Vincent Danel

Impact of intra-arrest therapeutic hypothermia in outcomes of prehospital cardiac arrest: a randomized controlled trial

PurposeMild therapeutic hypothermia (TH) is recommended as soon as possible after the return of spontaneous circulation to improve outcomes after out-of-hospital cardiac arrest (OHCA). Preclinical data suggest that the benefit of TH could be increased if treatment is started during cardiac arrest. We aimed to study the impact of intra-arrest therapeutic hypothermia (IATH) on neurological injury and inflammation following OHCA.MethodsWe conducted a 1:1 randomized, multicenter study in three prehospital emergency medical services and four critical care units in France. OHCA patients, irrespective of the initial rhythm, received either an infusion of cold saline and external cooling during cardiac arrest (IATH group) or TH started after hospital admission (hospital-cooling group). The primary endpoint was neuron-specific enolase (NSE) serum concentrations at 24xa0h. Secondary endpoints included IL-6, IL-8, and IL-10 concentrations, and clinical outcome.ResultsOf the 245 patients included, 123 were analyzed in the IATH group and 122 in the hospital-cooling group. IATH decreased time to reach temperature ≤34xa0°C by 75xa0min (95xa0% CI: 4; 269). The rate of patients admitted alive to hospital was not different between groups [IATH nxa0=xa041 (33xa0%) vs. hospital cooling nxa0=xa036 (30xa0%); pxa0=xa00.51]. Levels of NSE and inflammatory biomarkers were not different between groups [median NSE at 24xa0h: IATH 96.7xa0μg/l (IQR: 49.9–142.8) vs. hospital cooling 97.6xa0μg/l (IQR: 74.3–142.4), pxa0=xa00.64]. No difference in survival and cerebral performance were found at 1xa0month.ConclusionsIATH did not affect biological markers of inflammation or brain damage or clinical outcome.

New syndromes in mushroom poisoning

Several new mushroom poisoning syndromes have been described since the early 1990s. In these syndromes, the onset of symptoms generally occurs >6 hours after ingestion. Treatment is mainly supportive. The syndrome induced by Amanita smithiana/proxima consists of acute tubulopathy, which appears earlier and does not have the same poor prognosis as the orellanine-induced syndrome. It has been described since 1992 in the US and Canada with A. smithiana; in France, Spain and Italy with A. proximo; and in Japan with A. pseudoporphyria. The responsible toxin is probably 2-amino-4,5-hexadienoic acid. The erythromelalgia syndrome has been described as early as the late 19th century in Japan and South Korea with Clitocybe acromelalga, and since 1996 in France and then Italy with C. amoenolens. Responsible toxins are probably acromelic acids identified in both species. Several cases of massive rhabdomyolysis have been reported since 1993 in France and 2001 in Poland after ingestion of large amounts of an edible and, until then, valuable species called Tricholoma equestre. These cases of rhabdomyolysis are associated with respiratory and cardiac (myocarditis) complications leading to death. Rhabdomyolysis with an apparently different mechanism was described in Taiwan in 2001 with Russula subnigricans. Finally, cases of encephalopathy were observed twice after ingestion of Hapalopilus rutilans in Germany in 1992 and Pleurocybella porrigens in Japan in 2004, where a convulsive encephalopathy outbreak was reported in patients with history of chronic renal failure.

Outcome after severe accidental hypothermia in the French Alps: A 10-year review

OBJECTIVEnTo describe the factors associated with outcome after accidental deep hypothermia.nnnMETHODSnWe conducted a retrospective cohort study on patients with accidental hypothermia (core temperature <28 °C) admitted to a Level I emergency room over a 10-year period.nnnRESULTSnForty-eight patients were included with a median temperature of 26 °C (range, 16.3-28 °C) on admission. The etiology of hypothermia was exposure to a cold environment (n = 27), avalanche (n = 13) or immersion in cold water (n = 8). Mean age was 47 ± 22 years, and 58% were males. Thirty-two patients had a cardiac arrest (CA): 15 patients presented unwitnessed cardiac arrest (UCA) and 17 patients presented rescue collapse (RC). Extracorporeal life support (ECLS) was implemented in 21 patients with refractory cardiac arrest and in two patients with hemodynamic instability. Overall mortality was 50%. For cardiac arrest patients, only three out of 15 patients with UCA survived at day 28, whereas eight out of 17 patients with RC survived. The cerebral performance category score was 4 for all the survivors of UCA and 1 [range, 1-2] for survivors of RC. Patients with poor outcome presented more UCA, a lower pH, a higher serum potassium, creatinine, serum sodium or lactate level as well as more severe coagulation disorders.nnnCONCLUSIONnCardiac arrest related to rescue collapse was associated with favorable outcome. On-scene rescue collapse should prompt prolonged resuscitation and ECLS rewarming in all CA patients with deep hypothermia. Conversely, unwitnessed cardiac arrest was associated with unfavorable outcome and will likely not benefit from ECLS.

