Utilidad del cribado toxicológico en pediatría / Toxicology screening in paediatrics

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Urine methanol concentration and alcohol hangover severity.

BACKGROUND: Congeners are substances, other than ethanol, that are produced during fermentation. Previous research found that the consumption of congener-rich drinks contributes to the severity of alcohol hangover. Methanol is such a congener that has been related to alcohol hangover. Therefore, the aim of this study was to examine the relationship between urine methanol concentration and alcohol hangover severity. METHODS: N = 36 healthy social drinkers (22 females, 14 males), aged 18-30 years old, participated in a naturalistic study, comprising a hangover day and a control day (no alcohol consumed the previous day). N = 18 of them had regular hangovers (the hangover group), while the other N = 18 claimed to be hangover-immune (hangover-immune group). Overall hangover severity was assessed, and that of 23 individual hangover symptoms. Urine methanol concentrations on the hangover and control days were compared, and correlated to hangover (symptom) severity. RESULTS: Urine methanol concentration was significantly higher on hangover days compared to control days (p = 0.0001). No significant differences in urine methanol concentration were found between the hangover group and hangover-immune group. However, urine methanol concentration did not significantly correlate with overall hangover severity (r = -0.011, p = 0.948), nor with any of the individual hangover symptoms. These findings were observed also when analyzing the data separately for the hangover-immune group. In the hangover group, a significant correlation with urine methanol concentration was found only with vomiting (r = 0.489, p = 0.037). CONCLUSION: No significant correlation was observed between urine methanol concentration and hangover severity, nor with individual core hangover symptoms.

The breathtaking truth about breath alcohol readings of zero.

INTRODUCTION: It has been postulated that the hangover state starts when breath alcohol concentration is zero. METHODS: Data from 2 studies that assessed ethanol in breath, blood and urine were compared. RESULTS: The data revealed that ethanol may still be present in the blood and urine during the hangover state, despite breath analyser readings of zero. DISCUSSION: As ethanol is still present in the body despite zero breath alcohol readings, the current consensus to postpone cognitive testing in hangover studies until breath alcohol concentration is zero should be reconsidered.

Urine ethanol concentration and alcohol hangover severity.

BACKGROUND: The aim of this study was to examine the relationship between urine ethanol concentration and alcohol hangover severity. METHODS: N = 36 healthy social drinkers participated in a naturalistic study, comprising a hangover day and a control day. N = 18 of them have regular hangovers (the hangover group), while the other N = 18 claim to be hangover immune (hangover-immune group). On each test day at 9.30 am, urine samples were collected. Participants rated their overall hangover severity on a scale from 0 (absent) to 10 (extreme), as well as 18 individual hangover symptoms. RESULTS: Urine ethanol concentration was significantly higher on the hangover day when compared to the control day (p = 0.006). On the hangover day, urine ethanol concentration was significantly lower in the hangover-immune group when compared to the hangover group (p = 0.027). In the hangover-immune group, none of the correlations of urine ethanol concentration with individual hangover symptoms was significant. In contrast, in the hangover group, significant correlations were found with a variety of hangover symptoms, including nausea, concentration problems, sleepiness, weakness, apathy, sweating, stomach pain, thirst, heart racing, anxiety, and sleep problems. CONCLUSION: Urine ethanol levels are significantly associated with the presence and severity of several hangover symptoms.

Identification and quantification of acidosis inducing metabolites in cases of alcohols intoxication by GC-MS for emergency toxicology.

A simple, cost effective, and fast gas chromatography method with mass spectrometry detection (GC-MS) for simultaneous measurement of formic acid, glycolic acid, methoxyacetic acid, ethoxyacetic acid and 2-hydroxyethoxyacetic acid in serum and urine was developed and validated. This multi-analyte method is highly suitable for clinical and emergency toxicology laboratory diagnostic, allowing identification and quantification of five most common acidosis inducing organic acids present in cases of alcohol intoxication. Furthermore, when patients are admitted to emergency unit at late stage of toxic alcohol intoxication, the concentration of parent compound may be already low or not detectable. This new method employs a relatively less used class of derivatization agents - alkyl chloroformates, allowing the efficient and rapid derivatization of carboxylic acids within seconds. The entire sample preparation procedure is completed within 5 min. The optimal conditions of derivatization procedure have been found using chemometric approach (design of experiment). The calibration dependence of the method was proved to be quadratic in the range of 25-3000 mg L(-1), with adequate accuracy (97.3-108.0%) and precision (<12.8%). The method was successfully applied for identification and quantification of the selected compounds in serum of patients from emergency units.

Toxicology screening in oral and maxillofacial trauma patients.

