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Reliable gas chromatographic-mass spectrometric method combined with a headspace autosampler for isoflurane determination in blood.

Isoflurane is a nonflammable, liquid, volatile inhalation anesthetic administered by vaporizing. Although it is now commonly used, fatal cases resulting from its abuse or misuse have been reported. A combined system of a gas chromatograph-mass spectrometer and a headspace autosampler is therefore proposed for the detection of blood isoflurane. This analytic method showed sharp and well separated peaks, and revealed a good linear relationship (r=0.9994) with a function of y = 7.3768x - 0.0222 at concentrations between 18.7 and 299.2 microg/ml. The limits of detection and quantitation of this method were 1.2 and 4.7 microg/ml, respectively. The within- and between-run precision for spiked samples, assessed by the coefficient of variations, ranged from 1.7 to 10.0% and from 4.1 to 12.8%, respectively. The within- and between-run accuracy, assessed by errors from theoretical values, were 2.2-7.8% and 2.4-9.6%, respectively. In addition, practical sample analysis showed a good applicability, with a within-run precision rate of 5.6 to 7.7% and a between-run precision rate of 5.2-10.6%. In summary, the present work presents a valid alternative for blood isoflurane analysis.

Anesthetics, Inhalation↗

Effects of inhaled toluene and 1,1,1-trichloroethane on seizures and death produced by N-methyl-D-aspartic acid in mice.

Evidence exists that some abused solvents have N-methyl-D-aspartic acid (NMDA) antagonist activity, although which of their effects may be related to this mechanism is not well understood. The effects of toluene and 1,1,1-trichloroethane (TCE) on NMDA-induced seizures in mice were studied using three experimental protocols: (a) animals injected i.p. with 120 or 170 mg/kg NMDA and immediately afterwards exposed to solvent vapors or air for 30 min (co-exposure protocol); (b) mice exposed for 30 min to solvent or air, then injected with NMDA and placed in the chamber for a second 30-min exposure (pre-exposure+co-exposure protocol); and (c) mice that inhaled 4000 ppm toluene or air for 30 min twice a day, 6 h apart, for 7 days, and were injected with 120 mg/kg NMDA immediately before a 30-min toluene exposure (repeated exposure protocol). When given acutely, toluene, but not TCE, produced concentration-dependent protection against NMDA-induced seizures. Higher concentrations of toluene were also effective against the lethal effects produced by 170 mg/kg NMDA. Clearer effects were seen when the pre-exposure+co-exposure protocol was followed. Under these conditions the IC(50) for toluene was 739 ppm (653-825) against seizure occurrence and 2127 ppm (1966-2288) against lethality. Repeated exposure to toluene did not result in tolerance to its anticonvulsant effects. These results are consistent with the in vitro effects described for toluene as a noncompetitive NMDA antagonist and as a compound that enhances GABAergic transmission. The lack of protective effects of TCE is not consistent with its in vitro actions.

Animals↗

Role of nicotine pharmacokinetics in nicotine addiction and nicotine replacement therapy: a review.

Smoking is a complex behaviour involving both pharmacological and psychological components. Nicotine is the main alkaloid found in tobacco, and is responsible for its addictive potential. Nicotine-positive effects on mood and cognition are strong reinforcements for smokers that contribute to their addiction, and cigarette smoking is particularly addictive because inhaled nicotine is absorbed through the pulmonary venous rather than the systemic venous system, and thus reaches the brain in 10-20 seconds. As the likelihood that a substance will be abused depends on the time between administration and central reinforcement, tobacco smoking can easily become addictive. Nicotine replacement therapy (NRT) is available in different forms (gum, transdermal patch, nasal spray, inhaler, sublingual tablet and lozenge), and has been shown to relieve withdrawal symptoms and to double abstinence rates compared to placebo. Most NRT forms deliver nicotine more slowly than smoking, and the increase in nicotine blood levels is more gradual. Compared to tobacco smoking or even tobacco chewing, few positive (reinforcing) effects are obtained from NRT use. Nasal spray provides faster withdrawal relief than other NRT, but compared to smoking absorption is slower and nicotine blood levels obtained are lower than with smoking. These differences in pharmacokinetic profiles compared with smoking may explain that some smokers still have difficulties quitting smoking even when using NRT (apart from psychological and/or social factors). Combination therapy (e.g., patch+gum, patch+inhaler), higher dosage, temporary abstinence or smoking reduction (using NRT to reduce smoke intake) may be needed to help more smokers to quit.

Affect↗

Passive freebase cocaine ('crack') inhalation by infants and toddlers.

