Éric Notebaert

Lipid emulsions in the treatment of acute poisoning: a systematic review of human and animal studies

Objective. To assess the evidence regarding the efficacy and safety of intravenous fat emulsion (IFE) in the management of poisoned patients. Methods. We performed a systematic review of the literature with no time or language restriction. The electronic databases were searched from their inception until June 1, 2009 (Medline, EMBASE, ISI web of science, Biological abstract, LILACS, ChemIndex, Toxnet, and Proquest). We also examined the references of identified articles and the gray literature. The target interventions eligible for inclusion were administration of any IFE before, during, or after poisoning in human or animals. All types of studies were reviewed. Eligibility for inclusion and study quality scores, based on criteria by Jadad and the STROBE statement, were evaluated by independent investigators. The primary outcome was mortality. Secondary outcomes included neurologic, hemodynamic, and electrocardiographic variables, as well as adverse effects. Results. Of the 938 publications identified by the search strategies, 74 met the inclusion criteria. We identified 23 animal trials, 50 human, and 1 animal case reports. Overall, the quality of evidence was weak and significant heterogeneity prevented data pooling. Available data suggest some benefits of IFE in bupivacaine, verapamil, chlorpromazine, and some tricyclic antidepressants and beta-blockers toxicity. No trial assessed the safety of IFE in the treatment of acute poisoning. Conclusion. The evidence for the efficacy of IFE in reducing mortality and improving hemodynamic, electrocardiographic, and neurological parameters in the poisoned patients is solely based on animal studies and human case reports. The safety of IFE has not been established.

Bench-to-bedside review: Iron metabolism in critically ill patients

Critically ill patients frequently develop anemia due to several factors. Iron-withholding mechanisms caused by inflammation contribute to this anemia. The iron metabolism imbalances described or reported in all intensive care studies are similar to the values observed in anemia of inflammation. The administration of iron could be useful in the optimization of recombinant human erythropoietin activity, but this could be at the expense of bacterial proliferation. Since there is a lack of evidence to support either oral or intravenous iron administration in intensive care patients, further studies are necessary to determine the efficacy and safety of iron supplementation in conjunction with recombinant human erythropoietin in critically ill patients. We review the mechanisms leading to iron sequestration in the presence of inflammation. The present article also reviews the literature describing the iron status in critically ill patients and explores the role of iron supplementation in this setting.

Short-term benefits and risks of intravenous iron: a systematic review and meta-analysis

BACKGROUND: Intravenous (IV) iron may correct anemia more efficiently than oral iron, but it has been associated with allergic and hemodynamic reactions, and it may increase the risks of infectious complications. The objective of this systematic review and meta‐analysis was to clarify these controversial issues.

Recombinant Human Erythropoietin Use in Intensive Care

OBJECTIVE: To review the literature concerning the role of recombinant human erythropoietin (rHuEPO) in reducing the need for transfusion in critically ill patients. DATA SOURCES: Articles were obtained through searches of the MEDLINE database (from 1990 to June 2001) using the key words erythropoietin, epoetin alfa, anemia, reticulocytes, hemoglobin, critical care, intensive care, critical illness, and blood transfusion. Additional references were found in the bibliographies of the articles cited. The Cochrane library was also consulted. STUDY SELECTION AND DATA EXTRACTION: Controlled, prospective, and randomized studies on the use of rHuEPO in critically ill adults were selected. DATA SYNTHESIS: Anemia is a common complication in patients requiring intensive care. It is caused, in part, by abnormally low concentrations of endogenous erythropoietin and is mainly seen in patients with sepsis and multiple organ dysfunction syndrome, in whom inflammation mediator concentrations are often elevated. High doses of rHuEPO produce a rapid response in these patients, despite elevated cytokine concentrations. There have been 3 studies on rHuEPO administration in intensive care and 1 trial in acutely burned patients. Only 2 of these studies looked at the impact of rHuEPO administration on the need for transfusion. CONCLUSIONS: Few randomized, controlled trials explore the role of rHuEPO in critical care. Only 1 was a large, randomized clinical trial, but it presents many limitations. Future outcome and safety studies comparing rHuEPO with placebo must include clinical endpoints such as end-organ morbidity, mortality, transfusion criteria, and pharmacoeconomic analysis. rHuEPO appears to provide an erythropoietic response. Optimal dosage and the real impact of rHuEPO on the need for transfusion in intensive care remain to be determined. Currently, based on the evidence available from the literature, rHuEPO cannot be recommended to reduce the need for red blood cell transfusions in anemic, critically ill patients.

