Optimal regimen of levetiracetam for prevention of busulfan-induced seizure in patients undergoing hematopoietic stem cell transplantation: A review of available evidence.

OBJECTIVE: This review aimed to summarize the available data and offer a practical recommendation regarding the optimal regimen of levetiracetam (LEV) for the prevention of busulfan-induced seizure (BIS) in patients undergoing hematopoietic stem cell transplantation (HSCT). DATA SOURCES: Published articles by searching databases (PubMed, Google Scholar, Cochrane Library, ScienceDirect) were reviewed. All types of original studies performed in pediatric and adult populations have been investigated and required data was extracted. DATA SUMMARY: Eleven articles were eligible to be included in this review. A loading dose was not used in any of the studies. LEV had been started from 6 to 48 h before busulfan (Bu) initiation and continued up to 24 to 48 h after its termination. The dose range of LEV was 10 to 20 mg/kg/day divided every 12 h in pediatrics and 500 to 1000 mg twice daily in adults. Both oral and intravenous (IV) routes of administration were used. Except for three studies, no seizure had occurred in patients who had received LEV. CONCLUSIONS: Considering the available evidence, LEV with the dose range from 500 to 1000 mg twice daily in adults and 10 mg/kg twice daily (20 mg/kg/day in 2 divided doses) in children orally or IV started from 6 to 24 h before Bu initiation up to 24 to 48 h after the last dose of Bu seems to prevent BIS appropriately. More prospective clinical trials with a larger population are needed to validate the optimal dosing of LEV for BIS prophylaxis in patients undergoing HSCT.

Evaluation of the Effectiveness of an Herbal Formulation of Boswellia sacra Flueck. In Improving Cognitive and Behavioral Symptoms in Patients with Cognitive Impairment and Alzheimer's Disease.

Objective: This study aimed to assess the efficacy of an herbal formulation based on Boswellia sacra in improving cognitive and behavioral symptoms in patients with mild cognitive impairment (MCI) and mild-to-moderate stages of Alzheimer's disease (AD). Methods: A 3-month, parallel-group, placebo-controlled trial was implemented from October 2021 to April 2022. Patients with MCI and mild-to-moderate stages of AD aged above 50 years (n = 60; 40 women, 20 men) enrolled in the study using clinical diagnosis and a score of 10-30 on the mini-mental state examination (MMSE) test. They were assigned into two groups; one receiving a herbal formulation) include B. sacra, Melissa officinalis, Piper longum, Cinnamomum verum, and Physalis alkekengi) three times a day and the other receiving a placebo for 3 months. The main efficacy measures were the changes in cognitive domains based on the MMSE and changes in behavioral and psychiatric symptoms based on neuropsychiatric inventory (NPI) scores compared with baseline. Side effects were also recorded. Findings: Results of this study showed significant differences between the two groups after 3 months in terms of all the assessed variables, including the overall result of the mean score of MMSE and NPI tests (P ≤ 0.001). The herbal formulation had the most considerable effects on the domains of orientation, attention, working memory, delay recall, and language of the MMSE test. Conclusion: Herbal formulation based on B. sacra was significantly effective compared to a placebo in improving cognitive and behavioral symptoms in patients with MCI and mild-to-moderate AD.

High-dose amikacin for achieving serum target levels in critically ill elderly patients.

INTRODUCTION: To achieve target concentrations, the application of higher-than-standard doses of amikacin is proposed for the treatment of sepsis due to an increase in volume of distribution and clearance, but little data are available on aminoglycoside administration in critically ill elderly patients. PATIENTS AND METHODS: Forty critically ill elderly patients (aged over 65 years) who required amikacin therapy due to severe documented, or suspected gram-negative infections, were randomly assigned to two treatment groups. Group A (20 patients) received 15 mg/kg amikacin and Group B (20 patients) received 25 mg/kg amikacin per day as a single daily dose. All the patients were monitored for renal damage by the daily monitoring of serum creatinine. The amikacin peak (Cmax) and trough (Cmin) serum concentrations were measured on Days 3 and 7 postadministration. RESULTS: Data from 18 patients in Group A and 15 patients in Group B were finally analyzed. On Day 3, the amikacin mean Cmax levels in the standard and high-dose treatment groups were 30.4±11 and 52.3±16.1 µg/mL (P<0.001), and the Cmin levels were 3.2±2.1 and 5.2±2.8 µg/mL, respectively (P=0.035). On Day 7, the Cmax levels in the standard and high-dose groups were 33±7.3 and 60.0±17.6 µg/mL (P=0.001), and the Cmin levels were 3.2±2.9 and 9.3±5.6 µg/mL, respectively (P=0.002). In only six (40%) of the patients in the high-dose groups and none of the patients in the standard-dose group, amikacin Cmax reached the target levels (>64 µg/mL), whereas the amikacin mean Cmin levels in the high-dose group were above the threshold of toxicity (5 µg/mL). CONCLUSION: Our results suggest that the optimum dose of amikacin should be determined for elderly critically ill patients. It seems that higher-than-standard doses of amikacin with more extended intervals might be more appropriate than standard once-daily dosing in the elderly critically ill patients.

Optimal aminoglycoside therapy following the sepsis: how much is too much?

