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Children are potential victims of chemical or biological terrorism. In recent years, children have been victims of terrorist acts such as the chemical attacks (2017-2018) in Syria. Consequently, it is necessary to prepare for and respond to the needs of children after a chemical or biological attack. A broad range of public health initiatives have occurred since the terrorist attacks of September 11, 2001. However, in many cases, these initiatives have not ensured the protection of children. Since 2001, public health preparedness has broadened to an all-hazards approach, in which response plans for terrorism are blended with those for unintentional disasters or outbreaks (eg, natural events such as earthquakes or pandemic influenza or man-made catastrophes such as a hazardous-materials spill). In response to new principles and programs that have evolved over the last decade, this technical report supports the accompanying update of the American Academy of Pediatrics 2006 policy statement "Chemical-Biological Terrorism and its Impact on Children." The roles of the pediatrician and public health agencies continue to evolve, and only their coordinated readiness and response efforts will ensure that the medical and mental health needs of children will be met successfully. In this document, we will address chemical and biological incidents. Radiation disasters are addressed separately., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Several toxic substances, inhaled or swallowed, can cause similar respiratory symptoms. We present two young patients with respiratory symptoms, one after inhaling chlorine gas and the other after ingesting lamp oil. Pathophysiology and clinical effects of these two substances differ. No specific antidotes exist for most toxic substances. Inhalation of respiratory irritants, such as chlorine gas, can lead to wheezing or bronchial obstruction, which can generally be handled by the family physician. In mild cases, administration of a bronchodilator is sufficient. Hydrocarbons such as lamp oil, however, can cause severe respiratory problems which develop over days, even when only small amounts are ingested. Hospitalization is therefore warranted in these cases, even when initial symptoms appear to be mild.

Nitrous oxide is increasingly consumed during parties for its euphoric properties. But unfortunately, in several cases it leads to real addictions. Unfortunately because its use leads to neurological, psychiatric, pulmonary and even death -by hypoxia-. It is important that the medical community be informed. It is important that the medical community be informed that in the face of atypical and poorly explained disorders doctors may think about the use of laughing gas, especially among young students., Competing Interests: Y. Auffret déclare avoir été pris en charge lors de congrès par Aspen, Mundipharma, Daiichi Sankyo et AstraZeneca.

Objective: Hypothermia, the gold standard after a hypoxic-ischemic insult, is not beneficial in all treated newborns. Cannabidiol is neuroprotective in animal models of newborn hypoxic-ischemic encephalopathy. This study compared the relative efficacies of cannabidiol and hypothermia in newborn hypoxic-ischemic piglets and assessed whether addition of cannabidiol augments hypothermic neuroprotection., Methods: One day-old HI (carotid clamp and FiO 2 10% for 20 min) piglets were randomized to vehicle or cannabidiol 1 mg/kg i.v. u.i.d. for three doses after being submitted to normothermia or 48 h-long hypothermia with a subsequent rewarming period of 6 h. Non-manipulated piglets (naïve) served as controls. Hemodynamic or respiratory parameters as well as brain activity (aEEG amplitude) were monitored throughout the experiment. Following termination, brains were obtained for histological (TUNEL staining, apoptosis; immunohistochemistry for Iba-1, microglia), biochemical (protein carbonylation, oxidative stress; and TNFα concentration, neuroinflammation) or proton magnetic resonance spectroscopy (Lac/NAA: metabolic derangement; Glu/NAA: excitotoxicity)., Results: HI led to sustained depressed brain activity and increased microglial activation, which was significantly improved by cannabidiol alone or with hypothermia but not by hypothermia alone. Hypoxic-ischemic-induced increases in Lac/NAA, Glu/NAA, TNFα or apoptosis were not reversed by either hypothermia or cannabidiol alone, but combination of the therapies did. No treatment modified the effects of HI on oxidative stress or astroglial activation. Cannabidiol treatment was well tolerated., Conclusions: cannabidiol administration after hypoxia-ischemia in piglets offers some neuroprotective effects but the combination of cannabidiol and hypothermia shows some additive effect leading to more complete neuroprotection than cannabidiol or hypothermia alone., (Copyright © 2018. Published by Elsevier Ltd.)

