Publications by authors named "Mojtaba Mojtahedzadeh"

87 Publications

Antibiotic therapy in sepsis: No next time for a second chance!

J Clin Pharm Ther 2021 Mar 12. Epub 2021 Mar 12.

Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

What Is Known And Objective: Sepsis is a life-threatening organ dysfunction associated with a high rate of morbidity and mortality. Appropriate antibiotic therapy remains the cornerstone of sepsis and septic shock management.

Comment: Although the early initiation of antimicrobial agents in the treatment of sepsis is widely acknowledged, the selection and adjustment to optimal dosage can be equally important. Since significant pathophysiological changes in the critically ill patients lead to altered pharmacokinetics of antibiotics, early consideration of pharmacokinetic/pharmacodynamic (PK/PD) properties is necessary for optimal antibiotic dosing in sepsis and should be integrated in practice.

What Is New And Conclusion: Where possible, an individualized antibiotic dosing approach through the application of therapeutic drug monitoring (TDM) service should replace the conventional dosing in critically ill patients with sepsis. Finally, antimicrobial stewardship can help improve clinical outcomes.
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http://dx.doi.org/10.1111/jcpt.13403DOI Listing
March 2021

Comparison of Preoperative Hypertonic Saline versus Mannitol for Intraoperative Brain Relaxation and Early Postoperative Outcome among Patients with Cerebral Low-grade Glioma: A Prospective Study.

Asian J Neurosurg 2020 Oct-Dec;15(4):941-945. Epub 2020 Oct 19.

Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.

Introduction: Hypertonic saline (HS) has an important role in the treatment of raised intracranial pressure after traumatic brain injury. This study evaluates the efficacy and safety of HS and its impact on the postoperative course of patients undergoing craniotomy for low-grade gliomas.

Materials And Methods: Sixty patients with supratentorial low-grade glioma were enrolled. All patients were anesthetized and operated with the same team and protocol. They successively received either HS or mannitol just before surgery. The amount of brain edema was classified according to the dural tension score (I-III) just after craniotomy and before dural opening. Other intraoperative measurements (such as urine output, need, and dosage of other diuretic agents) and postoperative findings (intensive care unit [ICU] and hospital stay, corticosteroid demand, and confusion period) were also assessed. Pre- and postoperative serum S100B levels were documented in both groups.

Results: The dural tension score was not significantly different among the two groups: severe tension in six and five patients in the mannitol and HS groups, respectively. HS group had a significantly lower amount of diuresis (609 vs. 725 ml) during surgery. Patients in the HS group had shorter ICU stay (16.3 vs. 27.9 h) and shorter duration of corticosteroid therapy after surgery (3.4 vs. 5.2 days).

Conclusion: HS infusion just before the onset of craniotomy is at least as effective as mannitol in controlling intraoperative brain edema in patients with supratentorial glioma. Improved early postoperative course and lower degrees of S100B rise after craniotomy seen in the HS group needs to be explained in more detailed studies.
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http://dx.doi.org/10.4103/ajns.AJNS_224_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869255PMC
October 2020

Area under the Curve-Based Dosing of Vancomycin in Critically Ill Patients Using 6-Hour Urine Creatinine Clearance Measurement.

Crit Care Res Pract 2020 24;2020:8831138. Epub 2020 Dec 24.

Department of Clinical Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Background: The area under the curve- (AUC-) guided vancomycin dosing is the best strategy for individualized therapy in critical illnesses. Since AUC can be calculated directly using drug clearance (CL), any parameter estimating CL will be able to achieve the goal of 24-hour AUC (AUC). The present study was aimed to determine CL based on 6-hour urine creatinine clearance measurement in critically ill patients with normal renal function.

Method: 23 adult critically ill patients with an estimated glomerular filtration rate (eGFR) ≥60 mL/min who received vancomycin infusion were enrolled in this pilot study. Vancomycin pharmacokinetic parameters were determined for each patient using serum concentration data and a one-compartment model provided by MONOLIX software using stochastic approximation expectation-maximization (SAEM) algorithm. Correlation of CL with the measured creatinine clearance in 6-hour urine collection (CL) and estimated creatinine clearance by the Cockcroft-Gault formula (CL) was investigated.

Results: Data analysis revealed that CL had a stronger correlation with CL rather than CL ( = 0.823 vs. 0.594; < 0.001 vs. 0.003). The relationship between CL and CL was utilized to develop the following equation for estimating CL: CL (mL/min) = ─137.4 + CL (mL/min) + 2.5 IBW (kg) (  = 0.826, < 0.001). Regarding the described model, the following equation can be used to calculate the empirical dose of vancomycin for achieving the therapeutic goals in critically ill patients without renal impairment: total daily dose of vancomycin (mg) = (─137.4CL (mL/min) + 2.5 IBW (kg)) × 0.06 AUC (mg.hr/L).

Conclusion: For AUC estimation, CL can be obtained by collecting urine in a 6-hour period with good approximation in critically ill patients with normal renal function.
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http://dx.doi.org/10.1155/2020/8831138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775160PMC
December 2020

Short-term Effects of Metformin on Cardiac and Peripheral Blood Cells Following Cecal Ligation and Puncture-induced Sepsis.

Drug Res (Stuttg) 2020 Dec 21. Epub 2020 Dec 21.

Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.

Aim Of The Study: Sepsis has well-documented inflammatory effects on cardiovascular and blood cells. This study is designed to investigate potential anti-inflammatory effects of metformin on cardiac and blood cells 12 and 24 h following cecal ligation and puncture (CLP)-induced sepsis.

Methods: For the purpose of this study, 36 male Wistar rats were divided into six groups: two groups underwent CLP, two groups underwent CLP and received metformin, and two groups only received sham operations. 12 h later, 18 rats (half of rats in each of the three aforementioned groups) were sacrificed and cardiac and blood cells were harvested. Subsequently, 12 h later, the rest of the rats were euthanatized. In all harvested blood and cardiac cells, oxidative stress indicators, antioxidant properties, count of blood cells, neutrophil infiltration, percentage of weight loss and pathological assessment were conducted.

