Withdrawal-induced delirium associated with a benzodiazepine switch: a case report

<p>Abstract</p> <p>Introduction</p> <p>Introduced in the early 1960s, diazepam remains among the most frequently prescribed benzodiazepine-type sedatives and hypnotics. Patients with chronic use of short-acting benzodiazepines are frequently switched to diazepam because the accumulating, long-acting metabolite, N-desmethyl-diazepam, prevents benzodiazepine-associated withdrawal symptoms, which can occur during trough plasma levels of short-acting benzodiazepines. Although mild to moderate withdrawal symptoms are frequently observed during benzodiazepine switching to diazepam, severe medical complications associated with this treatment approach have thus far not been reported.</p> <p>Case presentation</p> <p>A 64-year-old female Caucasian with major depression, alcohol dependence and benzodiazepine dependence was successfully treated for depression and, after lorazepam-assisted alcohol detoxification, was switched from lorazepam to diazepam to facilitate benzodiazepine discontinuation. Subsequent to the benzodiazepine switch, our patient unexpectedly developed an acute delirious state, which quickly remitted after re-administration of lorazepam. A newly diagnosed early form of mixed dementia, combining both vascular and Alzheimer-type lesions, was found as a likely contributing factor for the observed vulnerability to benzodiazepine-induced withdrawal symptoms.</p> <p>Conclusion</p> <p>Chronic use of benzodiazepines is common in the elderly and a switch to diazepam often precedes benzodiazepine discontinuation trials. However, contrary to common clinical practice, benzodiazepine switching to diazepam may require cross-titration with slow tapering of the first benzodiazepine to allow for the build-up of N-desmethyl-diazepam, in order to safely prevent severe withdrawal symptoms. Alternatively, long-term treatment with low doses of benzodiazepines may be considered, especially in elderly patients with chronic use of benzodiazepines and proven vulnerability to benzodiazepine-associated withdrawal symptoms.</p

Genetic Variations and Haplotype Diversity of the UGT1 Gene Cluster in the Chinese Population

Vertebrates require tremendous molecular diversity to defend against numerous small hydrophobic chemicals. UDP-glucuronosyltransferases (UGTs) are a large family of detoxification enzymes that glucuronidate xenobiotics and endobiotics, facilitating their excretion from the body. The UGT1 gene cluster contains a tandem array of variable first exons, each preceded by a specific promoter, and a common set of downstream constant exons, similar to the genomic organization of the protocadherin (Pcdh), immunoglobulin, and T-cell receptor gene clusters. To assist pharmacogenomics studies in Chinese, we sequenced nine first exons, promoter and intronic regions, and five common exons of the UGT1 gene cluster in a population sample of 253 unrelated Chinese individuals. We identified 101 polymorphisms and found 15 novel SNPs. We then computed allele frequencies for each polymorphism and reconstructed their linkage disequilibrium (LD) map. The UGT1 cluster can be divided into five linkage blocks: Block 9 (UGT1A9), Block 9/7/6 (UGT1A9, UGT1A7, and UGT1A6), Block 5 (UGT1A5), Block 4/3 (UGT1A4 and UGT1A3), and Block 3′ UTR. Furthermore, we inferred haplotypes and selected their tagSNPs. Finally, comparing our data with those of three other populations of the HapMap project revealed ethnic specificity of the UGT1 genetic diversity in Chinese. These findings have important implications for future molecular genetic studies of the UGT1 gene cluster as well as for personalized medical therapies in Chinese

Predictive Value of Skin Color for Illness Severity in the High-Risk Newborn

The relationship between skin color and illness severity in the newborn remains untested. We have evaluated the predictive value of skin color readings for illness severity in a population of high-risk newborn infants. A prospective study was conducted on 107 white newborns in the intensive care unit, which were categorized as either high or low severity of illness, defined by the presence of severe neonatal morbidity. Illness severity was also determined using a Score for Neonatal Acute Physiology (SNAP). Color readings were obtained at 10 different body sites using a portable tristimulus colorimeter during the first 24 h, and color was expressed using the standard CIE L*a*b* system. Skin CIE b* values were significantly lower in the high severity group (p 0.0001), and a significant inverse correlation with SNAP was observed (rs range, 0.37 to 0.71, p 0.0001). In particular a low b* value for the abdomen was found to be a significant predictor of illness severity (92.6% sensitivity; 96.6% specificity; 96% positive predictive value; 93.7% negative predictive value; adjusted odds ratio, 14.7; 95% confidence interval, 6.4 to 33.8). Our findings indicate that skin color reflects clinical severity in the newborn and that skin colorimetry can accurately identify higher risk infants

Avaliação da hemorragia feto-materna em puérperas com indicação para ministração de imunoglobulina anti-D Evaluation of fetomaternal hemorrhage in postpartum patients with indication for administration of anti-D immunoglobulin

Avaliamos a ocorrência da hemorragia feto-materna entre 343 puérperas que receberiam profilaxia da aloimunização Rh com emprego de imunoglobulina anti-D. Realizamos o teste de roseta para triagem dos casos que necessitariam determinação quantitativa do volume de sangue fetal transferido para circulação materna, que foi então apurado pelo teste de Kleihauer-Betke (K-B). O teste de roseta apresentou resultado positivo em 22 casos (6,4%). Em cinco dessas amostras o teste de K-B não apontou hemorragia feto-materna (falso positivo do teste de roseta de 1,45%) e noutra a leitura do teste não foi conclusiva. Tivemos oito casos com volume apurado de hemorragia feto-materna < 10ml (2,3%), seis com hemorragia feto-materna entre 10 e 30ml (1,7%) e duas puérperas apresentaram transferência sangüínea feto-materna maior que 30ml (0,58%), necessitando suplementação além da dose padrão de anti-D. O teste de roseta dispensou 93,6% das pacientes da avaliação adicional da hemorragia feto-materna por método quantitativo.<br>This study evaluated fetomaternal hemorrhage (FMH) in 343 postpartum patients who required prophylaxis of Rh alloimmunization with anti-D immunoglobulin. The rosette test was applied to screen for patients needing quantitative determination of fetal blood transferred from the maternal circulation, which was then measured by the Kleihauer-Betke test (K-B). The rosette test was positive in 22 cases (6.4%). In five of these cases, K-B did not show fetomaternal hemorrhage (a 1.45% false-positive rate for the rosette test), and in one case the test was inconclusive. There were 8 cases with FMH < 10ml (2.3%), 6 cases with FMH from 10 to 30ml (1.7%), and two cases with FMH > 30ml (0.58%), requiring a supplementary dose of anti-D. The study concludes that following the rosette test, additional evaluation of FMH using a quantitative test was unnecessary in 93.6% of the cases