Toxicokinetics of a dipyridamole (Persantin) intoxication: case report.

We report a case of a 51-year-old woman who was admitted to the hospital after ingestion of large doses of dipyridamole (12 g), temazepam (1 g) and oxazepam (0.2 g) with suicidal intent. The highest dipyridamole concentration that was measured in serum was 9.2 mg/L, which was paralleled by impaired platelet activation. For temazepam and oxazepam, peak serum concentrations were 8.5 and 1.3 mg/L, respectively. The patient was treated with activated charcoal, magnesium sulfate and aminophylline and could be discharged in good physical condition within 17 hours. This is the first report that provides toxicokinetic data and a corresponding pharmacodynamic effect after an intoxication with dipyridamole.

Alleged breaches of "standards of medical care" in a patient overdose death possibly related to chronic opioid analgesic therapy, application of the controlled substances model guidelines: case report.

OBJECTIVES: The objectives of this medicolegal case report are the following: 1) to present details of a chronic pain patient (CPP) who was placed on chronic opioid analgesic therapy (COAT), and subsequently overdosed on multiple drugs, some of which were not prescribed by his COAT physician; 2) to present both the plaintiff's and defendant's (the COAT prescriber) expert witnesses' opinions as to the allegation that COAT prescribing was the cause of death; and 3) based on these opinions, to develop some recommendations on how pain physicians can utilize the use of Controlled Substances Model Guidelines in order to protect the patient and themselves from such an occurrence. METHODS: This is a case report of a CPP treated by a pain physician. RESULTS: Differences between the plaintiff's and defendant's expert's opinions are explained utilizing the Controlled Substances Model Guidelines. CONCLUSIONS: Some CPPs may withhold information critical to their COAT treatment. Application of the Controlled Substances Model Guidelines and the newer Federation of State Medical Boards' policy on opioid prescribing can be helpful in improving patient care and may be helpful in protecting the physician medicolegally.

Serotonin syndrome.

Serotonin syndrome is an under-reported and under-recognised condition that occurs on administration of selective serotonin re-uptake inhibitors alone, or in combination with other medication known to increase levels of 5-hydroxytryptamine. This case report demonstrates signs and symptoms associated with their overdose and illustrates the importance of recognition of this syndrome to instigate appropriate treatment for the patient.

Drug concentration in selected skeletal muscles.

We evaluated the homogeneity of drug concentrations in muscle in 14 cadavers, comprising 11 drug overdoses and three cases of chronic therapeutic drug use. Analyses were performed on samples from twelve named muscles and femoral venous blood. Standard analytical techniques and instrumentation were used throughout. There was marked within-case variability in drug concentrations with highest:lowest concentrations ranging up to 21.7. Overall highest concentrations were found in the diaphragm and mean diaphragm:blood ratios ranged from 1.1 (temazepam, two cases) and 1.2/1.3 (paracetamol, six cases) up to 6.5/13.5 (amitriptyline, three cases) and 5.3/21.3 (propoxyphene, four cases). Excluding the diaphragm, mean muscle:blood ratios ranged from 0.4 (prothiaden), 0.5 (temazepam), and 0.7 (paracetamol) up to 3.7 (temazepam), 4.3 (propoxyphene) and 5.7 (amitriptyline). We suggest that muscle is suitable for qualitative analysis but not for quantitative corroboration of a blood sample or as a quantitative alternative to blood.

Site-to-site variability of drug concentrations in skeletal muscle.

The homogeneity of drug concentrations in skeletal muscle was assessed in eight fatal overdoses. Ten to 30 random samples were taken from leg muscle weighing 1,650 to 7,985 g. For cases involving paracetamol the mean muscle-to-blood ratio ranged from 0.1 to 1.1 (n = 4) for amitriptyline 1.1 to 3.6 (n = 3), and for dothiepin 0.8 to 2.1 (n = 2). The coefficient of variance was large for all drugs, ranging from 10.5 (carbamazepine) to 50 (thioridazine). Skeletal muscle is not homogeneous with respect to drug concentrations in fatal overdose cases. Of 16 instances of drug detection in blood 2 (nortriptyline and promethazine) were not detected in muscle. Muscle-to-blood drug ratios varied significantly among cases, possibly influenced by survival time after drug ingestion. Quantitative interpretations of muscle drug levels present significant difficulties. However, skeletal muscle can be used for qualitative corroboration of blood analyses and is a suitable specimen for drug detection where none other is available.

Clinical and toxicological findings in two young siblings and autopsy findings in one sibling with multiple hospital admissions resulting in death. Evidence suggesting Munchausen syndrome by proxy.