Results: In our experiment, metformin elevated antioxidant levels, improved function of blood cells and percentage of weight loss. Moreover, in the groups which received metformin, oxidative stress and neutrophil infiltration markers were decreased significantly. Moreover, pathological investigations of cardiac cell injury were reduced in the metformin group.

Conclusions: Our findings suggest that in CLP induced sepsis model, metformin can improve the function of blood and cardiac cells through alleviating inflammation, improvement of anti-inflammation properties, and enhancement of blood profile, and all these effects are more pronounced after 24 h in comparison with 12 h after induction of sepsis.
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http://dx.doi.org/10.1055/a-1322-7478DOI Listing
December 2020

Evaluation of Neuroprtective Effects of L-Carnitine and Fat Emulsion in the CVA Patients: A Prospective, Randomized, Double Blind, Clinical Trial.

Iran J Pharm Res 2020 ;19(1):111-119

Department of Neurology, Bu Ali Sina General Hospital, Mazandaran University of Medical Sciences, Sari, Iran.

Cerebral infarction presents with neurological deficits caused by the death of neurons in a focal area of the brain. S100B is a biomarker that increases in brain damage. Neuroprotectives can reduce the brain sequels after neurological insult. The purpose of this study was to evaluate the neuroprotective effects of L-carnitine and Fat emulsion (Lipofundin) alone and in combination in patients with ischemic stroke. In a prospective, RCT, and double-blind study 100 patients with MCA ischemic cerebrovascular accident who were admitted in the first 24 h of injury entered the study. The patients were randomly assigned into four groups of L-carnitine, fat emulsion, L-carnitine plus fat emulsion and control. Fat emulsion 10%, 500 mL, was infused over 6 to 12 h and 1 gr of L-carnitine (10 mL of solution) was administered orally to patients in addition to common therapies, according to the American Heart Association and American Stroke Association (AHA/ASA) guidelines. The patients in the control group received only the usual treatment according to stroke guidelines. Blood samples before the intervention, then after 24 h, 48 h, and 7 days later were taken and immunoenzymatic colorimetric method was used for quantitative determination of S100B concentration in the patients' serum. In the within group analysis, all of our treatment interventions (except control group) have decreased S100B levels statistically significant ( < 0.05). Moreover, changes in observed levels of S100B before and after intervention were different between the groups and the observed differences were statistically significant ( = 0.01). In the GEE model, it was found that S100B levels in the L-carnitine plus fat emulsion group decreased more than the control group and this decline has been statistically significant [ = 0.02, 20.47 (CI 95%: 6.25-34.41)], but in comparison of L-carnitine and fat emulsion group with control group, did not reached statistical significance ( > 0.05). Based on the results obtained from this study, it seems that L-carnitine with fat emulsion could lead to neuroprotective effects with a significant reduction in the S100B biomarker.
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http://dx.doi.org/10.22037/ijpr.2020.1100952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462480PMC
January 2020

Metformin Attenuates Brain Injury by Inhibiting Inflammation and Regulating Tight Junction Proteins in Septic Rats.

Cell J 2020 Jul 18;22(Suppl 1):29-37. Epub 2020 Jul 18.

Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran. Electronic Address:

Objective: Metformin has a potent inhibitory activity against inflammation and oxidative stress, which inevitably occur in sepsis-associated encephalopathy (SAE). The precise mechanisms underlying neuroprotective effects of metformin in SAE, are still unclear. In the present work, the protective effect of metformin on SAE using cecal ligation and puncture (CLP) model of sepsis, was assessed.

Materials And Methods: In this experimental study, CLP procedure was performed in Wistar rats and 50 mg/kg metformin was administered immediately. Specific markers of sepsis severity, inflammation, blood brain barrier (BBB) dysfunction, and brain injury, were investigated. Specific assay kits and real-time polymerase chain reaction (RT-PCR) were used. Histopathological assessment was also carried out.

Results: Treatment with metformin decreased murine sepsis score (MSS), lactate, platelet lymphocyte ratio (PLR), and high mobility group box (HMGB1) levels. The expression levels of claudin 3 () and claudin 5 () were increased following treatment with metformin. Metformin decreased the expression of S100b, neuron specific enolase (), and glial fibrillary acidic protein ().

Conclusion: Our study suggests that metformin may inhibit inflammation and increase tight junction protein expressions which may improve BBB function and attenuate CLP-induced brain injury. Hence, the potential beneficial effects of metformin in sepsis, should be considered in future.
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http://dx.doi.org/10.22074/cellj.2020.7046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481907PMC
July 2020

Management of Hypotension and Bradycardia Caused By Spinal Cord Injury. The Usefulness of Midodrine and Methylxanthines.

Iran J Pharm Res 2019 ;18(4):2131-2135

Department of Clinical Pharmacy, Faculty of Pharmacy, Gilan University of Medical Sciences, Rasht, Iran.

Spinal cord injury is a devastating chronic condition resulting in temporary or permanent motor, sensory or autonomic dysfunction of the cord. The manifestation of spinal cord injury based on the severity and involved areas could be different. Numerous studies have demonstrated that bradycardia, hypotension, and orthostatic hypotension are present insignificant number of patients after spinal cord injury which peaks at 4 day of injury. Although vasopressors are common drugs that have been used to restore blood pressure and heart rate in patients with neurogenic shock, there is limited data regarding pharmacologic management of bradycardia and hypotension after spinal cord injury. Midodrine is a potent vasopressor approved for the management of symptomatic orthostatic hypotension. Theophylline and aminophylline are methylxanthine derivatives. There are very few case reports concerning the use of midodrine and methylxanthines for treatment of hypotension in patients with spinal cord injury. In this case report and review of the articles we report a 45 year old woman with a diagnosis of spinal cord injury who was successfully managed with midodrine and aminophylline and then we review current case reports. Based on our case report and other available data, midodrine as well as methylxanthines can be suggested as therapeutic options for managing symptoms in spinal cord injury patients.
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http://dx.doi.org/10.22037/ijpr.2019.1100824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059064PMC
January 2019

Clinical effectiveness of high dose versus standard dose of meropenem in ventilator-associated pneumonia caused by multidrug-resistant bacteria: a randomized single-blind clinical trial.

