Fahmi Dachraoui

Prednisone in COPD exacerbation requiring ventilatory support: an open-label randomised evaluation

Recommendation of the use of systemic steroids in chronic obstructive disease (COPD) exacerbation rely on trials that excluded patients requiring ventilatory support. In an open-label, randomised evaluation of oral prednisone administration, 217 patients with acute COPD exacerbation requiring ventilatory support were randomised (with stratification on the type of ventilation) to usual care (n=106) or to receive a daily dose of prednisone (1 mg·kg−1) for up to 10 days (n=111). There was no difference regarding the primary end-point, intensive care unit mortality, which was 17 (15.3%) deaths versus 15 (14%) deaths in the steroid-treated and control groups, respectively (relative risk 1.08, 95% CI 0.6–2.05). Analysis according to ventilation modalities showed similar mortality rates. Noninvasive ventilation failed in 15.7% and 12.7% (relative risk 1.25, 95% CI 0.56–2.8; p=0.59), respectively. Both study groups had similar median mechanical ventilation duration and intensive care unit length of stay, which were 6 (interquartile range 6–12) days versus 6 (3.8–12) days and 9 (6–14) days versus 8 (6–14) days, respectively. Hyperglycaemic episodes requiring initiation or alteration of current insulin doses occurred in 55 (49.5%) patients versus 35 (33%) patients in the prednisone and control groups, respectively (relative risk 1.5, 95% CI 1.08–2.08; p=0.015). Prednisone did not improve intensive care unit mortality or patient-centred outcomes in the selected subgroup of COPD patients with severe exacerbation but significantly increased the risk of hyperglycaemia. In COPD exacerbation needing ventilatory support, prednisone has no impact on ICU mortality or related patient outcome http://ow.ly/qxGq0

Family cluster of Middle East respiratory syndrome coronavirus infections, Tunisia, 2013.

In 2013 in Tunisia, 3 persons in 1 family were infected with Middle East respiratory syndrome coronavirus (MERS-CoV). The index case-patient’s respiratory tract samples were negative for MERS-CoV by reverse transcription PCR, but diagnosis was retrospectively confirmed by PCR of serum. Sequences clustered with those from Saudi Arabia and United Arab Emirates.

Meta-analysis of controlled studies on immunotherapy in severe scorpion envenomation

Background Despite conflicting evidence, specific serotherapy is recommended for scorpion envenomation. Methods A meta-analysis of prospective or observational controlled studies, comparing intravenous scorpion antivenin (SAV) with control, was performed. Binary outcomes are reported as risk difference for clinical improvement and mortality rates. Analysis was performed both for the whole number of included studies and for two subgroups (set up according to the geographic origin of scorpions). Results Nine studies (four randomised controlled trials (RCTs), five observational) enrolling 687 patients were identified. Six dealt with Old World scorpions and three originated from Arizona. Overall, the rate of clinical improvement was similar in SAV treated and untreated patients (risk difference=0.22, 95% CI −0.35 to 0.79; p=0.45 for effect). Subgroup analysis showed favourable effects of SAV in the Arizona scorpion envenomation (risk difference=0.53; 95% CI 0.16 to 0.91; p<0.001), and non-significant unfavourable effects in Old World scorpion envenomation (risk difference=−0.05; 95% CI −0.28 to 0.18; p=0.65; p=0.003 for z-value, indicating a true heterogeneity of treatment effects). In Old World scorpion envenomation, there was no statistical difference in the risk of death in SAV treated and untreated scorpion envenomated patients (risk difference=0.007, 95% CI −0.02 to 0.03; p=0.6 for effect). Overall, administration of scorpion antivenin was associated with a reduction by 13 h in the mean time of symptom resolution (95% CI −17 to −9; p<0.0001). Serious adverse events were reported at a rate of 1–2% while minor adverse events occurred in up to 40% of patients. Conclusions SAV should not be administered in Old World scorpion envenomation until its efficacy is established by an appropriately designed RCT. In the Arizona scorpion sting, SAV hastens the recovery process.