Background: The national Adverse Events Following Immunization (AEFI) surveillance system in China (CNAEFIS) has collected AEFI reports -including deaths following all vaccines used in China since 2008., Aims: To review reports of AEFI-associated death cases from 2010 to 2015 to assess potential vaccine safety issues., Methods: Descriptive analysis of epidemiologic characteristic of AEFI-associated death cases and standard causality assessment for reported causes of deaths. To estimate the risk of death after vaccination, we used population data, administered doses and live births to calculate denominators., Results: During 2010-2015, 753 deaths were reported to CNAEFIS from mainland China. Highest numbers were reported in 2013 and 2014 when reporting peak of AEFI-associated deaths occurred after media reports concerning "death following Hepatitis B vaccination" in China. About 95% of deaths were in children <5 years of age and males accounted for 60%. Most common vaccines associated with reports of fatal AEFIs were vaccines in national immunization schedule. In causality assessment, 120 (16.0%) deaths were classified as vaccine-associated reactions such as anaphylactic reactions and disseminated BCG infections; 594 (78.9%) deaths were identified as coincidental events. The main causes of death were asphyxia, and Sudden Infant Death Syndrome. The overall estimated AEFI-associated death rates were: 0.26 per million vaccination doses administered and 0.09 per million population. The neonatal AEFI death rate was 0.77 per million live births., Conclusions: These data provide reassuring information about the small risk of death following immunization. They also illustrate sensitivity of passive reporting to public information and that peaks in serious AEFI reports should be interpreted with caution. Continuous monitoring and scientific causality assessment for serious AEFIs, including AEFI-associated deaths is imperative to ensure public confidence in the immunization program., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: Maternal asthma increases adverse neonatal respiratory outcomes, and pollution may further increase risk. Air quality in relation to neonatal respiratory health has not been studied., Methods: Transient tachypnea of the newborn (TTN), asphyxia, and respiratory distress syndrome (RDS) were identified using medical records among 223,375 singletons from the Consortium on Safe Labor (2002-2008). Community Multiscale Air Quality models estimated pollutant exposures. Multipollutant Poisson regression models calculated adjusted relative risks of outcomes for interquartile range increases in average exposure. Maternal asthma and preterm delivery were evaluated as effect modifiers., Results: TTN risk increased after particulate matter (PM) less than or equal to 10-micron exposure during preconception and trimester one (9-10%), and whole-pregnancy exposure to PM less than or equal to 2.5 microns (PM 2.5 ; 17%) and carbon monoxide (CO; 10%). Asphyxia risk increased after exposure to PM 2.5 in trimester one (48%) and whole pregnancy (84%), CO in trimester two and whole pregnancy (28-32%), and consistently for ozone (34%-73%). RDS risk was associated with increased concentrations of nitrogen oxides (33%-42%) and ozone (9%-21%) during all pregnancy windows. Inverse associations were observed with several pollutants, particularly sulfur dioxide. No interaction with maternal asthma was observed. Restriction to term births yielded similar results., Conclusions: Several pollutants appear to increase neonatal respiratory outcome risks., (Published by Elsevier Inc.)

Postoperative analgesia after primary total knee arthroplasty (TKA) and revision knee arthroplasty (RKA) can be reliant on the use of opioids and may lead to opioid-related adverse events (ORAEs). This study evaluated the risk of ORAEs following TKA and RKA using the 5% Medicare claims (2010-2013) database. There were 41,702 TKA and 3817 RKA patients who met the inclusion criteria. At 90 days, respiratory complications were the most common complication (TKA: 6.12%; RKA: 8.01%), followed by postoperative nausea and vomiting (TKA: 2.86%; RKA: 3.95%), and urinary retention complications (TKA: 2.79%; RKA: 3.20%). For TKA, risk factors for respiratory complications included older age, lower socioeconomic status, more comorbidities, obesity, chronic obstructive pulmonary disease, white race, and patients in the Midwest and West (vs. South) (p 002). The average Medicare payment for treating complications within 90 days of a TKA was $6206 and $6222 following RKA. Awareness risks for ORAEs in select patients can assist in developing a multimodal postoperative pain control and patient education protocols. (Journal of Surgical Orthopaedic Advances 27(2):148-154, 2018).

In 1887, American dentist Samuel J. Hayes published reports associating unoxygenated anesthetics with asphyxia and insanity, and then British psychiatrist George H. Savage published a report of cases of insanity following nitrous-oxide anesthesia in British journals., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Though most patients survived the hypoxic challenge, some patients likely suffered asphyxial brain damage from GQ Colton's nitrous-oxide techniques and were admitted to insane or lunatic asylums., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Suicide using a combination of a plastic bag over the head and inhalation of a non-irritating gas, such as helium, argon or nitrogen, has been reported in the literature. Here an unusual suicide method in a 17-year old man by suffocation from covering the face with household plastic wrap, combined with nitrous oxide inhalation, is presented. The case was reviewed based on police, autopsy and hospital reports. A PubMed search for scientific literature related to nitrous oxide abuse and suicide by suffocation was performed and our findings discussed in relation to the scientific literature found. The deceased was a 17-year old man who was found with the nose and mouth closed with a piece of kitchen plastic wrap. The plastic wrap had been removed prior to autopsy. Autopsy findings were suggestive of asphyxia, but were otherwise negative. Nitrous oxide was detected in the brain and lung tissue with headspace-gas chromatography-mass spectrometry (headspace-GCMS). The cause of death was assumed to be suffocation caused by plastic wrap covering the face, combined with nitrous oxide inhalation. Suicide was suspected because of a history of depression for several months. Nitrous oxide, also known as laughing gas, has a euphoric effect and is used as a recreational inhalant drug that can be purchased legally. Deaths caused by recreational nitrous oxide abuse are rare but may occur if used in combination with a plastic bag over the head. This is the first report of suicide by suffocation by external obstruction combined with nitrous oxide inhalation.

