Comprehensive Toxicological Screening Research Articles

Fluoxetine-induced cardiotoxicity with response to bicarbonate therapy

This report describes a patient with an acute intentional fluoxetine exposure who developed unique cardiovascular and neurovascular toxicity. The patient presented with lethargy and cardiac conduction delays (QRS 110 msec, QT c 458 msec) and developed a delayed seizure. On admission, therapy with intravenous sodium bicarbonate promptly narrowed the QRS to 90 msec. A comprehensive toxicology screen demonstrated only a serum fluoxetine concentration of 901 ng/mL (therapeutic range, 37–301), a serum norfluoxetine concentration of 451 ng/mL (29–329) and a serum acetaminophen concentration of 174 mg/L. Tricyclic antidepressants were specifically noted to be absent. A self-limiting generalized seizure was witnessed 16 hours after ingestion. At this time the bicarbonate infusion had been ceased and the QRS interval was not prolonged. The patient improved over time and no other apparent causes for the observed clinical effects could be discovered. Emergency physicians need to be aware of the uncommon occurrence of fluoxetine-induced cardiotoxicity and the potential benefit of sodium bicarbonate therapy.

Analysis of the antiepileptic phenyltriazine compound lamotrigine using gas chromatography with nitrogen phosphorus detection.

A method is described for the determination of lamotrigine in serum or plasma, based on gas chromatography with nitrogen-phosphorus detection. The method requires minimal sample preparation. The drug is extracted from 1.0 ml of serum at pH 11 into butylacetate containing prazepam as internal standard. An aliquot of the organic phase is then injected onto an HP-5 fused silica capillary column and analyzed with temperature programming from 90 degrees to 250 degrees C. Lamotrigine is characterized by a relative retention time of 0.832 (+/-0.03) compared with prazepam. The method is competitive with the reported high-performance liquid chromatography procedures in terms of precision and sensitivity. Coefficients of variation, calculated from the results of between-run reproducibility tests, were 6.7%, 4.6%, 4.8%, and 6.2% for samples spiked with 0.20, 1.21, 2.42 and 10.84 micrograms/ml lamotrigine, respectively. The lower limit of quantitation of the method is 0.15 microgram/ml. The proposed procedure can be integrated easily in a comprehensive toxicology screening.

Results of LimitedVersusComprehensive Toxicology Screening in a University Medical Center

Both comprehensive toxicology screening (COM) and limited toxicology screening (LIM) were performed on the same urine in 1,734 consecutive cases over a 6-month period at a university medical center. About half of the screens originated from inpatient services and half from outpatient services (mostly emergency department). In 71 % of the cases, there was agreement between the results of LIM and COM, with 47% of cases being negative. For 500 screens (accounting for 655 individual discrepant findings), at least one discrepancy was noted between LIM and COM. Of these, 399 cases demonstrated at least one finding with COM, but not with LIM ("false-negative" LIM). Topical anesthetics (including cocaine and cocaethylene), antiepileptics, and sympathomimetic amines accounted for 65% of findings. In contrast, 147 cases showed a finding with LIM, but not with COM ("false-positive" LIM), mostly amphetamines. In certain specified clinical circumstances, LIM may be a more cost effective and efficient approach than COM.

Toxicology screening of the trauma patient: A changing profile

To determine the current ingestants found in the multiply injured trauma patient and to determine if this select group of ingestants affected the resuscitation, evaluation, or convalescent management of these patients. A one-year retrospective analysis was performed on all patients who were admitted to an urban trauma center with a discharge diagnosis of multiple trauma and who received a comprehensive toxicology screening test. One hundred twenty-seven of the 177 patients (72%) who fulfilled the criteria had positive toxicology screens. Ethyl alcohol was the only drug present in 26 of these patients (20%); 57 (45%) were positive for drugs other than ethyl alcohol. A combination of ethyl alcohol and at least one other drug was quantified in 44 patients (35%). The most often encountered substances were ethyl alcohol (55%), marijuana (24%), and cocaine (21%). Twelve drug screens (9%) demonstrated pharmaceuticals (eg, acetylsalicylic acid, acetaminophen, or cyclic antidepressants) that may require specific antidotal treatment. The ingestant profile found in this subgroup of trauma patients differed from those of previous studies. Although a select group of these ingestants requires specific treatment or affects the physical assessment of the patient, none of these trauma patients received more than supportive care.