Scorpion-related cardiomyopathy: Clinical characteristics, pathophysiology, and treatment

Abstract Context. Scorpion envenomation is a threat to more than 2 billion people worldwide with an annual sting number exceeding one million. Acute heart failure presenting as cardiogenic shock or pulmonary edema, or both is the most severe presentation of scorpion envenomation accounting for 0.27% lethality rate. Objective. The purpose of this review is to characterize the scorpion-related cardiomyopathy, clarify its pathophysiological mechanisms, and describe potentially useful treatments in this particular context. Methods. We searched major databases on observational or interventional studies (whether clinical or experimental) on the cardiorespiratory consequences of scorpion envenomation and their treatment. No limit of age or language was imposed. A critical appraisal of the literature was conducted in order to provide a pathophysiological scheme that reconciles reported patterns of cardiovascular toxicity and hypotheses and assumptions made so far. Results. Early cardiovascular dysfunction is related to the so-called “vascular phase” of scorpion envenomation, which is related to a profound catecholamine-related vasoconstriction leading to a sharp increase in left ventricular (LV) afterload, thereby impeding LV emptying, and increasing LV filling pressure. Following this vascular phase, a myocardial phase occurs, characterized by a striking alteration in LV contractility (myocardial stunning), low cardiac output, and hypotensive state. The right ventricle involvement is symmetric to that of LV with a profound and reversible alteration in right ventricular performance. This phase is unique in that it is reversible spontaneously or under inotropic treatment. Scorpion myocardiopathy combines the features of takotsubo myocardiopathy (or stress myocardiopathy) which is linked to a massive release in catecholamines leading to myocardial ischemia through coronary vasomotor abnormalities (epicardial coronary spasm and/or increase in coronary microvascular resistance). Treatment of pulmonary edema due to scorpion envenomation follows the same principles as those applied for the treatment of cardiogenic pulmonary edema in general: this begins with oxygen supplementation targeting an oxygen saturation of 92% or more, by oxygen mask, continuous positive airway pressure, noninvasive ventilation, or conventional mechanical ventilation. Dobutamine effectively improves hemodynamic parameters and may reduce mortality in severe scorpion envenomation. Conclusion. Scorpion cardiomyopathy is characterized by a marked and reversible alteration in biventricular performance. Supportive treatment relying on ventilatory support and dobutamine infusion is a bridge toward recovery in the majority of patients.

Weaning difficult-to-wean chronic obstructive pulmonary disease patients: A pilot study comparing initial hemodynamic effects of levosimendan and dobutamine

PURPOSE To compare the short-term hemodynamic effects of levosimendan and dobutamine in chronic obstructive pulmonary disease (COPD) patients experiencing weaning difficulties in relation with increased left ventricular filling pressure. MATERIALS AND METHODS This prospective, sequential, pilot study included 10 COPD patients experiencing weaning difficulties in relation with increased left ventricular filling pressure ascertained by an increase >10 mm Hg of pulmonary artery occlusion pressure (PAOP) at the shift from mechanical to spontaneous breathing (SB). Patients received 1 h infusion of 7 μg/kg per minute of dobutamine, followed by 24-hour infusion of 0.2 μg/kg per minute levosimendan. Hemodynamic variables were measured under MV and 15 to 30 minutes after SB at baseline, at the end of dobutamine infusion, at a washout period, and after levosimendan infusion. RESULTS At baseline, the shift from mechanical ventilation to spontaneous ventilation was associated with a significant increase in PAOP from a median of 15 (interquartile range [IQR], 6) to 29 (9) mm Hg. Both drugs reduced significantly the level of PAOP increase at SB, but levosimendan had a greater effect than dobutamine [median PAOP increase (IQR): 5 (2) vs 9 (4) mm Hg, respectively; P < .01]. CONCLUSIONS Both drugs reduced the magnitude of PAOP increase at SB in difficult-to-wean COPD patients. PAOP increase was reduced to a greater extent by levosimendan.

