Management of pharmaceutical and recreational drug poisoning.

BACKGROUND: Poisoning is one of the leading causes of admission to the emergency department and intensive care unit. A large number of epidemiological changes have occurred over the last years such as the exponential growth of new synthetic psychoactive substances. Major progress has also been made in analytical screening and assays, enabling the clinicians to rapidly obtain a definite diagnosis. METHODS: A committee composed of 30 experts from five scientific societies, the Société de Réanimation de Langue Française (SRLF), the Société Française de Médecine d'Urgence (SFMU), the Société de Toxicologie Clinique (STC), the Société Française de Toxicologie Analytique (SFTA) and the Groupe Francophone de Réanimation et d'Urgences Pédiatriques (GFRUP) evaluated eight fields: (1) severity assessment and initial triage; (2) diagnostic approach and role of toxicological analyses; (3) supportive care; (4) decontamination; (5) elimination enhancement; (6) place of antidotes; (7) specificities related to recreational drug poisoning; and (8) characteristics of cardiotoxicant poisoning. Population, Intervention, Comparison, and Outcome (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Analysis of the literature and formulation of recommendations were then conducted according to the GRADE® methodology. RESULTS: The SRLF-SFMU guideline panel provided 41 statements concerning the management of pharmaceutical and recreational drug poisoning. Ethanol and chemical poisoning were excluded from the scope of these recommendations. After two rounds of discussion and various amendments, a strong consensus was reached for all recommendations. Six of these recommendations had a high level of evidence (GRADE 1±) and six had a low level of evidence (GRADE 2±). Twenty-nine recommendations were in the form of expert opinion recommendations due to the low evidences in the literature. CONCLUSIONS: The experts reached a substantial consensus for several strong recommendations for optimal management of pharmaceutical and recreational drug poisoning, mainly regarding the conditions and effectiveness of naloxone and N-acetylcystein as antidotes to treat opioid and acetaminophen poisoning, respectively.

Extracorporeal life support in the treatment of colchicine poisoning.

CONTEXT: Ingestions of Colchicum autumnale may lead to severe poisoning. It begins with gastrointestinal symptoms and leukocytosis, followed by multi-organ failure with shock and a possible late recovery phase. Mortality is highly dependent on the ingested dose. We report a case of accidental C. autumnale poisoning with refractory cardiogenic shock and eventual survival after extracorporeal life support (ECLS). CASE DETAILS: A 68-year-old woman was admitted to the intensive care unit (ICU) on day 3 after ingestion of C. autumnale in a meal. She first suffered from nausea and vomiting leading to severe dehydration. She then developed multi-organ failure and refractory cardiogenic shock, with a mean arterial pressure nadir of 50 mmHg despite high doses of catecholamines and a left ventricular ejection fraction at 5-10%. Venous-arterial ECLS was therefore started at an initial rate of 3.5 L/min and 3,800 rev/min. Her symptoms also included pancytopenia on day 4 with diffuse bleeding requiring iterative blood product transfusion. Platelet and leukocyte count nadirs were 13 × 10(9)/L (normal range: 150-400 × 10(9)/L) and 0.77 × 10(9)/L (normal range: 4.2-10.7 × 10(9)/L), respectively. ECLS allowed good cardiac contractility recovery within a few days, with complications including bleeding made controllable. Indeed, because of hemostasis disorders, the patient presented hemoptysis and hematuria. She was treated with tranexamic acid and transfused with blood products. She received 15 erythrocyte concentrates, 13 platelet concentrates, and 7 fresh frozen plasma. ECLS was removed by day 10, with subsequent weaning from mechanical ventilation as well as from hemodialysis in the following days. DISCUSSION: This patient survives after the use of ECLS in Colchicum poisoning, with controllable complications. Thus, ECLS might be indicated to overcome the potentially refractory cardiogenic shock phase.

Predictors of mortality in verapamil overdose: usefulness of serum verapamil concentrations.

Verapamil poisoning may result in life-threatening cardiovascular morbidities and fatalities. To date, prognosticators of mortality have been poorly investigated and the use of serum verapamil concentration for prognosis remains unclear. We aimed to evaluate the ability of usual clinical and laboratory parameters including serum verapamil concentrations measured on admission to predict outcome (survival versus death) in verapamil poisoning. We reviewed the medical records of all intentional and symptomatic verapamil poisonings admitted over 8 years to two medical intensive care units. Clinical and laboratory parameters were measured in 65 patients, and final outcomes of survival or death recorded. A multivariable analysis was conducted to evaluate the prognostic values of recorded parameters. Life-threatening complications of verapamil poisonings included shock (62%), atrioventricular blocks (24%), sinoatrial blocks (20%), acute respiratory distress syndrome (19%) and cardiac arrest (11%) resulting in death (8%). Verapamil concentration measured on intensive care unit admission was the only independent factor associated with mortality (p = 0.01). The optimal verapamil cut-off point was 5.0 µM (100% sensitivity, 91% specificity), which conferred a 2.76-times increase in odds of fatality. In conclusion, cardiovascular monitoring and assessment of organ failure are vital in symptomatic verapamil poisonings. The serum verapamil concentration has excellent prognostic ability for predicting fatality in verapamil overdose.

