The role for high flow nasal cannula as a respiratory support strategy in adults: a clinical practice guideline.

PURPOSE: High flow nasal cannula (HFNC) is a relatively recent respiratory support technique which delivers high flow, heated and humidified controlled concentration of oxygen via the nasal route. Recently, its use has increased for a variety of clinical indications. To guide clinical practice, we developed evidence-based recommendations regarding use of HFNC in various clinical settings. METHODS: We formed a guideline panel composed of clinicians, methodologists and experts in respiratory medicine. Using GRADE, the panel developed recommendations for four actionable questions. RESULTS: The guideline panel made a strong recommendation for HFNC in hypoxemic respiratory failure compared to conventional oxygen therapy (COT) (moderate certainty), a conditional recommendation for HFNC following extubation (moderate certainty), no recommendation regarding HFNC in the peri-intubation period (moderate certainty), and a conditional recommendation for postoperative HFNC in high risk and/or obese patients following cardiac or thoracic surgery (moderate certainty). CONCLUSIONS: This clinical practice guideline synthesizes current best-evidence into four recommendations for HFNC use in patients with hypoxemic respiratory failure, following extubation, in the peri-intubation period, and postoperatively for bedside clinicians.

How to ventilate obstructive and asthmatic patients.

Exacerbations are part of the natural history of chronic obstructive pulmonary disease and asthma. Severe exacerbations can cause acute respiratory failure, which may ultimately require mechanical ventilation. This review summarizes practical ventilator strategies for the management of patients with obstructive airway disease. Such strategies include non-invasive mechanical ventilation to prevent intubation, invasive mechanical ventilation, from the time of intubation to weaning, and strategies intended to prevent post-extubation acute respiratory failure. The role of tracheostomy, the long-term prognosis, and potential future adjunctive strategies are also discussed. Finally, the physiological background that underlies these strategies is detailed.

Scorpion envenomation: state of the art.

Scorpion envenomation is common in the tropical and subtropical regions. It poses a major public health problem with some patients having serious clinical manifestations and severe complications including death. Old World and New World scorpions are usually contrasted because of differences in venom composition, clinical presentation and severity, and, accordingly, different therapeutic approaches. The majority of scorpion stings are either dry or result in low amounts of injected venom, thus explaining why up to 95% of scorpion stings ensue only in local signs. For a clinical envenomation to occur, it has been suggested that the interaction between the quantity of venom introduced in the body of the prey and the distribution volume should ensue in a critical threshold of scorpion toxin plasma concentration. In this case, there is a massive release of neurohormonal mediators (mainly catecholamine), with systemic vasoconstrictor effects eliciting a sharp increase in systemic arterial pressure and LV-filling pressure and decreased cardiac output. This early phase of cardiac dysfunction, also called "vascular phase", is followed by a severe cardiomyopathy, a form of Takotsubo cardiomyopathy, involving both ventricles and reversible in days to weeks. The more comprehensive understanding of the disease pathophysiology has allowed for a well-codified symptomatic treatment, thus contributing to a substantial reduction in the death toll of scorpion envenomation over the past few decades. The standard intensive-care treatment (when available) overcomes envenomation's consequences such as acute pulmonary edema and cardiogenic shock. Even though it continues to inspire many evaluative studies, immunotherapy seems less attractive because of the major role held by mediators in the pathogenesis of envenomation, and unfavorable pharmacokinetic properties to existing sera compared to venom. Meta-analyses of controlled trials of immunotherapy in severe scorpion envenomation reached similar conclusions: there is an acceptable level of evidence in favor of the use of scorpion antivenom (Fab'2) against Centruroides sp. in USA/Mexico, while there is still a need for a higher level of evidence for immunotherapy in the Old World envenomation.

Prevalence of anxiety and depressive symptoms among medical residents in Tunisia: a cross-sectional survey.