N-terminal proB-type natriuretic peptide levels aid the diagnosis of left ventricular dysfunction in patients with severe acute exacerbations of chronic obstructive pulmonary disease and renal dysfunction

Background and objective:  The aim of this study was to assess the performance of N‐terminal proB‐type natriuretic peptide (NT‐proBNP) levels for the diagnosis of left ventricular dysfunction in patients with severe acute exacerbations of chronic obstructive pulmonary disease (COPD) and renal dysfunction.

Systemic corticosteroids in acute exacerbation of COPD: a meta-analysis of controlled studies with emphasis on ICU patients.

Guidelines on systemic corticosteroids in chronic obstructive pulmonary disease (COPD) exacerbation rely on studies that excluded patients requiring ventilatory support. Recent publication of studies including ICU patients allows estimation of the level of evidence overall and in patients admitted to the ICU. We included RCTs evaluating the efficacy and safety of systemic corticosteroids in COPD exacerbation, compared to placebo or standard treatment. The effect size on treatment success was computed by a random effects model overall and in subgroups of non-ICU and ICU patients. Effects on mortality and on the rate of adverse effects of corticosteroids were also computed. Twelve RCTs (including 1,331 patients) were included. Pooled analysis showed a statistically significant increase in the treatment success rate when using systemic corticosteroids: odds ratio (OR) = 1.72, 95% confidence interval (CI) = 1.15 to 2.57; p = 0.01. Subgroup analysis showed different patterns of effect in ICU and non-ICU subpopulations: a non-significant difference of effect in the subgroup of ICU patients (OR = 1.34, 95% CI = 0.61 to 2.95; p = 0.46), whereas in the non-ICU patients, the effect was significant (OR = 1.87, 95% CI = 1.18 to 2.99; p = 0.01; p for interaction = 0.72). Among ICU patients, there was no difference in the success whether patients were ventilated with tracheal intubation (OR = 1.85, 95% CI = 0.14 to 23.34; p = 0.63) or with non-invasive ventilation (OR = 4.88, 95% CI = 0.31 to 75.81; p = 0.25). Overall, there was no difference in the mortality rate between the steroid-treated group and controls: OR = 1.07, 95% CI = 0.67 to 1.71; p = 0.77. The rate of adverse events increased significantly with corticosteroid administration (OR = 2.36, 95% CI = 1.67 to 3.33; p < 0.0001). In particular, treatment with systemic corticosteroids significantly increased the risk of hyperglycemic episodes requiring initiation or alteration of insulin therapy (OR = 2.96, 95% CI = 1.69 to 5; p < 0.0001). We found corticosteroids to be beneficial in the whole population (non-critically ill and critically ill patients) in terms of treatment success rate. However, subgroup analysis showed that this effect of corticosteroids was only observed in non-critically ill patients whereas critically ill patients derived no benefit from systemic corticosteroids regardless of the chosen ventilatory mode (invasive or non-invasive ventilation). Further analyses showed no effect on mortality of corticosteroids, but higher side effects, such as hyperglycemic episodes requiring the initiation or alteration of insulin therapy.

Study of severe scorpion envenoming following subcutaneous venom injection into dogs: Hemodynamic and concentration/effect analysis