To characterize the accumulated hazards associated with the inhalation of gases typical of combustion products, a time-integrated value known as the fractional effective dose (FED) is used. This FED is maintained by the International Organization for Standardization (ISO) and made publicly available as the Standard ISO 13571. The current FED calculation related to asphyxiant gases is based on non-human primate data to estimate the 50% probability of humans to be incapacitated or not being able to execute any escape paradigm from fires. The objective of this paper was to compare two to calculate FEDs of the most common mixture of asphyxiant fire gases CO, HCN, and CO 2 . The first was based on the current ISO 13571 (draft) standard, the alternative second method applied the conceptual principles established for the derivation of Acute Emergency Response Planning Guideline values. The alternative approach applied one third of the non-lethal threshold concentration (LC 01 ) as the most suitable and robust Point of Departure (POD) to estimate the threshold characterizing 'impairment of escape' in the absence of post-exposure mortality. The hyperventilation correction factor for CO 2 of ISO 13571 was replaced by a separate term that accounts for the inherent acute toxicity of CO 2 . This analysis supports the conclusion that the current ISO 13571 standard misjudges the impact of the acute toxicity elicited by concentrations of CO 2 exceeding ≈6%. While underestimating the hazards attributable to CO 2 , the hyperventilation adjustment factor suggested by this standard is biased to markedly overestimate the hazards assigned to CO and HCN in fire effluents., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Opioids are frequently used as part of multimodal pain management protocols for knee arthroscopy; however, their use may be associated with opioid-related adverse events. The purpose of this study was to evaluate the risk of potential analgesic-related complications after knee arthroscopy using a nationally representative database. Using 2010\endash 2012 Medicare claims data, patients undergoing knee arthroscopy procedures (including ligament repair, meniscectomy, and chondroplasty) were identified. The risk of complications related to typical modalities of analgesia, including opioids, within 90 days following surgery was assessed using multivariate Cox regression. Based on follow-up of 16,567 cases, respiratory complications (bradypnea, pulmonary insufficiency, asphyxia, and hypoxemia) were the most frequently diagnosed complications ( n = 418; 2.52%), followed by postoperative nausea and vomiting ( n = 174; 1.05%) and urinary retention complications ( n = 166; 1.00%). Risk factors including older age, male gender, lower socioeconomic status, and a high number of comorbidities were associated with development of postsurgical complications.

Livestock workers are involved in a variety of tasks, such as caring for animals, maintaining the breeding facilities, cleaning, and manure handling, and are exposed to health and safety risks. Hydrogen sulfide is considered the most toxic by-product of the manure handling process at livestock facilities. Except for several reports in developed countries, the statistics and cause of asphyxiation incidents in farms have not been collected and reported systematically, although the number of these incidents is expected to increase in developing and underdeveloped countries. In this study, the authors compiled the cases of work-related asphyxiation incidents at livestock manure storage facilities and analyzed the main causes. In this survey, a total of 17 incidents were identified through newspapers or online searches and public reports. Thirty workers died and eight were injured due to work-related tasks and rescue attempts from 1998 to 2013 in Korea. Of the 30 fatalities, 18 occurred during manure handling/maintenance tasks and 12 during rescue attempts. All incidents except for one case occurred during the warm season from the late spring (April) to early autumn (September) when manure is likely to decompose rapidly. It is important to train employees involved in the operation of the facilities (i.e., owners, managers, employees) regarding the appropriate prevention strategies for confined space management, such as hazard identification before entry, periodical facility inspection, restriction of unnecessary access, proper ventilation, and health and safety. Sharing information or case reports on previous incidents could also help prevent similar cases from occurring and reduce the number of fatalities and injuries.

First popularized in Japan, hydrogen sulfide (H2S) gas suicide is an underreported form of suicide with known risk for secondary disaster. Mortality rate commonly exceeds 90% because of the gas's lethal, noncontained nature. Instances in the United States are increasing, up from 2 cases in 2008 to 18 in 2010. Because H2S poisonings remain rare, there exists a lack of knowledge regarding the residual effects of gas venting after victim extrication. Identifying instances of the efficacious use of personal protection equipment (PPE) is critical in the effort to alleviate risks faced by hospital and rescue personnel. The current case demonstrates the effective use of PPEs after prolonged H2S exposure. In 2011, a 20-year-old man threatened suicide using H2S gas inside a vehicle on a remote rural highway. First responders identified a "rotten egg smell" and subsequently experienced low poisoning symptoms. After prolonged Hazmat-assisted extrication (4 hours) the patient was unconscious and experiencing seizures. He was decontaminated on-scene (20 minutes) and transported to the closest hospital (22 minutes). Ambulance personnel who wore PPE and used the ambulance's reverse ventilation system (RVS)reported no adverse effects. The patient was transferred to the authors' burn facility by helicopter (38 minutes). Life-flight personnel, who did not wear PPE (no ventilatory system available), complained of watery eyes, headache, and dizziness. Hospital personnel, who did not use PPE (or RVS), complained of watery eyes or headache. Exposed personnel demonstrated no deficits or residual effects. In spite of spontaneous movement, the patient began to seize and died. This case is unique given the multiple primary and secondary H2S gas exposures involved. Exposed personnel without RVS and not using PPE demonstrated moderate H2S symptoms. PPE (self-contained breathing apparatuses) and RVS were shown to be effective during an H2S emergency; however, there are currently limited data supporting their appropriate use. Until data demonstrating duration of H2S venting for small enclosed spaces are made available, PPEs should be required.

