Once versus individualized multiple daily dosing of aminoglycosides in critically ill patients

The purpose of this study was to evaluate the once daily dosing [ODD] program in critically ill Egyptian patients compared to individualized multiple daily dosing [MDD] in terms of clinical and bacteriological efficacy. In addition, the incidence of nephrotoxicity associated with both regimens in this specific group of patients was assessed. Fifty-two patients with suspected or confirmed bacterial infections admitted to the Critical Care Medicine Department, Kasr El-Aini-Cairo University Hospitals comprised the study population. The amikacin group [30 patients] was sub-divided into 14 patients receiving amikacin ODD [1 g i.v.] and 16 patients receiving amikacin in MDD [500 mg i.v./dose]. The gentamicin group [22 patients] was sub-divided into 10 patients receiving the drug ODD [240 mg i.v.] and 12 patients receiving gentamicin MDD [80 mg i.v./dose]. Amikacin or gentamicin serum levels were determined by the enzyme multiplied immunoassay technique using Emit 2000. MDD regimen was adjusted based on the individual pharmacokinetic parameters using the Sawchuk-Zaske method. There was no significant difference between the two dosing regimens with regard to clinical and antibacterial efficacy or incidence of nephrotoxicity of both gentamicin and amikacin groups. In the ODD regimen, duration of treatment had no effect on increasing incidence of nephrotoxicity unlike the individualized MDD regimen. No dose adjustments were needed in the once daily dosing regimen since trough concentrations have never been above toxic level. The study showed that the ODD regimen is preferred in critically ill patients to individualized MDD as shown by comparable efficacy, nephrotoxicity and lesser need for therapeutic drug monitoring and frequent dose adjustments required in the individualized MDD regimen

Non-invasive fibrosis seromarkers as a predictor of liver fibrosis in chronic hepatitis C and/or non-alcoholic steatohepatitis

In patients with chronic hepatitis C, the precise stage of hepatic fibrosis is the most important predictor of disease progression and it determines the need for antiviral therapy. Although liver biopsy is acknowledged as the gold standard for evaluating fibrosis, it is occasionally prone to sampling error and complications. We aimed to correlate an index of biochemical markers with histological features of fibrosis to predict hepatic fibrosis in patients with chronic hepatitis C virus, patients with combined hepatitis C virus and non-alcoholic steatohepatitis and those with non-alcoholic steatohepatitis, aiming to reduce the use of the liver biopsy. Out of those attending our out patient clinic for clinical, haematological, biochemical, virological, histological and ultrasonographic assessment prior to interferon therapy for hepatitis C virus, we enrolled 41 patients and grouped them according to histopathological examination of their liver biopsies into: Group I: 21 chronic hepatitis C virus patients as defined by positive 3rd generation ELISA; Group II: 20 patients with combined hepatitis C virus and NASH. We added a third group [Group III] of 15 patients having non alcoholic steatohepatitis as defined clinically, biochemically and through diagnostic percutanous liver biopsy. There were 33 male 23 female patients; 35 [62.5%] of them were from rural areas and 21 [37.5%] were from urban areas; the mean ages were 40.5 +/- 9, 46.6 +/- 7.7 and 42.13 +/- 11.06 in Group I, II and III respectively. Twenty apparently healthy individuals served as the control group. All the patients and the control group were submitted to full clinical history and examination, abdominal ultrasonography, CBC, liver biochemical profile and fibrosis biomarkers [apolipoprotein A1, haptoglobin, alpha2 marcoglobulin, GGT]. Liver biopsy was done for suitable patients after taking a consent and the results of fibrosis seromarkers were compared with the results of liver biopsy using the Metavir scoring system, We also estimated patients' body mass index, fasting and post prandial blood glucose. We excluded patients with other causes of chronic liver disease and co-morbidities that could confound the results of the non-invasive markers adopted, including schistosomiasis which was excluded by serological test. 43% of Group I and 40% of Group II had advanced fibrosis. None of Group III had advanced fibrosis; mild fibrosis was detected in 80% of them. gamma-GT was found positively correlated to the degree of hepatic fibrosis in Groups I, II and III [r = 0.667, 0.656 and 0.121, respectively] with P values of 0.001, 0.002, 0.668, respectively. alpha2 macroglobulin was found to be a reliable predictor of fibrosis [r = 0.30, P = 0.02] with ROC curve [area under the curve = 0.70] best cutoff value 2.55 g/L with sensitivity of 0.80 and specificity of 0.50. The results of haptoglobin were negatively related to the degree of hepatic fibrosis in Group I and II with ROC curve area under the curve of 0.33 and P value of 0.04. Significant direct correlation was seen in Group III [r = 0.55, P = 0.03], so by regression analysis, haptoglobin can be used as a good predictor for fibrosis in Group III [r = 0.54, P=0.04]. Apolipoprotein A1 has negative correlation to the stage of fibrosis in Groups I and II although the results were statistically insignificant. APRI index was found significantly directly correlated to the fibrosis stage and the grade of inflammation of all studied groups [r= 0.57, P< 0.01 and r = 0.36, P< 0.01, respectively] with a best cutoff value of 0.62, with sensitivity of 0.86 and specificity of 0.57. In patients with advanced fibrosis the best cutoff value was found to be 0.72 with sensitivity of 0.94 and specificity of 0.67. Mordified APRI test showed AUC of 0.79 [P<0.01] with a best cutoff value of 0.067 at which sensitivity and specificity were 0.82 and 0.61, respectively. Alpha macroglobulin, haptoglobin, apolipoprotein A1, APRI index and a modified APRI index, were found be significant predictors of hepatic fibrosis and were reprocessed by stepwise logistic regression