The role of alcohol in facial trauma is recognised but we know of no research on the possible contribution made by the use of illicit drugs in patients with facial injuries, or the interactions that may occur during anaesthesia. We aimed to find out whether illegal drugs were identified in the urine of patients with maxillofacial injuries, what substances were present, and whether patients were willing to disclose use of drugs at the time of injury. Over a 12-month period we prospectively studied consecutive patients with facial injuries who were referred by accident and emergency (A&E) to the department of oral and maxillofacial surgery (OMFS) for inpatient assessment and treatment within 24 h of injury. Anonymised data on patients were obtained from questionnaires that were linked to a urine sample provided on admission. Results were obtained using immunoassay and gas chromatography with mass spectrometry. A total of 105 patients with facial injuries were eligible and 95 (90%) provided a urine sample and completed the questionnaire; 2 samples were of insufficient volume and were discarded before analysis. Twelve patients (13%) admitted using drugs at the time of injury but 44 (47%) samples tested positive for illegal drugs; fewer showed the presence of alcohol (n=37; 40%). Use of drugs, although often denied, is widespread among patients with facial injuries. It is important to consider the role that drugs have in patients who present with traumatic injuries, the interactions misused drugs may have with anaesthesia, and any possible benefits that targeted prevention strategies would have in this group.

Preliminary investigations on ethyl glucuronide and ethyl sulfate cutoffs for detecting alcohol consumption on the basis of an ingestion experiment and on data from withdrawal treatment.

Ethyl glucuronide (EtG) and ethyl sulfate (EtS) are commonly used alcohol markers for previous alcohol consumption. Nevertheless, the optimum EtG cutoff for urinary abstinence tests is still being discussed, and no cutoff has been recommended for EtS yet. The aim of this study was to verify cutoffs by investigating EtG and EtS concentrations (c(EtG) and c(EtS)) in the urine of healthy persons after drinking small, but realistic amounts of alcohol (one or two glasses of beer or white wine), and to look for the window of detection in strongly alcohol-intoxicated patients who were beginning withdrawal treatment. Very high EtG and EtS concentrations were measured in the first urine samples of patients under withdrawal treatment. However, 24 h later, concentrations decreased considerably, and c (EtG) < 0.5 mg/l and c (EtS) < 0.1 mg/l were determined in 26.7 % (4/13) and 13.3 % (2/13) of the samples, respectively. Concentrations above 0.1 mg/l (EtG) and 0.05 mg/l (EtS) were measured for 23.5 and 20.5 h after consuming 0.1 l of white wine or 0.33 l of beer, and 24 h after the experiment, 75 % (9/12) of the urine samples were tested negative for EtG and EtS using the following cutoffs: EtG 0.5 mg/l and EtS 0.1 mg/l. In half of the samples, concentrations below 0.1 mg/l (EtG) and 0.05 mg/l (EtS) were detected. Urinary cutoffs for EtG of 0.5 mg/l or higher are not suitable for testing abstinence. Even 0.1 mg/l is not effective to detect the intake of small amounts of alcohol in the context of abstinence tests. For EtS, 0.05 mg/l were found to be a potential cutoff to exclude the repeated intake of alcohol. Yet, further research is required to verify this cutoff. For a limited time period, EtG and EtS concentrations within the range of these cutoffs are also detectable after unintentional consumption of alcohol. Participants of abstinence programs have to be informed about the alcohol content of certain foods and beverages whose consumption is in conflict with strict abstinence.

Effects of energy drinks mixed with alcohol on information processing, motor coordination and subjective reports of intoxication.

The consumption of alcohol mixed with energy drinks (AmED) has become a popular and controversial practice among young people. Increased rates of impaired driving and injuries have been associated with AmED consumption. The purpose of this study was to examine if the consumption of AmED alters cognitive processing and subjective measures of intoxication compared with the consumption of alcohol alone. Eighteen participants (nine men and nine women) attended four test sessions where they received one of four doses in random order (0.65 g/kg alcohol, 3.57 ml/kg energy drink, AmED, or a placebo beverage). Performance on a psychological refractory period (PRP) task was used to measure dual-task information processing and performance on the Purdue pegboard task was used to measure simple and complex motor coordination following dose administration. In addition, various subjective measures of stimulation, sedation, impairment, and level of intoxication were recorded. The results indicated that alcohol slowed dual-task information processing and impaired simple and complex motor coordination. The coadministration of the energy drink with alcohol did not alter the alcohol-induced impairment on these objective measures. For subjective effects, alcohol increased various ratings indicative of feelings of intoxication. More importantly, coadministration of the energy drink with alcohol reduced perceptions of mental fatigue and enhanced feelings of stimulation compared to alcohol alone. In conclusion, AmED may contribute to a high-risk scenario for a drinker. The mix of behavioral impairment with reduced fatigue and enhanced stimulation may lead AmED consumers to erroneously perceive themselves as better able to function than is actually the case.

