An acute oral intoxication with haloperidol decanoate.

Haloperidol decanoate is a typical antipsychotic drug used as maintenance therapy for schizophrenia and mood disorders formulated as an ester for intramuscular injection. Cases of oral haloperidol decanoate intoxications have not been described in literature. In this report, we present for the first time a case of an oral ingestion of haloperidol decanoate of a young woman who presented to the emergency department following an intentional oral ingestion of 1 ampoule of haloperidol decanoate 100mg. At presentation, she had a bilateral rest tremor of both hands and mild hypothermia. No other obvious signs of an intoxication were observed. She was treated with a single dose of activated charcoal and laxative and was admitted to the intensive care for rhythm monitoring and observation. During the night the QTc interval increased to 453ms, but stayed within the normal range. Haloperidol plasma levels increased as well, but also stayed within therapeutic ranges. These findings indicate that treatment with oral activated charcoal was sufficient to prevent any serious events.

[Haloperidol poisoning in pediatric patients]. / Intoxicación por haloperidol en el paciente pediátrico.

Exposing a child to a potentially toxic substance is an uncommon cause of consultation in childhood. Poisoning by drugs in this age group is commonly due to improper administration by parents or error in dosage by the doctor; also ingestion at own initiative, i.e. self-poisoning. CASE REPORT: A 11 years-old male, drowsy, unresponsive, with bradypsychia, assisted ambulation without increased support arch, resting tremor; obeying orders without verbal response, isochoric pupils, difficulty opening the eyes without facial asymmetry, muscle contracture of platysma, increased muscle tone, tendon reflexes slightly increased, arrhythmic heart sounds without murmurs. On interrogation, the subject mentioned his own decision to ingest about 0.7-0.9 mg of haloperidol (0.35-0.45 ml / 7-9 drops). Laboratory studies: BUN 12 mg/dl; creatinine 0.5 mg/dl; Na 140 mmol/l; K 3.38 mmol/l; Cl 100.2 mmol/l; LDH 363 U/l; CK 130 U/l; CK-MB 13 U/l. Electrocardiogram DII length (13:00 h) with sinus rhythm, FC 100 x, corrected QT 0.57; stroke control (19:20 h) FC 70 x, QTc of 0.41 (Fig. 1). He was treated with diphenhydramine 1 mg/kg/dose with clear improvement at 12 hours after admission, so his discharge at 24 hours was decided without any additional medication.

Black esophagus: acute esophageal necrosis in fatal haloperidol intoxication.

Herein, we present a case of 53-year-old psychotic woman with acute esophageal necrosis (black esophagus), who was found lying on the floor in the living room of her flat. Pillboxes of antipsychotic drugs were located in the bin. External examination of the body was unremarkable. On internal examination, we found acute esophageal necrosis. Histologically, there was complete epithelial necrosis with focal involvement of muscularis mucosae, dense infiltrate of leukocytes, and ulcerations without any viable cells. There was no evidence of underlying organic diseases or trauma. Toxicological analysis revealed a fatal blood level of antipsychotics (haloperidol, zotepine, and chlorprothixene). Death of the deceased was attributed to fatal intoxication with three various types of antipsychotics. As far we know, this is the first described association between so-called black esophagus and fatal blood level of neuroleptics.

Is acute dystonia an emergency? Sometimes, it really is!

Most cases of acute dystonia are mild and easy to manage; nevertheless, some of them can be fatal because of the involvement of certain muscle groups such as the laryngeal muscles, thus requiring urgent intervention. In the literature, approach to life-threatening acute dystonia has not been investigated thoroughly, although the diagnosis is a challenge, and treatment should be offered immediately. Herein the management of life-threatening acute dystonia is discussed via 2 case reports.

Accidental haloperidol poisoning in children.

Haloperidol, a butyrophenone neuroleptic drug, is an antipsychotic used in the treatment of adult schizophrenia and mania. It is used in children with neurological disorders like chorea and developmental disorders such as hyperactivity. With the advent of newer selective neuroleptics use of haloperidol is now on decline. However, in adults it is still the preferred drug especially in resource challenged settings. Extrapyramidal reactions occur frequently with haloperidol predominantly as parkinsonian symptoms. There are few case reports of accidental haloperidol poisoning in children and this one of them.