Erythromelalgia and Mushroom Poisoning

Objective: To report the first European observations of erythromelalgia due to mushroom poisoning. Methods: Clinical features of erythromelalgia were observed in 7 cases seen over 3 years. All patients had eaten the same mushrooms species, gathered in the same French alpine valley. Erythromelalgia was first described in Japan after Clitocybe acromelalga ingestion. Clitocybe amoenolens was identified as the possible cause of poisoning in our cases.

Self-Poisoning with Colchicum autumnale L. Flowers

Case Report: A 44-year-old man ingested about 40 flowers of Colchicum autumnale L. The patient presented with nausea, vomiting, and abdominal pain 2 hours after ingestion and had diarrhea 14 hours after ingestion. Hematological values remained within normal range. Treatment was mainly supportive. The outcome was favorable. The intoxication was confirmed by high-performance liquid chromatography–mass spectrometry. Maximal colchicine levels were 4.34 ng/mL at 13 hours in plasma and 5.43 ng/mL at 16 hours in erythrocytes. Conclusion: We report one of the few symptomatic cases of Colchicum autumnale L. poisoning confirmed by toxicological analysis.

Prolonged QT interval and torsade de pointes following astemizole overdose

A 26 year-old woman was admitted to the hospital two hours after astemizole overdose. Electrocardiograph showed a prolonged QT interval. Torsade de pointes occurred 13 h after ingestion. Plasma levels of astemizole plus hydroxylated metabolites showed an apparent plasma half-life of 17 h. The possible occurrence of torsade de pointes in astemizole overdose, and the long elimination time of astemizole and hydroxylated metabolites, makes it necessary to maintain ECG monitoring until QT interval has returned to normal.

Severity of Deliberate Acute Baclofen Poisoning: A Nonconcurrent Cohort Study

Interest in high‐dose baclofen treatment for alcohol dependence has increased over the past few years. In the meantime, the rate of acute baclofen poisoning has increased and life‐threatening cases have been reported. Thus, severity of acute poisoning could lessen the benefit of baclofen treatment. Our aim was to evaluate the severity of acute baclofen poisoning independently of confounders and to assess whether severity is correlated with the reported ingested dose. We prospectively included consecutive patients with acute and deliberate baclofen overdose and compared them with gender and age‐matched patients from a retrospective cohort of common acute medicine self‐poisoning. The primary end‐point was the adjusted risk ratio of mechanical ventilation. We also analysed the lengths of mechanical ventilation and risks of aspiration pneumonitis and convulsions. We finally examined the correlation between the supposed reported ingested dose and the severity of poisoning. Fourteen baclofen‐poisoned patients were included and matched to 56 poisoned patients. Median age was 45y/o (40–58), and men comprised 43% of patients. In logistic regression, the adjusted risk ratio of mechanical ventilation was 7.9 (1.4–43.5; p = 0.02) for baclofen‐treated patients. Aspiration pneumonitis was more frequent in baclofen‐treated patients (29% versus 2%; p = 0.005), and the length of mechanical ventilation was significantly correlated with the reported ingested dose of baclofen (Spearman coefficients: 0.48; p < 0.001). Our results show that acute baclofen poisoning is more severe than other acute medicine overdoses, and severity seems to be correlated with the ingested dose of baclofen. These results raise some questions about the safety of high‐dose baclofen treatment for alcohol dependence.

Deliberate drug poisoning with slight symptoms on admission: Are there predictive factors for intensive care unit referral? A three-year retrospective study

Deliberate drug poisoning leads to 1% of emergency department (ED) admissions. Even if most patients do not exhibit any significant complication, 5% need to be referred to an intensive care unit (ICU). Emergency physicians should distinguish between low‐ and high‐acuity poisoned patients at an early stage to avoid excess morbidity. Our aim was to identify ICU transfer factors in deliberately self‐poisoned patients without life‐threatening symptoms on admission. We performed a 3‐year retrospective observational study in a university hospital. Patients over 18 years of age with a diagnosis of deliberate drug poisoning were included. Clinical and toxicological data were analysed with univariate tests between groups (ED stay versus ICU transfer). Factors associated with ICU admission were then included in a logistic regression analysis. Two thousand five hundred and sixty‐five patients were included. 63.2% were women, and median age was 40 (28–49). 142 patients (5.5%) were transferred to ICU. Cardiac drugs [adjusted OR (aOR) = 19.81; 95% confidence interval (95% CI): 7.93–49.50], neuroleptics (aOR = 2.78; 95% CI: 1.55–4.97) and meprobamate (aOR = 2.71; 95% CI: 1.27–5.81) ingestions were significantly linked to ICU admission. A presumed toxic dose ingestion (aOR = 2.27; 95% CI: 1.28–4.02), number of ingested tablets (aOR = 1.01; 95% CI: 1.01–1.02 for each tablet) and delay between ingestion and ED arrival <2 hr (aOR = 2.85; 95%CI: 1.62–5.03) were also factors for ICU referral. The Glasgow Coma Scale was the only clinical feature associated with ICU admission (aOR = 1.57; 95% CI: 1.44–1.70 for each point loss). These results suggest that emergency physicians should pay particular attention to toxicological data on ED admission to distinguish between low‐ and high‐acuity self‐poisoned patients.

