Seizures due to maprotiline overdose

Maprotiline, a new tetracyclic antidepressant, has a pattern of toxicity that is different from that of tricyclics. Maprotiline overdosage appears more likely to cause seizures but less likely to cause the peripheral autonomic and cardiac manifestations seen with tricyclics. Two cases of maprotiline overdose resulting in seizures without significant anticholinergic or cardiotoxic effects are presented. Both patients were treated acutely with gastric emptying and were observed to have no further seizures during subsequent drug-free hospital and outpatient follow up. Physostigmine salicylate has been used as an antidote for the anticholinergic syndrome of tricyclic overdose, but probably offers less in maprotiline overdose. Careful observation for seizures appears to be warranted.     

Morbidity associated with non-fatal heroin overdose

Aims To estimate the range and severity of heroin overdose related morbidity. Design Cross‐sectional survey. Setting Sydney, Australia. Participants 198 heroin users. Findings Sixty‐nine per cent had experienced a heroin overdose, 28% in the preceding 12 months. Of those who had overdosed, 79% had experienced at least one overdose‐related morbidity symptom. An ambulance had attended overdoses for 59% of subjects, 33% had required hospital treatment for overdose, and 14% had experienced overdose‐related complications of sufficient severity to be admitted to a hospital ward. Indirect overdose‐related morbidity included: physical injury sustained when falling at overdose (40%), burns (24%) and assault while unconscious (14%). Direct overdose‐related morbidity included: peripheral neuropathy (49%), vomiting (33%), temporary paralysis of limbs (26%), chest infections (13%) and seizure (2%). Conclusions There appears to be extensive morbidity associated with non‐fatal overdose. This is clearly an area that requires more research to document the prevalence and nature of these harms, and factors associated with them.     

Acute drug overdose: one hospital's experience

A retrospective review of all patients admitted to an urban teaching hospital emergency department with the complaint of overdose, poisoning, or ingestion during a 10-month period was conducted. Analysis of these 82 episodes involving 69 individuals revealed: 1) a preponderance of women in the 20- to 40-year old range; 2) poly-drug character of the ingestion, with alcohol the most common secondary drug; 3) increased utilization of antidepressants and minor tranquilizers and decreased use of barbiturates; 4) non-concordance between drug history of ingested drug and toxicological findings. All patients survived and there was no apparent residual morbidity. Except for one patient requiring hemodialysis and peritoneal dialysis, all patients were treated with aggressive supportive care.     

Non-fatal cocaine overdose among injecting and non-injecting cocaine users in Sydney, Australia

AIM: To investigate the frequency of non-fatal cocaine overdose, and responses to overdoses, among injecting and non-injecting cocaine users. DESIGN: Cross-sectional study. SETTING: Sydney, Australia. PARTICIPANTS: Two hundred current cocaine users. MEASUREMENTS: Structured interview. FINDINGS: Thirteen per cent of the sample had overdosed on cocaine, 7% in the preceding 12 months. Cocaine injectors were more likely to have overdosed, both ever (17 v 6%) and in the preceding 12 months (9 v 3%). The most common symptoms of overdose were palpitations (68%), intense sweating (44%) and seizures (40%). The use of other drugs in combination with cocaine prior to the most recent overdose was prevalent (64%), most commonly opioids (40%), alcohol (24%) and cannabis (24%). Those who had overdosed were more likely to be female, had longer cocaine use careers, had used more cocaine in the preceding month and preceding 6 months, had higher levels of cocaine dependence and more extensive polydrug use. Twenty-four per cent had witnessed a cocaine overdose, 13% in the preceding 12 months. Injectors were more likely to have witnessed overdoses, both ever (35% v 8%) and in the preceding 12 months (20% v 3%). CONCLUSIONS: Experience of, and exposure to, overdose were not rare events. Cocaine users need to be aware of the possibility and nature of overdose, and that cocaine overdose can occur irrespective of method of use. There is a need to emphasise the potential danger of combining cocaine with other drugs.     

