Quantitative determination of nitrous oxide in human blood by HS-GC-MS: forensic application of two fatal poisoning cases.

Nitrous oxide (N2O), also known as laughing gas, has a euphoric effect and is becoming increasingly popular as a recreational inhalant drug. Deaths caused by recreational nitrous oxide abuse are rare, but may still occur. Although some methods for the quantification of N2O by GC-MS have been reported, elimination of carbon dioxide interference and the choice of a suitable internal standard remain current limitations to accurate N2O quantification. Here, a validated method using headspace-gas chromatography-mass spectrometry (HS-GC-MS) is described that allows the quantification of N2O in human blood samples: sodium hydroxide is used to remove carbon dioxide, and n-pentane is chosen as a suitable internal standard. Collectively, the validation results show a good linear relationship of N2O in blood within the concentration range of 0.02 ∼ 0.5 mL/mL and an LOD of 0.005 mL/mL. Subsequent application of the validated method to two real mortality cases due to N2O intoxication provided reference values for blood concentrations in forensic cases. Other biological specimens (gaseous samples and tissues) of the deceased were also analyzed to demonstrate that the deaths were caused by asphyxia due to the inhalation of N2O.

[Acute neuropathy and liver injury following the abuse of nitrous oxide].

This is a case report about two young men with extensive recreational use of nitrous oxide (N2O) in bulbs. Vitamin B12 deficiency was found in the first patient as well as signs of myelopathy on magnetic resonance imaging, and the second patient had acute liver injury. Physical examinations showed severe pathology with loss of motor function and affected sensory function in both patients. Recreational use of N2O is increasing in Denmark, but the extent of N2O abuse is not known. Attention to these effects of N2O abuse may be important when treating patients with acute N2O-intoxication.

Suffocation caused by plastic wrap covering the face combined with nitrous oxide inhalation.

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.

Death from Nitrous Oxide.

Nitrous oxide is an inflammable gas that gives no smell or taste. It has a history of abuse as long as its clinical use, and deaths, although rare, have been reported. We describe two cases of accidental deaths related to voluntary inhalation of nitrous oxide, both found dead with a gas mask covering the face. In an attempt to find an explanation to why the victims did not react properly to oncoming hypoxia, we performed experiments where a test person was allowed to breath in a closed system, with or without nitrous oxide added. Vital signs and gas concentrations as well as subjective symptoms were recorded. The experiments indicated that the explanation to the fact that neither of the descendents had reacted to oncoming hypoxia and hypercapnia was due to the inhalation of nitrous oxide. This study raises the question whether nitrous oxide really should be easily, commercially available.

Subacute combined degeneration of the spinal cord following recreational nitrous oxide use.

We describe a case of a young woman who developed myelopathy and peripheral neuropathy following 1 year of recreational nitrous oxide (N2O) use. She presented with uncomfortable tingling sensation in her feet and poor balance. Physical examination revealed mild weakness and hyper-reflexia in the lower limbs. Proprioception and vibration were absent in the lower limbs. Pinprick and light touch sensations were reduced below the sixth thoracic dermatome. A broad-based gait and a positive Romberg sign were noted. The level of vitamin B12 was low (76 pmol/l). T2-weighted MRI scans showed hyperintensity changes at the posterior column from the second to the fifth cervical vertebrae. She made a full recovery following injections of vitamin B12 and physiotherapy. This case discusses subacute combined degeneration of the spinal cord on a background of N2O abuse.

Subacute combined degeneration caused by nitrous oxide intoxication: case reports.

