Norbert Felgenhauer

Publications of Norbert Felgenhauer

• Clinical and analytical features of severe suicidal quetiapine overdoses--a retrospective cohort study.

  Authors: Florian Eyer, Rudolf Pfab, Norbert Felgenhauer, Tim Strubel, Bernd Saugel, Thomas Zilker

  Clinical toxicology (Philadelphia, Pa.). 11/2011; 49(9):846-53.

  Detailed data on severe overdoses with quetiapine are relatively sparsely reported in the literature. To describe a cohort of 20 acute quetiapine overdoses and provide additional data on theDetailed data on severe overdoses with quetiapine are relatively sparsely reported in the literature. To describe a cohort of 20 acute quetiapine overdoses and provide additional data on the pharmacokinetics and clinical features of intoxication with this drug. A retrospective study was conducted on patients with quetiapine poisoning admitted to our institution. We included moderate to severe overdoses between 2005-2011 who required admission to ICU. Predominantly female patients (n = 17) ingested a median dose of 9.8 g quetiapine. Poison Severity Score was moderate in 9 patients, severe in 10 patients and in one case fatal. Quetiapine was analytically confirmed in all cases. Clinical manifestations included drowsiness or coma (all patients), tachycardia (12 patients) and hypotension (10 patients). Seizures and arrhythmia occurred in 4 patients, each. Intubation and mechanical ventilation was required in 14 patients due to seizures, respiratory depression or loss of airway protection and 15 patients developed pneumonia. Hypokalaemia and hyperglycaemia were present at admission in 10 and 5 patients, respectively. Despite frequent prolongation of the QT(c) in 13 patients, QT interval was normal in most cases and QRS-interval was prolonged in only one patient. Presumably anticholinergic delirium was recognised in 8 patients and 6 patients received physostigmine with good clinical response. In 13 cases quetiapine was analysed quantitatively in serum with a relevantly prolonged half-life (16 ± 12 h) and a median peak serum concentration of 3074 ng/mL. In 4 of these 13 patients we observed an increase of quetiapine serum concentration in the further course. In this study, quetiapine overdoses were associated with significant toxicity and a fairly high number of complications. A careful and often prolonged clinical observation in the more severe cases of overdose seems mandatory.

• Atropine maintenance dosage in patients with severe organophosphate pesticide poisoning.

  Authors: Horst Thiermann, Dirk Steinritz, Franz Worek, Maria Radtke, Peter Eyer, Florian Eyer, Norbert Felgenhauer, Thomas Zilker

  Toxicology letters. 09/2011; 206(1):77-83.

  Although the importance of atropine in therapy of organophosphate (OP) poisoning is generally recognized, its dosing is a matter of debate. A retrospective analysis of atropine dosing was undertakenAlthough the importance of atropine in therapy of organophosphate (OP) poisoning is generally recognized, its dosing is a matter of debate. A retrospective analysis of atropine dosing was undertaken in 34 patients who had been enrolled in a clinical study assessing obidoxime effectiveness in OP-poisoning. All patients were severely intoxicated (suicidal attempts) and required artificial ventilation. Atropine was administered routinely by intensive care physicians for life-threatening muscarinic symptoms, with the recommendation to favor low dosage. The pharmacological active enantiomere S-hyoscyamine was determined by a radioreceptor assay. When RBC-AChE activity ranged between 10% and 30%, S-hyoscyamine plasma concentrations of approx. 5 nmol L⁻¹ were sufficient. This concentration could be maintained with about 0.005 mg h⁻¹ kg⁻¹ atropine. Only when RBC-AChE was completely inhibited, therapy of cholinergic crisis required atropine doses up to 0.06 mg h⁻¹ kg⁻¹. Elimination half-life of S-hyoscyamine was 1.5 h, showing occasionally a second slow elimination phase with t(½)=12 h. Malignant arrhythmias were observed in some 10% of our cases, which occurred late and often in the absence of relevant glandular cholinergic signs, when the S-hyoscyamine concentration was below 2.5 nmol L⁻¹. Arrhythmias mostly resolved on reinstitution of atropine.

• Risk assessment of severe tricyclic antidepressant overdose.

