Relationship between blood remifentanil concentration and stress hormone levels during pneumoperitoneum in patients undergoing laparoscopic cholecystectomy.

OBJECTIVE: The effect of remifentanil on stress response to surgery is unclear. However, there are not clinical studies investigating the relationship between blood remifentanil concentrations and stress hormones. Therefore, the aim of the present study was to assess the association between blood remifentanil concentrations measured after pneumoperitoneum and cortisol (CORT) or prolactin (PRL) ratio (intraoperative/preoperative value), in patients undergoing laparoscopic cholecystectomy. PATIENTS AND METHODS: Patients did not receive any pre-anesthetic medication. Anesthesia induction was standardized. Anesthesia maintenance was performed with inhaled sevoflurane at age-adjusted 1.0 minimum alveolar concentration and intravenous remifentanil at infusion rate ranging from 0.1 to 0.4 mcg/kg/min. Blood samples were withdrawn before anesthesia induction and 5 min after achieving a pneumoperitoneum pressure of 12 mmHg. Correlation analyses were performed to evaluate the relationship between measured blood remifentanil concentrations, CORT or PRL ratio (intraoperative/preoperative value) and remifentanil dose delivered by the pump. RESULTS: A significant inverse correlation was found between CORT ratio and measured blood remifentanil concentration (p=0.03) or planned remifentanil dose (p=0.04). No correlations were found between blood remifentanil concentration and PRL ratio (p=0.83). CONCLUSIONS: Our data suggest that the CORT response to surgical stress is more efficiently counteracted by increased blood remifentanil concentration.

Prevalence of alcohol and other drugs in injured drivers and their association with clinical outcomes.

OBJECTIVE: Driving under the influence of alcohol or drugs is a risk factor for motor vehicle accidents (MVAs). This issue has become an increasing concern for the governments of many European and North American countries, thereby encouraging the adoption of preventive policies. The aim of this study was to investigate the associations between major clinical outcomes and alcohol or drug abuse among drivers involved in MVAs who were referred to an Italian Emergency Department. PATIENTS AND METHODS: The study population consisted of consecutive injured drivers who were admitted to the Emergency Department following an MVA during a period of one year. The patients' blood alcohol concentrations (BACs) and the presence of the most common drugs of abuse [amphetamine, methamphetamine, methylenedioxymethamphetamine (MDMA), barbiturates, benzodiazepines, benzoylecgonine (cocaine main metabolite), cannabinoids, methadone, and opiates)] were determined and evaluated in association with major clinical outcomes and demographic data. RESULTS: Overall, 347 injured drivers were enrolled. Of the 347 enrolled patients, 164 (47.3%) had a positive BAC (greater than 5 mg/dL). A subgroup of 107 injured drivers was also screened for drugs of abuse. Thirty-seven of these subjects (34.5%) were positive for at least one drug. A statistically significant association was found between BAC and triage at admission (p<0.01), hospitalization (p<0.01), and lesions of internal organs (p=0.04). CONCLUSIONS: The results of this study show that a significant proportion of injured drivers had detectable levels of BAC and/or illegal drugs. Positive BACs were significantly associated with worse clinical outcomes. These findings suggest that the implementation of methods to prevent alcohol and drug abuse is of paramount importance in the effort to reduce the rates of MVAs and their dramatic consequences.

The current status of sweat testing for drugs of abuse: a review.

Sweat is an alternative biological matrix useful to detect drugs of abuse intake. It is produced by eccrine and apocrine glands originating in the skin dermis and terminating in secretory canals that flow into the skin surface and hair follicles. Since many years it has been demonstrated that endogenous and exogenous chemicals are secreted in this biological sample hence its collection and analysis could show the past intake of xenobiotics. From the seventies the excretion of drugs of abuse has been investigated in human skin excretion; later in nineties forensic scientists began to experiment some techniques to trap sweat for analyses. Even if the use of skin excretions for drug testing has been restricted mainly by difficulties in sample recovery, the marketing of systems for the sample collection has allowed successful sweat testing for several drugs of abuse. In the recent years sweat testing developed a noninvasive monitoring of drug exposure in various contexts as criminal justice, employment and outpatient clinical settings. This paper provides an overview of literature data about sweat drug testing procedures for various xenobiotics especially cocaine metabolites, opiates, cannabis and amphetamines. Issues related to collection, analysis and interpretation of skin excretions as well as its advantages and disadvantages are discussed. Moreover the chance to apply the technique to some particular situation such as workplace drug testing, drivers, doping or prenatal diagnosis, the comparison between sweat and other non conventional matrices are also reviewed. According to literature data the analysis of sweat may be usefully alternative for verifying drug history and for monitoring compliance.