Infect Disord Drug Targets 2020 Feb 26. Epub 2020 Feb 26.

Department of Clinical Pharmacy, Faculty of Pharmacy, Pharmaceutical Research Center, Mazandaran University of Medical Sciences, Sari. Iran.

Background: Meropenem standard doses are based on the minimum inhibitory concentration of sensitive pathogens and the pharmacokinetic parameter of not critically ill patients. We compared the efficacy of high versus standard dose of meropenem in ventilator-associated pneumonia (VAP).

Methods: 24 out of 34 eligible patients were randomized to receive meropenem 3 g q8h (high dose group, 11 patients) or 2 g q8h (standard dose group, 13 patients) as a 3h infusion. Primary outcome was considered as clinical success that was defined as stable hemodynamic, improved sequential organ failure assessment (SOFA) score, stable or improved PaO2/FiO2 after 7 days. A sputum culture was taken before intervention.

Results: Clinical success rate was not significantly different between the high and standard dose group (54.5% vs. 38.5%, P= 0.431). There was a significant difference in reduction of clinical pulmonary infection score (CPIS) compared to high dose with standard group (P=0.038). SOFA score declined significantly in high dose group through the study (P=0.006). A shorter duration of VAP treatment was recorded in high dose group (P=0.061). We did not observe any significant adverse event related to meropenem. Acinetobacter spp. (34.8%), Klebsiella spp. (32.6%) and, Pseudomonas aeruginosa (19.5%) isolated more frequently from sputum cultures.

Conclusion: Treatment with high dose of meropenem seems to be safe. However, it did not provide significantly higher clinical success rate in comparison with the standard dose, but could be considered as an appropriate empirical treatment in patients with severe infection due to reducing in SOFA and CPIS.
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http://dx.doi.org/10.2174/1871526520666200227102013DOI Listing
February 2020

Evaluation of Amikacin Pharmacokinetics in Critically Ill Patients with Intra-abdominal Sepsis.

Adv Pharm Bull 2020 Jan 11;10(1):114-118. Epub 2019 Dec 11.

Department of Clinical Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Although the current widespread use of amikacin is in intra-abdominal sepsis treatment, its pharmacokinetic changes in the present setting are not yet well known. This study was aimed to evaluate the amikacin pharmacokinetic profile in critically ill patients with intraabdominal sepsis compared to pneumosepsis. Adult septic patients received amikacin therapy were studied. Patients with intraabdominal sepsis were enrolled in group 1 (n=16), and patients with pneumosepsis were enrolled in group 2 (n=13). The amikacin serum concentrations were evaluated in the first, second, fourth and sixth hours after initiating 30-minute infusion. The pharmacokinetic parameters were calculated for each patient. There was no significant difference in the volume of distribution between the two groups (0.33±0.08 vs. 0.28±0.10 L/kg, =0.193). The amikacin clearance was significantly lower in group 1 compared to group 2 (58.5±21.7 vs. 83.9±37.0 mL/min, =0.029). There was no significant correlation between amikacin clearance and creatinine clearance estimated by Cockcroft-Gault formula in all patients (=0.206). The half-life was significantly longer in group 1 compared to group 2 (5.3±2.8 vs. 3.4±3.2 hours, =0.015). Pathophysiologic changes following intra-abdominal sepsis can affect amikacin pharmacokinetics behavior. The clearance and half-life may change, but the alteration of the volume of distribution is not significantly different in comparison with pneumosepsis. Further studies are required to evaluate the pharmacokinetic variables of amikacin in critically ill patients with intra-abdominal sepsis.
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http://dx.doi.org/10.15171/apb.2020.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983982PMC
January 2020

Extraction and Evaluation of Outer Membrane Vesicles from Two Important Gut Microbiota Members, Bacteroides fragilis and Bacteroides thetaiotaomicron.

Cell J 2020 Oct 15;22(3):344-349. Epub 2019 Dec 15.

Microbiology Research Centre, Pasteur Institute of Iran, Tehran, Iran.

Objective: The gastrointestinal tract (GI) is colonized by a complex microbial community of gut microbiota. Bacteroides spp. have significant roles in gut microbiota and they host interactions by various mechanisms, including outer membrane vesicle (OMVs) production. In the present study, we extracted and assessed () and () OMVs in order to evaluate their possible utility for studies.

Materials And Methods: In this experimental study, OMVs extraction was performed using multiple centrifugations and tris-ethylenediaminetetraacetic acid (EDTA)-sodium deoxycholate buffers. Morphology, diameter, protein content, profile, and lipopolysaccharide (LPS) concentrations of the OMVs were assessed by scanning electron microscopy (SEM), nanodrop, Bradford assay, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), and the Limulus Amoebocyte Lysate (LAL) test, respectively. Zeta potential (ζ-P) was also assessed. The viability effect of OMVs was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay in Caco-2 cells.

Results: Spherical OMVs with diameters of 30-110 nm were produced. The OMVs had different protein profiles. The LPS concentrations of the and OMVs were 1.80 and 1.68 EU/mL, respectively. ζ-P of the OMVs was -34.2 mV and, for . it was -44.7 mV. The viability of Caco-2 cells treated with OMVs was more than 95%.

Conclusion: The endotoxin concentrations of the spherical OMVs from and were within the safe limits. Both OMVs had suitable stability in sucrose solution and did not have any cytotoxic effects on human intestinal cells. Based on our results and previous studies, further molecular evaluations can be undertaken to design OMVs as possible agents that promote health properties.
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http://dx.doi.org/10.22074/cellj.2020.6499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947009PMC
October 2020

A Cost-effectiveness Analysis of Albumin in Septic Shock: A Patient-level Data Analysis.

Clin Ther 2019 11 25;41(11):2297-2307.e2. Epub 2019 Oct 25.

Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Purpose: Albumin-based fluid therapy in septic shock is a matter of debate and criticism. The aim of this study was to assess the cost-effectiveness of albumin therapy in patients with septic shock.

Methods: A retrospective cohort study was conducted in Imam Khomeini, Sina, and Shariati hospitals on patients with septic shock admitted to intensive care units from March 31, 2016 to September 22, 2017. Data sources were the health information system database and patient medical records. The patients with potential septic shock were identified based on norepinephrine use. Septic shock was confirmed after medical record review based on systemic inflammatory response syndrome criteria, antibiotic use, and fluid therapy. Patients who received albumin in the fluid therapy were compared with patients treated without albumin. The 28-day mortality, life-year gain, and cost-effectiveness were evaluated.

Findings: The addition of albumin had no significant increase in life-year gain (mean difference = 0.67; 95% CI, -2.25 to 3.58). However, the addition of albumin increased the total cost of treatment by US $3846.07 (95% CI, US $2093.46-US $5598.98). The incremental cost-effectiveness ratio calculated based on the mean life-years gained was US$5740.40 per a life-year gained. The net monetary benefit was negative (-355.4; 95% CI, -15,387.61 to 14,676.81), and the probability that the addition of albumin will be cost-effective at a gross domestic product per capita was 40.0%.

Implications: Albumin-based fluid therapy does not improve the 28-day mortality of patients with septic shock. The addition of albumin in the fluid therapy of patients with septic shock was not cost-effective. Both the observational and retrospective nature of the study was expected to introduce bias. We recommend a cost-effectiveness analysis combined with clinical trials to settle the debate once and for all.
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http://dx.doi.org/10.1016/j.clinthera.2019.08.023DOI Listing
November 2019

A Review on The Protective Effects of Metformin in Sepsis-Induced Organ Failure.

Cell J 2020 Jan 29;21(4):363-370. Epub 2019 Jul 29.

The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran. Electronic

Despite advances in sepsis management, it remains a major intensive-care-unit (ICU) concern. From new prospective, positive effects of metformin, such as anti-oxidant and anti-inflammatory properties are considered potentially beneficial properties for management of septic patients. This article reviewed the potential ameliorative effects of metformin in sepsis-induced organ failure. Information were retrieved from PubMed, Scopus, Embase, and Google Scholar. Multi-organ damage, oxidative stress, inflammatory cytokine stimulation, and altered circulation are hallmarks of sepsis. Metformin exerts its effect via adenosine monophosphate-activated protein kinase (AMPK) activation. It improves sepsis-induced organ failure by inhibiting the production of reactive oxygen species (ROS) and pro-inflammatory cytokines, preventing the activation of transcription factors related to inflammation, decreasing neutrophil accumulation/infiltration, and also maintaining mitochondrial membrane potential. Studies reported the safety of metformin therapeutic doses, with no evidence of lactic acidosis, in septic patients.
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http://dx.doi.org/10.22074/cellj.2020.6286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722446PMC
January 2020

A randomized controlled trial on the efficacy, safety, and pharmacokinetics of metformin in severe traumatic brain injury.

J Neurol 2019 Aug 16;266(8):1988-1997. Epub 2019 May 16.

Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, 14155-6451, Tehran, Iran.

Objective: Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide. Metformin is reported to have pleiotropic neuroprotective effects through anti-inflammatory, antioxidative, and anti-ischemic activity, and improvements in vascular hemodynamics and endothelial function. The aim of this study is to examine the efficacy and safety of metformin therapy in severe TBI patients.

Methods: This single-blind, parallel-group, randomized controlled trial enrolled adult TBI patients. Of 158 trauma patients assessed, 30 met the eligibility criteria and were randomly allocated in a one-to-one ratio to receive 1 g metformin every 12 h for five consecutive days (intervention group) or to usual management only (control group). For efficacy analysis, temporal profiles of serum levels of S100b, neutrophil to lymphocyte ratio (NLR), and glial fibrillary acidic protein (GFAP) were assessed. For pharmacokinetic analysis, serum concentrations of metformin were evaluated in the intervention group.

Results: The two study groups were similar in terms of demographics, baseline clinical characteristics, and on-admission biomarkers' serum levels. Longitudinal analysis of S100b and NLR levels showed statistically significant declines in values toward normal levels in the intervention group (p values of < 0.001 and 0.030, respectively), different from the profiles of the control group (p values of 0.074 and 0.645, respectively). Pharmacokinetic analysis demonstrated that metformin absorption is delayed in TBI patients. No events of hypoglycemia and lactic acidosis occurred.

Conclusions: Metformin could potentially be an effective and safe therapeutic intervention in patients with severe TBI. Large-scale, multicentre studies are needed to confirm our encouraging results.
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http://dx.doi.org/10.1007/s00415-019-09366-1DOI Listing
August 2019

Is Albumin-based Resuscitation in Severe Sepsis and Septic Shock Justifiable? An Evidence from a Cost-effectiveness Evaluation.

Ethiop J Health Sci 2019 Jan;29(1):869-876

Department of Clinical Pharmacy, Faculty of Pharmacy, TUMS, Tehran, Iran.

Background: Fluid and antimicrobial therapy are the essential parts of sepsis management. The type of fluid to resuscitate with is an unsettled issue in the treatment of severe sepsis and septic shock. The objective of this study was to evaluate the cost-effectiveness of albumin-based resuscitation over crystalloids.

Methods: A cost-effectiveness analysis was conducted by extracting data from a database of Sina Hospital, Islamic Republic of Iran. A decision tree was constructed by using Tree Age Pro 2011. The patients were grouped based on the types of fluids used for resuscitation into crystalloid alone or crystalloid + albumin groups at the initial decision node. The patients were followed from the onset of severe sepsis and septic shock upto 28 days. The healthcare payers' perspective was considered in constructing the model. The cost was measured in US dollars and the effectiveness was measured by life years gained.

Results: The addition of albumin during resuscitation of patients with severe sepsis and septic shock has an effectiveness gain of 0.09 life years and cost increment of 495.00 USD. The estimated ICER for this analysis was 5500.00 USD per life year gained. The probability that albumin is cost-effective at one GDP per capita is 49.5%.

