The Efficacy of Antivenin Latrodectus (Black Widow) Equine Immune F(ab')2 Versus Placebo in the Treatment of Latrodectism: A Randomized, Double-Blind, Placebo-Controlled, Clinical Trial.

STUDY OBJECTIVE: The antivenom currently available for treatment of systemic black widow envenomation (latrodectism) is composed of equine whole immunoglobin. Although considered effective, it has been associated with anaphylaxis and 2 reported fatalities. We test the efficacy and safety of new equine antivenom composed of purified F(ab')2 antibody fragments. METHODS: A randomized, double-blind, placebo-controlled trial was conducted at 16 sites across the United States. Subjects aged 10 years or older with moderate to severe pain because of black widow spider envenomation received F(ab')2 antivenom or placebo. The primary outcome measure was treatment failure, which was defined as failure to achieve and maintain clinically significant reduction in pain for 48 hours posttreatment. Secondary measures of pain intensity differences and summed pain intensity difference were computed. Adverse events were recorded. RESULTS: Sixty patients were treated (29 antivenom and 31 placebo). The mean age was 39 years and 68% were male. There were 15 treatment failures in the antivenom group and 24 in the placebo group (P=.019). Differences in pain intensity difference between groups were lower at each postbaseline point, and the mean summed pain intensity difference was greater for the antivenom group (difference 2,133; 95% confidence interval 177 to 4,090). No deaths or serious drug-related adverse events were detected. CONCLUSION: The F(ab')2 antivenom met the predefined primary outcome of reduced treatment failures. Secondary outcomes of pain intensity difference and summed pain intensity difference also supported efficacy. The rate of symptom improvement in the placebo group was higher than expected, which may be related to enrollment criteria or placebo effect.

Energy drink exposures reported to Texas poison centers: Analysis of adverse incidents in relation to total sales, 2010-2014.

The ill-defined term "energy drink" includes a disparate group of products (beverages, shots, concentrates, and workout powders) having large differences in caffeine content and concentration and intended use. Hence, inaccurate conclusions may be drawn when describing adverse events associated with "energy drinks". The FDA is considering new regulation of these products but product specificity is needed to evaluate safety. To help address this, we queried Texas Poison Center Network data for single substance exposures to "energy drinks" from 2010 to 2014, then analyzed adverse events by product type. We specifically compared energy beverage exposures with sales data for the same time period to evaluate the safety profile of this category of energy drinks. Among 855 documented "energy drink" exposures, poison center-determined outcome severity revealed 291 with no/minimal effects, 417 judged nontoxic or minor/not followed, 64 moderate and 4 major effects, and no deaths. Serious complications included 2 seizures and 1 episode of ventricular tachycardia. Outcome severity by category for beverages: 11 moderate/1 major effects (none in children <17 years); shots: 19 moderate/2 major; non-liquids: 16 moderate/1 major; concentrates: 7 moderate; unknown: 10 moderate. Call incidence to poison centers for beverage type exposures was 0.58 (for moderate effects) and 0.053 (for major) per hundred million units sold. Small volume and concentrated products were associated with a greater number of adverse effects than beverage versions of "energy drinks".

Effect of Bag-Mask Ventilation vs Endotracheal Intubation During Cardiopulmonary Resuscitation on Neurological Outcome After Out-of-Hospital Cardiorespiratory Arrest: A Randomized Clinical Trial.

