐glucuronide with the cerebrospinal fluid and plasma concentration of the proinflammatory cytokine interleukin‐6 and the passive marker of blood‐brain barrier permeability, albumin. Measurements and Main Results: Acute brain injury produced a robust inflammatory response in the central nervous system as reflected by the elevated concentration of interleukin‐6 in cerebrospinal fluid. Penetration of morphine metabolites into the central nervous system increased in proportion to the neuroinflammatory response as demonstrated by the positive correlation between cerebrospinal fluid interleukin‐6 exposure and the area under the curve cerebrospinal fluid/plasma ratio for morphine‐3‐glucuronide (r = .49, p < .001) and morphine‐6‐glucuronide (r = .51, p < .001). In contrast, distribution of morphine into the brain was not linked with cerebrospinal fluid interleukin‐6 exposure (r = .073, p = .54). Albumin concentrations in plasma and cerebrospinal fluid were consistently in the normal range, indicating that the physical integrity of the blood‐brain barrier was likely undisturbed. Conclusions: Our results suggest that central nervous system inflammation following acute brain injury may selectively inhibit the activity of specific drug efflux transporters within the blood‐brain barrier. This finding may have significant implications for patients with neuroinflammatory conditions when administered centrally acting drugs normally excluded from the brain by such transporters.

Should ancillary brain blood flow analyses play a larger role in the neurological determination of death? Les analyses secondaires du debit sanguin cerebral devraient-elles jouer un role plus important dans le diagnostic de deces neurologique?

PurposeWe present two patients who regained spontaneous respiration following clinical neurological determination of death (NDD) while ancillary radiological imaging demonstrated brain blood flow.Clinical featuresA 26-yr-old male with chronic otitis media presented with a Glasgow Coma Scale (GCS) score of 3 and fixed 7-mm pupils. Computed tomography demonstrated right-sided mastoiditis and a temporal lobe abscess associated with uncal herniation. The patient was diagnosed brain dead seven-hr later when motor responses and brainstem reflexes were absent and his apnea test was positive. Approximately 28-hr after NDD, during post-declaration organ resuscitation, the patient regained spontaneous respiration and magnetic resonance imaging revealed brain blood flow. Spontaneous respirations persisted for five-days before cardiovascular collapse occurred. In the second case, a 50-yr-old female presented with a GCS score of 3 and fixed 6-mm pupils following a traumatic brain injury and a five-minute cardiac arrest. The patient was deemed clinically brain dead six-hr later when physical examination revealed absent motor responses and brainstem reflexes and her apnea test was positive. As confirmation of brain death, a cerebral radionuclide angiogram was performed, which surprisingly revealed intracranial arterial flow. During organ resuscitation, 11-hr after NDD, the patient regained spontaneous respiration. She expired hours after family decision to withdraw treatment.ConclusionFor both patients, several unrecognized confounding factors for NDD were present. These cases illustrate the difficulties encountered by experienced clinicians in determining brain death using clinical criteria alone, and they suggest that more routine use of ancillary brain blood flow analyses should be recommended.RésuméObjectifNous présentons les cas de deux patients qui ont recommencé à respirer spontanément après avoir reçu un diagnostic de décès neurologique clinique alors que l’imagerie radiologique secondaire démontrait un débit sanguin cérébral.Éléments cliniquesUn homme de 26 ans souffrant d’otite moyenne chronique s’est présenté avec un score de 3 sur l’échelle de coma de Glasgow (GCS) et des pupilles fixes à 7xa0mm. La tomodensitométrie a montré une antro-mastoïdite droite et un abcès au lobe temporal associé à une herniation uncinée. La mort cérébrale a été diagnostiquée chez le patient sept heures plus tard, lorsque les réponses motrices et les réflexes du tronc cérébral ont cessé et que le test d’apnée était positif. Environ 28xa0h après le diagnostic du décès neurologique, pendant la réanimation pour préserver les organes, le patient a recommencé à respirer spontanément et l’imagerie par résonance magnétique a révélé un débit sanguin cérébral. Les respirations spontanées ont continué durant cinq jours avant la survenue d’un collapsus cardiovasculaire. Dans le deuxième cas, une femme de 50 ans s’est présentée avec un score de 3 sur l’échelle GCS et des pupilles fixes à 6xa0mm à la suite d’une lésion cérébrale traumatique et d’un arrêt cardiaque de cinq minutes. La mort cérébrale a été diagnostiquée chez la patiente six heures plus tard lorsque l’examen physique a révélé qu’il n’y avait plus de réponse motrice ni de réflexe du tronc cérébral et que le test d’apnée était positif. Pour confirmer la mort cérébrale, une angiographie isotopique cérébrale a été réalisée, laquelle a curieusement révélé un débit artériel intracrânien. Pendant la réanimation des organes 11xa0h après le diagnostic du décès neurologique, la patiente a recommencé à respirer spontanément. Elle est décédée quelques heures après la décision de la famille de ne pas la traiter.ConclusionChez les deux patients, plusieurs variables parasites non reconnues pour le diagnostic du décès neurologique étaient présentes. Ces cas illustrent les difficultés rencontrées par des cliniciens d’expérience lorsqu’ils doivent déterminer la mort cérébrale sur la base de critères cliniques seulement, et suggèrent qu’une utilisation plus fréquente d’analyses secondaires du débit sanguin cérébral pourrait être de mise.

Cost-effectiveness of Dalteparin vs Unfractionated Heparin for the Prevention of Venous Thromboembolism in Critically Ill Patients

IMPORTANCEnVenous thromboembolism (VTE) is a common complication of acute illness, and its prevention is a ubiquitous aspect of inpatient care. A multicenter blinded, randomized trial compared the effectiveness of the most common pharmocoprevention strategies, unfractionated heparin (UFH) and the low-molecular-weight heparin (LMWH) dalteparin, finding no difference in the primary end point of leg deep-vein thrombosis but a reduced rate of pulmonary embolus and heparin-induced thrombocytopenia among critically ill medical-surgical patients who received dalteparin.nnnOBJECTIVEnTo evaluate the comparative cost-effectiveness of LMWH vs UFH for prophylaxis against VTE in critically ill patients.nnnDESIGN, SETTING, AND PARTICIPANTSnProspective economic evaluation concurrent with the Prophylaxis for Thromboembolism in Critical Care Randomized Trial (May 2006 to June 2010). The economic evaluation adopted a health care payer perspective and in-hospital time horizon; derived baseline characteristics and probabilities of intensive care unit and in-hospital events; and measured costs among 2344 patients in 23 centers in 5 countries and applied these costs to measured resource use and effects of all enrolled patients.nnnMAIN OUTCOMES AND MEASURESnCosts, effects, incremental cost-effectiveness of LMWH vs UFH during the period of hospitalization, and sensitivity analyses across cost ranges.nnnRESULTSnHospital costs per patient were

Failure of anticoagulant thromboprophylaxis: risk factors in medical-surgical critically ill patients

39,508 (interquartile range [IQR],