Evaluation of beneficial effects of steroids in head trauma

Road traffic crashes account for most serious head injuries, and the global burden of head injury can be expected to rise with the increasing use of vehicles in Asia and Africa. The overall incidence of adrenal insufficiency in critically ill patients approximates 30%, with an incidence as high as 50 to 60% in patients with septic shock. To re-evaluate the beneficial effects of I.V. steroids [dexamethasone], for 48 hours in the critically ill head trauma patients; to assess the prevalence of adrenal insufficiency in the critically ill head trauma patients, its relation to the seventy of the lesion and outcome. Prospective randomized controlled study, included 19 cases [patients who received I.V. steroids 8mg dexamethasone within 8 hours of injury, every 8 hours for 48 hours and 22 controls [patients who did not receive steroids]. 10.53% of cases died compared to 18.18%. of controls, the difference was not statistically significant, impaired circadian rhythm defined as p.m./a.m. cortisol >0.5 was found in 84% of mild head trauma, 80% moderate head trauma and 66.67% of severe head trauma, a.m. and p.m. cortisol levels were higher in moderate than mild TBI and the difference was statistically significant p-values 0.006 and 0.023 respectively. Altered circadian rhythm and adrenal insufficiency is common among critically ill head trauma patients, steroids resulted in decreased mortality among patients who received steroids and among patients with adrenal insufficiency who received steroids, however, the difference was not statistically significant

Pharmacogenetics oriented therapeutic drug monitoring of digoxin in critically ill patients

This study was performed to outline the different MDR-1 [Multi-Drug Resistance-1] genotypes in a sample of 37 Egyptian patients suffering from atrial fibrillation [AF] and/or congestive heart failure [CHF] and are using digoxin, to assess the role of MDR-1 genotypes polymorphism in affecting steady state serum digoxin therapeutic levels, and studying the consequences on patients' clinical outcome. Two venous blood samples were drawn from each patient; the 1[st] sample was taken, on admission, for DNA extraction and genotyping and the 2 [nd] was taken, 6 hours post dose after reaching steady state concentration, for serum digoxin assay. Serum digoxin. levels were assayed using EMIT 2000 analyzer, and MDR-1 genotyping was done using polymerase chain reaction-restriction fragment length polymorphism [PCR-RFLP] technique. Twenty patients [54.1%] showed serum digoxin levels within the therapeutic range, 12 patients [32.4%] showed serum digoxin levels under the minimum effective concentration [p< 0.9 ng/ml], while 5 patients [13.5%] showed serum digoxin levels over maximum safety concentration [> 2 ng/ml], with P value of 0.0001 among the three groups. MDR-1 genotyping revealed ten patients [27%] carrying the homozygous mutant TT genotype, 27 patients [73%] carrying the heterozygous mutant CT genotype, with no patient showing the wild CC genotype. Allelic distribution showed 42% for the wild type C allele while 58% for the homozygous mutant T allele. Patients carrying the homozygous mutant TT genotype showed significantly lower serum digoxin levels compared with those carrying the heterozygous mutant CT genotype [P value: 0.009]. Patients with significant improvement carried the CT genotype and had serum digoxin levels within the therapeutic range. In conclusion, patients with different MDR-1 genotypes had variations in their serum digoxin levels and identification of MDR-1 variations was found useful in predicting therapy outcome. We recommend further extensive work on large samples to study the important role of MDR-1 gene in affecting the disposition of different substrates, to be able for individualizing them according to the patients' genetic profile in order to improve drug therapy and reduce inter-patient variability