PURPOSE: Case reports with a comprehensive review of the current literature concerning subacute combined degeneration induced by nitrous oxide inhalation. A differential diagnosis should be considered when young patients present with progressive myelopathy because that the misuse of nitrous oxide has potentially serious outcomes. CASES REPORT: Three young patients aged from 18 to 24, one male and two females, were diagnosed with progressive ascending numbness in four limbs or both legs and ataxia. They all had been inhaling nitrous oxide from whipped-cream containers for several months. A cervicothoracic magnetic resonance imaging scan revealed long segmental hyperintensity changes at the posterior column of the spinal cord. Serological examination showed a low level of vitamin B12. Subacute combined degeneration of the spinal cord was diagnosed and the etiology was considered related to nitrous oxide misuse. Their neurological status, neuroimage, and neurophysiologic condition improved after vitamin B12 supplementation and cessation of nitrous oxide inhalation. CONCLUSION: Iatrogenic usage of nitrous oxide apparently resulted in subacute combined degeneration in our three patients. Recently, nitrous oxide misuse has increased among young people. Subacute combined degeneration of the spinal cord should be considered as a possible outcome of such abuse.

Trends and pattern of drug abuse deaths in Maryland teenagers.

The Office of the Chief Medical Examiner of Maryland recorded a total of 149 drug abuse deaths of teenagers aged 13-19 years between 1991 and 2006. Of these deaths, 96 (64.4%) were caused by the use of narcotic drugs only, 29 (19.5%) by both narcotics and cocaine, four (2.7%) by both narcotics and methylenedioxymethamphetamine, six (4.0%) by cocaine only, and 14 (9.4%) by volatile substances (e.g., butane, Freon, nitrous oxide, and propane). The annual death rate from drug abuse for teenagers increased from 1.4 deaths per 100,000 population in 1991 to 2.7 deaths per 100,000 population in 2006 (chi-square test for time trend, p<0.01). The increase in teenager drug abuse deaths occurred in 1999 and since has remained at a higher rate. Further analysis revealed that the increase in drug abuse deaths was attributable to a large degree to narcotic drugs, particularly heroin/morphine and methadone, and was confined to teenagers residing in the suburban and rural areas.

Death caused by addictive inhalation of nitrous oxide.

Intoxications with nitrous oxide have been, and still are, a rarity in forensic medicine. Apart from accidental overdose during hospital procedures, intoxication with this gas is the result of voluntary inhalation. We report the fatal case of a 32-year-old male who died during inhalation of nitrous oxide from whipped dairy cream cans and hint on the role of the internet in creating new behaviors among drug addicts. We rely on the autopsy report from the Department of Forensic Medicine, Pomeranian Medical University in Szczecin, on laboratory tests, and court files. Neither the autopsy nor the toxicologic and histopathologic tests disclosed the exact cause of death. However, circumstances in which the body was discovered were indicative that death resulted from cardiorespiratory failure. The present case is interesting with regard to its rarity, diagnostic difficulties and potential harm from nitrous oxide used by the food industry.

Severe myeloneuropathy from acute high-dose nitrous oxide (N2O) abuse.

BACKGROUND: Myeloneuropathy from chronic exposure to nitrous oxide has been described. Nitrous oxide irreversibly alters B(12) activation, causing signs and symptoms of B(12) deficiency. OBJECTIVES: We describe a case of myeloneuropathy secondary to acute use of high-dose nitrous oxide. CASE REPORT: A 24-year-old man presented to the Emergency Department complaining of numbness and tingling of his hands and feet, as well as worsening clumsiness and gait disturbances after escalating use of nitrous oxide in the prior 2 weeks. He was found to have dysmetria, poor proprioception, decreased sensation to vibration and light touch over his extremities, and a mildly positive Romberg sign. Laboratory test values revealed a normal B(12) level but increased methylmalonic acid and homocysteine levels. The patient was admitted to the hospital and started on a course of B(12) injections. He was discharged after 3 days with daily B(12) supplementation. CONCLUSIONS: This case demonstrates myeloneuropathic changes secondary to acute high-dose nitrous oxide exposure.

Nitrous oxide determination in postmortem biological samples: a case of serial fatal poisoning in a public hospital.