[Chemical toxicological analysis of haloperidol metabolite 4-(4-chlorophenyl)-4-hydroxypipiridine in urine by high-performance liquid chromatography].

Haloperidol is extensively used in current psychiatric practice for the treatment of various psychotic disorders. However, this substance is known to be toxic and sometimes cause poisoning despite its generally positive therapeutic effect. Moreover, some of its metabolites also possess high toxic activity. It has been shown in the literature that haloperidol is metabolized to 4-(4-chlorophenyl)-4-hydroxypiperidine (CPHP) and 3-(4-fluorobenzoyl)-propionic acid (FBPA). We have developed the most efficacious method for isolation of both CPHP and FBPA from aqueous solutions ensuring the output of 99.6% and 99.8% of the respective product. Also, their spectral characteristics were studied by the UV spectrophotometric technique. Animal experiments demonstrated that only CPHP was excreted in the urea whereas the second metabolite was not detected in any sample, probably because it is further metabolized to 3-(4-fluorophenyl)-acetic acid. Methods for the isolation of CPHP from urine, its identification, and quantitative determination were developed based on the use of high-performance liquid chromatography (HPLC).

Endovascular cooling in a patient with neuroleptic malignant syndrome.

We report a case of severe neuroleptic malignant syndrome with hyperthermia, rhabdomyolysis and hepatic failure where we applied endovascular cooling in order to reverse hyperthermia. After rapid normalization of core temperature at 37.5 degrees C, the patient's condition improved and CK levels dropped. However, upon withdrawl of endovascular temperature control there was a relapse. This is the first case where endovascular cooling was applied successfully in neuroleptic malignant syndrome.

Antipsychotic poisoning in young children: a systematic review.

The aim of this review was to determine the spectrum and severity of effects of unintentional antipsychotic poisoning in children. A computerised literature search of MEDLINE (1966 to February 2005) and EMBASE (1980 to February 2005) was undertaken. The Internet was searched using URL: www.google.com. The proceedings of the North American Congress of Clinical Toxicology (NACCT) and the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) were hand searched. All cases of unintentional antipsychotic (all classes) poisoning in children aged 0-6 years were included. The data extracted included the age, weight, antipsychotic, dose, clinical effects, treatment and outcomes. The toxic dose was estimated as the lowest dose causing objective adverse effects.Sixty-eight reports were identified. Few contained all of the required information. Most of the case series included multiple antipsychotics with limited information on individual drugs or all ages with limited paediatric information. For most antipsychotics the ingestion of one tablet caused symptoms that were sometimes severe and usually lasted from 1 to 3 days. Extrapyramidal symptoms (EPS) were often delayed for up to 12-24 hours. Chlorpromazine caused CNS depression, hypotension and miosis; EPS and cardiac effects were rare, and the toxic dose was estimated to be 15 mg/kg. Haloperidol caused drowsiness (rarely coma) and over one-half of patients had neuromuscular effects (mainly EPS), with a toxic dose estimated at 0.15 mg/kg. Thioridazine caused CNS depression and potentially cardiac effects, with a toxic dose of 1.4 mg/kg. Atypical antipsychotics caused significant CNS depression (except risperidone); EPS were less common. Toxic doses were clozapine 2.5 mg/kg, olanzapine 0.5 mg/kg and aripiprazole 3 mg/kg. EPS responded to anticholinergic drug treatment. In summary, unintentional antipsychotic ingestion in children can cause severe effects that last 1-3 days, often with one tablet. Children potentially ingesting a toxic dose or who are symptomatic should be considered for assessment in hospital. Most cases resolve with good supportive care. Toxic doses are only estimates that are based on limited data and should be used with caution until prospective studies are undertaken.

High-performance liquid chromatographic method with diode array detection to identify and quantify atypical antipsychotics and haloperidol in plasma after overdose.

For toxicological purposes, an HPLC assay was developed for the simultaneous determination of haloperidol and atypical antipsychotics (risperidone, 9-hydroxyrisperidone, olanzapine, clozapine) in human plasma. After a double-step liquid-liquid extraction, compounds were separated on a C(8) column eluted with a gradient of acetonitrile and phosphate buffer 50 mM pH 3.8. A sequential ultraviolet detection was used (260, 280 and 240 nm). Calibration curves were linear in the range 10-1000 ng/ml. The limits of quantification were 5 ng/ml for all drugs. Average accuracy at four concentrations ranged from 93 to 109%. Both inter- and intra-day variation coefficients were lower than 11% for all drugs. This simple and rapid method (run time<15 min) is currently used for poison management.