Although worker injury and fatalities have decreased since adoption of the Occupational Safety and Health Act in 1970, it remains an important safety issue. This article describes a 27-year-old white male who died from occupational exposure to airborne chemicals. Several trends in the last several decades, both in the types of injuries and the occupations associated with fatalities, are noted. Additionally, individual risk factors such as age, gender, chronic disease, smoking, and alcohol and drug use are implicated in worker health and safety. The role of the forensic pathologist in the investigation of workplace deaths is highlighted, in addition to the future of occupational safety and current improvements brought about by such incidents., (© 2014 American Academy of Forensic Sciences.)

Asphyxiants deprive the body of oxygen. Simple asphyxiants displace oxygen from the lungs, whereas systemic asphyxiants interfere with transport of oxygen by hemoglobin or with mitochondrial oxidative phosphorylation. Asphyxiants may be gases, liquids, or solids, or their metabolites. The typical clinical picture of asphyxiant poisoning is one of progressive mental status changes, alteration of breathing, progressively abnormal vital signs, coma, seizures, and eventually cardiovascular collapse and death. Treatment of asphyxiant poisoning is aggressive supportive care, with control of the airway and ventilation and maintenance of cardiac output. Supportive care is often enhanced by the administration of specific antidotes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The aim of this is to review deaths associated with the use of Riot Control Agents (RCAs) and to assess how the presenting pathologies is such cases may better inform cause of death conclusions upon autopsy. We also sought to present which additional steps should be added to the Minnesota protocol and the European harmonization of medico-legal autopsy rules in suspected cases of deaths associated with the use of RCAs. We included 10 lethal cases in our study. In three cases, RCAs were found to be the sole cause of death, in three cases RCAs were ruled a secondary cause of death due asphyxia or asthma subsequent to exposure to RCAs and in four cases RCAs were contributory factors to death. In three cases the responsible agents were identified as Chloroacetophenone (CN), Chlorobenzylidene malononitrile (CS) and Oleoresin capsicum (OC) and in the remaining 7 cases, the agent was OC alone. As there are no specific findings in suspected cases of death associated with RCA use, establishing cause of death and whether RCAs are the sole cause or only a contributory factor will be based on the elimination of other possible causes of death. For this reason, a specifically structured autopsy is essential. This specifically structured autopsy should contain basic principles of the Minnesota Protocol and the European harmonization of medico-legal autopsy rules with the following additional steps taken: examination of clothing, eyes, and skin; examination of pharyngeal, tracheobronchial, and eusophegeal mucosas; and a thorough recording of the steps taken by the party conducting the arrest, including other possible causes of in-custody death, as well as a detailed medical history of the deceased., (Copyright © 2014 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

The Occupational Medicine Forum is prepared by the ACOEM Occupational and Environmental Medical Practice Committee and does not necessarily represent an official ACOEM position. The Forum is intended for health professionals and is not intended to provide medical or legal advice, including illness prevention, diagnosis or treatment, or regulatory compliance. Such advice should be obtained directly from a physician and/or attorney.

A 29-year-old man was found dead lying on the bed in a hotel room in a famous Slovak mountain resort. He had a full-face diving mask on his face, connected through a diving breath regulator to a valve of an industrial (nondiving) high-pressure tank containing pure 100% nitrogen. The breath regulator (open-circuit type) used allowed inhalation of nitrogen without addition of open air, and the full-face diving mask assured aspiration of the gas even during the time of unconsciousness. At autopsy, we found the typical signs of suffocation. Toxicological analysis revealed 94.7% content of nitrogen in alveolar air. Following the completion of the police investigation, the manner of death was classified as a suicide. Within the medico-legal literature, there has been only one similar case of suicidal nitrogen inhalation described., (© 2013 American Academy of Forensic Sciences.)