Severe sepsis and septic shock are major problems as the result of high rates morbidity and mortality in intensive care units (ICUs). In the presence of septic shock, each hour of delay in the administration of effective antibiotics is associated with a measurable increase in mortality. Aminoglycosides are effective broad-spectrum antibiotics that are commonly used in ICUs for the treatment of life-threatening Gram-negative infections and as a part of empiric therapy for severe sepsis and septic shock. Knowledge of the pharmacokinetic (PK) and pharmacodynamic (PD) properties of the antibiotics used for the management of critically ill patients is essential for selecting the antibiotic dosing regimens and improving patient outcome. Volume of distribution (Vd) and clearance (CL) of aminoglycosides in critically ill patients differs from general population and these parameters change considerably during the therapy. Pathophysiological changes during the sepsis alter the pharmacokinetic and pharmacodynamic profile of many drugs (increase in Vd and variable changes in CL have been reported for aminoglycosides during the sepsis), therefore, dosing regimen optimization is necessary for achieving therapeutic goal, and critically ill patients should receive larger loading doses of aminoglycosides in order to achieve therapeutic blood levels and due to the considerable variation in kinetic parameters, the use of standard doses of aminoglycosides or dosing nomograms is not recommended in these populations.

Randomized trial of the effect of intravenous paracetamol on inflammatory biomarkers and outcome in febrile critically ill adults.

BACKGROUND AND THE PURPOSE OF THE STUDY: The febrile reaction is a complex response involving immunologic and other physiologic systems. Antipyretics are commonly used in critically ill patients with fever. We investigated the inflammatory responses following application of antipyretic therapy in febrile critically ill patients with Systemic Inflammatory Response Syndrome (SIRS). PATIENTS AND METHODS: In a prospective, randomized controlled study, critically ill patients with fever (T ≥ 38.3°C), SIRS diagnosed within 24 hours of Intensive Care Unit (ICU) admission and Acute Physiology and Chronic Health Evaluation II (APACHE II) score ≥10 were randomized into two groups. Upon appearance of fever, one group received intravenous paracetamol 650 mg every 6 hours for 10 days and other group received no treatment unless temperature reached 40°C. Body temperature, Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sepsis-related Organ Failure Assessment (SOFA) scores, length of ICU stay, ICU mortality and infectious complications were recorded. Levels of Interleukin-1 alpha (IL-1α), IL-6, IL-10, Tumour Necrosis Factor alpha (TNFα) and High-Sensitive C-Reactive Protein (HS-CRP) were assessed at baseline and 2, 6 and 24 hours after intervention. RESULTS AND DISCUSSION: During a period of 15-month screening, 20 patients met the criteria and randomized to the control or paracetamol group. Body temperature decreased significantly in the paracetamol group (p = 0.004) and control group (p = 0.001) after 24 hours, but there was no significant difference between two groups at this time point (p = 0.649). Levels of IL-6 and IL-10 decreased significantly (p = 0.025 and p = 0.047, respectively) in the paracetamol group at 24 hours but this was not of statistical significance in control group. No patterns over time in each group or differences across two groups were found for HS-CRP, TNFα, and IL-1α (p > 0.05). There were no differences regarding ICU length of stay, mortality and infectious complications between both groups. CONCLUSION: These results suggest that antipyretic therapy may not be indicated in all ICU patients. Allowing fever to take its natural course does not appear to have detrimental effects on critically ill patients with SIRS and may avoid unnecessary expenses.

The relationship between body mass index and outcomes in leukemic patients undergoing allogeneic hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT) is being used increasingly in an attempt to cure many hematological disorders. Obesity has become a world wide phenomenon and is a known risk factor for numerous medical conditions, but its role in transplant outcomes remained controversial. Total of 192 patients with acute leukemia who underwent sibling HLA matched HSCT were analyzed to find the effect of pre-transplant body mass index (BMI) on transplant outcomes such as time to engraftment, infections, graft vs. host disease (GvHD), and overall survival (OS) for the period of three yr (April 2006-March 2009). There was a significant correlation between higher pre-transplant BMI and shorter engraftment time (p = 0.010); but no relation between BMI and GvHD, infection, and OS was found. The results of this study showed that patients with higher BMI may have a shorter engraftment time; but lower, although not significant, survival rate compared to non-obese patients.

Effects of Pantoprazole on Systemic and Gastric Pro- and Anti-inflammatory Cytokines in Critically Ill Patients.

Stress-related mucosal damage (SRMD) is a significant cause of morbidity and mortality in critically ill patients due to the gastrointestinal blood loss. Prophylaxis of SRMD with proton pump inhibitors or histamine-2 blockers has gained widespread use in intensive care units. Both demonstrated to be effective in reducing clinically significant bleedings, while PPIs has shown to exert some anti inflammatory effects including the inhibition of producing pro-inflammatory cytokines. As cytokines have role in developing SRMD, the aim of this study was to evaluate the effect of PPIs on the inhibition of cytokine release following the critical illness. A total of 27 critically ill patients with risk factors of developing stress ulcer and intragastric pH < 3.0 enrolled to this Randomized clinical trial study. Patients were randomly assigned in three treatment groups; group one received 40 mg of intravenous pantoprazole every 12 h for 48 h (four doses), group two received 80 mg of intravenous pantoprazole every 24 h continuous infusion for 48 h and the third group received 150 mg of ranitidine intravenously as 24 h continuous infusion for 48 h. Plasma and gastric juice samples were obtained at 0th, 12th, 24th and 48th h for the measurement of EGF, IL-1ß, IL-6, IL-10 and TNF-α. Pantoprazole infusion have decreased the plasma IL-1ß concentrations (p = 0.041). No other significant differences in concentrations of EGF, IL-6, IL-10 and TNF-α were detected. There were reverse correlations between the intragastric pH with gastric juice IL-1ß and TNF-α concentrations and a direct correlation between the intragastric pH and gastric juice EGF in pantoprazole groups. Our data suggest that pantoprazole may have some anti-inflammatory effects on patients. However, the exact impact of this effect on patients should be assessed by further studies.