Importance: Bag-mask ventilation (BMV) is a less complex technique than endotracheal intubation (ETI) for airway management during the advanced cardiac life support phase of cardiopulmonary resuscitation of patients with out-of-hospital cardiorespiratory arrest. It has been reported as superior in terms of survival. Objectives: To assess noninferiority of BMV vs ETI for advanced airway management with regard to survival with favorable neurological function at day 28. Design, Settings, and Participants: Multicenter randomized clinical trial comparing BMV with ETI in 2043 patients with out-of-hospital cardiorespiratory arrest in France and Belgium. Enrollment occurred from March 9, 2015, to January 2, 2017, and follow-up ended January 26, 2017. Intervention: Participants were randomized to initial airway management with BMV (n = 1020) or ETI (n = 1023). Main Outcomes and Measures: The primary outcome was favorable neurological outcome at 28 days defined as cerebral performance category 1 or 2. A noninferiority margin of 1% was chosen. Secondary end points included rate of survival to hospital admission, rate of survival at day 28, rate of return of spontaneous circulation, and ETI and BMV difficulty or failure. Results: Among 2043 patients who were randomized (mean age, 64.7 years; 665 women [32%]), 2040 (99.8%) completed the trial. In the intention-to-treat population, favorable functional survival at day 28 was 44 of 1018 patients (4.3%) in the BMV group and 43 of 1022 patients (4.2%) in the ETI group (difference, 0.11% [1-sided 97.5% CI, -1.64% to infinity]; P for noninferiority = .11). Survival to hospital admission (294/1018 [28.9%] in the BMV group vs 333/1022 [32.6%] in the ETI group; difference, -3.7% [95% CI, -7.7% to 0.3%]) and global survival at day 28 (55/1018 [5.4%] in the BMV group vs 54/1022 [5.3%] in the ETI group; difference, 0.1% [95% CI, -1.8% to 2.1%]) were not significantly different. Complications included difficult airway management (186/1027 [18.1%] in the BMV group vs 134/996 [13.4%] in the ETI group; difference, 4.7% [95% CI, 1.5% to 7.9%]; P = .004), failure (69/1028 [6.7%] in the BMV group vs 21/996 [2.1%] in the ETI group; difference, 4.6% [95% CI, 2.8% to 6.4%]; P < .001), and regurgitation of gastric content (156/1027 [15.2%] in the BMV group vs 75/999 [7.5%] in the ETI group; difference, 7.7% [95% CI, 4.9% to 10.4%]; P < .001). Conclusions and Relevance: Among patients with out-of-hospital cardiorespiratory arrest, the use of BMV compared with ETI failed to demonstrate noninferiority or inferiority for survival with favorable 28-day neurological function, an inconclusive result. A determination of equivalence or superiority between these techniques requires further research. Trial Registration: clinicaltrials.gov Identifier: NCT02327026.

Intentional Misuse and Abuse of Loperamide: A New Look at a Drug with "Low Abuse Potential".

BACKGROUND: Despite its opioid properties, loperamide has long been thought to have low abuse potential due to its poor absorption from the gastrointestinal tract and limited potential to cross the blood-brain barrier. A recent patient reportedly taking loperamide to avoid heroin withdrawal symptoms, at doses approximately 100 times those recommended, directed our attention to this issue. OBJECTIVES: 1) Investigate number of cases of intentional loperamide abuse and misuse reported to poison centers between 2009 and 2015; 2) Compile reports of clinical effects of loperamide abuse; and 3) Search for evidence of increasing Internet interest in the central opioid effects of loperamide. METHODS: For the years 2009 thru 2015, we reviewed exposure calls related to misuse/abuse of loperamide in the Texas Poison Center Network's database and the National Poison Data System. We used Google trend analysis to detect evidence of increased Internet interest in the illicit use of loperamide. RESULTS: Between 2009 and 2015, the number of misuse/abuse calls related to loperamide alone nearly doubled, with about one-third of cases occurring in teens and young adults in their 20s. Of particular concern are reports of significant cardiotoxic effects (∼18% of cases), including conduction defects and various dysrhythmias, sometimes leading to death. Google Trends analysis demonstrates an increasing number of searches for "loperamide high" and "loperamide withdrawal" beginning in 2011. CONCLUSIONS: Loperamide misuse/abuse seems to be on the rise. Given its propensity to induce conduction disturbances and dysrhythmias at very high doses, emergency physicians should be vigilant for this form of drug abuse.

Family presence during cardiopulmonary resuscitation.