Objective: To Evaluate the effects of different oxygen therapies on the rats with acute nitrogen asphyxia and to study the best oxygen therapic protocol for patients with acute nitrogen asphyxia on the spot., Methods: Sixty healthy male Wistar rats were divided into 5 groups: control, exposure to nitrogen, 33% oxygen treatment, 50% oxygen treatment and hyperbaric oxygen treatment groups. The behavioral performance, arterial oxygen pressure (PO2), carbon dioxide partial pressure (PCO2) and oxygen saturation (SPO2), biochemical changes in liver and kidney function and myocardial enzymes in 5 groups were measured., Results: The rats exposed to nitrogen firstly were excited then inactive symptoms, but consciousness was recovered after oxygen therapy. The PO2 and SPO2 in nitrogen exposure group were (79.67 +/- 9.12) and (94.92 +/- 2.78) mm Hg, respectively, which were significantly lower than those in control group (P<0.01). The PO2 and SPO2 of 3 oxygen treatment groups were (94.75 +/- 7.24), (94.92 +/- 8.98), (104.58 +/- 7.12)mm Hg and (97.17 +/- 0.83), (96.92 +/- 1.16), (97.42 +/- 0.67)mm Hg, respectively, which were significantly higher than those in nitrogen exposure group (P<0.05). The PO2 in hyperbaric oxygen treatment group was significantly higher than those in other 2 oxygen treatment groups (P<0.05). The SPO2 in hyperbaric oxygen treatment group was (51.42 +/- 6.60) mm Hg which was significantly higher than that [(44.58 +/- 3.42)mm Hg] in 50% oxygen treatment groups (P< 0.05). AST [(270.50 +/- 49.05 )U/L], ALT [(122.67 +/- 55.44 )U/L], BUN [(7.31 +/- 0.93 )mmol/L], Cr[(28.32 +/- 4.35) micromol/L], CK [(1808.42 +/- 582.05)U/L] and CtnI [(22.52 +/- 14.29 )ng/ml] in nitrogen exposure group were significantly higher than those in control group (P<0.05). AST [(165.25 +/- 30.87) U/L], HBDH [(350.83 +/- 103.00)U/L] and CtnI [(11.23 +/- 5.38) ng/ml] in hyperbaric oxygen treatment group were significantly lower than those in other 2 oxygen treatment groups (P<0.05)., Conclusion: Timely and effective oxygen therapy can significantly increase arterial pressure of oxygen and oxygen saturation in the rats with acute nitrogen asphyxia, and can improve liver function and cardiac damage. The hyperbaric oxygen chamber can significantly increase the therapeutic effects on rats with acute nitrogen asphyxiation.

Background/objectives: There are concerns about the effectiveness of head lice treatments because of increasing resistance and safety. This trial compared the safety and efficacy of a suffocant-based head lice treatment to malathion in children., Methods: The trial used strict entry criteria, standardized treatment and assessment regimens, sibling treatment where appropriate and a primary efficacy end-point defined as the absence of live head lice., Results: A total of 216 children were enrolled. One hundred and sixty-nine were per-protocol. The suffocant was significantly more effective than malathion for the intention-to-treat population (53.9% vs 40.4% louse-free, unadjusted P = 0.052; adjusted P = 0.024), as well as for the per-protocol population (57.8% vs 43.0% louse-free, unadjusted P = 0.054; adjusted P = 0.045). Adverse events were limited to itching or stinging and there were no serious or systemic adverse events. Repeat insult patch testing with the suffocant resulted in no adverse reactions. In vitro tests confirmed that the suffocant is a potent ovicide and pediculicide with 100% mortality of eggs and lice following a 20-min contact time., Conclusions: The suffocant is shown to be significantly more effective in eliminating head lice than malathion in children, while being associated with a low incidence of mild, transient adverse events.

During a routine truck-tank washing operation, five healthy workers were found motionless inside an empty tanker. Four of them died inside the tanker while the fifth died the following day in hospital. Since the true nature of the fatal compound(s) were not known, a rigorous environmental and toxicological approach supported by autopsy findings was essential to clarify the cause of death. Environmental results indicated that H(2)S fumes arising from the liquid sulfur previously shipped were responsible for the serial deaths, also confirmed by a simulation performed on two similar truck-tanks. These environmental findings were supported by toxicological analyses through the measurement of thiosulfate, one of the main H(2)S metabolites. Abnormal thiosulfate concentrations from 1.1 to 186.2 mg/kg were revealed in all post-mortem biological samples (blood, lung, liver, kidney, brain and fat). Finally, the cluster analysis performed on thiosulfate body distribution contributed to establishing the time of death according to the accident scene reconstruction. This report presents valuable findings in correctly identifying the cause of death in gas asphyxiation cases by unknown compound(s)., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

Nitrogen is an inert gas that is a normal constituent of the air that we breathe. It is a suffocating gas that does not support life and that can be a cause of death by the displacement of oxygen in the atmosphere. The majority of deaths associated with nitrogen have occurred in the setting of scuba diving. Although other suffocating gases have been used as a means of committing suicide, the literature contains little information about the use of nitrogen as a suicidal agent. A case of a 50-year-old man who committed suicide using a homemade suicide device and nitrogen gas is presented.

The present investigation was undertaken to study the comparative effectiveness of beta-adrenergic antagonist propranolol and calcium channel blocker verapamil on L-thyroxine-induced alteration on glycemic control and histamine sensitivity on rats and guinea pigs, respectively. Injection of L-thyroxine sodium every alternate day for 3 weeks in guinea pigs (75 microg/kg, i.p.) and rats (75 mg/kg, s.c.) produced a condition similar to thyrotoxicosis. Verapamil and propranolol administered daily in the third week along with L-thyroxine to two separate groups of hyperthyroid animals reversed thyroxine-induced loss in body weight, reduction in serum TSH levels, and rise in body temperature. Effect on glucose metabolism and insulin sensitivity was studied on rats. Compared to normal rats, L-thyroxine-treated animals showed a state of hyperglycemia, hyperinsulinemia, impaired glucose tolerance, and insulin resistance. Propranolol (10 mg/kg, i.p.) treatment significantly decreased fasting serum glucose levels without affecting serum insulin levels, AUC glucose, and K(ITT) values. Treatment with verapamil (5 mg/kg, i.p.) significantly reduced fasting serum glucose and insulin levels, AUC glucose, and significantly increased K(ITT) values. Effect of propranolol (15 mg/kg, orally) and verapamil (20 mg/kg, orally) treatment on histamine sensitivity was studied on L-thyroxine-treated guinea pigs. Compared to normal guinea pigs, L-thyroxine-treated guinea pigs showed an increased sensitivity to histamine-induced asphyxia. Verapamil treatment reversed this increased histamine sensitivity while propranolol aggravated it. In conclusion, compared to propranolol, verapamil has advantageous effects on glucose metabolism, insulin and histamine sensitivity and could therefore be a valuable addition as an adjunctive therapy option currently available for thyrotoxicosis associated with diabetes and/or anaphylaxis.