Drug Use in Patients Admitted to a University Trauma Center: Results of Limited (Rather than Comprehensive) Toxicology Screening

The results of rapid toxicology screening of paired blood and urine samples from 936 patients admitted to a university trauma center during the calendar year 1988 were reviewed in order to determine the drugs detected by use of a relatively limited (rather than comprehensive) screening procedure and to define the demographic characteristics of the positive population. Of the 936 cases, 65% (610) were positive for one or more drugs: ethanol (436), cocaine and/or benzoylecgonine (164), sympathomimetic amines (142), phencyclidine (40), narcotic analgesics (36), salicylates (17), and barbiturates (9). Of the positive screens, 70% (426) demonstrated only one drug or parent drug/metabolite combination. Positives were obtained from 69% of men, 50% of women, 80% of American Indians, 75% of Blacks, 66% of Latins, 65% of Caucasians, 60% of undetermined race, and 38% of Orientals screened. The age group 21-40 years accounted for 69% of positives. Rapid, limited admission toxicology screening of trauma patients can still provide useful information.

Implications of Discordance Between Clinical Impression and Toxicology Analysis in Drug Overdose

Two hundred nine cases of intentional drug overdose were reviewed to determine the importance of discordance between drugs identified by toxicology analysis and those suspected clinically. The laboratory agreed exactly with the clinical impression in 47% of cases. Clinically unsuspected drugs were identified by the laboratory in 27% of cases; the characteristics of these patients did not differ significantly from those of other patients. Unexpected toxicology findings led to changes in therapy in only three cases, and none of these changes appeared to have a major impact on outcome. Although routine comprehensive toxicology screening frequently may identify unsuspected drugs, it is likely that a policy of more selective use of the laboratory would not compromise the care of patients with drug overdose.

Comprehensive toxicology screening in patients admitted to a university trauma center.

The utility of performing comprehensive toxicology screening in patients admitted to a university trauma center was evaluated by retrospective review of the results of such screening for a one-year period. Eighty-five percent of the screens were performed on males. Sixty-nine percent of the screens were positive for one or more drugs, and eighty-five percent of the positive screens occurred in males. More than half of the positives were in individuals 30 years of age or less. Ethanol was present in 81% of the positive screens, and of these it was the only drug found in 84% of the cases. Blood ethanol concentrations for the entire series ranged from 0.01 to 0.41% (mean, 0.15%; SD, 0.08%). Blood ethanol measurement alone is more cost effective than comprehensive toxicology screening and may be nearly as useful as the comprehensive screen in the majority of trauma cases.

Comprehensive toxicology screening: the frequency of finding other drugs in addition to ethanol.

The efficacy of performing a comprehensive toxicology screen whenever ethanol is found was evaluated in 289 consecutive emergency-room cases. Males predominated in both the "pure" (ethanol only) and the "mixed" (ethanol plus other drugs) groups. The mean ethanol concentration was significantly higher for pure cases than for mixed cases (P less than 0.01). For half of the 289 cases comprehensive screening demonstrated at least one to four other drugs per case in addition to ethanol. Barbiturates, narcotic analgesics, and stimulants in that order were the most frequently found classes of drugs. The age range 21 to 40 years accounted for most of the mixed ingestions, and ethanol concentrations less than 0.20% were more commonly associated with other drugs than were those above 0.20%. Whenever ethanol is found, comprehensive toxicology screening may yield important additional information.