[Toxicological screening of medicines and drugs of abuse in emergency cases]. / Legemiddel- og rusmiddelanalyser som øyeblikkelig hjelp.

BACKGROUND: In some situations, and particularly when intoxications are suspected, it would be advantageous if medicines and drugs of abuse could be swiftly detected in serum or urine. MATERIAL AND METHODS: The Department of Clinical Pharmacology at St. Olav University Hospital has since 2004 been developing a comprehensive toxicology service (at all hours 7-days/week) for immediate quantitative analysis of between 80 and 90 substances. We here present the service in further detail and evaluate its usefulness during its first full year, 2005. Two case reports are presented to further illustrate the possible benefits of this service. RESULTS: Urgent testing was requested for a total of 390 samples; 351 serum and 39 urine samples. The most common indications for requesting such analyses were suspected acute intoxication (46%) and suspected therapeutic failure/adverse drug reaction (31%). 88% of the serum samples obtained for acute intoxications were positive, and 48 different substances were detected. The substances most often found were various benzodiazepines, various antiepileptic drugs, ethanol, carisoprodol, lithium, and other psychotropic drugs. In urine, amphetamine and zopiclone were the substances most often detected. INTERPRETATION: The service seems to be used according to its intentions, and the high number of samples received indicate that clinicians consider the service to be useful. An early and continuous dialogue between the clinician and the laboratory physician is a prerequisite for rational use of the service.

[Epidemiological analysis of cases with confirmed presence of amphetamine and THC in the material of Department of Analytical Toxicology and Drug Monitoring UJ CM]. / Analiza epidemiologiczna przypadków z potwierdzona obecnoscia amfetaminy i THC w materiale Zakladu Toksykologii Analitycznej i Terapii Monitorowanej UJ CM.

UNLABELLED: The aim of this paper is epidemiological analysis of poisonings with amphetamine and tetrahydrocanabinols (THC), particularly in three aspects: (1) co-occurrence of other substances (mixed poisonings); (2) factors shaping dynamics in number of poisonings and 3) average age of patients. The data this paper is based on come from the data set "Duch" which is run by the Department of Analytical Toxicology and Drug Monitoring UJ CM in Kraków. The data were collected between 1 Dec. 2001 and 28 Feb. 2005 (1186 days). Amphetamine and THC were determined in patient's urine in semi-quantitative manner by means of EMIT and FPIA methods. RESULTS: Amphetamine: In the studied period amphetamine was confirmed in 493 patients. Other substances were confirmed in 57.6% of patients: opiates--28.6% THC--14.2%, opiates and THC--5.9%. Since the beginning of the studied period till mid Aug 2003 daily number of cases showed increasing trend (0.062% per day), then the tendency was reversed (-0.074% per day). We observed more males than females (3.24:1). Most cases were poisoned on Mondays, less during the week and least on weekends. At the beginning of the studied period males were older than females (27 vs. 20 years). As the time progressed average age of males was stable but in women average age was increasing at the rate 0.004 year per day. As a consequence of this trend in winter 2004/2005 average age of both sexes was equal. THC: We observed 410 cases with confirmed presence of THC in urine. Other substances were confirmed in 40.2% of patients: amphetamine 17.1% amphetamine and opiates 7.1, opiates 7.1%. There were 17 various substances accompanying THC. In our material the sex ratio was biased toward males (7.8 to 1). Weekly dynamics of poisonings with THC have the same pattern as the one observed in amphetamine. At the beginning of the studied period males were older than females (28 vs. 20 years). Changes in averages followed the same pattern as in amphetamine.

A study of patients presenting to an emergency department having had a "spiked drink".

OBJECTIVES: To assess the scale of drink spiking in our area and identify which drugs are being used to spike drinks and also to assess whether there is a problem with drink spiking in any particular establishment. METHODS: A prospective study of all patients presenting to an emergency department with alleged drink spiking over a 12-month period. Samples were analysed for levels of alcohol and drugs of misuse. Information was collected as to where the alleged spiking took place and the involvement of the police. RESULTS: 75 patients attended with alleged drink spiking over the period of 12 months. 42 samples were analysed and tested positive for drugs of misuse in 8 (19%) cases. 65% of those tested had alcohol concentrations >160 mg%. The alleged spiking took place in 23 different locations, with 2 locations accounting for 31% of responses. Only 14% of those questioned had informed the police. CONCLUSIONS: Most patients allegedly having had a spiked drink test negative for drugs of misuse. The symptoms are more likely to be a result of excess alcohol.