[Neuroleptic malignant syndrome with rhabdomyolysis and muscle rupture]. / Neurolepticki maligni sindrom sa rabdomiolizom i rupturom misica.

We report a case of neuroleptic malignant syndrome (NMS) development after the ingestion of 960 mg of haloperidol in 18-year old male on the previous long-term neuroleptic treatment. Beside the severe rigidity and laboratory signs of rhabdomyolysis, firm swelling of gluteal and femoral areas, accompanied by pain and difficulty in the extension of the right leg, was noticed. The ultrasonography of the affected limb revealed partial rupture of quadriceps muscle. Since no signs of trauma or any other causes of muscle rupture were observed, we concluded that it developed due to the severe hypertonia and rhabdomyolysis in NMS. As there were no such cases previously reported, we wished to point out the possibility of muscle rupture development in NMS and propose the adequate diagnostic procedures and treatment.

A case of child abuse: haloperidol poisoning of a child caused by his mother.

This presentation focused on a hyperactive child admitted to the emergency department because of ataxia and imbalance. It was later discovered that the child had been abused by his mother. In cases where there is conflict between the clinical findings, the patient and the family's history in a clinical state which cannot be explained satisfactorily by the medical staff, the need for taking the history again from other relatives whilst taking into account the parents' physiological well-being, is time well spent.

Phenothiazine, butyrophenone, and other psychotropic medication poisonings in children and adolescents.

OBJECTIVE: To describe the presentation, epidemiology, management, and outcome of phenothiazine and butyrophenone ingestions in children requiring hospitalization. METHOD: Retrospective case series in two pediatric hospitals. RESULTS: Eighty-six cases were identified among 83 patients. The majority (69.7%) of ingestions occurred in children <6 years of age and there was no gender predominance. These ingestions were more common in African Americans (65.1%). They occurred more commonly in the patient's (64.0%) or a relative's (22.1%) home and haloperidol and thioridazine accounted for 58.1% of exposures. Depressed levels of consciousness and dystonia were the most common presenting signs, present in 90.7% and 51.2% of patients, respectively. Miosis occurred in only 13.9% of the patients. Fluid boluses were administered to 28.7% of the patients but about a quarter of these had coingested potentially cardiotoxic drugs. In addition, 2 of the 12 (13.9%) patients with abnormal electrocardiograms had also ingested potentially cardiotoxic drugs. Numerous diagnostic tests were performed in these patients including electrolyte panels (80.2%), complete blood counts (69.8%), liver function tests (31.4%), serum osmolality (20.9%), blood cultures (10.5%), lumbar punctures (17.4%), head computed tomographies (15.1%), and electroencephalograms (3.5%). The median length of hospitalization was 1.78 (range 1-9) days and there were no deaths. Patients presenting with dystonias were more likely to have extensive diagnostic testing for neurologic disease than those presenting without dystonias. CONCLUSION: The presentation of phenothiazine and butyrophenone ingestions in children and adolescents may be nonspecific and confounded by coingestants. Patients with dystonias had more extensive neurologic testing than patients without dystonias, suggesting that physicians may not recognize dystonias as a clinical finding characteristic of phenothiazine or butyrophenone exposure.

[Mental disorders in acute neuroleptic poisoning]. / Psikhicheskie rasstroistva pri ostrykh otravleniiakh neiroleptikami.

110 patients (52 men, 58 women) in a state of acute intoxication were examined in emergency department of psychoneurologic hospital. Neuroleptics of different groups were used to commit a suicide (91.3% of the cases), to obtain a toxicomanic effect (6.3%) and accidentally (1.8%). The patients suffered from borderline mental disorders (39.2%), schizophrenia (40.9%), manic-depressive psychosis in depressive phase (10.9%), chronic alcoholism (4.5%) and organic damages of CNS (4.5%). The patients with borderline states used various drugs and had more light disorders of consciousness (deafness). Meanwhile, the patients with endogenic mental disorders used strong neuroleptics, as a rule, that resulted in coma. In residual period there were different syndromes from asthenic to psychoorganic ones. They were more severe after poisoning with aminazinum, haloperidol, leponex.