A 15-month-old girl underwent several emergency department (ED) visits and two admissions for parent-reported histories of ingestions, apnea, and seizures. She was initially admitted following reports of several unusual episodes of syncope accompanied by convulsive movements and was discharged on mephobarbital with a diagnosis of atypical seizure disorder. The day after discharge, she was brought to the ED in cardiopulmonary arrest and was resuscitated after a prolonged period. She was declared brain dead 2 days later. Ante- and postmortem toxicology produced several inconclusive findings, none of which explained death. Autopsy findings, including neuropathology, failed to demonstrate any significant disease processes. Approximately 3 months later, a 4-month-old female sibling was brought to the ED with a parent-reported history of apnea and seizures similar to the deceased child. A stool specimen obtained 2 days after admission contained numerous tiny seeds, which were found by gas chromatography-mass spectrometry analysis to contain lorazepam and temazepam. The role of these benzodiazepines in the apnea episodes in this infant was unknown, but the presence of the seeds in such a young infant coupled with the parent's aberrant behavior, led to the tentative diagnosis of Munchausen syndrome by proxy. This diagnosis was strengthened when results from these studies persuaded legal authorities to remove the surviving sibling from the parents, resulting in an asymptomatic recovery.

Site to site variability of postmortem drug concentrations in liver and lung.

We evaluated postmortem diffusion of gastric drug residue into tissues and blood in eight suicidal overdoses. Analyses were performed on liver (five sites), lung (four sites), spleen, psoas muscle and kidney (left and right), blood (peripheral and torso), vitreous, pericardial fluid, bile and, urine as well as residual gastric contents. Standard analytical techniques and instrumentation gas chromatograph/mass spectrometer and high performance liquid chromatography (GC-MS and HPLC) were used throughout. These case studies confirm previous studies of an animal and human cadaver model of gastric diffusion, in that in several instances there was drug accumulation in the left posterior margin of the liver and, to a lesser extent, the left basal lobe of the lung. Uncontrollable variables, such as postmortem interval, refrigeration before autopsy, and position of the body appear to influence significantly drug accumulation in a specific site. We suggest that autopsy sampling techniques should be standardized on blood taken from a ligated peripheral (preferably femoral or external iliac) vein, and liver from deep within the right lobe.

Relative toxicity of benzodiazepines in overdose.

OBJECTIVE: To assess the sedative effects in overdose of temazepam and oxazepam compared with other benzodiazepines to determine if this explains reported differences in fatal toxicity. DESIGN: Cohort study of patients admitted with benzodiazepine poisoning. SETTING: Newcastle, Australia. SUBJECTS: 303 patients who had ingested benzodiazepine alone or in combination with alcohol and presented to a general hospital which served a well defined geographical area. MAIN OUTCOME MEASURES: Degree of sedation: Glasgow coma score, McCarron Score, and whether patients were stuporose or comatose. RESULTS: Oxazepam produced less and temazepam more sedation than other benzodiazepines. Unadjusted odds ratios for coma with oxazepam and temazepam compared with other benzodiazepines were 0.0 (95% confidence interval 0.0 to 0.85) and 1.86 (0.68 to 4.77) respectively, chi 2 = 7.08, 2df, P = 0.03. After adjustment for potentially confounding effects of age, dose ingested, and coingestion of alcohol, the odds ratios were 0.22 (0.0 to 1.43) for oxazepam and 1.94 (0.57 to 6.23) for temazepam. Similar results were obtained for other measures of sedation. CONCLUSIONS: These results were in accordance with fatal toxicity indices derived from coroners' data on mortality and rates of prescription. The relative safety of benzodiazepines in overdose should be a consideration when they are prescribed.

Pneumocephalus following nasotracheal intubation.

A 75-year-old woman with a previous repair of a cribiform plate fracture was nasotracheally intubated following a suicide attempt. Twenty-one days later she was readmitted to the hospital with a massive pneumocephalus, followed by a terminal intracranial hemorrhage. Nasotracheal intubation as a contributing factor in the development of pneumocephalus is previously unreported.

Complete heart block after flumazenil.

Flumazenil is a competitive benzodiazepine antagonist. It is indicated for reversal of excess benzodiazepine sedation under certain circumstances, including the reversal of overdosage effects when it is felt best to avoid ventilation, such as in the very old or the very young. We report a case where the use of flumazenil was associated with complete heart block in an elderly patient.

The use of flumazenil (Anexate, Ro 15-1788) in the management of drug overdose.

This is a report of a large selfadministered overdose of temazepam and meprobamate. The administration of flumazenil (Ro 15-1788) led to the partial antagonism of the depressant action of the drugs which was sufficient to avoid the need for invasive respiratory and cardiovascular support.