Cocaine and its principal metabolite, benzoyl ecgonine, were isolated from the urine of four hospitalized children who had been exposed to the smoke of freebase cocaine ("crack") used by their adult caretakers. Two of the children had transient neurological symptoms (drowsiness and unsteady gait) and two had seizures whose cause could not be determined by laboratory investigation. Passive cocaine inhalation may have caused or contributed to these symptoms. Children in the care of adults who abuse freebase cocaine should be considered at risk not only for disruption of their social environment but also for the effects of cocaine toxicity.

Child, Preschool↗

Glue-sniffing as a cause of a positive radio-isotope brain scan.

Convulsions are a known complication of the acute intoxicant effects of solvent abuse. A radio-isotope brain scan done 9 months following status epilepticus secondary to toluene inhalation, in a previously normal school-boy, demonstrated several wedge-shaped areas of increased uptake, in both cerebral hemispheres, consistent with infarcts. It is worth remembering that a positive brain scan in a young person, with recent onset of epilepsy, may be due to glue-sniffing.

Adolescent↗

Tuberculosis: disease of the past, disease of the present.

Once thought to be under control, tuberculosis is now the number one cause of infection-related death worldwide and the sixth most significant cause of death overall. Transmission occurs by inhalation of airborne droplet nuclei that can be viable for days, and is facilitated by substance abuse, poverty, overcrowding, malnutrition, and, most importantly coinfection with human immunodeficiency virus. This article describes the history and current status of tuberculosis as a growing global health problem, transmission of the disease, risk factors for the general public and health care workers, and prevention of the disease.

Health Personnel↗

Methamphetamine laboratory explosions: a new and emerging burn injury.

The proliferation of clandestine methamphetamine laboratories (meth labs) as a result of the growing popularity of the drug has resulted in an increasing incidence of burn injuries associated with laboratory accidents. We undertook this study to characterize these injuries. Fifteen consecutive patients were identified and case-matched by age and TBSA to 45 control subjects. Most meth lab patients were men, Caucasian, unemployed, and positive for polysubstance abuse. Resuscitation requirements were 1.8 times greater in these patients. There was a higher incidence of inhalational injury corresponding to higher intubation and tracheostomy rate and longer ventilator days among meth lab patients. The rate of nosocomial pneumonia, skin graft loss, and mortality were not different between the two groups. Meth lab injury is unique and requires more critical care resources. It also is associated with lack of insurance coverage and poor follow-up after injury. This injury has a significant impact not only on patients but also on the healthcare system.

Accidents↗

Alcohol and drug abuse in burn injuries.

Two studies are described in this paper. In the first study 225 acutely, severely burned patients were retrospectively investigated as to admission blood alcohol level and history of chronic alcohol abuse. The influence of further risk factors, circumstances and therapeutic data was studied, in particular the influence of gender, full-thickness burns, smoke inhalation injury, smoking, length of total and ICU stay, and suicide attempt. The 70 patients with positive blood alcohol levels on admission had a significantly higher fatality rate (31.5 per cent) in comparison with the 18.1 per cent fatality rate of patients with a negative blood alcohol level. Both groups had nearly identical mean TBSA and mean age. Chronic alcohol abuse was noted in 59 patients. These patients were found to have a higher fatality rate (31.4 per cent, 22/70) compared with that of patients without a history of chronic alcohol abuse who had an overall fatality rate of 18.1 per cent (28/155). No significant difference was found between non-intoxicated and acutely intoxicated alcoholics (31.4 vs 29.3 per cent). Our conclusion is that intake of alcohol before burn injury represents an independent risk factor. The second study was a prospective study of 16 consecutively admitted burn patients, who were evaluated for both drug and alcohol intake. Five patients had positive drug levels and five had positive alcohol levels. Five patients had a history of chronic drug and/or alcohol abuse. This incidence of alcohol and drug abuse supports the findings of our retrospective study.

Adolescent↗

Correlation between 'on admission' blood toluene concentrations and the presence or absence of signs and symptoms in solvent abusers.

For 1 year, from June 1987 to June 1988, toluene concentrations in blood samples of patients admitted to a psychiatric hospital after inhaling solvent vapor, collected on admission and 4 h later, were analyzed by gas chromatograph. Toluene levels in the first urine samples collected after admission were also analyzed and case histories were kept listing age, sex and physical and psychiatric effects. In all, 51 cases were studied--34 males and 17 females. (1) The average age of the males was 21.4 years and of the female 16.2 years. (2) The toluene concentrations in the blood collected on admission ranged from 0.3 to 22.8 micrograms/g. (3) Physical signs were observed in 9 patients with an "on admission" blood toluene concentrations of more than 3.0 micrograms/g; twice as many subjects (18), however, with blood toluene concentration greater than 3.0 micrograms/g were without physical signs. (4) The blood toluene concentrations of three cases in the condition known as twilight state were more than 10.0 micrograms/g. (5) In 24 cases with blood toluene concentrations below 3.0 micrograms/g, there were no physical signs. (6) Five subjects with blood toluene concentrations in the 0.8-5.2 micrograms/g range showed neuropsychiatric effects; however, 23 subjects in the same blood toluene concentration range did not exhibit psychiatric effects, and none of the subjects with blood toluene concentrations greater than 5.2 micrograms/g, 15 in all, had such effects.

