No additional neuroprotection provided by barbiturate-induced burst suppression under mild hypothermic conditions in rats subjected to reversible focal ischemia.

Westermaier T, Zausinger S, Baethmann A, Steiger HJ, Schmid-Elsaesser R.

Department of Neurosurgery and Institute for Surgical Research, Klinikum Grosshadern, Ludwig Maximilians University, Munich, Germany.

OBJECT: Mild-to-moderate hypothermia is increasingly used for neuroprotection in humans. However, it is unknown whether administration of barbiturate medications in burst-suppressive doses-the gold standard of neuroprotection during neurovascular procedures-provides an additional protective effect under hypothermic conditions. The authors conducted the present study to answer this question. METHODS: Thirty-two Sprague-Dawley rats were subjected to 90 minutes of middle cerebral artery occlusion and randomly assigned to one of four treatment groups: 1) normothermic controls; 2) methohexital treatment (burst suppression); 3) induction of mild hypothermia (33 degrees C); and 4) induction of mild hypothermia plus methohexital treatment (burst suppression). Local cerebral blood flow was continuously monitored using bilateral laser Doppler flowmetry and electroencephalography. Functional deficits were quantified and recorded during daily neurological examinations. Infarct volumes were assessed histologically after 7 days. Methohexital treatment, mild hypothermia, and mild hypothermia plus methohexital treatment reduced infarct volumes by 32%, 71%, and 66%, respectively, compared with normothermic controls. Furthermore, mild hypothermia therapy provided the best functional outcome, which was not improved by additional barbiturate therapy. CONCLUSIONS: The results of this study indicate that barbiturate-induced burst suppression is not required to achieve maximum neuroprotection under mild hypothermic conditions. The magnitude of protection afforded by barbiturates alone appears to be modest compared with that provided by mild hypothermia.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11059666&dopt=Abstract barbiturate Butalbital Fioricet





Shoulder-hand syndrome in neurosurgical patients treated with barbiturates. A long term evaluation.

De Santis A, Ceccarelli G, Cesana BM, Bello L, Spagnoli D, Villani RM.

Institute of Neurosurgery, University of Milan, Ospedale Maggiore, IRCCS, Italy.

OBJECTIVES: To assess the incidence of shoulder-hand syndrome (SHS) in neurosurgical patients (head injuries, intracranial ruptured aneurysms and intracranial meningiomas), treated with barbiturates. SHS is a chronic condition characterized by intense tenderness and functional impairment affecting one hand, the shoulder or both. Barbiturates have been identified as cause of SHS, although there is controversial evidence on the incidence of this disorder in patients started on long-term Phenobarbital (PB) therapy. METHODS: One hundred and twenty-six neurosurgical patients, treated with barbiturates, and a control group of 108 patients, treated with carbamazepine or phenytoin, were enrolled. Both groups were followed up for at least 24 to 36 months. RESULTS: Thirty-five PB-treated patients (27.6%) experienced SHS. In these patients SHS developed during the first 7 months of therapy and regressed after PB discontinuation or, in 2 cases, after dosage reduction. None of the patients in the control group developed SHS. CONCLUSIONS: The occurrence of SHS in the study group was much more common than that reported previously. This higher incidence should depend upon the coexistence of separate risk factors such as age over 50 years, surgery and intracranial pathology. Early diagnosis and rapid withdrawl of treatment are important for symptomatic relief and full functional recovery.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11105834&dopt=Abstract barbiturate Butalbital Fioricet





New fluorescence polarization immunoassays for analysis of barbiturates and benzodiazepines in serum and urine: performance characteristics.

Schwenzer KS, Pearlman R, Tsilimidos M, Salamone SJ, Cannon RC, Wong SH, Gock SB, Jentzen JJ.

Roche Diagnostic Systems, Somerville, New Jersey 08876, USA.