Validation of the standardized field sobriety test battery at 0.08% blood alcohol concentration.

OBJECTIVE: A field study was conducted to evaluate the accuracy of the Standardized Field Sobriety Test (SFST) battery to assist officers in making arrest decisions at blood alcohol concentrations (BACs) below 0.10%. BACKGROUND: The SFST Battery was validated at 0.10% BAC in 1981, but since then many states have reduced statutory limits for driving while intoxicated to 0.08% BAC. METHODS: During routine patrols, participating officers followed study procedures in administering SFSTs, scoring results, making arrest/no arrest decisions, and completing a data collection form for each of the 297 motorists evaluated during the study period. The officers' final step in each case was the administration of an evidentiary breath alcohol test. RESULTS: Overall, officers' decisions were correct in more than 91% of the cases at the 0.08% BAC level. Cohen's kappa tests found all officers' scores to be within the categories of "substantial" and "near perfect" agreement, indicating low variance among the officers and a high degree of interrater reliability. CONCLUSION: The results of this study provide evidence of the validity of the SFST Battery as an accurate and reliable decision aid for discriminating between BACs above and below 0.08%. APPLICATION: The SFST Battery presently is used by law enforcement officers throughout the United States to help make roadside arrest decisions for impaired driving.

[Diagnostic implication of blood and urine morphine content in alcohol intoxication].

A total of 198 cases of acute parenteral poisoning with opiates are characterized. The range of concentrations of opiates metabolites in the blood and urine, main causes of death due to opiate poisoning in alcohol intoxication are analysed. Opiates toxicity was assessed with the logit-regression method and dose-effect curves valid for analysis of relationships between probability of death and opiate metabolites concentration in blood and urine. Correlation between probability of death and detection of morphine and ethanol in biological media of the victims is considered. Concentrations of morphine in blood and urine definitely indicating opiates poisoning in alcohol intoxication as a cause of death are determined.

Utilizing the urinary 5-HTOL/5-HIAA ratio to determine ethanol origin in civil aviation accident victims.

Specimens from fatal aviation accident victims are submitted to the FAA Civil Aerospace Medical Institute for toxicological analysis. During toxicological evaluations, ethanol analysis is performed on all cases. Care must be taken when interpreting a positive ethanol result due to the potential for postmortem ethanol formation. Several indicators of postmortem ethanol formation exist; however, none are completely reliable. The consumption of ethanol has been shown to alter the concentration of two major serotonin metabolites, 5-hydroxytryptophol (5-HTOL) and 5-hydroxyindole-3-acetic acid (5-HIAA). While the 5-HTOL/5-HIAA ratio is normally very low, previous studies using living subjects have demonstrated that the urinary 5-HTOL/5-HIAA ratio is significantly elevated for 11-19 h after acute ethanol ingestion. Recently, our laboratory developed and validated an analytical method for the simultaneous determination of both 5-HTOL and 5-HIAA in forensic urine samples using a simple liquid/liquid extraction and LC/MS/MS and LC/MS/MS/MS. In this previous work a 15 pmol/nmol serotonin metabolite ratio cutoff was established in postmortem urine, below which it could be conclusively determined that no recent antemortem ethanol consumption had occurred. In the current study this newly validated analytical method was applied to five ethanol-positive aviation fatalities where the origin of the ethanol present could not previously be conclusively determined. In four of the five cases examined the detected ethanol was demonstrated to be present due to postmortem microbial formation, and not consumption, even though some indication of ethanol consumption may have been present.

[Pathomorphological manifestations of various forms of alcohol disease]. / Patomorfologicheskie proiavleniia razlichnykh form alkogol'noi bolezni.

In acute poisoning with ethanol a cardiac variant of tanatogenesis prevails. Signs for ethanol surrogates of DIC syndrome are more characteristic. Alcohol cardiomyopathy and liver cirrhosis are typical as causes of death for chronic forms of alcoholic disease. Histochemical features in the brain are found characteristic for some forms of alcoholic disease.

Blood analysis by headspace gas chromatography: does a deficient sample volume distort ethanol concentration?

