Pharmacokinetic evaluation of haemoperfusion in phenobarbital poisoning

Jacobsen, Dag; Wiik-Larsen, E; Dahl, T; Enger, E; Lunde, P. K. M.

doi:10.1007/bf00546717

Cited by 24 publications

(5 citation statements)

References 10 publications

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“…• Clearance values achieved by multiple-dose activated charcoal in the case of carbamazepine, [89][90][91] dapsone, 43 and phenobarbital 96,96 are comparable to those produced by the more invasive techniques of hemodialysis and hemoperfusion.…”

Section: Clinical Studiesmentioning

confidence: 79%

Position Statement and Practice Guidelines on the Use of Multi-Dose Activated Charcoal in the Treatment of Acute Poisoning

Toxicologists¹

1999

Journal of Toxicology: Clinical Toxicology

294

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In preparing this Position Statement, all relevant scientific literature was identified and reviewed critically by acknowledged experts using agreed criteria. 1-124 Well-conducted clinical and experimental studies were given precedence over anecdotal case reports and abstracts were not usually considered. A draft Position Statement was then produced and subjected to detailed peer review by an international group of clinical toxicologists chosen by the American Academy of Clinical Toxicology and the European Association of Poisons Centres and Clinical Toxicologists. The Position Statement went through multiple drafts before being approved by the Boards of the two societies.The Position Statement includes a summary statement for ease of use and is supported by detailed documentation which describes the scientific evidence on which the Statement is based. Although many studies in animals and volunteers have demonstrated that multiple-dose activated charcoal increases drug elimination significantly, this therapyhas not yet been shown in a controlled study in poisoned patients to reduce morbidity and mortality. Further studies are required to establish its role and the optimal dosage regimen of charcoal to be administered. Based on experimental and clinical studies, multiple-dose activated charcoal should be considered only if a patient has ingested a life-threatening amount of carbamazepine, dapsone, phenobarbital, quinine, or theophylline. With all This Position Statement is endorsed by the Canadian Association of Poison Control Centres. 731 Clinical Toxicology Downloaded from informahealthcare.com by Nyu Medical Center on 07/28/15For personal use only. ORDER REPRINTS 732AACT and EAPCCT of these drugs there are data to confirm enhanced elimination, though no controlled studies have demonstrated clinical benefit.Although volunteer studies have demonstrated that multiple-dose activated charcoal increases the elimination of amitriptyline, dextropropoxyphene, digitoxin, digoxin, disopyramide, nadolol, phenylbutazone, phenytoin, piroxicam, and sotalol, there are insufficient clinical data to support or exclude the use of this therapy.The use of multiple-dose charcoal in salicylate poisoning is controversial. One animal study and 2 of 4 volunteer studies did not demonstrate increased salicylate clearance with multiple-dose charcoal therapy. Data in poisoned patients are insufficient presently to recommend the use of multiple-dose charcoal therapy for salicylate poisoning.Multiple-dose activated charcoal did not increase the elimination of astemizole, chlorpropamide, doxepin, imipramine, meprobamate, methotrexate, phenytoin, sodium valproate, tobramycin, and vancomycin in experimental and/or clinical studies.Unless a patient has an intact or protected airway, the administration of multiple-dose activated charcoal is contraindicated. It should not be used in the presence of an intestinal obstruction. The need for concurrent administration of cathartics remains unproven and is not recommended. In particular, cathartics shoul...

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Section: Clinical Studiesmentioning

confidence: 79%

Position Statement and Practice Guidelines on the Use of Multi-Dose Activated Charcoal in the Treatment of Acute Poisoning

Toxicologists¹

1999

Journal of Toxicology: Clinical Toxicology

294

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“…The numbers show that the resin filter is fairly effective in adsorbing levomepromazine and the metabolites. The effect of haemoperfusion on the total clearance of various substances must, however, be compared with the intrinsic clearance of each substance (Jacobsen et al, 1984). We know only the intrinsic clearance of levomepromazine, which has been published previously.…”

Section: Discussionmentioning

confidence: 99%

Resin Haemoperfusion in Levomepromazine Poisoning: Evaluation of Effect on Plasma Drug and Metabolite Levels

Hals

Jacobsen

1984

Human Toxicology

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1 Plasma levels of levomepromazine and two of its major metabolites N-desmethyl-levomepromazine and levomepromazine sulphoxide were studied in two poisoned patients treated with resin haemoperfusion at a constant blood flow of 200 ml/min. 2 The mean haemoperfusion clearance of levomepromazine, N-desmethyl-levomepromazine and levomepromazine sulphoxide was 114, 123 and 151 ml/min, respectively, in patient no. 1, and 153, 148 and 184 ml/min, respectively, in patient no. 2. Patient no. 2 had also ingested amitriptyline, and the mean haemoperfusion clearance of amitriptyline and its metabolite nortriptyline was 183 and 183 ml/min respectively. 3 Haemoperfusion did not seem to alter the elimination profile of levomepromazine or the two metabolites in either patient. 4 We conclude that haemoperfusion is of little value in removing levomepromazine, N-desmethyl-levomepromazine or levomepromazine sulphoxide from the body. This is probably due to the large apparent volume of distribution and the high intrinsic hepatic metabolic clearance of these compounds.