  Authors: Florian Eyer, Jochen Stenzel, Tibor Schuster, Norbert Felgenhauer, Rudi Pfab, Christian von Bary, Thomas Zilker

  Human & experimental toxicology. 10/2009;

  Prognostic factors for severe complications in tricyclic antidepressant (TCA) overdose remain unclear. We therefore evaluated the value of clinical characteristics and electrocardiograph (ECG)Prognostic factors for severe complications in tricyclic antidepressant (TCA) overdose remain unclear. We therefore evaluated the value of clinical characteristics and electrocardiograph (ECG) parameters to predict serious events (seizures, arrhythmia, death) in severe TCA overdose of 100 patients using logistic regression models for risk assessment. The overall fatality rate was 6%, arrhythmia occurred in 21% and 31% of the patients developed seizures. Using an univariable logistic regression model, the maximal QRS interval (OR 1.22; 95% CI 1.06-1.41; p = .005), the time lag between ingestion and occurrence of first symptoms of overdose (OR 1.13; 95% CI 0.99-1.29; p = .072) and the age (OR 0.73; 95% CI 0.55-0.98; p = .038) were determined as the solely predictive parameters. In the multivariable logistic regression model, the QRS interval could not be established as independent predictor, however, the terminal 40-ms frontal plane QRS vector (T40) reached statistical significance regarding prediction of serious events (odds ration [OR] 1.70; 95% confidence interval [CI] 1.02-2.84; p = .041), along with age and time lag between ingestion and onset of symptoms of overdose with a sensitivity and specificity of 71% and 70%, respectively. Evaluation of both clinical characteristics and ECG-parameters in the early stage of TCA overdose may help to identify those patients who urgently need further aggressive medical observation and management.

• Obidoxime in acute organophosphate poisoning: 1 - clinical effectiveness.

  Authors: Florian Eyer, Franz Worek, Peter Eyer, Norbert Felgenhauer, Mike Haberkorn, Thomas Zilker, Horst Thiermann

  Clinical toxicology (Philadelphia, Pa.). 09/2009;

  Objective. The effects of obidoxime in the treatment of organophosphate poisoning were assessed by comparing the clinical course with its effects on laboratory parameters relevant to poisoning. InObjective. The effects of obidoxime in the treatment of organophosphate poisoning were assessed by comparing the clinical course with its effects on laboratory parameters relevant to poisoning. In this article we report clinical findings and activity of cholinesterase in plasma and acetylcholinesterase (AChE) in red blood cells. In a linked paper we describe changes in neuromuscular transmission and atropine concentrations in the same patient cohort. Methods. We studied 34 atropinized patients with severe parathion, oxydemeton methyl, and dimethoate self-poisoning who were treated with obidoxime in a standard protocol. We measured the AChE activity in blood and related it to clinical features of organophosphate poisoning. Results. Patients poisoned with parathion responded promptly to obidoxime (250 mg bolus followed by continuous infusion at 750 mg/day up to 1 week) with improvement of neuromuscular transmission and increased AChE activity. The effects were only transient in cases with the other poisons. Death (7/34) occurred late and was mostly due to complications rather than due to ongoing cholinergic crisis. Conclusions. Obidoxime appeared safe and reactivated AChE in parathion poisoning.

• Obidoxime in acute organophosphate poisoning: 2 - PK/PD relationships.

  Authors: Horst Thiermann, Franz Worek, Peter Eyer, Florian Eyer, Norbert Felgenhauer, Thomas Zilker

  Clinical toxicology (Philadelphia, Pa.). 09/2009; 47(8):807-13.

  OBJECTIVE: The effects of obidoxime in the treatment of organophosphate poisoning were assessed by biochemical and biological effect monitoring. In this article we report effects on neuromuscularOBJECTIVE: The effects of obidoxime in the treatment of organophosphate poisoning were assessed by biochemical and biological effect monitoring. In this article we report effects on neuromuscular function, oxime and atropine concentration, and relate them to acetylcholinesterase (AChE) activity. METHODS: We measured the activity of cholinesterase in plasma and AChE in red blood cells (RBC) and related these data with neuromuscular transmission analysis (ulnar nerve stimulation). Concomitantly, poison and oxon along with plasma obidoxime and atropine levels were measured at regular intervals. RESULTS: We found a close correlation between RBC-AChE activity and neuromuscular transmission and a reciprocal correlation between both the atropine maintenance dose and/or its plasma concentration. The steady state of RBC-AChE activity of reactivation and re-inhibition followed the course predicted by laboratory-determined reaction constants. CONCLUSIONS: Intense monitoring of organophosphate-poisoned patients allowed assessment of why a given obidoxime concentration was, or was not, able to counteract the re-inhibition of the RBC-AChE. RBC-AChE activity mirrors the function of n-receptor- and m-receptor-mediated cholinergic signaling as measured by neuromuscular transmission and atropine requirements.