Conclusion: Albumin-based resuscitation is not cost-effective in Iran when a GDP per capita was considered for a life year gain. The cost-effectiveness was insensitive to the cost of standard care. We recomend the caustious use albumin as per the Surviving Sepsis Campaign guideline.
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http://dx.doi.org/10.4314/ejhs.v29i1.8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341442PMC
January 2019

Neuroprotective Agents in the Intensive Care Unit: -Neuroprotective Agents in ICU.

J Pharmacopuncture 2018 Dec 31;21(4):226-240. Epub 2018 Dec 31.

Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Neuroprotection or prevention of neuronal loss is a complicated molecular process that is mediated by various cellular pathways. Use of different pharmacological agents as neuroprotectants has been reported especially in the last decades. These neuroprotective agents act through inhibition of inflammatory processes and apoptosis, attenuation of oxidative stress and reduction of free radicals. Control of this injurious molecular process is essential to the reduction of neuronal injuries and is associated with improved functional outcomes and recovery of the patients admitted to the intensive care unit. This study reviews neuroprotective agents and their mechanisms of action against central nervous system damages.
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http://dx.doi.org/10.3831/KPI.2018.21.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333194PMC
December 2018

Response to letter to the editor: Fluid volume, fluid balance and patient outcome in severe sepsis and septic shock: A systematic review.

J Crit Care 2019 04 15;50:314-315. Epub 2018 Nov 15.

Department of Clinical Pharmacy, Faculty of Pharmacy, TUMS, Tehran, Iran; Sina Hospital, Division of Critical Care Medicine, Tehran, Iran.

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http://dx.doi.org/10.1016/j.jcrc.2018.11.011DOI Listing
April 2019

Monomethyl fumarate alleviates sepsis-induced hepatic dysfunction by regulating TLR-4/NF-κB signalling pathway.

Life Sci 2018 Dec 7;215:152-158. Epub 2018 Nov 7.

Toxicology and Poisoning Research Centre, Tehran University of Medical Sciences, Tehran, Iran; Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Aims: Sepsis is a potentially fatal illness that can lead to impairment of multiple organs such as liver. The condition is deeply associated with oxidative stress and inflammation. Monomethyl fumarate (MMF) has manifested antioxidant and immunomodulatory properties. The aim of current study was to evaluate protective effects of MMF in sepsis-induced hepatic dysfunction.

Main Methods: Sepsis was induced by cecal ligation and puncture (CLP). Wistar rats were assigned to one of sham, CLP, CLP + dexamethasone (as positive control of inflammation) and CLP + MMF groups. Levels of serum IL-1β, IL-6, IL-10, AST, ALT and γ‑GT were quantified. Furthermore, Hepatic levels of GSH and MDA and mRNA expression of TNF and NFKBIA along with hepatic protein level of TLR-4 were assessed. Also, histopathological study of liver was carried out to evaluate hepatic injuries.

Key Findings: Septic rats demonstrated risen levels of IL-1β, IL-6, IL-10, AST, ALT and γ‑GT, while treatment with dexamethasone or MMF attenuated these levels. Moreover, enhancements in protein level of TLR-4 and mRNA levels of TNF and NFKBIA were observed in CLP rats. These elevations were mitigated in CLP-induced rats that were treated with either dexamethasone or MMF. Treatment with dexamethasone or MMF also shifted sepsis-induced disturbance in the levels of GSH and MDA towards sham levels. Hepato-protective effects of dexamethasone and MMF were further confirmed by histopathological observations.

Significance: Our findings imply that MMF alleviates sepsis-induced hepatic dysfunction by mitigating the inflammatory and oxidative state and this effect is at least partly mediated by the inhibition of TLR-4/NF-κB signalling pathway.
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http://dx.doi.org/10.1016/j.lfs.2018.11.010DOI Listing
December 2018

Fluid volume, fluid balance and patient outcome in severe sepsis and septic shock: A systematic review.

J Crit Care 2018 12 20;48:153-159. Epub 2018 Aug 20.

Department of Clinical Pharmacy, Faculty of Pharmacy, TUMS, Tehran, Iran; Sina Hospital, Division of Critical Care Medicine, Tehran, Iran.

Purpose: This systematic review and meta-analysis was conducted to evaluate the mortality risk in severe sepsis and septic shock with a low and high fluid volume/balance.

Methods: Cohort studies that compared the mortality of patients with low or high fluid volume/balance were included. Electronic databases: PubMed/Medline PLUS, Embase, Scopus, and Web of Science were searched. Patient mortality at the longest follow-up was the primary outcome measure. The data were analyzed using STATA 14 statistical software.

Results: The current study included fifteen studies with 31,443 severe sepsis and/or septic shock patients. Patients with a high fluid balance have a 70% increased risk of mortality (pooled RR: 1.70; CI: 1.20, 2.41; P = .003). Survivors of severe sepsis and/or septic shock received higher fluid volume in the first three hours. However, fluid volume administered in the first 24 h was higher for non-survivors. Low volume resuscitation in the first 24 h had a significant mortality reduction (P = .02).

Conclusion: High fluid balance from the first 24 h to ICU discharge increases the risk of mortality in severe sepsis and/or septic shock. However, randomized clinical trials should be conducted to resolve the dilemma of fluid resuscitation.
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http://dx.doi.org/10.1016/j.jcrc.2018.08.018DOI Listing
December 2018

The Role of Epigenetic Alterations Involved in Sepsis: An Overview.

Curr Pharm Des 2018 ;24(24):2862-2869

The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.

Background: Sepsis is among the leading causes of death with no specific etiology or treatment. Increase in health burden in terms of cost, morbidity, and mortality is the reason behind the continuous search for different treatment modalities which involve several targets/approach and one of them includes the involvement of epigenetics in sepsis.

Objective: This review was carried out to explain the epigenetic alterations involved in sepsis, as it affects the disease progression, diagnosis, and treatment.