BACKGROUND: The effect of family presence during cardiopulmonary resuscitation (CPR) on the family members themselves and the medical team remains controversial. METHODS: We enrolled 570 relatives of patients who were in cardiac arrest and were given CPR by 15 prehospital emergency medical service units. The units were randomly assigned either to systematically offer the family member the opportunity to observe CPR (intervention group) or to follow standard practice regarding family presence (control group). The primary end point was the proportion of relatives with post-traumatic stress disorder (PTSD)-related symptoms on day 90. Secondary end points included the presence of anxiety and depression symptoms and the effect of family presence on medical efforts at resuscitation, the well-being of the health care team, and the occurrence of medicolegal claims. RESULTS: In the intervention group, 211 of 266 relatives (79%) witnessed CPR, as compared with 131 of 304 relatives (43%) in the control group. In the intention-to-treat analysis, the frequency of PTSD-related symptoms was significantly higher in the control group than in the intervention group (adjusted odds ratio, 1.7; 95% confidence interval [CI], 1.2 to 2.5; P=0.004) and among family members who did not witness CPR than among those who did (adjusted odds ratio, 1.6; 95% CI, 1.1 to 2.5; P=0.02). Relatives who did not witness CPR had symptoms of anxiety and depression more frequently than those who did witness CPR. Family-witnessed CPR did not affect resuscitation characteristics, patient survival, or the level of emotional stress in the medical team and did not result in medicolegal claims. CONCLUSIONS: Family presence during CPR was associated with positive results on psychological variables and did not interfere with medical efforts, increase stress in the health care team, or result in medicolegal conflicts. (Funded by Programme Hospitalier de Recherche Clinique 2008 of the French Ministry of Health; ClinicalTrials.gov number, NCT01009606.).

Fatal heat stroke associated with topiramate therapy.

A 40-year-old man with diabetes and seizure disorder was found at home unresponsive and "very hot to touch" by his father 40 minutes before emergency medical services arrival. His usual medications included topiramate, divalproex sodium, and rosiglitazone/metformin. Paramedics administered oxygen, intravenous fluids, and naloxone. They did not witness or report seizure activity. Upon emergency department arrival, the patient was unresponsive (Glasgow Coma Scale 3), hypotensive (94/50 mm Hg), and tachypneic (32 breaths per minute), with a heart rate of 60 beats per minute and elevated rectal temperature peaking at 43.2°C. His skin was hot and dry, without rash; physical examination was otherwise normal. Laboratory studies revealed severe metabolic acidosis with acute renal failure and rhabdomyolysis. In spite of sedation, intubation, and aggressive cooling measures, the patient had cardiac arrest and died approximately 2 hours after arrival. Serum topiramate and valproate concentrations were within therapeutic ranges at 8.8 µg/mL (therapeutic 2-12) and 97 µg/mL (therapeutic 50-100), respectively.

Intraosseous line placement for antidote injection by first responders and receivers wearing personal protective equipment.

STUDY OBJECTIVE: Early antidotal therapy may be lifesaving in hazardous materials victims. Intravenous line placement is difficult while wearing personal protective equipment (PPE). We assessed the ability of protected, experienced first responders and limited-experience first receivers to place intraosseous (IO) lines for antidote administration. METHODS: Six first responders donned 4 (A, B, C, and D) and 12 first receivers donned 2 (C and D) United States Environmental Protection Agency PPE levels in random order and then placed IO lines in 1 of 4 anatomical sites in 12 anesthetized Spanish goats. Observers timed interventions until bolus injection of isotonic sodium chloride solution. RESULTS: First responders placed IO lines successfully in 100% of cases. The median (interquartile range) times to completion (in seconds) were as follows: level A, 43.5 (23.0); B, 45.0 (29.0); C, 40.0 (15.0); D, 30.0 (17.0). First receivers placed IO lines successfully in 91% of cases. The median (interquartile range) times to completion (in seconds) were as follows: level C, 42.0 (19.5); D, 37.0 (11.0). There were no significant differences in time to completion among PPE levels (overall or pairwise) or between operator groups. Two (4%) of 48 line placements resulted in recognized extravasation due to penetration of the opposite cortex. Infusions were completed successfully. CONCLUSION: Hazardous materials first responders and receivers can effectively place IO lines in a goat while wearing PPE. Intraosseous lines may facilitate earlier administration of antidotes in hazardous materials victims.