• Treatment of severe intravenous phenytoin overdose with hemodialysis and hemoperfusion.

  Authors: Florian Eyer, Norbert Felgenhauer, Rudi Pfab, Klaus Thurmel, Thomas Zilker

  Medical science monitor : international medical journal of experimental and clinical research. 01/2009; 14(12):CS145-148.

  Background: Phenytoin is a widely used anticonvulsant agent responsible for a number of intentional and unintentional overdoses. However, besides supportive care, specific treatment recommendationsBackground: Phenytoin is a widely used anticonvulsant agent responsible for a number of intentional and unintentional overdoses. However, besides supportive care, specific treatment recommendations to enhance elimination of the parent compound have been discussed controversially and effectiveness of hemoperfusion is under debate. Case Report: A women with a prehistory of cerebral seizures was presented following a severe iatrogenic phenytoin overdose with a peak plasma concentration of 117 mg/L. A Phenytoin overdose could be contributed to both inadequate dosing and missed repeated drug monitoring. Native phenytoin body clearance failed to relevantly lower phenytoin concentration. Thus, three sessions of a four-hour long combination of activated charcoal hemoperfusion and high-flux hemodialysis were performed resulting in considerably reduced half-life during these measures of about 7-13 hours compared to the native half-life wavering between 40-100 hours. This resulted in a substantial clinical improvement in terms of central nervous system toxicity. Conclusions: Hemodiaperfusion with activated charcoal seems to be a reasonable measure for forced lowering of highly toxic phenytoin plasma concentration and should be considered especially in circumstances following intravenous overdose (e.g. inadequate iatrogenic dosing). Its narrow therapeutic range enforces strictly adequate dosing and subsequent repeated drug monitoring of phenytoin.

• Fetal Risk through Maternal Amanita phalloides Poisoning at the End of Pregnancy.

  Authors: Annette Wacker, Joachim Riethmüller, Thomas Zilker, Norbert Felgenhauer, Harald Abele, Christian Poets, Rangmar Goelz

  American journal of perinatology. 12/2008;

  There is a paucity of knowledge about prenatal and perinatal risks through maternal amatoxin poisoning. No symptoms of amatoxin intoxication, except for a slight temporary increase in liver enzymesThere is a paucity of knowledge about prenatal and perinatal risks through maternal amatoxin poisoning. No symptoms of amatoxin intoxication, except for a slight temporary increase in liver enzymes activity, occurred in a term newborn after delivery despite an AMANITA PHALLOIDES intoxication of the mother 2 days before. Considering previous reports, severe fetal intoxication may not occur during the entire pregnancy.

• Reassessment of predictors of fatal outcome in amatoxin poisoning: some critical comments.

  Authors: Martin Ganzert, Norbert Felgenhauer, Thomas Zilker

  Journal of hepatology. 10/2007; 47(3):424-5; author reply 425-6.

• Lithium poisoning: pharmacokinetics and clearance during different therapeutic measures.

  Authors: Florian Eyer, Rudolf Pfab, Norbert Felgenhauer, Jens Lutz, Uwe Heemann, Werner Steimer, Sabine Zondler, Burkhard Fichtl, Thomas Zilker

  Journal of clinical psychopharmacology. 07/2006; 26(3):325-30.