Methods: Information used in this review was obtained from different databases including PUBMED, SCOPUS, Web of Science, and EMBASE. Keywords were used as search terms.

Result: In this review, we provided a concise overview of the significant role of epigenetic alterations in sepsis pathophysiology as it relates to disease progression, diagnosis and treatment derived from , and human studies. These mechanisms affected various targets and pathways involved in sepsis modulation, which correlates with morbidity and mortality. Change in DNA methylation pattern, histone modification, and microRNA regulation has been shown in sepsis models to silence or activate pro-inflammatory genes such as TNF-α and interleukins, anti-oxidant enzymes, and many signaling pathways. Drugs that target these pathways have proven effective in sepsis treatment.

Conclusion: Epigenetic processes involve specific enzymes detected in the blood and other body fluids which can potentially serve as diagnostic, therapeutic, as well as prognostic tools in sepsis. Epigenetic mechanisms can provide a highly sensitive and accurate method for sepsis diagnosis using blood and other body fluids.
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http://dx.doi.org/10.2174/1381612824666180903114253DOI Listing
October 2019

Cotreatment with Furosemide and Hypertonic Saline Decreases Serum Neutrophil Gelatinase-associated Lipocalin (NGAL) and Serum Creatinine Concentrations in Traumatic Brain Injury: A Randomized, Single-Blind Clinical Trial.

Iran J Pharm Res 2018 ;17(3):1130-1140

Department of Clinical Pharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.

Acute kidney injury (AKI) occurs both after traumatic brain injury (TBI) and after hypertonic saline administration; furosemide may be useful in preventing AKI indirectly. Serum neutrophil gelatinase-associated lipocalin (sNGAL) is superior to serum creatinine (sCr) in diagnosing early AKI. We compared the administration of hypertonic saline plus furosemide (HTS+F) versus hypertonic saline (HTS), using sCr and sNGAL to investigate kidney injury in patients with TBI. This randomized, single-blind clinical trial was conducted from August 2016 to July 2017 in a neurosurgical intensive care unit, and included patients with a Glasgow Coma Score (GCS) 7-13 and brain edema. One group (n = 22) received hypertonic saline 5% (100 mL over 60 min then 20 mL/h) plus furosemide (40 mg over 60 min then 0.05 mg/kg per hour) for 72 h. The other group (n 21) received only hypertonic saline 5%, in the same dose as noted above. The sCr and sNGAL concentrations, GCS, and length of stay were measured. Mean ± SD differences were -51.15 (47.07) and 9.96 (64.23) ng/mL for sNGAL and -0.12 (0.22) and -0.005 (0.2) mg/dL for sCr in HTS+F group and HTS group respectively (both < 0.001). The incidence of stage one AKI according to Improving Global Outcomes (KDIGO) criteria was 4.5% in the HTS+F group and 19.0% in the HTS group ( = 0.16). Hypokalemia was common in both groups. HTS+F group, compared with HTS group, was associated with lower concentrations of sCr and sNGAL. Incidence AKI (KDIGO criteria) did not have difference between groups.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6094412PMC
January 2018

Analgesic and sedative agents used in the intensive care unit: A review.

J Cell Biochem 2018 11 4;119(11):8684-8693. Epub 2018 Aug 4.

Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Pain is a common experience for most patients in the intensive care unit (ICU). In the current study, the advantages and disadvantages of analgesic and sedative drugs used in the ICU are reviewed. An ideal sedative and analgesic agent should have features such as rapid onset of action, rapid recovery after discontinuation, predictability, minimal accumulation of the agent and metabolites in the body, and lack of toxicity. None of the sedative and analgesic agents have all of these desired characteristics; nevertheless, clinicians must be familiar with these classes of drugs to optimize pharmacotherapy and ensure as few side-effects as possible for ICU patients.
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http://dx.doi.org/10.1002/jcb.27141DOI Listing
November 2018

Prevalence of candidemia and associated candida subtypes following severe sepsis in non-neutropenic critically ill patients.

Acta Biomed 2018 06 7;89(2):193-202. Epub 2018 Jun 7.

Clinical Pharmacy Department, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: Invasive candidiasis management through the rapid initiation of appropriate antifungal therapy has been shown to be associated with the better prognosis, improved clinical outcome and reduced mortality in critically ill patients. Therefore, selection of  an appropriate antifungal therapy should be based on the distribution of candida species and the pattern of antifungal resistance. This study aimed to assess the prevalence of candidemia and associated subtypes following severe sepsis in non-neutropenic critically ill patients.

Methods: This study was a cross-sectional study that was conducted on severe sepsis patients stayed at least seven days in intensive care unit. Patients less than 18 years old, pregnant and breastfeeding patients, immunocompromised patients, neutropenic patients, patients with concurrent use of antifungal medicines and cytotoxic agents were excluded.To asses the candidemia, one mililiter of patients' blood sample was collected. Sample analysis was performed by Real-Time PCR and high resolution melting curve analysis method.

Results: Thirty-one critically ill patients were recruited in this study over 12-month period. Candidemia with a detection limit of 100 pg per 0.2 ml blood sample was not recognized in any of the included patients.

Conclusion: The present result indicates low incidence of candidemia in the targeted intensive care units, but other factors such as small sample size, exclusion of patients with compromised immune system and the low fungal load at the time of sampling may also account for our observation.
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http://dx.doi.org/10.23750/abm.v89i2.5385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179014PMC
June 2018

Adaptation of the Pharmacological Management of Delirium in ICU Patients in Iran: Introduction and Definition.