Expert consensus guidelines for stocking of antidotes in hospitals that provide emergency care.

STUDY OBJECTIVE: We developed recommendations for antidote stocking at hospitals that provide emergency care. METHODS: An expert panel representing diverse perspectives (clinical pharmacology, clinical toxicology, critical care medicine, clinical pharmacy, emergency medicine, internal medicine, pediatrics, poison centers, pulmonary medicine, and hospital accreditation) was formed to create recommendations for antidote stocking. Using a standardized summary of the medical literature, the primary reviewer for each antidote proposed guidelines for antidote stocking to the full panel. The panel used a formal iterative process to reach their recommendation for the quantity of an antidote that should be stocked and the acceptable period for delivery of each antidote. RESULTS: The panel recommended consideration of 24 antidotes for stocking. The panel recommended that 12 of the antidotes be available for immediate administration on patient arrival. In most hospitals, this period requires that the antidote be stocked in the emergency department. Another 9 antidotes were recommended for availability within 1 hour of the decision to administer, allowing the antidote to be stocked in the hospital pharmacy if the hospital has a mechanism for prompt delivery of antidotes. The panel identified additional antidotes that should be stocked by the hospital but are not usually needed within the first hour of treatment. The panel recommended that each hospital perform a formal antidote hazard vulnerability assessment to determine the need for antidote stocking in that hospital. CONCLUSION: The antidote expert recommendations provide a tool to be used in creating practices for appropriate and adequate antidote stocking in hospitals that provide emergency care.

Hemodynamics after intraosseous administration of hydroxocobalamin or normal saline in a goat model.

STUDY OBJECTIVE: Hydroxocobalamin may be lifesaving in cyanide (CN) poisoning, but personal protective equipment (PPE) wear, rescue, and decontamination may delay intravenous administration. Intraosseous (IO) lines may be rapidly placed even when wearing PPE. We assessed the hemodynamics of hydroxocobalamin (OHCo) and normal saline (NS) by the IO route. METHODS: Twelve anesthetized Spanish goats underwent arterial line catheterization. Operators in PPE placed IO lines. After placement confirmation by fluoroscopy, animals randomly received hydroxocobalamin 75 mg/kg (3 mL/kg) (n = 6) or normal saline (NS) 3 mL/kg (n = 6) IO over approximately 7.5 minutes. Blood pressures and heart rates were monitored for 240 minutes after infusion initiation. RESULTS: In the OHCo group, mean systolic and diastolic pressures peaked at 120 minutes, with mean increases of 14% and 17%, respectively, relative to infusion start, returning to near preinfusion values at 240 minutes. Heart rate changes were virtually nil. In the NS group, mean systolic pressures peaked at 60 minutes, with a mean increase of 36%, whereas diastolic pressures peaked at about 110 minutes, increasing 42%, returning to near preinfusion values at 240 minutes. Heart rate changes were minimal. CONCLUSION: Hemodynamic effects of OHCo given by the IO route in non-CN-poisoned goats are mild and well tolerated. Increases in mean blood pressure at peak after baseline were greater in the NS group, but the mean values over time were not significantly different from those observed in the OHCo group. Hemodynamic effects would likely differ somewhat in a CN-poisoned goat. Intraosseous OHCo administration warrants additional investigation.

Digoxin-specific Fab fragments as single first-line therapy in digitalis poisoning.