Induction of reactive oxygen species in neurons by haloperidol.

Haloperidol (HP) is widely prescribed for schizophrenia and other affective disorders but has severe side effects such as tardive dyskinesia. Because oxidative stress has been implicated in the clinical side effects of HP, rat primary cortical neurons and the mouse hippocampal cell line HT-22 were used to characterize the generation of reactive oxygen species (ROS) and other cellular alterations caused by HP. Primary neurons and HT-22 cells are equally sensitive to HP with an IC50 of 35 microM in the primary neurons and 45 microM in HT-22. HP induces a sixfold increase in levels of ROS, which are generated from mitochondria but not from the metabolism of catecholamines by monoamine oxidases. Glutathione (GSH) is an important antioxidant for the protection of cells against HP toxicity because (1) the intracellular GSH decreases as the ROS production increases, (2) the exogenous addition of antioxidants, such as beta-estradiol and vitamin E, lowers the level of ROS and protects HT-22 cells from HP, and (3) treatments that result in the reduction of the intracellular GSH potentiate HP toxicity. The GSH decrease is followed by the increase in the intracellular level of Ca2+, which immediately precedes cell death. Therefore, HP causes a sequence of cellular alterations that lead to cell death and the production of ROS is the integral part of this cascade.

[Acute encephalomyopathy and persistent cerebellar syndrome after lithium salt and haloperidol poisoning]. / Encéphalomyopathie aiguë et syndrome cérébelleux persistant après intoxication par sel de lithium et halopéridol.

A 44-year-old maniacodepressive woman developed acute encephalopathy due to the association of lithium carbonate and haloperidol. She was treated with lithium salts for many years and the serum level of lithium was within the therapeutic range. The encephalopathy was worsened by hyperthermia, dehydration, and reintroduction of haloperidol, 5 days after the first discontinuation of the neuroleptic. The clinical features were characterized by a persistent cerebellar syndrome, more than one year after the interruption of these medications.

Haloperidol overdose during pregnancy.

BACKGROUND: Suicide attempts during pregnancy are rare. Over-the-counter and psychotropic medications are most commonly used. Although intentional overdose of haloperidol has been reported in nonpregnant adults, it has not, to our knowledge, been reported previously during pregnancy. In this case of suicide attempt by haloperidol overdose, maternal and fetal responses were studied extensively. CASE: Intentional ingestion of 300 mg haloperidol by a pregnant woman at 34 weeks' gestation caused maternal unresponsiveness, an extrapyramidal reaction, temporary fetal akinesia, and a nonreactive nonstress test. The mother recovered in 48 hours. The fetus did not reach a biophysical profile score of ten until 5 days after presentation. CONCLUSION: Haloperidol overdose during pregnancy causes a maternal extrapyramidal reaction, temporary fetal akinesia, and prolonged fetal neuromuscular depression.

The Osborn wave of hypothermia in normothermic patients.

The Osborn wave (also referred to as "the J wave," "the J deflection," or "the camel's hump") is a distinctive deflection occurring at the QRS-ST junction of approximately 80% of hypothermic patients (core body temperature < or = 95 degrees F). Generally, the amplitude and duration of Osborn waves are inversely related to core temperature. We report on eight normothermic patients whose 12-lead electrocardiograms demonstrated QRS-ST junction notches similar to those seen in hypothermia. These data support the concept that the Osborn wave is not pathognomonic of hypothermia.

Acute accidental overdosage of haloperidol in children.

We report the details of an accidental overdosage of haloperidol in 24 children in one hospital in Kyushu, Japan. Evidence of acute toxicity included disturbances in consciousness (24/24), tremors in the extremities (16/24), an oculogyric or similar crisis (14/24), dysarthria (9/17), drooling (8/24), akathisia (6/20), hyperreflexia (6/24) and opisthotonos (3/24). Laboratory examinations revealed late-onset transient thrombocytosis (5/24), elevated AST and GPT (1/24) and abnormal ECG with prolonged QT interval in 2 of 8 children. We detected haloperidol in 11 of 18 children whose blood was specifically examined within four days after the final haloperidol administration. The maximum serum haloperidol level was 28.9 ng/ml. The mean half-life of haloperidol in the serum of five children (age range 2-10 years) was 18.6 +/- 12.2 h (mean +/- SD) (range 9.1-39.4 h).