  The clinical features and pharmacokinetics of 22 lithium overdoses are described. Effectiveness of different treatment regimens regarding elimination of lithium is discussed. Origin of overdose wasThe clinical features and pharmacokinetics of 22 lithium overdoses are described. Effectiveness of different treatment regimens regarding elimination of lithium is discussed. Origin of overdose was due to deliberate poisoning or precipitated by concomitant diseases, coadministration of drugs, or combination of both. Treatment included supportive care, diuretics (15/22), hemodialysis (HD; 9/22), and mechanical ventilation (3/22). Severity of lithium intoxication was classified in 50% as I degrees, in 41% as II degrees, and in 9% as III degrees according to Hansen and Amdisen. Renal impairment on admission was diagnosed in 82% of the patients. Half-life of lithium in serum was 3.5 +/- 0.8 hours during the first HD, and 29 +/- 14 and 29 +/- 6 hours during therapy with diuretics or supportive treatment, respectively. Lithium clearance during HD was 160 +/- 15 mL/min, and renal clearance during HD or treatment with diuretics was approximately 20 and 15 +/- 9 mL/min, respectively. Renal lithium clearance was not influenced by HD therapy. There was no difference regarding half-life and clearance between the group that had an unspecific treatment or the group treated with diuretics. Hemodialysis is the therapy of choice for emergent extracorporeal lithium elimination. Renal impairment and interaction with other drugs were the main reasons for intoxication; thus, more cautious prescription or more frequent supervision of this patient group is warranted. It seems that treatment with diuretics does not have a beneficial effect in the overdose setting.

• Neither DMPS nor DMSA is effective in quantitative elimination of elemental mercury after intentional IV injection.

  Authors: Florian Eyer, Norbert Felgenhauer, Rudolf Pfab, Gustav Drasch, Thomas Zilker

  Clinical toxicology (Philadelphia, Pa.). 02/2006; 44(4):395-7.

  BACKGROUND: Intravenous injection of elemental mercury (Hg) is rare and considered relatively harmless. Treatment recommendations vary and the effectiveness of chelation therapy is controversial.BACKGROUND: Intravenous injection of elemental mercury (Hg) is rare and considered relatively harmless. Treatment recommendations vary and the effectiveness of chelation therapy is controversial. CASE REPORT: A 27-year-old man intravenously injected 1.5 mL of elemental Hg. Within 12 hours he became febrile, tachycardic and dyspneic. Physical examination was unremarkable. X-rays showed scattered radiodense deposits in the lung, heart, intestinal wall, liver and kidney. The serum Hg level on admission was 172 microg/L and peaked on day 6 at 274 microg/L. Cumulative renal elimination during a five day oral treatment period with 2,3-dimercaptopropane-1-sulfonate (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) was 8 mg and 3 mg, respectively. CONCLUSION: Although urinary excretion could be enhanced during chelation therapy, Hg deposits in organs resulted in negligible elimination of mercury compared to the exposed dose.

• Acute valproate poisoning: pharmacokinetics, alteration in fatty acid metabolism, and changes during therapy.

  Authors: Florian Eyer, Norbert Felgenhauer, Klaus Gempel, Werner Steimer, Klaus-Dieter Gerbitz, Thomas Zilker

  Journal of clinical psychopharmacology. 09/2005; 25(4):376-80.

  The clinical features, complications, and pharmacokinetics of intentional acute valproic acid (VPA) overdoses are described. Alteration in fatty acid metabolism is evaluated and therapy-inducedThe clinical features, complications, and pharmacokinetics of intentional acute valproic acid (VPA) overdoses are described. Alteration in fatty acid metabolism is evaluated and therapy-induced changes are discussed. Central nervous system features were the predominant clinical manifestations (6/6), followed by respiratory failure (5/6) and multiorgan failure (2/6). Mechanical ventilation was required in 5 of 6 patients because of respiratory depression or deep coma. Hemodialysis was applied in 4/6 of the cases due to hyperammonemia, worsening neurologic condition, or organ dysfunction. Cerebral edema and hemorrhagic pancreatitis ensued in 2/6 of the patients and ICU mortality was 2/6. VPA peak levels ranged from 520 to 1700 mg/L with a mean of 1127 mg/L. Ammonia was elevated in all cases with a mean of 550 microg/dL. All patients showed signs of impaired mitochondrial beta-oxidation with increase of medium- and long-chain acylcarnitines in serum. Severe VPA overdose is associated with a high mortality rate requiring early medical interventions. Beside supportive intensive care, hemodialysis can be considered as an adjunctive measure.