Prehospital Advanced Cardiac Life Support for Out‐of‐hospital Cardiac Arrest: A Cohort Study

OBJECTIVES Out-of-hospital advanced cardiac life support (ACLS) has not consistently shown a positive impact on survival. Extracorporeal cardiopulmonary resuscitation (E-CPR) could render prolonged on-site resuscitation (ACLS or basic cardiac life support [BCLS]) undesirable in selected cases. The objectives of this study were to evaluate, in patients suffering from out-of-hospital cardiac arrest (OHCA) and in a subgroup of potential E-CPR candidates, the association between the addition of prehospital ACLS to BCLS and survival to hospital discharge, prehospital return of spontaneous circulation (ROSC), and delay from call to hospital arrival. METHODS This cohort study targets adult patients treated for OHCA between April 2010 and December 2015 in the city of Montreal, Canada. We defined potential E-CPR candidates using clinical criteria previously described in the literature (65 years of age or younger, initial shockable rhythm, absence of ROSC after 15 minutes of prehospital resuscitation, and emergency medical services-witnessed collapse or witnessed collapse with bystander cardiopulmonary resuscitation). Associations were evaluated using multivariate regression models. RESULTS A total of 7,134 patients with OHCA were included, 761 (10.7%) of whom survived to discharge. No independent association between survival to hospital discharge and the addition of prehospital ACLS to BCLS was found in either the entire cohort (adjusted odds ratio [AOR] = 1.05 [95% confidence interval {CI} = 0.84-1.32], p = 0.68) or among the 246 potential E-CPR candidates (AOR = 0.82 [95% CI = 0.36-1.84], p = 0.63). The addition of prehospital ACLS to BCLS was associated with a significant increase in the rate of prehospital ROSC in all patients experiencing OHCA (AOR = 3.92 [95% CI = 3.38-4.55], p < 0.001) and in potential E-CPR candidates (AOR = 3.48 [95% CI = 1. 76-6.88], p < 0.001) compared to isolated prehospital BCLS. Delay from call to hospital arrival was longer in the ACLS group than in the BCLS group (difference = 16 minutes [95% CI = 15-16 minutes], p < 0.001). CONCLUSIONS In a tiered-response urban emergency medical service setting, prehospital ACLS is not associated with an improvement in survival to hospital discharge in patients suffering from OHCA and in potential E-CPR candidates, but with an improvement in prehospital ROSC and with longer delay to hospital arrival.

Erythropoietic response to two epoetin alfa regimens in critically ill patients : A pilot study

Study Objective. To compare the erythropoietic responses and tolerability of two recombinant human erythropoietin (EPO) regimens.

Impact of the direct transfer to percutaneous coronary intervention-capable hospitals on survival to hospital discharge for patients with out-of-hospital cardiac arrest

AIMS Patients suffering from out-of-hospital cardiac arrest (OHCA) are frequently transported to the closest hospital. Percutaneous coronary intervention (PCI) is often indicated following OHCA. This studys primary objective was to determine the association between being transported to a PCI-capable hospital and survival to discharge for patients with OHCA. The additional delay to hospital arrival which could offset a potential increase in survival associated with being transported to a PCI-capable center was also evaluated. METHODS This study used a registry of OHCA in Montreal, Canada. Adult patients transported to a hospital following a non-traumatic OHCA were included. Hospitals were dichotomized based on whether PCI was available on-site or not. The effect of hospital type on survival to discharge was assessed using a multivariable logistic regression. The added prehospital delay which could offset the increase in survival associated with being transported to a PCI-capable center was calculated using that regression. RESULTS A total of 4922 patients were included, of whom 2389 (48%) were transported to a PCI-capable hospital and 2533 (52%) to a non-PCI-capable hospital. There was an association between being transported to a PCI-capable center and survival to discharge (adjusted odds ratio = 1.60 [95% confidence interval 1.25-2.05], p < .001). Increasing the delay from call to hospital arrival by 14.0 min would offset the potential benefit of being transported to a PCI-capable center. CONCLUSIONS It could be advantageous to redirect patients suffering from OHCA patients to PCI-capable centers if the resulting expected delay is of less than 14 min.