OBJECTIVE: Despite administration of Fab fragments in digitalis poisoning, high mortality rates are consistently reported. A previous study suggested that Fab fragments prescribed as first-line therapy might improve mortality rate. Our objective was to evaluate this approach. DESIGN: Retrospective chart review (January 1990 to January 2004). SETTING: University hospital intensive care unit. PATIENTS: Consecutive patients admitted for cardiac glycoside poisoning. INTERVENTION: First-line therapy with Fab fragments (with or without atropine) in either curative or prophylactic doses. MEASUREMENTS AND MAIN RESULTS: A total of 141 patients were admitted for digitalis poisoning of whom 66 received first-line Fab fragment therapy. Their median age was 74 years (25th to 75th percentiles: 51-83); 76% were women. Half were intoxicated by digitoxin and half by digoxin. Median serum concentration was 168 (108-205) ng/mL for digitoxin and 6.2 (4.3-13.5) ng/mL for digoxin. Conduction disturbances were reported in 45 cases (68%) and ventricular arrhythmia in six cases (9%). Fab fragments were administered as curative treatment in 21 patients (32%) and prophylactically in 45 patients (68%). The median cumulative dose was 4 (4-6) vials. No adverse effects were reported. Five patients (7.6%) died. CONCLUSIONS: First-line therapy with Fab fragments in patients with digitalis poisoning was associated with a low mortality rate.

Assessment of digoxin antibody use in patients with elevated serum digoxin following chronic or acute exposure.

OBJECTIVE: To evaluate the use of antidotal therapy in patients with an elevated digitalis concentration following chronic or acute exposure. DESIGN AND SETTING: Retrospective review of patient records over 2 years in 20 city hospitals in France. PATIENTS: Overall 838 patients with an elevated serum digitalis concentration (digoxin > 1.95ng /ml or digitoxin > 23ng /ml) were included in the study. Of these, 67 (8%) had received antidotal therapy with Fab fragments. MEASUREMENTS AND RESULTS: The relationships between previously reported prognostic criteria and use of antidotal therapy were investigated. We identified five independent factors that were associated with the use of antidotal therapy: acute overdose (OR 15.74), Fab fragment availability in the hospital (11.06), serum potassium (1.81), and heart rate (0.96). Mortality was significantly lower in Fab-treated (6%, 4/67) than untreated patients (15%, 117/770). CONCLUSIONS: Antidotal therapy is underused in patients with an elevated digitalis concentration especially in patients with chronic digitalis exposure. These patients in our series presented a higher mortality rate than patients with acute poisoning. Although they were older and tended to have a history of cardiac disease, they did not differ from patients with acute poisoning with regard to the main severity criteria and prognostic factors. The use of identical criteria for antidotal treatment after acute and chronic poisoning should help optimize outcomes. Fab fragment availability is insufficient in France but ranks only second after type of poisoning (acute or chronic) in the multivariate association with Fab treatment.

Norepinephrine weaning in septic shock patients by closed loop control based on fuzzy logic.

INTRODUCTION: The rate of weaning of vasopressors drugs is usually an empirical choice made by the treating in critically ill patients. We applied fuzzy logic principles to modify intravenous norepinephrine (noradrenaline) infusion rates during norepinephrine infusion in septic patients in order to reduce the duration of shock. METHODS: Septic patients were randomly assigned to norepinephrine infused either at the clinician's discretion (control group) or under closed-loop control based on fuzzy logic (fuzzy group). The infusion rate changed automatically after analysis of mean arterial pressure in the fuzzy group. The primary end-point was time to cessation of norepinephrine. The secondary end-points were 28-day survival, total amount of norepinephine infused and duration of mechanical ventilation. RESULTS: Nineteen patients were randomly assigned to fuzzy group and 20 to control group. Weaning of norepinephrine was achieved in 18 of the 20 control patients and in all 19 fuzzy group patients. Median (interquartile range) duration of shock was significantly shorter in the fuzzy group than in the control group (28.5 [20.5 to 42] hours versus 57.5 [43.7 to 117.5] hours; P < 0.0001). There was no significant difference in duration of mechanical ventilation or survival at 28 days between the two groups. The median (interquartile range) total amount of norepinephrine infused during shock was significantly lower in the fuzzy group than in the control group (0.6 [0.2 to 1.0] microg/kg versus 1.4 [0.6 to 2.7] microg/kg; P < 0.01). CONCLUSIONS: Our study has shown a reduction in norepinephrine weaning duration in septic patients enrolled in the fuzzy group. We attribute this reduction to fuzzy control of norepinephrine infusion. TRIAL REGISTRATION: Trial registration: Clinicaltrials.gov NCT00763906.