Recurrent episodes of life-threatening vasodilatory shock following unintentional intoxication with amlodipine

Calcium channel blockers (CCBs) have a narrow therapeutic index, and their intake in excess is associated with a critical clinical presentation of sustained hypotension and non-cardiogenic pulmonary edema, which are difficult to treat. Unfortunately, the available treatments fail to resuscitate a significant number of patients poisoned by CCBs, rendering them the main cardiovascular drugs involved in death due to overdose. Importantly, in all cases reported until now in the literature, CCB intoxication was known at the time of patients' presentation and the medical challenge solely consisted of the therapeutic approach. In this case report, we describe our experience in treating a 72-year-old patient with recurrent episodes of sustained hypotension refractory to crystalloid and vasoconstrictor infusions. Prolonged pharmacologic support and intermittent sessions of hemofiltration induced stabilization and recovery. The results of an extensive diagnostic workup to elucidate the cause were unfruitful. The recurrent and paroxysmal nature of the clinical presentation along with its incidence after the patient left the protected setting of the hospital led the diagnostic approach to search for a possible external factor, which was shown to be, after toxicological investigation, unintentional amlodipine intoxication.     

HYPOXIC CARDIOMYOPATHY: ACUTE MYOCARDIAL DYSFUNCTION AFTER SEVERE HYPOXIA

Abstract Five cases of acute transient myocardial dysfunction in previously well people after severe hypoxic episode are described. In all cases the hypoxic episode was associated with drug overdose and its complications. Pulmonary infiltrates on chest X-ray consistent with pulmonary edema developed in four cases and gated heart pool scanning confirmed severe cardiovascular dysfunction in all cases.     

Paracetamol overdose in a liver transplantation centre: An 8-year experience

BACKGROUND: Paracetamol is a readily available, widely used analgesic that can cause serious hepatic injury when taken in overdose. The aims of this study were to assess the frequency of attendance at the Austin and Repatriation Medical Centre for paracetamol overdose, the frequency of referral to the Victorian liver transplant unit after serious overdoses, the morbidity and mortality rates in all patients treated and the appropriateness of treatment. METHODS: A review of the Austin and Repatriation Medical Centre medical records and of the Victorian liver transplant unit database of all patients attending because of paracetamol overdose from 1988-1995 was undertaken. One hundred and fifty-two patients (103 females, 49 males) files were reviewed. RESULTS: One hundred and thirty-one patients presented directly from the community and 21 were referred specifically for consideration for possible transplantation. The most important predictor of liver injury was time between overdose and arrival at hospital (P< 0.01). Thirteen patients developed fulminant hepatic failure, one of whom received a liver transplant; this patient died post-transplantation and was the only death in the series. CONCLUSIONS: We found that serious liver injury following overdose was uncommon, liver transplantation was rarely needed and death was rare. Although inappropriate delay in instituting N-acetylcysteine treatment after admission to hospital or failure to treat still occurred in a number of cases, delay in presentation to hospital was the main predictor of liver damage.     

Unintentional self-intoxication with inorganic calcium

A 40-year-old woman with previous parathyroidectomy for adenoma was found to have a serum calcium level of 5.35 mmol l-1 (21.4 mg dl-1). Inadvertent calcium overdose had occurred because of her mistaken belief that if some prescribed calcium was good, then more was better. Her misconception is in contrast with that of patients with Münchausen's syndrome, who deliberately made themselves hypercalcaemic by ingesting calcium or Vitamin D surreptitiously. Inorganic calcium is increasingly promoted for its presumed, though unproven, effectiveness in prevention and treatment of osteoporosis. Massive overdose can be associated with serious risks, as illustrated by the present case, which we believe represents the highest serum calcium level yet reported in an ambulatory patient.     

Pentazocine overdose

A patient who ingested 1.5 g pentazocine developed status epilepticus, coma, respiratory depression, acidosis, profound hypotension, and ventricular arrhythmias. Although this patient survived after institution of general supportive measures, she did not respond to usual doses of naloxone. We describe the clinical symptoms and course of recovery of a patient with pentazocine overdose. Our case suggests that pentazocine overdose may require higher doses of naloxone (5 to 20 mg) than are customarily used for narcotic overdoses.     

The prevalence and correlates of gamma-hydroxybutyrate (GHB) overdose among Australian users

Aim The aim of this study was to examine the correlates, context and risk perceptions regarding gamma‐hydroxybutyrate (GHB) overdose among a sample of recreational GHB users in Australia. Design A cross‐sectional survey of 76 GHB users who were administered a structured interview on GHB use. They were asked a series of questions regarding whether they had ever experienced a GHB overdose, the context of their most recent GHB overdose, and about their perceptions of the risks of GHB overdose. Findings This sample of GHB users had not had a long or extensive experience with GHB use; despite this, half (53%) had experienced a GHB overdose. This sample of GHB users appeared to be well‐educated, employed and a history of either drug treatment or incarceration was uncommon. There were no differences between those who had or had not overdosed in terms of socio‐demographic characteristics, extent of other drug use or typical patterns of other drug use when using GHB. However, those who had overdosed on GHB had used it more times during their life‐time, and had been using it for a longer period of time. Conclusions GHB‐related overdoses were common among a sample of GHB users who had only recently begun using the drug. The only apparent distinguishing factor between those who had and had not overdosed on GHB was the amount of experience with GHB use.     