The performance of the new fluorescence polarization immunoassay reagents Cassette COBAS INTEGRA Serum Benzodiazepines assay (SBENZ) and Cassette Serum Barbiturates assay (SBARB) was evaluated as compared to other immunoassays (Abbott TDx Serum Benzodiazepines, Abbott TDx Urine Benzodiazepines, Behring EMIT Serum Benzodiazepines, Abbott ADx Serum Barbiturates, Behring EMIT Serum Barbiturates, and the COBAS INTEGRA Barbiturates (BARB) urine assay) and gas chromatography-mass spectrometry (GC-MS). Recoveries of nordiazepam and secobarbital using the SBENZ and SBARB assays, respectively, were equivalent for serum, plasma, and urine. Cross-reactivities of structurally related benzodiazepines, barbiturates, and their metabolites were very similar in serum and urine for the SBENZ and SBARB assays. Precision was within 5.4% for SBENZ serum and within 11% from 10 to 100 ng/mL for urine. Precision was within 5% for SBARB serum and within 7% from 136 to 277 ng/mL for the urine application. The standard curves for SBENZ and SBARB were stable for at least 16 weeks with the reagents stored open on the COBAS INTEGRA analyzer. Clinical comparison of the SBENZ serum assay indicated an increased pickup rate, as confirmed by GC-MS, compared to TDx and EMIT. The diagnostic sensitivities of the SBENZ serum application, TDx, and EMIT versus GC-MS were 100%, 89%, and 36%, respectively. The diagnostic specificities were 71%, 79%, and 100%, respectively. The diagnostic sensitivities of the SBENZ urine application and TDx versus GC-MS were 100% and the diagnostic specificities were 88%. The increased positive pick-up of the SBENZ assay compared to the other immunoassays is most probably due to the difference in the limit of detection (LOD) and the increased cross-reactivity for the low-dose benzodiazepines. Clinical comparison of the SBARB serum assay indicated an increased positive pick-up rate, as confirmed by GC-MS. The diagnostic sensitivities of the SBARB serum application, ADx, and EMIT versus GC-MS were 96%, 65%, and 35%, respectively. The diagnostic specificities were all 100%. The diagnostic sensitivities for the SBARB urine application and BARB versus GC-MS were all 100%, and the diagnostic specificities were all 91%. The SBENZ and SBARB kits demonstrated increased sensitivity for the detection of benzodiazepines and barbiturates in both serum and urine compared to the other immunoassays.

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Is there an indication for the use of barbiturate-containing analgesic agents in the treatment of pain? Guidelines for their safe use and withdrawal management. Canadian Pharmacists Association.

McLean W, Boucher EA, Brennan M, Holbrook A, Orser R, Peachey J, Sellers E.

Ottawa Hospital, General Campus, Ottawa, Canada.

OBJECTIVE: To provide medical and pharmaceutical practitioners with information on the effectiveness, safety and risks associated with barbiturate-containing analgesic (BCA) agents and an approach to management of withdrawal from BCAs. METHODS: The benefits of using BCAs in the treatment of pain (compared with using non-BCAs) were weighed against potential risks. The procedures for discontinuation of BCAs in patients with pain were considered, and evidence showing that BCAs constitute a public health risk was reviewed. The evidence serving as the basis for the clinical guidelines was compiled from a number of sources, including key papers in the field, published and unpublished papers, and reports by Addiction Research Foundation researchers, a MEDLINE search from 1967 to November 1996, and communication with Canadian manufacturers of BCAs. RESULTS: There is no evidence that there is a clinically important enhancement of analgesic efficacy of BCAs due to the barbiturate constituent. No epidemiological studies on the relative frequency of abuse and dependence, or studies that have analyzed combination product use from a public health and social benefit to risk perspective, have been published to clarify the issues about the nature, extent and seriousness of these problems. RECOMMENDATIONS: No evidence exists to show a clinically important enhancement of analgesic efficacy of BCAs due to the barbiturate constituents. Because BCAs do not have a therapeutic advantage, there is no clinical reason to choose such a combination product when a simpler and often less expensive analgesic formulation (eg, acetaminophen, acetylsalicylic acid, nonsteroidal anti-inflammatory drug or narcotic) or a more specific anti-migraine drug (eg, dihydroergotamine or sumatriptan) is available. BCAs should be avoided in elderly people and should not be used in children. Extrapolation from published reports on abuse and withdrawal syndrome with these drugs suggests that BCAs have the potential to produce drug dependence and addictive behaviour, especially with regular use. In BCA overdose, the barbiturate component is only one of the clinically significant contributors to any morbidity, but its presence can complicate the management of additive or synergistic toxicities. Therefore, there is no reason to choose a combination product when a simpler product may be a safer alternative by minimizing the potential for addiction and the occurrence of additive side effects or toxicities. It is further recommended that prescribers re-evaluate treatment for patients using BCAs. Recommendations for withdrawal are provided, based on estimated consumption.

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