Compliance with a morphine protocol and effect on pain relief in out-of-hospital patients.

This study was carried out to evaluate the compliance with a morphine protocol and its effects on pain relief in pre-hospital care. In this prospective study, pain intensity was evaluated by the Visual Analog Scale (VAS) from the beginning and every 5 min until hospital arrival (Tend). Group 1: No major deviation from the protocol (intravenous morphine as a first bolus of 0.05 mg/kg followed by repeated boluses every 5 min until VAS < or = 30 mm). Group 2: Major deviation from the protocol. There were 216 patients included. The mean dose of morphine was 9.0 +/- 5.7 mg. The morphine protocol was respected in 123 patients (57%). The mean VAS score was significantly better at Tend in Group 1 vs. Group 2 (27.8 +/- 21.1 mm vs. 37.8 +/- 22.1 mm, respectively), the degree of pain relief was significantly better (73% vs. 53%, respectively) and the initiation time for pain relief was significantly shorter in Group 1 vs. Group 2 (10 min [5-15] vs. 15 min [10-26], respectively). Satisfaction was significantly better in patients expressing pain relief than in unrelieved patients (94% vs. 61%, respectively). Out-of-hospital pain management using morphine depends on careful attention to dosage and the time interval between re-injections. Emergency teams may employ these data to improve the quality of pain relief in the field.

Emergency department visits caused by adverse drug events: results of a French survey.

BACKGROUND: Adverse drug events (ADEs) are a substantial cause of hospital admissions. However, little is known about the incidence, preventability and severity of ADEs resulting in emergency department visits. To address this issue, we conducted a prospective survey in emergency departments of French public hospitals. METHODS: This study was performed over two periods of 1 week each, one in June 1999 and one in December 1999, in emergency departments of five university hospitals and five general hospitals throughout France. All patients aged>or=15 years presenting with medical complaints were included in the study. Trauma patients, those with gynaecological conditions and those with alcohol intoxication or intentional drug poisoning were excluded from the study. Each patient was assessed by two local emergency physicians to determine whether the visit was the result of an ADE. All medical records were subsequently validated by an independent group of medical lecturers in iatrogenic disorders. RESULTS: Out of a total of 1937 patients consulting, 1562 were taking at least one drug during the previous week and were included for analysis; 328 (21%; 95% CI 19, 23) of these patients consulted an emergency physician because of an ADE. Patients with ADEs were older than those without (mean age 63.5 vs 54.8 years; p<0.0001). Furthermore, ADE patients were more likely to have a higher severity presentation than the non-ADE group (p=0.019). The number of drug exposures was significantly higher in patients with an ADE than in those without (mean number of medications 5.17 vs 3.82; p<0.0001). On multivariate analysis, only age and the number of medications taken were significantly associated with adverse events. In total, 410 drugs were incriminated in the occurrence of 328 ADEs. The most frequently incriminated drug classes were: (i) psychotropic agents (n=84; 20.5%); (ii) diuretics (n=48; 11.7%), anticoagulants (n=38; 9.3%) and other cardiovascular drugs (n=63; 15.4%); and (iii) analgesics, including NSAIDs (n=57; 13.9%). Preventability could be assessed in 280 of the 328 cases. In 106 cases (37.9%), the ADE was judged to be preventable. CONCLUSION: ADEs leading to emergency department visits are frequent, and many are preventable, confirming that there is a need to develop prevention strategies.

Toxic doses of paraoxon alter the respiratory pattern without causing respiratory failure in rats.