Nonfatal Overdose Among Heroin Users in Southwestern China

Objective: To evaluate the prevalence of and risk factors for nonfatal overdose among heroin users in southwestern China. Methods: In 2005, 731 heroin users in Sichuan Province, China were interviewed for overdose experiences in the past 12 months. Factors hypothesized to be associated with overdose were evaluated with logistic regression models. Results: Eighty-eight (12%) drug users experienced at least one overdose, with a range from 1 to 20; 45 (51%) experienced 2 or more overdoses. Over half of participants with experience of overdose were recently released from prison (52%), and 56% used benzodiazepines before overdose. Longer methadone treatment in the past year (≥180 vs. 0 days; OR,. 3; 95% CI,. 1–.8; P = .02), longer duration of using drugs (≥7 vs. <7 years; OR, 2.2; 95% CI, 1.3–3.6; P = .002), and more frequency of injecting drugs in the past 3 months (≥7 vs. <7 times/week; OR, 5.4; 95% CI, 3.2–9.0; P < .001) were independently associated with increased risk of nonfatal heroin overdose. Conclusions: Nonfatal heroin overdoses are common among Chinese heroin users. Drug users should be encouraged to participate and remain in methadone treatment to prevent overdose and be educated about proper response to overdose to reduce risk of overdose death.     

Opiates,cocaine and alcohol combinations in accidental drug overdose deaths in New York City, 1990-98

Aims  Accidental drug overdose contributes substantially to mortality among drug users. Multi-drug use has been documented as a key risk factor in overdose and overdose mortality in several studies. This study investigated the contribution of multiple drug combinations to overdose mortality trends.
Design  We collected data on all overdose deaths in New York City between 1990 and 1998 using records from the Office of the Chief Medical Examiner (OCME). We standardized yearly overdose death rates by age, sex and race to the 1990 census population for NYC to enable comparability between years relevant to this analysis.
Findings  Opiates, cocaine and alcohol were the three drugs most commonly attributed as the cause of accidental overdose death by the OCME, accounting for 97.6% of all deaths; 57.8% of those deaths were attributed to two or more of these three drugs in combination. Accidental overdose deaths increased in 1990–93 and subsequently declined slightly in 1993–98. Changes in the rate of multi-drug combination deaths accounted for most of the change in overdose death rates, whereas single drug overdose death rates remained relatively stable. Trends in accidental overdose death rates within gender and racial/ethnic strata varied by drug combination suggesting different patterns of multi-drug use among different subpopulations.
Conclusions  These data suggest that interventions to prevent accidental overdose mortality should address the use of drugs such as heroin, cocaine and alcohol in combination.     

Extremely Elevated Procalcitonin in a Case of Acetaminophen Overdose and Acute Liver Injury

We herein report a 46-year-old man who suffered an intentional acetaminophen overdose. Laboratory results revealed leukocytosis and an elevated procalcitonin level (8.48 ng/mL). Computed tomography showed findings suggesting possible colitis. Due to concerns about sepsis in addition to acetaminophen overdose, oral N-acetyl cysteine and piperacillin/tazobactam were started. His procalcitonin levels further increased; however, the patient remained afebrile, and the C-reactive protein levels were normal. Piperacillin/tazobactam was discontinued, and he remained stable without antibiotics. The present case shows that the toxicokinetics of acetaminophen overdose can cause an elevated procalcitonin level. Furthermore, procalcitonin levels alone should not guide the need for antibiotics in such cases.     

Baclofen overdose

Reported is a case of baclofen overdose in a 23-year-old woman. The patient manifested typical symptoms of baclofen overdose, including hypotonia, respiratory depression, and seizures. She was treated successfully with positive pressure ventilation, sedation, and intravenous antibiotics, and was discharged from the hospital on the 14th day following admission with no residual neurological signs, to be followed up in medical and psychiatric outpatient clinics. As baclofen becomes increasingly popular in the treatment of muscle spasm in certain neurological disorders, its availability for misuse increases.     