A multicenter, randomized trial of noninvasive ventilation with helium-oxygen mixture in exacerbations of chronic obstructive lung disease.

OBJECTIVE: To assess the effect of a helium-oxygen mixture on intubation rate and clinical outcomes during noninvasive ventilation in acute exacerbation of chronic obstructive pulmonary disease. DESIGN: Multicenter, prospective, randomized, controlled trial. SETTING: Seven intensive care units. PATIENTS: A total of 204 patients with known or suspected chronic obstructive pulmonary disease and acute dyspnea, Paco2> 45 mm Hg and two among the following factors: pH <7.35, Paco2 <50 mm Hg, respiratory rate >25/min. INTERVENTIONS: Noninvasive ventilation randomly applied with or without helium (inspired oxygen fraction 0.35) via a face mask. MEASUREMENTS AND MAIN RESULTS: Duration and complications of NIV and mechanical ventilation, endotracheal intubation, discharge from intensive care unit and hospital, mortality at day 28, adverse and serious adverse events were recorded. Follow-up lasted until 28 days since enrollment. Intubation rate did not significantly differ between groups (24.5% vs. 30.4% with or without helium, p = .35). No difference was observed in terms of improvement of arterial blood gases, dyspnea, and respiratory rate between groups. Duration of noninvasive ventilation, length of stay, 28-day mortality, complications and adverse events were similar, although serious adverse events tended to be lower with helium (10.8% vs. 19.6%, p = .08). CONCLUSIONS: Despite small trends favoring helium, this study did not show a statistical superiority of using helium during NIV to decrease the intubation rate in acute exacerbation of chronic obstructive pulmonary disease.

Emergency step-by-step specific immunotherapy in severe digoxin poisoning: an observational cohort study.

OBJECTIVE: To evaluate the efficacy and safety of a step-by-step fixed dose of specific immunotherapy protocol in case of severe digoxin poisoning in an open uncontrolled prospective study. METHODS: Twenty consecutive patients were admitted because of severe digoxin poisoning. The inclusion criteria were: digoxin overdose and either life-threatening arrhythmia; high-degree atrioventricular block, ventricular arrhythmia, or bradycardia less than 50 bpm and hyperkalaemia (>5.5 mmol/l). A two-step protocol of antidigoxin antibodies treatment was carried out. At admission, every patient received two vials of specific Fab-fragments. If after 1 h following infusion ECG signs regressed, no more treatment was given. If ECG signs did not regress, patients were given two more vials. At inclusion and 6 h after immunotherapy, clinical (cardiac rhythm, ECG records) and biological (serum digoxin concentration, potassium) findings were recorded. RESULTS: Patients had a median (interquartile range) age of 83 (75-90) years. Four patients had acute poisoning and 16 chronic overdoses. Eleven patients showed ventricular arrhythmia, and five had high-degree atrioventricular block. Seventy percent of the patients needed only the first step. Significant decreases were observed in the number of cardiac dysrhythmia (16 vs. three patients), in the median (interquartile range) of serum digoxin concentration [5 microg/l (3.8-6.2) vs. 0.4 microg/l (0.3-2.2)] and in serum potassium [4.6 mmol/l (4.1-5.5) vs. 3.85 mmol/l (3.7-4.55)] before and after immunotherapy. The digoxin-related mortality was 5%. CONCLUSION: This protocol of step-by-step digoxin-specific immunotherapy seems to be as effective as the equimolar treatment, and there was significant cost reduction in case of acute poisoning.

Continuous positive airway pressure vs. proportional assist ventilation for noninvasive ventilation in acute cardiogenic pulmonary edema.

OBJECTIVE: To compare continuous positive airway pressure (CPAP) and proportional assist ventilation (PAV) as modes of noninvasive ventilatory support in patients with severe cardiogenic pulmonary edema. DESIGN AND SETTING: A prospective multicenter randomized study in the medical ICUs of three teaching hospitals. PATIENTS: Thirty-six adult patients with cardiogenic pulmonary edema (CPA) with unresolving dyspnea, respiratory rate above 30/min and/or SpO2 above 90% with O2 higher than 10 l/min despite conventional therapy with furosemide and nitrates. INTERVENTIONS: Patients were randomized to undergo either CPAP (with PEEP 10 cmH2O) or PAV (with PEEP 5-6 cmH2O) noninvasive ventilation through a full face mask and the same ventilator. MEASUREMENTS AND RESULTS: The main outcome measure was the failure rate as defined by the onset of predefined intubation criteria, severe arrythmias or patient's refusal. On inclusion CPAP (n=19) and PAV (n=17) groups were similar with regard to age, sex ratio, type of heart disease, SAPS II, physiological parameters (mean arterial pressure, heart rate, blood gases), amount of infused nitrates and furosemide. Failure was observed in 7 (37%) CPAP and 7 (41%) PAV patients. Among these, 4 (21%) CPAP and 5 (29%) PAV patients required endotracheal intubation. Changes in physiological parameters were similar in the two groups. Myocardial infarction and ICU mortality rates were strictly similar in the two groups. CONCLUSIONS: In the present study PAV was not superior to CPAP for noninvasive ventilation in severe cardiogenic pulmonary edema with regard to either efficacy and tolerance.