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“…Investigations have demonstrated the efficacy of extracorporeal methods for the elimination of phenobarbital [29,30]. In 1966, Setter demonstrated the comparative clearance rates of phenobarbital by hemodialysis (30 ml/min), peritoneal dialysis (4-8 ml/min), and diuresis (3-4 ml/min), [29].…”

Section: What About Extracorporeal Methods Of Elimination?mentioning

confidence: 99%

“…In 1966, Setter demonstrated the comparative clearance rates of phenobarbital by hemodialysis (30 ml/min), peritoneal dialysis (4-8 ml/min), and diuresis (3-4 ml/min), [29]. In 1986, Jacobsen demonstrated a 78-88% reduction in half-life in three cases of phenobarbital poisoning when hemoperfusion was performed [30]. The half-lives were 7.2 to 11.1 hours during hemoperfusion, and half-lives increased from 48 to 82 hours after hemoperfusion was discontinued [30] There has been debate as to whether hemoperfusion is preferable to hemodialysis in patients poisoned by phenobarbital.…”

Section: What About Extracorporeal Methods Of Elimination?mentioning

confidence: 99%

“…In 1986, Jacobsen demonstrated a 78-88% reduction in half-life in three cases of phenobarbital poisoning when hemoperfusion was performed [30]. The half-lives were 7.2 to 11.1 hours during hemoperfusion, and half-lives increased from 48 to 82 hours after hemoperfusion was discontinued [30] There has been debate as to whether hemoperfusion is preferable to hemodialysis in patients poisoned by phenobarbital. Hemoperfusion is often limited because of its lack of availability in many hospitals; conversely, hemodialysis is accessible in most hospitals.…”

Section: What About Extracorporeal Methods Of Elimination?mentioning

confidence: 99%

See 1 more Smart Citation

Case files of the Toxikon Medical Toxicology Fellowship in Chicago: The poisoned anesthesiologist

Thompson

Aks

2007

J. Med. Toxicol.

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A 58-year-old retired anesthesiologist presented unresponsive to the emergency department (ED). The patient's wife stated that she saw him as she was leaving the house at 8:00 a.m on the day of presentation, and he seemed well. A relative called the patient at 10:00 a.m. and noted that his speech was slurred. His wife returned home at 2:30 p.m. and noted that the doors to the house were locked. Subsequently she left because she did not have her key. She returned again at 5:30 p.m. and was unable to gain entry into the house. With the assistance of a locksmith, she entered the house to find the patient, in his study, unresponsive.The patient's wife activated emergency medical services (EMS). Paramedics arrived to find the patient unresponsive, hypotensive, and bradycardic. He was immediately intubated. He had an undetectable blood pressure and undetectable pulse. He was resuscitated with 2 mg each of intravenous atropine and epinephrine and rapidly transported. Upon arrival to the ED, he had a blood pressure of 70/40 mmHg, a pulse of 60/min, and a rectal temperature of 34.4°C (94°F). On physical examination there were no external signs of trauma, pupils were 3mm bilaterally with no reaction to light, and no skin breakdown or pressure ulcers were noted. The cardiopulmonary and abdominal exams revealed no gross abnormalities. The neurologic examination demonstrated a comatose patient with no purposeful movements and a Glasgow Coma Scale (GSC) of three.The patient has a history of type 2 diabetes mellitus and hypertension. His medications included metformin 500 mg, amlodipine 5 mg/benazepril 10 mg capsules, atorvastatin 10 mg, extended-release metoprolol 50 mg, and losartan 50 mg. The patient's wife stated that he had no history of depression or suicide attempts.The patient was further resuscitated with intravenous fluids, and a dopamine drip was titrated to maintain perfusion. The initial laboratory data are listed in Table 1. Hyperkalemia was treated with intravenous insulin and sodium bicarbonate. A computed tomography (CT) scan of the head was normal. A 12-lead EKG initially showed QRS duration of 100ms. After resuscitation, the QRS duration was 84ms. An EMIT urine drug screen was only positive for barbiturates. What are the unique characteristics of suicide attempts by physicians?Physician suicide rates have long been known to be higher than those among the general population [1][2][3][4]. Actual suicide rates are difficult to determine because suicide is a legal determination that requires a standard of proof: it is not a medical diagnosis [5]. As such, the forensic literature often differs from the medical literature regarding suicide rates. Because physicians may be more adept at disguising a suicide attempt, data about physician suicides is complicated [5]. However, recent studies have approximated physician suicide rates to be two-fold that of the general population, which has an annual suicide rate of approximately 11 per 100,000 people [5][6][7].Thirty to 70% of those who attempt suicide have an affective...

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Pharmacokinetic evaluation of haemoperfusion in phenobarbital poisoning

Cited by 24 publications

References 10 publications

Position Statement and Practice Guidelines on the Use of Multi-Dose Activated Charcoal in the Treatment of Acute Poisoning

Position Statement and Practice Guidelines on the Use of Multi-Dose Activated Charcoal in the Treatment of Acute Poisoning

Resin Haemoperfusion in Levomepromazine Poisoning: Evaluation of Effect on Plasma Drug and Metabolite Levels

Case files of the Toxikon Medical Toxicology Fellowship in Chicago: The poisoned anesthesiologist

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