Sweat testing in addicts under methadone treatment: an Italian experience.

In the last years the interest in monitoring drug exposure with human sweat as alternative biological fluid, is increasing. Sweat collection is convenient, less invasive and difficult to adulterate compared to traditional specimens. The objective of this study was to determine the excretion profile of methadone and other drugs into human sweat. Pharmscope sweat patches (Medical Europe Diagnostic, Madrid, Spain) were used on heroin abusers under methadone treatment. Sweat patches were applied to 10 heroin addicts and 3 drug free volunteers admitted into the study. Sweat patches were worn for about 1 week; urine, saliva and hair samples were collected at the time of the removal of patches. After the extraction, sweat eluates were directly analyzed by GC/MS for the presence of nicotine, cotinine, caffeine, methadone, EDDP and cocaine. The extracts were subsequently derivatized to detect benzoylecgonine, ecgonine methyl ester, morphine, codeine and 6-acetylmorphine. No false positive results were obtained on the drug free samples. All the patches showed positive results for methadone. Cocaine was detected in two cases. Mainly the parent drug was identified rather than the metabolites. The results obtained show the usefulness of sweat as complementary specimen to saliva and urine providing a longer detection window. Moreover, sweat testing offers the advantage of being a non-invasive means of obtaining information about drug exposure.

Suicide by multidrug ingestion: hypothesis on the role played by the self-administration of activated charcoal.

A fatal suicidal ingestion of drugs, together with activated charcoal, is reported. The death occurred 31 hours after the self-administration. The autopsy revealed a large amount of gastric content that appeared to be a compact mass of black color. Toxicologic analyses showed the presence of toxic levels of desalkylflurazepam and trazodone; metamizole and pridinol were also detected. The obtained results supported the hypothesis of a death due to acute intoxication delayed by the self-administration of activated charcoal, which elimination was probably hindered by the action of pridinol.

An evaluation of the Cozart RapiScan system as an on-site screening tool for drugs of abuse in a non-conventional biological matrix: vitreous humor.

The aim of this project was to evaluate the Cozart RapiScan Oral fluid Drug Testing System as an on-site screening tool for vitreous humor samples collected during post-mortem examinations. Vitreous humor is easy to collect and as it is contained within the eye it is almost completely unaffected by post-mortem redistribution. The ability to carry out an initial drug screen on vitreous humor at the earliest stage of the death investigation process could contribute significantly to the assessment of the role drugs may have played prior to confirmation with toxicological analyses at the laboratory. Vitreous humor (n = 146) was collected from autopsy examinations (111 males and 35 females) with a specific focus on cases where death occurred following a road traffic accident or where an overdose was suspected. All samples were screened using the five-panel methadone Cozart RapiScan Cartridge with an overall positive rate of 29%. Of the positive results, 43% screened positive for benzodiazepines, 17% for cocaine, 7% for methadone and 33% for opiates. Positive samples, with the exception of benzodiazepines, and 20% of negative samples were analysed by GC/MS. This is the first reported use of this system as an on-site forensic tool in death investigation and for screening for drugs of abuse in vitreous humor. The conclusions from this study show that the Cozart RapiScan System could play an important role in obtaining information on the toxicological state of the person at the time of death.

Death due to baclofen and dipyrone ingestion.

A fatal suicidal intoxication with unusual drugs is reported. A 56-year-old man was found dead in his house; near by the corpse several empty drugs boxes were found. An autopsy was performed and the biological fluids were submitted to a full toxicological work-up. The analytical results supported the hypothesis of a death due to the acute baclofen (4-amino-3-(p-chlorophenyl)butyric acid) and dipyrone (sodium [N-(1,5-dimethyl-3-oxo-2-phenylpyrazolin-4-yl)-N-methylamino] methanesulfonate) intoxication.

SPME-GC analysis of THC in saliva samples collected with "EPITOPE" device.

In this study we examined the presence of cannabinoids in saliva samples obtained from 24 drug-abusers. The saliva specimens were collected by "EPITOPE" system and the subsequent elution of samples was achieved by centrifugation. The resulting ultrafiltrates have been directly sampled with solid phase micro-extraction (SPME) and then analyzed by GC/MS. Saliva sampling is less invasive than collection of blood.

Adulterants encountered in the illicit cocaine market.