Iran J Psychiatry 2018 Jan;13(1):65-79

Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Delirium is a brain dysfunction syndrome. In most cases, this syndrome is neither diagnosed accurately nor treated properly. The incidence of delirium by itself increases hospitalization period, mortality rate and the cost in health spectrum. If appropriate attempts are not made to treat this complication, the outcomes could become worse. Thus, the present study aimed at conducting a review on medications which are prescribed to treat delirium and establishing a general view on their advantages and disadvantages. By searching Google Scholar, PsycINFO, Scopus, and PubMed databases as well as hand searching in key journals, data were collected without time and language limitation. After collecting the data, comparing the similar or contradictory information, and sorting them, the views of specialists were inquired and duly received via email. By acquiring consensus of opinions, the secondary manuscript was written in a narrative review form. This narrative review paper aimed at providing a general view on defining delirium, the pathologic factors that create it, and treating this syndrome based on its development. Authentic evidence regarding delirium management was reviewed and a treatment strategy was suggested for Iranian patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5994234PMC
January 2018

Effect of Hypertonic Saline 5% on Early Graft Function and Urinary Interleukin 18 and Neutrophil Gelatinase-Associated Lipocalin in Deceased-Donor Kidney Transplantation.

Iran J Pharm Res 2017 ;16(4):1583-1592

Department of Pharmacotherapy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Ischemia reperfusion injury (IRI) is one of the main causes of delayed graft function (DGF) in deceased-donor kidney transplantation (DDKT). Evidences suggest that hypertonic saline (HS) has beneficial effects on IRI. The objective of the present study is to determine the effect of intraoperative HS, on graft function and urinary biomarkers of interleukin 18 (IL-18) and neutrophil gelatinase-associated lipocalin (NGAL), in patients with DDKT. The design of the study is a randomized, open-label, pilot trial in patients with DDKT. The intervention of the study is administration of 4 mL/kg HS, 5% before graft reperfusion. The primary endpoint was DGF. Fifty-eight (58) adult patients were randomized (HS, n = 32; control, n = 26). There were no significant differences between the two groups in terms of recipient, donor, and transplant characteristics. The rate of DGF was 20% in the HS group compared with 31.8% in the control group (Relative risk 0.63; 95% CI 0.23-1.67; = 0.36). Serial serum creatinine in the first two days after surgery in addition to urine volumes during the first day after transplantation was significantly different in the HS group ( ≤ 0.05). The urinary NGAL and IL-18 were significantly lower in HS vs. control, at 24 h after transplantation ( ≤ 0.05). The frequency of adverse reactions was similar between groups. This study did not show any significant benefits from HS administration immediately before allograft reperfusion in terms of reducing DGF, serum creatinine at hospital discharge or length of hospital stay in deceased-donor kidney transplant patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5843320PMC
January 2017

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

Infect Drug Resist 2018 13;11:223-228. Epub 2018 Feb 13.

Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

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 (C) and trough (C) 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 C levels in the standard and high-dose treatment groups were 30.4±11 and 52.3±16.1 µg/mL (<0.001), and the C levels were 3.2±2.1 and 5.2±2.8 µg/mL, respectively (=0.035). On Day 7, the C levels in the standard and high-dose groups were 33±7.3 and 60.0±17.6 µg/mL (=0.001), and the C levels were 3.2±2.9 and 9.3±5.6 µg/mL, respectively (=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 C reached the target levels (>64 µg/mL), whereas the amikacin mean C 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.
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http://dx.doi.org/10.2147/IDR.S150839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5815475PMC
February 2018

Evaluation of Epithelial Lining Fluid Concentration of Amikacin in Critically Ill Patients With Ventilator-Associated Pneumonia.

J Intensive Care Med 2020 Apr 22;35(4):400-404. Epub 2018 Feb 22.

Department of Clinical Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Introduction: Classically, aminoglycosides are known to have low penetration into the lung tissue. So far, no study has been conducted on human adult patients to evaluate amikacin concentration in epithelial lining fluid (ELF) of the alveoli. Therefore, convincing data are not available from the perspective of pharmacokinetics to support the fact that a dosage of 20 mg/kg of amikacin is sufficient to treat patients with ventilator-associated pneumonia (VAP).

Method: This was a pilot study of amikacin concentration measurement in the alveolar site of action in critically ill adult patients with VAP who required aminoglycoside therapy. A dose of 20 mg/kg of amikacin was administered over a 30-minute infusion. The serum concentrations of amikacin were evaluated in the first, second, fourth, and sixth hours. However, the ELF concentration of amikacin was evaluated in the second hour with the help of bronchoalveolar lavage sampling technique.

Results: A total number of 8 patients was included in the study. The mean (SD) administered dose was 20 (0.9) mg/kg. The mean (SD) peak plasma concentration of amikacin was 59.6 (23) mg/L, with the volume of distribution of 0.36 (0.13)L/kg. The amikacin concentration in ELF was successfully measured in 7 patients (6.3) mg/L. The lung tissue penetration of the drug was described as alveolar percentage, proportional to both the first- and second-hour plasma concentrations, with a mean (SD) of 10.1% (8.4%) and 18% (16.7%), respectively.

Conclusion: To our knowledge, the current study is the first that investigates whether standard doses of amikacin may lead to sufficient alveolar concentration of the drug. The results show that administration of amikacin in doses of 20 mg/kg in critically ill patients with VAP may not provide sufficient concentrations in ELF.
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http://dx.doi.org/10.1177/0885066618754784DOI Listing
April 2020

Pharmacokinetic Behavior of Phenytoin in Head Trauma and Cerebrovascular Accident Patients in an Iranian Population.

J Res Pharm Pract 2017 Oct-Dec;6(4):217-222

Department of Clinical Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Objective: Acute brain injury is one of the leading causes of morbidity and mortality worldwide. Phenytoin has been commonly used as an anticonvulsant agent for the treatment or prophylaxis of seizures following acute brain injury. After a severe head injury, several pharmacokinetic changes occur. The aim of this study is the comparative evaluation of phenytoin serum concentration in patients with traumatic and nontraumatic brain injury (TBI).

Methods: This prospective observational study was performed on twenty adult brain injury patients who were admitted to an Intensive Care Unit and required phenytoin for the treatment or prophylaxis of postinjury seizures. For all the patients, phenytoin serum concentration was determined in three scheduled time points. Phenytoin serum concentration and pharmacokinetic parameters were compared between patients with TBI and cerebrovascular accident (CVA).