• Indication of liver transplantation following amatoxin intoxication.

  Authors: Martin Ganzert, Norbert Felgenhauer, Thomas Zilker

  Journal of hepatology. 03/2005; 42(2):202-9.

  BACKGROUND/AIMS: Indication of liver transplantation in acute liver failure following amatoxin intoxication is still uncertain. METHODS: One hundred and ninety-eight patients were studiedBACKGROUND/AIMS: Indication of liver transplantation in acute liver failure following amatoxin intoxication is still uncertain. METHODS: One hundred and ninety-eight patients were studied retrospectively. The laboratory parameters alanine-aminotransferase, serum bilirubin, serum creatinine and prothrombin index were analyzed over time. Predictors of fatal outcome and survival were determined by receiver-operating-characteristic and sensitivity-specificity analysis. RESULTS: Twenty-three patients died in the median 6.1 days (range, 2.7-13.9 days) after ingestion. Using a single parameter as predictor of fatal outcome the area under the receiver-operating-characteristic curve of prothrombin index (0.96) and serum creatinine (0.93) were both significantly greater (P<0.05) compared with serum bilirubin (0.82) and alanine-aminotransferase (0.69). Prediction of fatal outcome had an optimum, if a prothrombin index less than 25% was combined with a serum creatinine greater than 106 micromol/l from day 3 after ingestion onwards (sensitivity 100%, 95% confidence interval 87-100; specificity 98%, 95% confidence interval 94-100). The median time period between the first occurrence of this predictor in non-survivors and death was 63h (range, 3-230h). CONCLUSIONS: A decision model of liver transplantation following amatoxin intoxication using prothrombin index in combination with serum creatinine from day 3 to 10 after ingestion enables an early and reliable assessment of outcome.

• Acute endosulfan poisoning with cerebral edema and cardiac failure.

  Authors: Florian Eyer, Norbert Felgenhauer, Elisabeth Jetzinger, Rudolf Pfab, Thomas R Zilker

  Journal of toxicology. Clinical toxicology. 02/2004; 42(6):927-32.

  BACKGROUND: Organochlorine insecticides are highly toxic compounds that are responsible for a number of severe intoxications worldwide with several deaths. Despite their widespread use in agricultureBACKGROUND: Organochlorine insecticides are highly toxic compounds that are responsible for a number of severe intoxications worldwide with several deaths. Despite their widespread use in agriculture during the 1940s to 1960s and the well-known signs and symptoms of intoxication, the clinical picture in case of poisoning varies. We report two cases of acute intentional endosulfan intoxication with cerebral edema and cardiac failure. CASE REPORTS: Both cases developed life-threatening signs like epileptic state, respiratory insufficiency and hemodynamic instability soon after ingestion. The survivor developed severe myocardial insufficiency and pulmonary edema documented by echocardiography and x-ray of the chest. The deceased patient developed severe cerebral edema and multiorgan failure ten days after ingestion of Thiodan 35. The peak serum concentration of endosulfan in the survivor was 0.12 mg/L approximately 23 hours after ingestion, whereas the peak blood concentration in the fatal case was 0.86 mg/L approximately 25 hours post-ingestion. Post-mortem endosulfan levels in different organs were determined. CONCLUSION: Endosulfan is a highly toxic organochlorine insecticide that produces well-known neurological symptoms of tonic-clonic convulsions, headache, dizziness and ataxia but also can cause gastrointestinal symptoms and metabolic disturbances. Life-threatening cerebral edema and hemodynamic instability may occur. Treatment is symptomatic and supportive.

• Human parathion poisoning. A toxicokinetic analysis.

  Authors: Florian Eyer, Veronika Meischner, Daniela Kiderlen, Horst Thiermann, Franz Worek, Michael Haberkorn, Norbert Felgenhauer, Thomas Zilker, Peter Eyer

  Toxicological reviews. 02/2003; 22(3):143-63.