Transient changes in behaviour lead to heroin overdose: results from a case-crossover study of non-fatal overdose

BACKGROUND AND AIMS: Heroin overdose is a serious consequence of heroin use and one of the leading causes of premature death and illness in Australia. Despite considerable research effort little is known about the effects of transient changes in heroin user behaviour and the links to overdose. This research is the first to use a suitable methodology to allow such ephemeral changes and their effects on non-fatal heroin overdose to be examined. METHODS: A case-crossover design was used in which non-fatal heroin overdose survivors' recall of risk behaviours in the 12 hours prior to overdose (hazard period) was compared to their recall of risk behaviours in the 12 hours prior to a selected non-overdose heroin injection (control period). RESULTS: A total of 155 participants were able to provide valid details of hazard and control periods. A dose-response relationship was observed between the self-reported amount of heroin used and likelihood of overdose (e.g. > AUD50, OR 12.97, 95% CI 2.54-66.31). The use of benzodiazepines (OR 28, 95% CI 3.81-205.79) or alcohol (OR 2.88, 95% CI 1.29-6.43), during the hazard period was related to overdose risk, but the effect of alcohol was attenuated by the effect of benzodiazepines. Shifting from private to public locations between control and hazard periods was also related to increased risk of overdose (OR 3.63, 95% CI 1.66-7.93). CONCLUSIONS: We demonstrate the value of a new methodology to explore heroin overdose, as well as discussing its limitations and ways to overcome them in future. In terms of our findings, overdose prevention messages need to highlight the impact of these transient changes in behaviour and to emphasize the risks of using higher doses of heroin as well as continuing to emphasize the risks of combining heroin with other central nervous system (CNS) depressants. Safer environments for heroin use, such as injecting rooms, may also reduce the chances of overdose.     

An increase in overdose mortality during the first 2 weeks after entering or re-entering methadone treatment in Amsterdam

Aims It has been suggested that starting and temporarily discontinuing methadone treatment is related to an increased risk in overdose mortality. This study describes the incidence of overdose mortality in relation to time after (re)entering or leaving treatment. Design A dynamic cohort of 5200 Amsterdam methadone clients was observed during treatment and (a maximum of 1 year) after treatment. Findings Between 1986 and 1998, 29 729 person‐years (py) and 68 overdose deaths were recorded, leading to an overdose mortality rate of 2.3/1000 py (2.2 during and 2.4 after treatment). A modest increase was observed during the first 2 weeks after (re)entering treatment; 6.0/1000 py (rate ratio: 2.9; 95% confidence interval 1.4; 5.8). Directly after leaving treatment no increase was observed. Conclusions Inhaling heroin, common among Amsterdam heroin users, is thought to account for low OD mortality rates both during and after treatment. Accumulation of methadone, inadequate assessment of tolerance of known clients re‐entering treatment and concurrent periods of stress or extreme heroin use when entering treatment are mentioned as possible explanations of the increased risk within the first 2 weeks. An Australian study reported a much higher increase. The modest increase in Amsterdam is explained by low background risk of overdose mortality, low starting dosage and the low threshold to treatment.     

Rhabdomyolysis Caused by Gefitinib Overdose

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are common therapeutic agents for EGFR mutation-positive advanced non-small-cell lung cancer. There has been no report of rhabdomyolysis caused by an overdose of EGFR-TKIs. We herein review the existing literature on the subject and report a rare case of rhabdomyolysis due to an overdose of gefitinib, an EGFR-TKI.     

Recent contact with health and social services by drug misusers in Glasgow who died of a fatal overdose in 1999

Aim  To explore the recent contact with health and social services by drug misusers who died of a fatal overdose and identify opportunities for preventive intervention.
Design  Retrospective case analysis.
Subjects  Eighty-seven residents of the Greater Glasgow area who died of a drug misuse-related overdose in 1999.
Methods  Analysis of matched data from several sources: Strathclyde Police; University of Glasgow Department of Forensic Medicine and Science; the Scottish Prison Service; general practitioners' medical notes, including records of accident and emergency attendances and psychiatric assessments; and five specialist agencies for drug misusers or the homeless.
Findings  Most of those who died of an overdose were males, long-standing heroin injectors and resident in a deprived area. Heroin caused most deaths, either alone or with other drugs. Twenty-three per cent died within 2 weeks of release from prison. For the 77 whose medical records were available, 90% had seen their general practitioner (32% in the month before death), 48% had attended accident and emergency services and 22% had received a psychiatric assessment in the year before death. Over 40% of the 87 used a drug agency in the year before death and 20% had used more than one agency.
Conclusions  Previous suicidal ideation, attempted suicide and depression were common among those who died of an overdose, as was recent release from prison. Almost all had been in contact with and several were receiving specific treatment from health or specialist addiction services in their last weeks or months. The findings highlight both the numerous opportunities for intervention and the challenge of using them to prevent death.