In a public hospital, eight cases of fatal poisoning by nitrous oxide (N(2)O) occurred under oxygen administration, due to an erroneous swapping of the lines in the gas system. The aim of the study was to clarify the factors involved in asphyxia by characterizing gases from different lines and measuring N(2)O concentrations in postmortem biological samples from bodies exhumed. Analyses carried out on the gas system confirmed the erroneous substitution of O(2) line with N(2)O and air line with O(2). Consequently, high N(2)O amounts were revealed in several tissues and gaseous biological samples. All specimens were analyzed by headspace gas chromatography technique. A rigorous quantitative analysis was possible only in blood (11.29-2152.04 mg/L) and urine (95.11 mg/L) and in air samples from stomach and trachea (from 5.28 to 83.63 g/m(3)). This study demonstrates that N(2)O can be detected in biological samples even 1 month after death.

Fatal errors in nitrous oxide delivery.

Nitrous oxide continues to be used frequently and the possibility of inadvertent fatal hypoxaemia resulting from technical errors with its administration still exists. A Medline analysis revealed only a few case reports over the last 30 years, and a closed claim analysis only reported 'claims involving oxygen supply lines' predating 1990. The aim of this study was to assess the frequency of nitrous oxide-related catastrophes during general anaesthesia in Germany, Austria, and Switzerland. As nitrous oxide-related anaesthesia casualties are rare but generally prosecuted, they almost invariably attract significant media attention. We scanned mass media archives from April 2004 until October 2006 for nitrous oxide-related disasters during general anaesthesia. This approach detected six incidents which were almost certainly nitrous oxide ventilation-related deaths. Searching non-scientific data bases demonstrates that severe incidents involving oxygen supply lines occurred after 1990, and may be much more frequent than previously thought.

Paralysis caused by "nagging".

A woman in her 20s presented to the emergency department, malnourished and dehydrated, and with acute paralysis of the lower limbs. Over the previous 10 days, she had inhaled nitrous oxide from "whipped-cream bulbs" (10-20 per day) for pain caused by a sprained ankle. She had a history of intravenous drug use and was on a methadone program. The nitrous oxide misuse combined with the malnutrition, with low vitamin B(12) levels, apparently resulted in subacute combined degeneration of the spinal cord--a rare complication of nitrous oxide misuse.

Spinal myoclonus in subacute combined degeneration caused by nitrous oxide intoxication.

A 26-year-old patient developed ascending weakness and paresthesias. Megaloblastic anemia and mildly reduced serum vitamin B12 (B12) concentration were noted. Myoclonus-like muscular contractions appeared over four extremities and in the trunk. She admitted inhaling nitrous oxide (N2O) as a euphoriant repeatedly at party. Following parenteral B12 administration, her neurological deficit promptly resolved. This case demonstrated the abuse of N2OI is an important cause of subacute combined degeneration (SCD) of the spinal cord. To our knowledge, this is the first report of involuntary movements in a patient with N2O intoxication. Although the mechanism remains unknown, involuntary movements similar to myoclonus should be considered as one of the extraordinary neurological manifestations of N2O intoxication.

Nitrous oxide "whippit" abuse presenting with cobalamin responsive psychosis.

INTRODUCTION: Nitrous oxide is a commonly abused inhalant drug. It is known to precipitate vitamin B12 deficiency when used chronically and acutely, especially in people having marginal vitamin B12 reserve. CASE REPORT: We are presenting a case of nitrous oxide "whippit" abuse in a thirty-three-year-old male with bizarre behavior and delusions. The patient had low normal levels of vitamin B12 (202 pg/ml), but he had markedly high methylmalonyl CoA (1078 nmol/L) and homocysteine (48.4 mcmol/L). Treatment with intramuscular cobalamin led to a resolution of his psychosis. DISCUSSION: This case report highlights the need to consider vitamin B12 deficiency in patients who arrive at a hospital with psychiatric manifestations and who report having a history of nitrous oxide exposure or abuse in the recent or remote past. A review of the literature on the neuropsychological manifestations of vitamin B12 deficiency is provided.