  The mortality rate of suicidal parathion poisoning is particularly high, the onset of fulminant cholinergic signs, and the patients frequently present to the emergency physician with life-threateningThe mortality rate of suicidal parathion poisoning is particularly high, the onset of fulminant cholinergic signs, and the patients frequently present to the emergency physician with life-threatening symptoms. Despite this uniformity, subsequent clinical course differs significantly among patients, mostly not as a result of different delays in treatment or insufficiency of primary care. Probably, the differences depend on the amount of poison absorbed and/or the disposition of the active poison, paraoxon. We followed the toxicokinetics of parathion and tried to quantify the actual poison load. To this end, we monitored parathion-intoxicated patients (patients requiring artificial ventilation) for plasma levels of parathion and paraoxon along with the activity of erythrocyte acetylcholinesterase and its reactivatability. Plasma obidoxime concentrations were followed as well as the cumulative urinary para-nitrophenol conjugate excretion as a measure of total poison load. All patients received a standard obidoxime scheme of a 250 mg bolus dose intravenously, followed by continuous infusion with 750 mg per 24 hours as long as reactivation could be expected (usually 1 week). All other treatment was instituted as judged by the physician. It was recommended to use atropine at low doses to achieve dry mucous membranes, no bronchoconstriction and no bradycardia. Usually 1-2 mg/h were sufficient. Seven selected cases are presented exemplifying toxicokinetic peculiarities. All patients were severely intoxicated, while the amount of parathion absorbed varied widely (between 0.12 and 4.4 g; lethal dose 0.02-0.1 g) and was generally much lower than anticipated from the reports of relatives. It remains open whether the discrepancies between reports and findings were due to exaggeration or to effective decontamination (including spontaneous vomiting, gastric lavage and activated charcoal). Absorption of parathion from the gastrointestinal tract was sometimes retarded, up to 5 days, resulting in fluctuating plasma profiles. The volume of distribution at steady-state (Vdss) of parathion was around 20 L/kg. Post-mortem analysis in one patient revealed a 66-fold higher parathion concentration in fat tissue compared with plasma, 16 days after ingestion. Biotransformation of parathion varied widely and was severely retarded in one patient receiving fluconazole during worsening of renal function, while phenobarbital (phenobarbitone) sedation (two cases) had apparently no effect. The proportion of plasma parathion to paraoxon varied from 0.3-30, pointing also to varying paraoxon elimination, as illustrated by one case with particularly low paraoxonase-1 activity. Obidoxime was effective at paraoxon concentrations below 0.5 microM, provided aging was not too advanced. This concentration correlated poorly with the paration concentration or the poison load. The data are discussed in light of the pertinent literature.

• Studies of strontium biokinetics in humans. Part 2: uptake of strontium from aqueous solutions and labelled foodstuffs.

  Authors: Vera Höllriegl, Pascale Louvat, Eckhard Werner, Paul Roth, Peter Schramel, Iris Wendler, Norbert Felgenhauer, Thomas Zilker

  Radiation and environmental biophysics. 01/2003; 41(4):281-7.

  The accidental release of radioactive isotopes of strontium, mainly (90)Sr, into the environment and its transfer into the biosphere results in an internal radiation exposure of the affectedThe accidental release of radioactive isotopes of strontium, mainly (90)Sr, into the environment and its transfer into the biosphere results in an internal radiation exposure of the affected population. In order to obtain reliable estimates of the committed dose due to an intake of Sr radionuclides, reliable information on its metabolic behaviour inside the human body is needed, i.e. biokinetic data on fractional uptake from contaminated foodstuffs, distribution to and retention in different organs and tissues of the human body. Such information can be obtained by tracer kinetic investigations. The committed effective dose is dependent on the fractional intestinal absorption of the ingested activity (f(1) value). The International Commission on Radiological Protection in its publication ICRP 67 adopted an f(1) value of 0.3 for adults. This study is aimed at investigating if the value corresponds with the actual uptake from contaminated foodstuffs. Aqueous solutions and contaminated vegetables, i.e. cress and salad (lettuce) were used as test materials. For this purpose, the methodology for intrinsic labelling of foodstuffs described in part 1 was applied. For aqueous solutions, a mean f(1) value of 0.63+/-0.14 (mean +/- SD) was obtained by administering 1 mg of strontium. The uptake of Sr from cress intrinsically labelled with about 1 mg Sr almost corresponds to that from aqueous solutions (f(1)=0.62+/-0.10), but from lettuce it is reduced by a factor of 2 (f(1)=0.27+/-0.08).