Respiratory failure, through a combination of muscarinic, nicotinic, and central effects, is the primary cause of death in acute organophosphate poisoning. However, the mechanisms inducing respiratory failure remain unclear. In rats poisoned subcutaneously with paraoxon at doses near the LD(50), we studied the pattern of respiration using whole body plethysmography and the occurrence of respiratory failure using arterial blood gases. Subsequently, we studied the effects of atropine on paraoxon-induced modification of ventilation and arterial blood gases. Fifty and 75%, but not 10% of the subcutaneous LD(50) of paraoxon induced marked and sustained signs and symptoms. At 30min post-injection and throughout the study, there was a significant decrease in the respiratory frequency (34% (50% versus solvent), and 29% (75% versus solvent)) and a significant increase in the expiratory time (72% (50% versus solvent) and 60% (75% versus solvent)) with no modifications of the inspiratory time. The tidal volume was significantly increased for the 75% but not for the 50% dose. Apnea was never detected. Even at the 75% dose, paraoxon had no effects on PaO(2), PaCO(2) or HCO(3)(-); however, a significant decrease in arterial pH was observed at 30min (7.34+/-0.07 versus 7.51+/-0.01, p=0.03). Atropine completely reversed the paraoxon-induced respiratory alterations. We conclude that paraoxon, at doses equal to 50 and 75% of the LD(50), alters ventilation at rest without inducing respiratory failure during the study period.

Prospective study of hydroxocobalamin for acute cyanide poisoning in smoke inhalation.

STUDY OBJECTIVE: To assess outcomes in patients treated with hydroxocobalamin at the fire scene or in the ICU for suspected smoke inhalation-associated cyanide poisoning. METHODS: Adult smoke inhalation victims with suspected cyanide poisoning as determined by soot in the face, mouth, or nose or expectorations and neurologic impairment received an intravenous infusion of hydroxocobalamin 5 g (maximum 15 g) at the fire scene or in the ICU in this observational case series conducted from 1987 to 1994. Blood cyanide specimens were collected before administration of hydroxocobalamin. The threshold for cyanide toxicity was predefined as greater than or equal to 39 micromol/L. RESULTS: The sample included 69 patients (mean age 49.6 years; 33 men), of whom 39 were comatose. Out-of-hospital deaths were excluded. Fifty of the 69 patients (72%) admitted to the ICU survived after administration of hydroxocobalamin. In the group in which cyanide poisoning was confirmed a posteriori (n=42), 67% (28/42) survived after administration of hydroxocobalamin. The most common adverse events were chromaturia (n=6), pink or red skin discoloration (n=4), hypertension (n=3), erythema (n=2), and increased blood pressure (n=2). No serious adverse events were attributed to hydroxocobalamin. Laboratory tests revealed transient alterations in renal and hepatic function consistent with the critical condition of the patients and mild anemia consistent with progressive hemodilution. CONCLUSION: Empiric administration of hydroxocobalamin was associated with survival among 67% of patients confirmed a posteriori to have had cyanide poisoning. Hydroxocobalamin was well tolerated irrespective of the presence of cyanide poisoning. Hydroxocobalamin appears to be safe for the out-of-hospital treatment of presumptive cyanide poisoning from smoke inhalation.

Hydroxocobalamin for severe acute cyanide poisoning by ingestion or inhalation.

This chart review was undertaken to assess efficacy and safety of hydroxocobalamin for acute cyanide poisoning. Hospital records of the Fernand Widal and Lariboisière Hospitals were reviewed for intensive care unit admissions with cyanide poisoning for which hydroxocobalamin was used as first-line treatment from 1988 to 2003. Smoke inhalation cases were excluded. Hydroxocobalamin (5-20 g) was administered to 14 consecutive patients beginning a median 2.1 hours after cyanide ingestion or inhalation. Ten patients (71%) survived and were discharged. Of the 11 patients with blood cyanide exceeding the typically lethal threshold of 100 micromol/L, 7 survived. The most common hydroxocobalamin-attributed adverse events were chromaturia and pink skin discoloration. Severe cyanide poisoning of the nature observed in most patients in this study is frequently fatal. That 71% of patients survived after treatment with hydroxocobalamin suggests that hydroxocobalamin as first-line antidotal therapy is effective and safe in acute cyanide poisoning.