A 27-yr-old postgraduate student was found lying at the floor of an unsealed underground dry area, where a valve-opened empty cylinder of liquid nitrogen (150 L) was connected to a cap-removed empty Dewar-flask (10 L) via a copper infusion tube. No injury was found externally or internally. There were petechiae in the bilateral conjunctivae and periorbital skin. The dry area, measuring 300 x 130 x 260 cm, had a communication to the basement of the research building by a window measuring 90 x 60 cm in size at 130 cm above the floor. The scene reconstruction and atmosphere gas analysis revealed that the O2 concentration at 60 cm above the base dropped to 12.0% in 3 min and 10 sec, 10.0% in 8 min and 53 sec, 6.0% in 18 min and 40 sec, and 4.2% in 20 min and 28 sec. The primary cause of death was asphyxia by evaporated liquid nitrogen.

Background: Lethal injection for execution was conceived as a comparatively humane alternative to electrocution or cyanide gas. The current protocols are based on one improvised by a medical examiner and an anesthesiologist in Oklahoma and are practiced on an ad hoc basis at the discretion of prison personnel. Each drug used, the ultrashort-acting barbiturate thiopental, the neuromuscular blocker pancuronium bromide, and the electrolyte potassium chloride, was expected to be lethal alone, while the combination was intended to produce anesthesia then death due to respiratory and cardiac arrest. We sought to determine whether the current drug regimen results in death in the manner intended., Methods and Findings: We analyzed data from two US states that release information on executions, North Carolina and California, as well as the published clinical, laboratory, and veterinary animal experience. Execution outcomes from North Carolina and California together with interspecies dosage scaling of thiopental effects suggest that in the current practice of lethal injection, thiopental might not be fatal and might be insufficient to induce surgical anesthesia for the duration of the execution. Furthermore, evidence from North Carolina, California, and Virginia indicates that potassium chloride in lethal injection does not reliably induce cardiac arrest., Conclusions: We were able to analyze only a limited number of executions. However, our findings suggest that current lethal injection protocols may not reliably effect death through the mechanisms intended, indicating a failure of design and implementation. If thiopental and potassium chloride fail to cause anesthesia and cardiac arrest, potentially aware inmates could die through pancuronium-induced asphyxiation. Thus the conventional view of lethal injection leading to an invariably peaceful and painless death is questionable.

Background: Studies of drug-related mortality rarely describe fatal injuries due to psychoactive drug intoxication (FIUI). The main aim of this study was to determine the nature, extent and pattern of FIUI., Methods: This observational study covered the period January 1999 to December 2001. Data were provided by members of a study panel of coroners in England using a standard protocol. Sources of data for this study included autopsy protocols, death certificates, hospital records, police reports, toxicology reports and inquest transcripts. Inclusion criteria for this were (i) the mention of one or more psychoactive substances as contributing to fatality; and (ii) the presence of a Controlled Drug at post mortem., Results: A total of 3,803 drug-related deaths of persons aged 16-64 years were reported by the study panel during the three-year period. The study panel accounted for 86% of drug-related deaths in England in this period. There were 147 FIUI cases (119 males, 28 females), giving a proportionate mortality ratio of approximately 4%. The majority of FIUI cases (84%) were aged 16-44 years, with a median age at death of 33 years (Quartile deviation = 7). Fifty-six percent of FIUI occurred in urban areas of England. The population of the study jurisdictions aged 16-64 years contributed 49,545,766 person-years (py) to the study, giving an annual crude rate of 3/1,000,000 person-years (py). Rates for male and females were 4.9 and 1.1/1,000,000 py respectively, giving a male/female rate ratio of 4.5 (95%CI = 2.9-6.8). The rates of intentional and unintentional FIUI were 2 and 1/1,000,000 py respectively. The leading mechanism for intentional FIUI was suffocation while the predominant mechanisms in unintentional FIUI were road traffic accidents and falls. There is a significant difference in the pattern of drug-specific risk between FIUI and fatal poisoning. Risks of intentional FIUI are elevated among Black and Minority Ethnic groups., Conclusion: There are differences in the nature, extent and pattern of intentional and unintentional FIUI that should necessitate targeted prevention strategies. Also, there is an opportunity for cross-discipline collaboration between injury prevention specialists and substance abuse/mental health specialists.