Potential impact of a prehospital redirection system for refractory cardiac arrest

AIM A change in prehospital redirection practice could potentially increase the proportion of E-CPR eligible patients with out-of-hospital cardiac arrest (OHCA) transported to extracorporeal cardiopulmonary resuscitation (E-CPR) capable centers. The objective of this study was to quantify this potential increase of E-CPR candidates transported to E-CPR capable centers. METHODS Adults with non-traumatic OHCA refractory to 15min of resuscitation were selected from a registry of adult OHCA collected between 2010 and 2015 in Montreal, Canada. Using this cohort, three simulation scenarios allowing prehospital redirection to E-CPR centers were created. Stringent eligibility criteria for E-CPR and redirection for E-CPR (e.g. age <60years old, initial shockable rhythm) were used in the first scenario, intermediate eligibility criteria (e.g. age <65years old, at least one shock given) in the second scenario and inclusive eligibility criteria (e.g. age <70years old, initial rhythm ≠ asystole) in the third scenario. All three scenarios were contrasted with equivalent scenarios in which patients were transported to the closest hospital. Proportions were compared using McNemars test. RESULTS The proportion of E-CPR eligible patients transported to E-CPR capable centers increased in each scenario (stringent criteria: 48 [24.5%] vs 155 patients [79.1%], p<0.001; intermediate criteria: 81 [29.6%] vs 262 patients [95.6%], p<0.001; inclusive criteria: 238 [23.9%] vs 981 patients [98.5%], p<0.001). CONCLUSIONS A prehospital redirection system could significantly increase the number of patients with refractory OHCA transported to E-CPR capable centers, thus increasing their access to this potentially life-saving procedure, provided allocated resources are planned accordingly.

Reproducibility, interchangeability of measures, time to measure stabilization, and reference values of two tissue oximeters in healthy volunteers

Abstract. This study aimed to compare two tissue oximeters, the INVOS 5100c and the Equanox 7600, in terms of their reproducibility and the interchangeability of their measures. In a randomized order, three measurements were taken at six different sites on both sides of the body in 53 healthy volunteers. Intraclass correlation coefficients (ICC) and within-subject standard deviation (Sw) were calculated for each device. The ICCs were compared using Fisher r-to-z transformation and the Sw were compared using paired-sample t-tests. We found no difference between the reproducibility of the INVOS {ICC=0.92 [95% confidence interval (CI) 0.90 to 0.93]} and Equanox [ICC=0.90 (95% CI 0.88 to 0.93)] in terms of ICCs (p=0.06). However, the Equanox [Sw=1.96 (95% CI 1.91 to 2.02)] showed a better Sw than the INVOS [Sw=2.11 (95% CI 2.05 to 2.17)] (p=0.019). Also, when compared directly to stable condition, the readings produced by the two oximeters varied considerably [ICC 0.43 (95% CI 0.36 to 0.49)]. When taken individually, both tissue oximeters displayed good reproducibility, the Equanox being slightly better than the INVOS in terms of absolute reproducibility. However, when compared, the oximeters showed poor interdevices agreement. Reference values were also described.

Comment: use of epoetin alfa in critically ill patients.

ing disease states for each different drug. To state the obvious, care for a patient with chronic renal failure will cost much more than care for a patient with depression; the statistical analysis does not account for this cost differential. A more appropriate cost evaluation would have been across the disease state variables; this was not reported in the article. Further, baseline pretreatment costs were higher for patients in the switching group, showing a cost bias in favor of oxycodone CR (OxyContin). In addition, pretreatment healthcare costs for transdermal fentanyl and CR morphine groups were significantly higher, again showing this bias. Funding for the study and 2 authors came from Purdue Pharma (OxyContin’s manufacturer) and the rest of the authors were from Policy Analysis, a statistics for-hire firm in Brookline, MA. Oxycodone CR, transdermal fentanyl, and CR morphine sulfate have all shown efficacy in pain relief in cancer and noncancer pain; oxycodone CR has shown a need for more rescue doses 2,3 and can cause fatal dose dumping if the controlled-release mechanism is broken4 when compared with CR morphine sulfate . There has not been a definitive trial showing patient preference of one opiate over another for pain relief. The types of studies Policy Analysis performs (retrospective, nonblinded post hoc analyses) are hypothesis generating, at best, and should not influence prescribing at any level.