To evaluate the dose-effects of Androctonus australis hector (Aah) venom injected subcutaneously on hemodynamics and neurohormonal secretions, 10 anesthetized and ventilated mongrel dogs, were split in two groups (n = 5/group). Subcutaneous injection was done with either 0.2 mg/kg or 0.125 mg/kg of the purified G50 scorpion toxic fraction. Hemodynamic parameters using right heart catheter were recorded and plasma concentrations of catecholamine, troponin, and serum toxic fraction were measured sequentially from baseline to 120 min. We identified the dose of toxic fraction evoking characteristic hemodynamic perturbation of severe envenomation, the time-lapse to envenomation, and the associated plasma level. The injection of 0.125 mg/kg toxic fraction was not associated with significant variations in hemodynamic parameters, whereas the 0.2 mg/kg dose caused envenomation characterized by significant increase in plasma catecholamines, increased pulmonary artery occluded pressure, mean arterial pressure, and systemic vascular resistance (p < 0.05), in association with sustained decline in cardiac output (p < 0.001). Envenomation occurred by the 30th minute, and the corresponding concentration of toxic fraction was 1.14 ng/ml. The current experiment allowed the identification of the sub-lethal dose (0.2 mg/kg) of the toxic fraction of Aah administered by the subcutaneous route. Two parameters with potential clinical relevance were also uncovered: the time-lapse to envenomation and the corresponding concentration of toxic fraction.

Intravenous salbutamol in ARDS and increased mortality

www.thelancet.com Vol 379 May 19, 2012 1875 rebuttals provided by the authors of those reviews. Our colleagues might not be familiar with the specifi cations given to authors in writing for The Lancet’s Seminar series. The remit is to create an article that is “clinically focused and up-to-date”, with a limit on the number of words and the quantity, nature, and age of the references cited. Owing to their uppermost position in the hierarchy of evidence, systematic reviews are relied on heavily. These prerequisites preclude detailed discussion of the strengths and weaknesses of the cited works. Our aim was to fulfi l our remit while stimulating refl ection and further enquiry by the interested reader. In the Seminar, we highlight the fact that epidemiological studies do not seem to support the notion of mechanical factors being independently causative of low back pain. Despite the enormous amount of research done in the specialty of biomechanics and ergonomics, there has been no notable improvement in the burden of non-specifi c low back pain. As clinicians, we are acutely aware of the potentially detrimental sideeff ects of repeated messages about “ergonomically correct behaviour” that in some patients merely serve to promote kinesiophobia or fear avoidance behaviour. With respect, we think the analogy with smoking and lung cancer is rather trite; one need only to look at another important Bradford-Hill aspect of causality, “experiment (reversibility)”, to realise that the benefi ts of ergonomic prevention programmes for back pain are in no way comparable to those of smoking cessation for cancer. Concerning the fi nal paragraph of van Dieën and colleagues’ letter, we deny any suggestion that occupational, mechanical loading should be neglected within the context of low back pain; however, for the aforementioned reasons, together with the fi nding that a high pro portion of teenagers report non-specifi c low back pain (yet have zero exposure to occupational loading) and data apportioning the contribution of sus pected explanatory variables (gen etic, mechanical, other), we maintain that a major causal role for occupational, mechanical loading remains questionable.

Chronic outpatient management of asthmatics attending the emergency department: a survey from a country with low income.

Purpose Little is known about compliance with international guidelines of asthma management in developing countries where some medications are prohibitively expensive. Methods A survey was conducted in asthmatic patients attending the emergency department for acute asthma. Asthma severity was evaluated and conformity of chronic treatment with international guidelines was assessed. Additional features of asthmatic education were also evaluated. Results A total of 127 consecutive patients (mean age 34±14 years) answered the questionnaire. Mild asthma was present in 19.7% patients, 56.7% had moderate asthma and 23.6% had severe asthma. Of the 124 known asthmatic patients, 33% had no treatment for chronic asthma. In the remaining, treatment adhered to international guidelines in 44% patients. The major cause of treatment inadequacy was the lack of inhaled corticosteroids (64%) or suboptimal dosage of corticosteroids (13%). Conformity to guidelines according to favorable or unfavorable economic conditions was 59% and 33%, respectively (P=0.036). Treating physicians provided an ‘action plan’ for managing acute symptoms to 19% patients. Forty percent of asthmatic patients performed correctly the five components of metered dose inhaler use. Conclusion Our study reveals an important proportion of non-treated asthmatic patients. In most asthmatic patients, treatment did not conform with guidelines because of an underutilization of corticosteroids, mainly because of economic obstacles.