Illicit cocaine samples (156), seized on Rome's illegal market between January 1996 and June 1997, were examined. Both the purity of the cocaine and the presence of substances employed for dilution were determined for each sample. Adulterants were found in many of the street samples analysed. Lidocaine (average 14.7%) followed by caffeine (average 9%) proved to be the adulterants most frequently encountered in the cocaine samples.

Simultaneous detection of cocaine and heroin metabolites in urine by solid-phase extraction and gas chromatography-mass spectrometry.

The present paper reports a method for the simultaneous extraction of cocaine, heroin and their metabolites from small amounts of urine (0.5 ml), using deuterated internal standards. Solid-phase extraction (SPE) on C18 columns followed by chromatographic separation coupled with mass spectrometry allowed the detection of all the substances after their derivatization. Mass spectrometry was performed in the electron-impact selected-ion monitoring (EI-SIM) mode. The limit of detection was found to be as low as 50 ng/ml for all the analytes; for reproducibility the C.V. was always better than 7%; the method was found to be linear with correlation coefficients between 0.989 and 1.00.

Effectiveness and side effects of two different doses of caffeine in preventing apnea in premature infants.

The effectiveness of caffeine citrate in preventing idiopathic apnea in premature infants was evaluated. Thirty-seven preterm infants born before the 32nd week of gestation were studied. After an intravenous loading dose of 10 mg/kg of caffeine citrate, two different oral maintenance regimens were followed: 5 mg/kg in Group I and 2.5 mg/kg in Group II. A significant decrease in the number of apneic spells occurred in both treated groups as compared with a control group. In Group II, the frequency of side effects such as tachycardia and gastrointestinal intolerance was significantly lower than in Group I. Group II theophylline plasma levels were significantly lower than those of Group I. The lower Group II theophylline levels presumably explain the reduced frequency of side effects.

Gas chromatographic-mass spectrometric analysis of buflomedil hydrochloride in biological samples after acute intoxication.

Two cases of acute intoxication of buflomedil hydrochloride are reported. The analysis of this compound was performed by an Extrelut extraction followed by a gas chromatographic-mass spectrometric determination. Analytical parameters of linearity, reproducibility and specificity were satisfactory.

Pharmacokinetic aspects of caffeine in premature infants.

The pharmacokinetic profile of caffeine was studied in 15 premature infants. Five infants received a single intravenous dose of 10 mg/kg of caffeine citrate 100% at birth and on the 15th day of life. Ten neonates were studied during daily therapy with caffeine for prophylaxis of idiopathic apnea. The time course of plasma and urinary concentrations of caffeine and theophylline shows that caffeine is transformed to theophylline at birth, while total urinary xanthines decrease significantly (p less than 0.001) 72 h after the loading dose given on the 15th day of life. During the whole period of treatment, the decrease in total urinary xanthines and the constant urinary percentage elimination of theophylline are due to further metabolism of theophylline. We confirm that the intravenous loading dose of 10 mg/kg can rapidly obtain therapeutic blood levels of caffeine. We also confirm that the maintenance therapy can be carried out with a single daily dose.

Analysis of benzodiazepines. II. High-performance liquid chromatography-fluorescence detection after molecular rearrangement to acridanones.

A molecular rearrangement of benzophenones (hydrolysis products of 1,4-benzodiazepines) to 9-acridones has been studied. The compounds synthesized were analysed by high-performance liquid chromatography coupled with a fluorescence detector, because of their high luminescence. The method, which can detect sixteen benzodiazepines simultaneously, is highly sensitive and adequately specific. It is reliable for the analysis of these compounds in biological samples at therapeutic concentrations.

Methadone extraction from minimal amounts of biological fluids.

A new solid phase extraction method was studied to extract methadone from small amounts of biological samples, by using little disposable columns prepacked with reverse phase sorbents. Two different commercial kinds of reversed phase columns prepacked with octadecylsilane (ODS) were tested; the results were compared to those obtained by a direct liquid/liquid extraction method. Gas chromatograms of extracts obtained by means of ODS reversed phase columns showed a good signal/noise ratio resulting in higher sensitivity (20 ng/ml as detection limit), in comparison with the liquid/liquid extraction method.

Methadone in pregnancy: clinical-toxicological aspects.

The authors describe their experience with methadone treatment in pregnancy. Thirteen abuser pregnant women were studied under defined obstetrical and toxicological protocol. Newborns were also included in this study. In some cases a complete adherence to therapeutic program, allowing labour under very low methadone dosage (5 mg/day), minimized toxicological neonatal risk. Withdrawal syndrome in newborns was well controlled pharmacologically. The role of the toxicological laboratory during clinical management of drug dependent pregnant women is also discussed.