Oxytocin is used to induce and control parturition; nevertheless, an increase in uterine contractions decreases blood flow and gaseous exchange through the uterus predisposing to intra-partum mortality in pigs. The objective of the present study was to evaluate the effect of different oxytocin administration routes on myometrial activity, fetal intrauterine hypoxia and postnatal asphyxia in crated farrowing sows. Yorkshire x Landrace hybrid sows (n = 300), that were approaching the time of parturition, were randomly assigned into six groups. Each group included 50 sows, 10 for each of the parities from one to five. A 40-IU oxytocin dosage was administered by intramuscular (IM), or intravulvar (IVU) routes, or 20 IU was administered via intravenous (IV) route. Groups 1 (G1), 3 (G3) and 5 (G5) were administered 0.9% saline solution (NaCl) IM, IVU and IV, respectively, whereas groups 2 (G2), 4 (G4) and 6 (G6) were treated with oxytocin IM, IVU and IV, respectively. There was a significantly (P < 0.05) greater number of intra-partum stillbirths (IPS) for the oxytocin treatments, as compared with the control groups, especially with the IVU and IV routes; a lesser number of IPS and lesser IPS with broken umbilical cords was observed with the IM administration route. Oxytocin and control IV administration resulted in longer farrowing durations. Administration of IV-oxytocin resulted in a greater number (P < 0.05) of intrauterine distressed neonates compared with its corresponding control and interpreted through dips II, a fetal cardiac frequency deceleration which determines acute fetal suffering. Independent of the route of oxytocin administration, the treatments resulted in twice as many dips II compared with the respective control groups. The use of the cardiotocograph proved to be an excellent tool for establishing the oxytocin response dose in farrowing sows. A greater number of piglets born alive, which had undergone bradycardia, also showed severe acidosis and greater meconium staining in oxytocin-treated sows, indicating that the administration time (at birth of the first piglet) as well as the dosage used were not adequate treatment regimens in the present study. Further studies will be conducted to evaluate different dosages and oxytocin administration timing to determine the most desirable treatment regimen to increase myometrial contractibility without compromising fetal welfare and neonatal survival.

Buprenorphine is an opioid agonist-antagonist with a 'ceiling effect' for respiratory depression. Compared with methadone, its unique pharmacology offers practical advantages and enhanced safety when prescribed as recommended and supervised by a physician. Buprenorphine has been approved in several countries as an efficient and safe maintenance therapy for heroin addiction. Its use resulted in a salutary effect with a reduction in heroin overdose-related deaths in countries that implemented office-based buprenorphine maintenance. In France, however, where high-dose buprenorphine has been marketed since 1996, several cases of asphyxic deaths were reported among addicts treated with buprenorphine. Death resulted from buprenorphine intravenous misuse or concomitant sedative drug ingestion, such as benzodiazepines. In these situations of abuse, misuse, or in association with elevated doses of psychotropic drugs, buprenorphine may cause severe respiratory depression. Unlike other opiates, the respiratory effects from buprenorphine are not responsive to naloxone. However, the exact mechanism of buprenorphine-induced effects on ventilation is still unknown. The role of norbuprenorphine, the main N-dealkylated buprenorphine metabolite with potent respiratory depressor activity, also remains unclear. Experimental studies investigating the respiratory effects of combinations of high doses of buprenorphine and benzodiazepines suggested that this drug-drug interaction may result from a pharmacodynamic interaction. A pharmacokinetic interaction between buprenorphine and flunitrazepam is also considered. As there are many questions regarding the possible dangers of death or respiratory depression associated with buprenorphine use, we aimed to present a comprehensive critical review of the published clinical and experimental studies on buprenorphine respiratory effects.

Fatalities due to 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") are rare in Austria, although the use of designer drugs has become quite common. This is the first published case of a fatal MDMA intoxication in Austria. A 19-year-old girl died after the consumption of ecstasy tablets in the apartment of a friend. Blood analysis gave a concentration of MDMA as 3.8 mg/L and traces of its metabolite MDA. Cannabinoids were found as well. This case shows that the consumption of MDMA, without physical stress, can lead to death.

Background/purpose: The aim of this study was to evaluate the effects of maternal nicotine exposure during gestation on injury severity of small intestine in the newborn rats subjected to hypoxia-reoxygenation and cold stress., Methods: A total of 21 Sprague-Dawley pregnant rats were divided into 3 equal groups. The groups were labeled as group 1, control group; group 2, hypoxia-reoxygenation group; and group 3, nicotine-hypoxia-reoxygenation group. The rats of group 3 were exposed to nicotine via subcuticular injection for the last week of gestation (2 mg/kg/d). Newborn rats were collected immediately after birth to prevent suckling of maternal milk (40 rat pups in group 1, 43 rat pups in group 2, and 41 rat pups in group 3). Litters in groups 2 and 3 were stressed twice daily with asphyxia followed by cold (4 degrees C for 10 minutes) stress to induce hypoxic intestinal injury which is relevant to human necrotizing enterocolitis. Breathing 100% CO2 for 10 minutes in a chamber followed by 10-minute 100% O2 breathing was the asphyxia model repeated twice daily. After hypoxia-reoxygenation and cold stress, newborn rats were returned to their mother's cages. This protocol was repeated for the following 2 days, and the rat pups were decapitated on the third day. Using this protocol of asphyxia and cold stress, all of neonatal rats developed clinical and pathological signs of hypoxia-induced intestinal injury. The entire gastrointestinal tract was removed and examined macroscopically. A 2-cm section of distal ileum from each animal was taken for histopathological and biochemical examinations. Histological changes in ileal architecture were scored and graded from 1 to 5. The remaining intestinal tissues of the animals were used for lipid peroxidation analysis., Results: Typical signs of hypoxia-induced intestinal injury were observed in the 2 experimental groups (groups 2 and 3) macroscopically. There were more grades 3 and 4 injuries in group 3 (P < .05). The malondialdehyde levels were elevated in groups 2 and 3 (P < .001). The malondialdehyde levels of the group 3 were also significantly higher than group 2 (P < .01)., Conclusions: Maternal nicotine exposure during gestation results in higher grade histological injury in newborn rats subjected to hypoxia-reoxygenation and cold stress.