This study was prompted by a recent judgment in the Royal Courts of Justice (Gregory v. Director of Public Prosecutions, 2002) in a case of driving a motor vehicle after consuming too much alcohol (Road Traffic Act 1988). An expert witness for the defence alleged that a deficient volume of blood in the tube sent for analysis meant an excess amount of sodium fluoride (NaF) preservative, which would increase the concentration of ethanol, determined by headspace gas chromatography (HS-GC), owing to a salting-out effect. The prosecution did not produce expert evidence to rebut this argument and the drunk driving suspect was acquitted. A small volume of blood and excess sodium fluoride might have increased the concentration of ethanol in the air-space in the tube sent for analysis but this does not mean that the result of the HS-GC analysis would be higher. This follows because prior to analysis an aliquot of blood is removed and diluted (approximately 10 times) with n-propanol as the internal standard. The dilution lowers the concentration of NaF in the blood and for quantitative analysis the ratio of the ethanol to n-propanol response is measured. The use of a ratio also helps to compensate for any salting-out effect of ethanol. Our experiments showed that a deficient volume of blood and excess NaF actually lowered the concentration of ethanol by 2-3% compared with heparinised blood. Seemingly, n-propanol (n-PrOH) a 3-carbon straight chain alcohol is salted out slightly more effectively than the 2-carbon ethanol (EtOH) causing a lower peak area ratio (EtOH/n-PrOH) and a lower apparent concentration of ethanol. In a separate study, we showed that the concentration of ethanol was lowered even more when a 4-carbon alcohol (t-butanol) was used as the internal standard.

Comparison of urinary excretion characteristics of ethanol and ethyl glucuronide.

This study compared the urinary excretion characteristics of ethyl glucuronide (EtG) with that of ethanol, with focus on the effect of water-induced diuresis. Six healthy volunteers ingested an ethanol dose of 0.5 g/kg (range 25.0-41.5 g) as 5% (v/v) beer in 30 min and the same volume of water after 3 h. Urine collections were made before starting the experiment and at timed intervals over 31.5 h. The concentration of EtG was determined by an LC-MS method (LOQ = 0.1 mg/L). The urine samples collected immediately before starting drinking were all negative for ethanol and EtG, thus confirming that the participants had not recently ingested alcohol. Intake of beer resulted in a marked increase in excreted urine volume and a concomitant drop in creatinine concentration. The concentration of ethanol peaked at a mean value of 17 mmol/L in the 1.5-h urine collection. Except for one subject, EtG was first detectable (range 0.9-5.5 mg/L) at 1 h. Intake of water at 3 h produced another increase in urine volume and a drop in creatinine. The ethanol concentration curve was not influenced by the water diuresis, whereas this caused a distinct drop in the EtG concentration. When EtG was expressed relative to the creatinine value, this ratio was seemingly not affected by the intake of water. The ethanol concentration returned to zero at 6.5 h, whereas EtG was still detectable for up to 22.5-31.5 h, albeit at low levels in the end (< 1 mg/l). Only about 0.02% of the administered dose of ethanol (on a molar basis) was recovered in the urine as EtG. The results demonstrated that EtG remains detectable in the urine for many hours after the ethanol itself has been eliminated. Moreover, it was possible to lower the concentration of EtG by drinking large amounts of water prior to voiding, whereas this strategy did not influence the EtG/creatinine ratio or the concentration of ethanol.

Urine drug screening in the medical setting.

BACKGROUND: The term drug screen is a misnomer since it implies screening for all drugs, which is not possible. Current practice is to limit the testing to the examination of serum for several drugs such as ethanol, acetaminophen, salicylate, and of urine for several specific drugs or classes of drugs. In the emergency setting the screen should be performed in less than one hour. Controversies continue to exist regarding the value of urine drug testing in the medical setting. The reasons for these include the drugs involved, the sample, the methods utilized to perform the tests, and the level of understanding of the physician using the data, all of which are closely related to the other. METHODS: Current automated methods provide rapid results demanded in emergency situations, but are often designed for, or adapted from, workplace testing and are not necessarily optimized for clinical applications. Furthermore, the use of these methods without consideration of the frequency in which the drugs are found in a given area is not cost-effective. The laboratory must understand the limitations of the assays used and provide this information to the physician. Additionally, the laboratory and the physicians using the data must cooperate to determine which drugs are appropriate and necessary to measure for their institution and clinical setting. In doing so it should be remembered that for many drugs, the sample, urine, contains the end product(s) of drug metabolism, not the parent drug. Furthermore, it is necessary to understand the pharmacokinetic parameters of the drug of interest when interpreting data. Finally, while testing for some drugs may not appear cost-effective, the prevention or reduction of morbidity and mortality may offset any laboratory costs. CONCLUSIONS: While the literature is replete with studies concerning new methods and a few regarding physician understanding, there are none that we could find that thoroughly, objectively, and fully addressed the issues of utility and cost-effectiveness.