OBJECTIVE: To assess the prevalence of anxiety and depressive symptoms and the associated risk factors among Tunisian medical residents. DESIGN: Cross-sectional survey. SETTING: Faculty of Medicine, Tunis. PARTICIPANTS: All Tunisian medical residents brought together between 14 and 22 December 2015 to choose their next 6-month rotation. INTERVENTION: The items of the Hospital Anxiety and Depression (HAD) questionnaire were employed to capture the prevalence of anxiety and/or depression among the residents. The statistical relationships between anxiety and depression (HAD score) and sociodemographic and work-related data were explored by Poisson regression. RESULTS: 1700 out of 2200 (77%) medical residents (mean age: 28.5±2 years, female: 60.8%) answered the questionnaire. The mean working hours per week was 62±21 hours; 73% ensured a mean of 5.4±3 night shifts per month; and only 8% of them could benefit from a day of safety rest. Overall, 74.1% of the participating residents had either definite (43.6%) or probable (30.5%) anxiety, while 62% had definite (30.5%) or probable (31.5%) depression symptoms, with 20% having both definite anxiety and definite depression. The total HAD score was significantly associated with the resident's age (OR=1.014, 95% CI 1.006 to 1.023, p=0.001); female gender (OR=1.114, 95% CI 1.083 to 1.145, p<0.0001); and the heavy burden of work imposed on a weekly or monthly basis, as reflected by the number of night shifts per month (OR=1.048, 95% CI 1.016 to 1.082, p=0.03) and the number of hours worked per week (OR=1.008, 95% CI 1.005 to 1.011, p<0.0001). Compared with medical specialties, the generally accepted difficult specialties (surgical or medical-surgical) were associated with a higher HAD score (OR=1.459, 95% CI 1.172 to 1.816, p=0.001). CONCLUSION: Tunisian residents experience a rate of anxiety/depression substantially higher than that reported at the international level. This phenomenon is worrying as it has been associated with an increase in medical errors, work dissatisfaction and attrition. The means of improving the well-being of Tunisian medical residents are explored, emphasising those requiring immediate implementation.

A global perspective on vasoactive agents in shock.

PURPOSE: We set out to summarize the current knowledge on vasoactive drugs and their use in the management of shock to inform physicians' practices. METHODS: This is a narrative review by a multidisciplinary, multinational-from six continents-panel of experts including physicians, a pharmacist, trialists, and scientists. RESULTS AND CONCLUSIONS: Vasoactive drugs are an essential part of shock management. Catecholamines are the most commonly used vasoactive agents in the intensive care unit, and among them norepinephrine is the first-line therapy in most clinical conditions. Inotropes are indicated when myocardial function is depressed and dobutamine remains the first-line therapy. Vasoactive drugs have a narrow therapeutic spectrum and expose the patients to potentially lethal complications. Thus, these agents require precise therapeutic targets, close monitoring with titration to the minimal efficacious dose and should be weaned as promptly as possible. Moreover, the use of vasoactive drugs in shock requires an individualized approach. Vasopressin and possibly angiotensin II may be useful owing to their norepinephrine-sparing effects.

Inverted Takotsubo syndrome in Androctonus australis scorpion envenomation.

CONTEXT: The nature of scorpion-related cardiomyopathy is still a matter of debate where specific toxin-induced cardiomyopathy, ischemic, or catecholaminergic cardiomyopathy is advocated as well. We report two cases of Takotsubo syndrome following envenomation by Androctonus australis, bringing new evidence for the fundamental role of catecholamines in the pathogenesis of this cardiomyopathy. Case 1: A woman aged 36 presented with pulmonary edema and shock following scorpion envenomation. Echocardiography-Doppler showed a LVEF at 30%. Cardiac magnetic resonance (CMR) imaging showed a basal ballooning of the left and right ventricles suggestive of an inverted biventricular Takotsubo syndrome. A second CMR performed after recovery was normal. Case 2: A woman aged 45 was admitted for pulmonary edema and shock consecutive to scorpion envenomation. Echocardiography showed a LVEF at 35%. CMR showed a basal ballooning. The patient was discharged four days following admission with a normal LV function on repeat echocardiography examination. CONCLUSIONS: Cardiomyopathy in these cases, following scorpion envenomation by Androctonus australis, fulfills the criteria of Takotsubo syndrome. These observations contribute to our understanding of the mechanism, prognosis, and treatment of scorpion-related cardiomyopathy.

Noninvasive ventilation with helium-oxygen mixture in hypercapnic COPD exacerbation: aggregate meta-analysis of randomized controlled trials.

When used as a driving gas during NIV in hypercapnic COPD exacerbation, a helium-oxygen (He/O2) mixture reduces the work of breathing and gas trapping. The potential for He/O2 to reduce the rate of NIV failure leading to intubation and invasive mechanical ventilation has been evaluated in several RCTs. The goal of this meta-analysis is to assess the effect of NIV driven by He/O2 compared to air/O2 on patient-centered outcomes in hypercapnic COPD exacerbation. Relevant RCTs were searched using standard procedures. The main endpoint was the rate of NIV failure. The effect size was computed by a fixed-effect model, and estimated as odds ratio (OR) with 95% confidence interval (CI). Additional endpoints were ICU mortality, NIV-related side effects, and the length and costs of ICU stay. Three RCTs fulfilled the selection criteria and enrolled a total of 772 patients (386 patients received He/O2 and 386 received air/O2). Pooled analysis showed no difference in the rate of NIV failure when using He/O2 mixture compared to air/O2: 17 vs 19.7%, respectively; OR 0.84, 95% CI 0.58-1.22; p = 0.36; I 2 for heterogeneity = 0%, and no publication bias. ICU mortality was also not different: OR 0.8, 95% CI 0.45-1.4; p = 0.43; I 2 = 5%. However, He/O2 was associated with less NIV-related adverse events (OR 0.56, 95% CI 0.4-0.8, p = 0.001), and a shorter length of ICU stay (difference in means = -1.07 day, 95% CI -2.14 to -0.004, p = 0.049). Total hospital costs entailed by hospital stay and NIV gas were not different: difference in means = -279$, 95% CI -2052-1493, p = 0.76. Compared to air/O2, He/O2 does not reduce the rate of NIV failure in hypercapnic COPD exacerbation. It is, however, associated with a lower incidence of NIV-related adverse events and a shortening of ICU length of stay with no increase in hospital costs.