Adolescent↗

Glue-sniffing neuropathies.

The commonly used term for solvent abuse, glue sniffing, generally encompasses a variety of substances, including spray paint, thinners, nail varnish remover, gasoline, marking pens, and lighter fluids. Inhaled vapours eventually reach the lipids in the nervous system, where they can be stored for long periods. In three cases of glue-sniffing-related neurotoxicity, the peripheral nervous system was affected in two cases and predominantly the central nervous system in the third. Unfortunately follow up is difficult with this patient population and symptoms are often complicated by alcohol abuse.

Adolescent↗

The relationship between chronic ethanol exposure and cigarette smoking in the laboratory and the natural environment.

Few studies have examined the association between ethanol use and cigarette smoking topography. In particular, no study has objectively investigated the relationship between chronic ethanol exposure and cigarette smoking. The aim of this study was to quantify the relationship between cigarette smoking and past and current ethanol use. Male and female cigarette smokers (n = 77) between the ages of 30 and 65 years were recruited and grouped as a function of their past and current ethanol use. Group 1 (n = 18) included subjects who were ethanol abstinent for the 3 months prior to the study and had no history of alcohol abuse (as defined by DSM-III criteria). Group 2 (n = 19) included subjects who were current regular ethanol users and had no history of alcohol abuse. Group 3 (n = 20) included subjects who were ethanol abstinent and had a history of alcohol abuse. Group 4 (n = 20) included current regular ethanol users with a history of alcohol abuse. A history of alcohol abuse was associated with an intensified pattern of cigarette smoking. Significant differences were observed for total daily smoke exposure, cigarette number, puff number, total puff and inhalation volume, and the nicotine, tar and carbon monoxide yields of the cigarettes smoked. Increased expired-air carbon monoxide and serum cotinine levels were also observed. Current ethanol use was not associated with an increased cigarette smoking pattern. These data suggest that alcohol abusers are at greater risk of contracting cigarette-related pathology.

Adult↗

Effectiveness of nitrous oxide in a rural EMS system.

Prehospital systems need a safe, effective analgesic agent for the treatment of patients suffering from pain. Recent studies have documented the efficacy of nitrous oxide in urban and rural settings. This study reviews the findings on 200 patients (157 trauma, 23 medical, 18 musculoskeletal problems) who received nitrous oxide during a 28-month period in a rural EMS system. Eighty-five percent of the patients reported pain relief. Only minor side effects were noted. Patient satisfaction was high, and there was no abuse noted among personnel.

Administration, Inhalation↗

Sudden death after isobutane sniffing: a report of two forensic cases.

The intentional inhalation of a volatile substance ("sniffing") causing euphoria and hallucinations is an under-recognised form of substance abuse in children and adolescents with a high morbidity and mortality. Sudden death can be caused by cardiac arrhythmia, asphyxia or trauma. Two fatal cases of isobutane sniffing of cigarette lighter refill containing isobutane are reported. Toxicological investigations revealed the presence of isobutane in the heart blood and brain tissue of both cases (case 1: heart blood 0.1 microg/g, brain tissue 2.3 microg/g; case 2: heart blood 4.6 microg/g, brain tissue 17.4 microg/g) and the presence of its metabolite 2-methyl-2-propanol in the heart blood of both cases (0.5 and 1.8 microg/g, respectively). The histological investigations of the inner organs showed similar results in both victims. Autopsy findings, results of the histological and immunohistochemical investigations, toxicological findings and analytical procedures are discussed.

Administration, Inhalation↗

Observed activities of serum creatine kinase: total and B subunit activity and other enzymes in young persons abusing solvents.

Serum enzymes (aspartate transaminase, alanine transaminase, alkaline phosphatase (ALP), gamma-glutamyltransferase, and creatine kinase (CK] were measured in 296 young persons who admitted to recent inhalation of solvents, usually toluene based glues. In general, results fell within expected adult reference ranges except for ALP and CK. About 60% of subjects had CK activities above the upper reference limit and these activities were investigated in terms of their isoenzyme composition. CK B subunit activity was measured in 90 subjects with raised total CK activities. In five instances the CK B subunit activity was judged abnormal and in two subjects the presence of CK BB was confirmed. These two subjects were thought to have a circulating macro CK, type 1. It is concluded that the increased total CK activity found in this group of solvent abusers was due to physical activity, but a contribution from specific muscle toxicity by solvents cannot be excluded.