More than half the families of mobile intensive care unit patients experience inadequate communication with physicians

PurposeThis study aimed to assess comprehension by family members of the patient’s severity in the prehospital setting.MethodWe conducted a cross-sectional study in four mobile intensive care units (ICUs, medicalized ambulances) in France from June to October 2012. Nurses collected data on patients, patient’s relatives, and mobile ICU physicians. For each patient, one relative and one physician independently rated the patient’s severity using a simplified version of the Clinical Classification of Out-of-Hospital Emergency Patients scale (CCMS). Relatives were also asked to assess their interview with the physician. The primary outcome was agreement between the relative’s and physician’s ratings of the patient’s severity.ResultsData were available for 184 patients, their relatives, and mobile ICU physicians. Full and partial agreement between relatives and physicians regarding the patient’s severity was found for 79 (43xa0%) and 121 (66xa0%) cases, respectively [weighted kappaxa0=xa00.32 (95xa0% confidence interval, CI, 0.23–0.42)]. Relatives overestimated the patient’s severity assessed by the physician [6 (5–8) vs. 4 (3–7), pxa0<0.001]. The interview lasted 5xa0min (range 5–10) with the physician talking 80xa0% (range 70–90) of that time. Overall, 171 (93xa0%) and 169 (92xa0%) relatives reported adequate interview time and use of understandable words by physicians. In multivariable analysis, the characteristics independently associated with increased odds of disagreement included (1) the relative not having a diploma (OR 4.88; 95xa0% CI 1.27–18.70) and (2) greater patient severity (OR 6.64; 95xa0% CI 1.29–16.71).ConclusionMore than half of family members reported inadequate comprehension of information on the patient’s severity as communicated by mobile ICU physicians.

Bromide Intoxication and Pseudohyperchloremia

1. Hirsh J, Dalen JE, Anderson DR, Poller L, Bussey H, Ansell J, et al. Oral anticoagulants. Mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 1998;114(suppl):445S-69S. 2. Cropp JS, Bussey HI. A review of enzyme induction of warfarin metabolism with recommendations for patient management. Pharmacotherapy 1997;17:917-28. 3. Michalets EL. Update: clinically significant cytochrome P-450 drug interactions. Pharmacotherapy 1998;18:84-112. 4. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45. 5. Miller LG. Recent developments in the study of the effects of cigarette smoking on clinical pharmacokinetics and clinical pharmacodynamics. Clin Pharmacokinet 1989;17:90-108. 6. Miller LG. Cigarettes and drug therapy: pharmacokinetic and pharmacodynamic considerations. Clin Pharm 1990;9:125-35. 7. Schein JR. Cigarette smoking and clinically significant drug interactions. Ann Pharmacother 1995;29:1139-48. 8. Zevin S, Benowitz NL. Drug interactions with tobacco smoking: an update. Clin Pharmacokinet 1999;30:425-38. 9. Mungall DR, Luden TM, Marshall J, Hawkins DW, Talbert RL, Crawford MH. Population pharmacokinetics of racemic warfarin in adult patients. J Pharmacokinet Biopharm 1985;13:213-27. 10. Bachmann K, Shapiro R, Fulton R, Carroll FT, Sullivan TJ. Smoking and warfarin disposition. Clin Pharmacol Ther 1979;25:309-15. 11. Weiner B, Faraci PA, Fayad R, Swanson L. Warfarin dosage following prosthetic valve replacement: effect of smoking history. Drug Intell Clin Pharm 1984;18:904-6. 12. Ahmad S. Lovastatin–warfarin interaction (letter). Arch Intern Med 1990;150:2407. 13. Grau E. Simvastatin–oral anticoagulant interaction (letter). Lancet 1996; 347:405-6. 14. Trilli LE, Kelley CL, Aspinall SL, Kroner BA. Potential interaction between warfarin and fluvastatin. Ann Pharmacother 1996;30:1399-402. 15. Hobbs WR, Rall TW, Verdoorn TA. Hypnotics and sedatives: ethanol. In: Hardman JG, Limbird LE, editors-in-chief, Goodman & Gilman’s the pharmacological basis of therapeutics. 9th ed. New York: McGraw-Hill, 1996:387-92.