Use of nuclear magnetic resonance spectroscopy to assess renal dysfunction after hypertonic-hyperoncotic resuscitation in rats.

BACKGROUND: The aim of this study was to evaluate the renal tolerance of a hypertonic-hyperoncotic solution (HHS) administration during uncontrolled hemorrhagic shock (UHS). METHODS: UHS was produced in rats by a preliminary bleed followed by tail amputation. Hydroxyethylstarch (HHS) 200/0.5 6% in NaCl 7.2% was administered to the HHS groups (n = 20) and normal saline (NS) to the NS group (n = 20). Infusion rates were adjusted to prevent mean arterial pressure (MAP) from falling either below 40 mm Hg in the HHS40 (n = 10) and NS40 groups (n = 10), or below 80 mm Hg in the HHS80 (n = 10) and NS80 groups (n = 10). Data obtained were compared with a sham group and a no resuscitation (NR) group. Nephrotoxicity was evaluated by nuclear magnetic resonance analysis in urine samples. RESULTS: Survival was 60% in the NS40 group and 40% in the NS80 group, 70% in the HHS40 group, and 60% in the HHS80 group (p = not significant). Within and between target groups of 40 mm Hg MAP and 80 mm Hg MAP, there was no significant difference in survival. The mean values of renal metabolites to creatinine (ct) ratios were not significantly different among the six groups. Principal component analysis showed that the HHS80 group was characterized by an increase in allantoin/ct and urea/ct ratios demonstrating acute renal dysfunction and failure of nitrogen metabolism. CONCLUSION: In prolonged UHS, an infusion of HHS may not increase the rate of survival. HHS infusion in normotensive resuscitation appears to be associated with renal toxicity.

Cardiopulmonary resuscitation duration and survival in out-of-hospital cardiac arrest patients.

AIM: Relationship between cardiopulmonary arrest and resuscitation (CPR) durations and survival after out-of-hospital cardiac arrest (OHCA) remain unclear. Our primary aim was to determine the association between survival without neurologic sequelae and cardiac arrest intervals in the setting of witnessed OHCA. METHODS: We analyzed 27,301 non-traumatic, witnessed OHCA patients in France included in the national registry from June 1, 2011 through December 1, 2015. We analyzed cardiac arrest intervals, designated as no-flow (NF; from collapse to start of CPR) and low-flow (LF; from start of CPR to cessation of resuscitation) in relation to 30-day survival without sequelae. We determined the influence of recognized prognostic factors (age, gender, initial rhythm, location of cardiac arrest) on this relation. RESULTS: For the entire cohort, the area delimited by a value of NF greater than 12min (95% confidence interval: 11-13min) and LF greater than 33min (95% confidence interval: 29-45min), yielded a probability of 30-day survival of less than 1%. These sets of values were greatly influenced by initial cardiac arrest rhythm, age, sex and location of cardiac arrest. Extended CPR duration (greater than 40min) in the setting of initial shockable cardiac rhythm is associated with greater than 1% survival with NF less than 18min. The NF interval was highly influential on the LF interval regardless of outcome, whether return of spontaneous circulation (p<0.001) or death (p<0.001). CONCLUSION: NF duration must be considered in determining CPR duration in OHCA patients. The knowledge of (NF, LF) curves as function of age, initial rhythm, location of cardiac arrest or gender may aid in decision-making vis-à-vis the termination of CPR or employment of advanced techniques.

Prehospital diagnosis of massive ethylene glycol poisoning and use of an early antidote.

We report the case of a patient suspected of voluntary massive poisoning by ethylene glycol. Prehospital diagnosis was established by portable blood analyser and an early antidote with 4 MP treatment initiated in out-of-hospital setting. Use of portable blood analyser in prehospital care should be considered in case of suspected massive poisoning by ethylene glycol.