A 17-day-old female infant with thrush was almost asphyxiated by miconazole oral gel that had been applied to the nipples of her mother's breasts. The infant recovered after her mother had removed the gel from her mouth. Thrush is most often self-limiting and medical treatment is usually unnecessary. When treatment is indicated, miconazole oral gel or nystatin can be given. To obtain a therapeutic effect, long-term contact with the oral mucosa is needed and therefore the oral gel is viscous. Small amounts of the gel should be applied to the oral mucosa. When prescribing miconazole oral gel, instructions should be given regarding the mode of administration and the risk of respiratory tract obstruction should be pointed out.

Dyspnea is a key symptom in panic attacks. This study investigated different types of dyspnea induced by the 35% CO2 challenge test given to patients with panic disorder (PD). The types of dyspnea provide room for possible conjectures on neurophysiological pathways involved in the experience of breathing discomfort in PD and in the panic-respiration connection. Factor analysis applied to the Dyspnea Questionnaire identified three main factors: breathing effort, sense of suffocation, and rapid breath. Factor scores for breathing effort and sense of suffocation significantly discriminated between patients who did and those who did not report CO2-induced panic attacks. Factor scores for breathing effort significantly discriminated between patients whose reaction resembled their unexpected panic attacks and those whose reaction did not. A dissociation between an increased central respiratory command and a decreased mechanical efficiency of the respiratory response in patients with PD may underlie the breathing effort factor during the CO2 challenge. The sense of suffocation factor was found to be linked to chemosensitivity. Although involved in CO2 reactivity, it may not be a central factor in unexpected panic attacks.

Construction workers account for a disproportionately large number of occupational fatalities. A small percentage of these deaths is attributable to poisoning. Risk factors for such deaths using national data have not been reported previously. Construction poisoning fatalities from 1990 to 1999 in the Occupational Safety and Health Administration Integrated Management and Information System data set were analyzed. Risk and risk factors were determined using Bureau of Labor Statistics and census data. Eighty-seven poisoning deaths of construction workers are characterized, all attributable to toxic inhalation. Cellular and simple asphyxiants accounted for the largest numbers of fatalities. The majority of these deaths occurred in confined spaces. Water, sewer, and utility line workers are at increased risk for poisoning fatality. Toxic inhalation fatalities in the construction industry are preventable. Extending the Occupational Safety and Health Administration's confined space standard could save lives, particularly among water, sewer, and utility line industry workers.

Café coronary deaths, as initially characterized, denote fatal occlusion of the upper airway by food substances. Such fatalities typically occur in individuals who either are clinically inebriated or have clinically significant neuromuscular dysfunction. Both conditions impair mastication and deglutition. The authors review the accidental deaths of two neurologically compromised patients under supervised care. Both subjects underwent complete medicolegal autopsy. In one case, ingestion of a prescribed emollient laxative precipitated death; in the other, death was attributable to aspiration of a contrast medium during a diagnostic radiographic procedure. These therapy-related deaths, which are regarded as a variation of the traditionally described café coronary fatalities summarized in the discussion, represent adverse events occurring during medical care. The adverse outcomes reviewed here are potentially avoidable and require special attentiveness by the clinicians directed to the particular condition of each patient. Such true aspiration-related deaths are confirmed on autopsy examination and are to be differentiated from the findings of agonal aspiration of gastric contents commonly encountered by the autopsy pathologist investigating deaths due to a great variety of natural and traumatic causes.

Two unusual suicides of a 19-year-old white man and a 47-year-old white man, involving propane inhalation and plastic bag suffocation, are described. The special characteristics of propane gas as an asphyxiant agent are discussed, as well as its effect on the human body. The discussion emphasizes the postmortem examination and the collection of samples for toxicologic analysis.

Two rates of carbon dioxide flow into the termination chamber were applied for the euthanasia of rats. The classical phases of asphyxia were observed in both groups of animals although their course was prolonged in rats exposed to the lower gas flow. The haemorrhages were assessed histologically in the following structures: the pericranium, compact bone and diploë of the skull, sagittal suture, nape muscle and its attachment, and the dura. The haemorrhages appeared regularly in the sagittal suture in all cases from both experimental groups. The possible significance of this phenomenon for the forensic practice was pointed out.