A Multicenter Randomized Trial Assessing the Efficacy of Helium/Oxygen in Severe Exacerbations of Chronic Obstructive Pulmonary Disease.

RATIONALE: During noninvasive ventilation (NIV) for chronic obstructive pulmonary disease (COPD) exacerbations, helium/oxygen (heliox) reduces the work of breathing and hypercapnia more than air/O2, but its impact on clinical outcomes remains unknown. OBJECTIVES: To determine whether continuous administration of heliox for 72 hours, during and in-between NIV sessions, was superior to air/O2 in reducing NIV failure (25-15%) in severe hypercapnic COPD exacerbations. METHODS: This was a prospective, randomized, open-label trial in 16 intensive care units (ICUs) and 6 countries. Inclusion criteria were COPD exacerbations with PaCO2 ≥ 45 mm Hg, pH ≤ 7.35, and at least one of the following: respiratory rate ≥ 25/min, PaO2 ≤ 50 mm Hg, and oxygen saturation (arterial [SaO2] or measured by pulse oximetry [SpO2]) ≤ 90%. A 6-month follow-up was performed. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was NIV failure (intubation or death without intubation in the ICU). The secondary endpoints were physiological parameters, duration of ventilation, duration of ICU and hospital stay, 6-month recurrence, and rehospitalization rates. The trial was stopped prematurely (445 randomized patients) because of a low global failure rate (NIV failure: air/O2 14.5% [n = 32]; heliox 14.7% [n = 33]; P = 0.97, and time to NIV failure: heliox group 93 hours [n = 33], air/O2 group 52 hours [n = 32]; P = 0.12). Respiratory rate, pH, PaCO2, and encephalopathy score improved significantly faster with heliox. ICU stay was comparable between the groups. In patients intubated after NIV failed, patients on heliox had a shorter ventilation duration (7.4 ± 7.6 d vs. 13.6 ± 12.6 d; P = 0.02) and a shorter ICU stay (15.8 ± 10.9 d vs. 26.7 ± 21.0 d; P = 0.01). No difference was observed in ICU and 6-month mortality. CONCLUSIONS: Heliox improves respiratory acidosis, encephalopathy, and the respiratory rate more quickly than air/O2 but does not prevent NIV failure. Overall, the rate of NIV failure was low. Clinical trial registered with www.clinicaltrials.gov (NCT 01155310).

Trends in use and impact on outcome of empiric antibiotic therapy and non-invasive ventilation in COPD patients with acute exacerbation.

BACKGROUND: Empiric antibiotic therapy is routinely prescribed in patients with acute COPD exacerbations (AECOPD) requiring ventilatory support on the basis of studies including patients conventionally ventilated. Whether this practice remains valid to current management with first-line non-invasive ventilation (NIV) is unclear. METHODS: In a cohort of ICU patients admitted between 2000 and 2012 for AECOPD, we analyzed the trends in empiric antibiotic therapy and in primary ventilatory support strategy, and their respective impact on patients' outcome. RESULTS: 440 patients admitted for 552 episodes were included; primary NIV use increased from 29 to 96.7 % (p < 0.001), whereas NIV failure rate decreased significantly (p = 0.004). In parallel, ventilator-associated pneumonia (VAP) rate, VAP density and empiric antibiotic therapy use decreased (p = 0.037, p = 0.002, and p < 0.001, respectively). These figures were associated with a trend toward lower ICU mortality rate (p = 0.058). Logistic regression showed that primary NIV use per se was protective against fatal outcome [odds ratios (OR) = 0.08, 95 %CI 0.03-0.22; p < 0.001], whereas NIV failure, VAP occurrence, and cardiovascular comorbidities were associated with increased ICU mortality [OR = 17.6 (95 %CI 5.29-58.93), 11.5 (95 %CI 5.17-25.45), and 3 (95 %CI 1.37-6.63), respectively]. Empiric antibiotic therapy was associated with decreased VAP rate (log rank; p < 0.001), but had no effect on mortality (log rank; p = 0.793). CONCLUSIONS: The sustained increase in NIV use allowed a decrease in empiric antibiotic prescriptions in AECOPD requiring ventilatory support. Primary NIV use and its success, but not empiric antibiotic therapy, were associated with a favorable impact on patients' outcome.

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.

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

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.

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.

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.

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.