• Carbamazepine and valproate as adjuncts in the treatment of alcohol withdrawal syndrome: a retrospective cohort study.

  Authors: Florian Eyer, Meike Schreckenberg, Daniela Hecht, Krisztina Adorjan, Tibor Schuster, Norbert Felgenhauer, Rudi Pfab, Tim Strubel, Thomas Zilker

  Alcohol and alcoholism (Oxford, Oxfordshire). 46(2):177-84.

  To compare the clinical course, incidence of withdrawal seizures (WS) or delirium tremens (DT) and side effects during treatment of alcohol withdrawal in patients treated with either carbamazepineTo compare the clinical course, incidence of withdrawal seizures (WS) or delirium tremens (DT) and side effects during treatment of alcohol withdrawal in patients treated with either carbamazepine (CBZ) or valproate (VPA) as an adjunct to clomethiazole and clonidine therapy. Retrospective analysis of charts of two cohorts of inpatients treated during 2000-2009: CBZ 374 patients, VPA 453 patients. At baseline, those treated with VPA and those treated with CBZ were similar except for a trend to younger age and a higher incidence of previous WS in the CBZ group. The median duration of pharmacological treatment (91 vs. 76 h; P < 0.001) and the length of stay (8 vs. 6 days; P < 0.001) as well as the need for intensive care treatment (7 vs. 2%; P = 0.001) were significantly higher in the CBZ than the VPA group. Additionally, withdrawal-related complications such as WS occurred more often in the CBZ group (9.6 vs. 5.5%; not significant after adjusting for potential confounders); the incidence of DT in the CBZ group was insignificantly higher (6.6 vs. 4.4%; P = 0.52). Admittance with seizures and older age were predictors of WS and DT, respectively. Adverse drug reactions, mainly affecting the central nervous system, were significantly more frequent with CBZ than VPA (7.6 vs. 2%; P < 0.001). During alcohol withdrawal, VPA may offer some benefits compared with CBZ due to favorable tolerability, possibly less incidence of WS and a shorter duration of pharmacological treatment.

• Risk assessment of moderate to severe alcohol withdrawal--predictors for seizures and delirium tremens in the course of withdrawal.

  Authors: Florian Eyer, Tibor Schuster, Norbert Felgenhauer, Rudi Pfab, Tim Strubel, Bernd Saugel, Thomas Zilker

  Alcohol and alcoholism (Oxford, Oxfordshire). 46(4):427-33.

  To develop a prediction model for withdrawal seizures (WS) and delirium tremens (DT) during moderate to severe alcohol withdrawal syndrome (AWS) in a large cohort of inpatients treated for AWS (n =To develop a prediction model for withdrawal seizures (WS) and delirium tremens (DT) during moderate to severe alcohol withdrawal syndrome (AWS) in a large cohort of inpatients treated for AWS (n = 827). Re-analysis of a cohort study population treated between 2000 and 2009. All patients received a score-guided and symptom-triggered therapy for AWS. Multivariable binary logistic regression models with stepwise variable selection procedures were conducted providing odds ratio (OR) estimates. In the multivariable regression, significant predictors of WS during AWS therapy were a delayed climax of withdrawal severity since admission [OR/10 h: 1.23; 95% confidence interval (CI): 1.1-1.4; P < 0.001)], prevalence of structural brain lesions in the patient's history (OR 6.5; 95% CI: 3.0-14.1; P < 0.001) and WS as the cause of admittance (OR 2.6; 95% CI: 1.4-4.8; P = 0.002). Significant predictors at admission for the occurrence of DT were lower serum potassium (OR/1 mmol/l 0.33; 95% CI: 0.17-0.65; P = 0.001), a lower platelet count (OR/100.000 0.42; 95% CI: 0.26-0.69; P = 0.001) and prevalence of structural brain lesions (OR 5.8; 95% CI: 2.6-12.9; P < 0.001). In this large retrospective cohort, some easily determinable parameters at admission may be useful to predict a complicated course of alcohol withdrawal regarding the occurrence of WS or DT. Using the provided nomograms, clinicians can estimate the percentage likelihood of patients to develop either WS or DT during their course of withdrawal. Prevalence of structural brain lesions in the patient's history does strongly warrant a careful observation of patients.