Adolescent↗

Sexual abuse, alcohol and other drug use, and suicidal behaviors in homeless adolescents.

Previous research has shown that homeless youth have high rates of suicidal ideation, sexual abuse, and abuse of alcohol and other drugs. However, little is known about how these rates differ by gender and ethnicity. Our objective was to describe patterns of sexual abuse, alcohol and other drug use, and indicators of suicidal behaviors in homeless adolescents and to determine gender and ethnic differences in these factors. We used secondary data analysis of data from surveys completed by 96 homeless youth whose average age was 17.9 years. Over 60% of the sample reported a history of sexual abuse; the majority were under the age of 12 years when they first tried alcohol, marijuana, and cocaine; 56.3% had injected drugs, and 46.9% had tried inhalants. During the past 12 months, 35.1% had seriously considered suicide and 12.3% had actually attempted suicide at least once. Significantly more Hispanics than Whites had considered suicide (chi 2 = 4.31, p = .038). A disproportionate number of Hispanics (95% of the sample) reported a history of sexual abuse. Participants with a history of sexual abuse were significantly more likely than those who did not have a history of sexual abuse to have used alcohol and/or marijuana (chi 2 = 9.93, p < .01) and to have considered suicide in the past 12 months (F = 14.93, p < .001). We found that sexual abuse history is greater in this sample than in the general population and is particularly prevalent among Hispanic/Latino subjects. As in other studies, sexual abuse was more common among females than among males. High prevalence of sexual abuse, alcohol and other drug use, and suicidal behaviors in this sample of homeless youth underscores the need to develop and test community-based interventions to improve their health status.

Adolescent↗

Paradoxic bronchospasm after inhalation of isoptroterenol.

Paradoxic bronchospasm induced by adrenergic aerosols, especially isoproterenol, is a well-known clinical entity. It normally occurs in patients who abuse the use of isoproterenol, but has also been reported in a small group of other patients. This study attempted to identify patients who exhibit paradoxic bronchospasm after administration of aerosolized isoproterenol. Forty-one stable, ambulant asthmatics, whose FEV 1.0 was less than 70 percent of predicted normal were studied. None of the asthmatics had taken isoproterenol for one year prior to evaluation. Baseline pulmonary function tests (FVC,FEV 1.09 MMEFR), blood pressure and ECG rhythm strips were recorded, and repeated at 15, 30, 60 and 120 min after administration of isoproterenol. Twenty-nine of the asthmatic patients had the expected normal response ( delta FEV 1.09 15 min: + 579; 30 min: + 464; 60 min: + 372; 120 min: + 307 ml: + 44, + 36, + 23 and + 24 percent) (delta MMEFR, 15 min: + 37; 60 min: + 29; 120 min: + 18L/Min: + 75, + 69, + 47 and + 37 percent). Twelve asthmatic patients (29 percent) had paradoxic bronchospasm (delta FEV 1.09 15 min: - 38; 30 min: - 60; 60 min: - 175; 120 min: - 27 ml; -1, -4, - 10 and - 4 percent) (delta MMEFR - 15 min: - .5; 30 min: - 3; 60 min: - 9; 120 min: - 2L/min; + 4, - 3, - 6 and - 5 percent, P less than 0.001).

Adult↗

[Pneumomediastinum following drug abuse].

Pneumomediastinum is termed spontaneous when not associated with trauma or other identifiable pathological process. There are several reports of pneumomediastinum following narcotic drug inhalation or smoking while applying positive pressure. We describe a 37-year-old male drug addict, hospitalized after having being found unconscious with shortness of breath. CT scan demonstrated bilateral pneumonia with pneumomediastinum. After a day of mechanical ventilation he gradually recovered and the mediastinal air disappeared. Pneumomediastinum may occur in addicts but usually has no dangerous clinical consequences. If there is respiratory deterioration another cause should be sought.

Adult↗

Acute neurologic complications of drug and alcohol abuse.

Recreationally abused substances include both legal and illegal agents, broadly classified as opioids, psychostimulants, sedatives, cannabis (marijuana), hallucinogens, inhalants, dissociative anesthetics (phencyclidine), anticholinergics, ethanol, and tobacco. These substances are associated with an array of neurological emergencies resulting from overdose, withdrawal, and other medical and neurological complications.

Alcohol Drinking↗