Findings: The Vand Kwere significantly higher in head trauma (HT) patients than the CVA group. The phenytoin concentration (C) and the C/dose ratio were significantly higher in the CVA group patients during the first sampling ( < 0.05). The Acute Physiology and Chronic Health Evaluation П (APACHE П) score was significantly lower than the baseline at the end of the study in each group of patients ( < 0.05). In addition, no significant correlation was observed between V, K, C, C/dose ratio, and APACHE II scores at the time of sampling.

Conclusion: Due to significant differences in phenytoin plasma concentration and pharmacokinetic parameters between HT and CVA patients, close attention must be paid to the pharmacokinetic behavior of phenytoin in the efforts to improve the patient's outcome after a severe HT.
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http://dx.doi.org/10.4103/jrpp.JRPP_17_58DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5787907PMC
February 2018

Melatonin Supplementation May Improve the Outcome of Patients with Hemorrhagic Stroke in the Intensive Care Unit.

J Res Pharm Pract 2017 Jul-Sep;6(3):173-177

Department of Clinical Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran.

Objective: Although mechanical ventilation is frequently a life-saving therapy, its use can result in unwanted side effects. It has been well documented that the choice of sedating agent may influence the duration of mechanical ventilation. Melatonin is a sedative and analgesic agent without any respiratory depressant effect which makes it an attractive adjuvant for sedation in the intubated patients. The aim of this study is to evaluate the effect of melatonin on the duration of mechanical ventilation in patients with hemorrhagic stroke.

Methods: Forty adult intubated patients with hemorrhagic stroke, who were admitted to the Intensive Care Unit (ICU) within 24 h of onset, were enrolled in this randomized double-blind study. Subjects in the melatonin group received 30 mg of melatonin every night throughout the nasogastric tube. Length of ICU stay, mortality, and duration of mechanical ventilation were recorded for all patients.

Findings: The duration of mechanical ventilation and length of ICU stay were shorter in patients who received melatonin in comparison with the control group, and this difference was statistically significant for the length of ICU stay and marginally significant for the duration of mechanical ventilation. Although not statistically significant, the mortality rate of the control group was 30%, almost double that of the study group (15%).

Conclusion: Melatonin possesses hypnotic, analgesic, anti-inflammatory, and anti-oxidative properties that distinguish it as an attractive adjuvant in patients under mechanical ventilation. In conclusion, the administration of melatonin may facilitate the weaning process through decreasing the consumption of sedatives with respiratory depressant properties as well as preventing ventilator-associated lung injury.
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http://dx.doi.org/10.4103/jrpp.JRPP_17_49DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5632938PMC
October 2017

Randomized Trial of Carnitine for the Prevention of Perioperative Atrial Fibrillation.

Semin Thorac Cardiovasc Surg 2018 24;30(1):7-13. Epub 2017 Aug 24.

Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.

Atrial fibrillation (AF) is one of the most common complications in patients who undergo coronary artery bypass graft surgery (CABG). The aim of this study was to evaluate the effect of L-carnitine administration on postoperative AF and the levels of C-reactive protein (CRP) following CABG. The effects of L-carnitine on the incidence of acute kidney injury after CABG were also assessed. One hundred thirty-four patients undergoing elective CABG, without a history of AF or previous L-carnitine treatment, were randomly assigned to an L-carnitine group (3000 mg/d L-carnitine) or a control group. CRP levels, as a biomarker of inflammation, were assessed in all the patients before surgery as baseline levels and 48 hours postoperatively. Neutrophil gelatinase-associated lipocalin, as a kidney biomarker, was also measured in the patients before surgery and 2 hours thereafter. The incidence of AF was 13.4% in our population. The incidence of AF was decreased in the L-carnitine group (7.5% in the L-carnitine group vs 19.4% in the control group; P = 0.043) and the postoperative CRP level (8.79 ± 6.9 in the L-carnitine group, and 10.83 ± 5.7 in the control group; P = 0.021). The postoperative neutrophil gelatinase-associated lipocalin concentration demonstrated no significant rise after surgery compared with the preoperative concentration (72.54 ± 20.30 in the L-carnitine group vs 67.68 ± 22.71 in the placebo group; P = 0.19). Our study showed that L-carnitine administration before CABG might inhibit and reduce the incidence of AF after CABG. It seems that a rise in the CRP level, as an inflammation marker, may be associated with the incidence of AF. Inflammation as measured by CRP was also reduced in the carnitine group, compared with the control group.
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http://dx.doi.org/10.1053/j.semtcvs.2017.08.006DOI Listing
October 2018

Vasopressin in Septic Shock; Assessment of Sepsis Biomarkers: A Randomized, Controlled Trial.

Indian J Crit Care Med 2017 Sep;21(9):578-584

Department of Clinical Pharmacy (Pharmacotherapy), School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Background And Aims: Vasopressin (VP) in sepsis apart from vasoconstrictive effect may have some immunomodulatory effects. The aim of this study was to evaluate the effect of VP on different aspect of sepsis by measuring of sepsis biomarkers.

Materials And Methods: In this trial, a total number of 42 septic shock patients were included. The first group received norepinephrine (NE) infusion to reach the target mean arterial pressure (MAP) of ≥ 65 mm Hg and the second group received arginine vasopressin (AVP) infusion in addition to NE. Serum lactate, C-reactive protein (CRP), interleukin-6 (IL-6), IL-10, pentraxin 3 (PTX3), angiopoietin 1 and 2 (Ang 1 and 2) levels were assessed.

Results: Level of IL-6 and IL-10 decreased, but there was no significant difference between the two groups after 48 h. CRP and PTX3 levels were not also significantly different between groups. Although Angs were not statistically different, there was a trend toward higher Ang-1 in and lower Ang 2 in AVP group after 24 and 48 h. In addition, lactate level did not differ between NE and AVP groups. There was no interaction between VP and hydrocortisone use on IL-6, IL-10, and PTX3, but a significant statistical interaction on Ang 1 and Ang 2 were observed.

Conclusions: Although analysis of sepsis biomarkers showed no significant difference between two groups, no immunomodulatory effect for VP alone, subgroup analysis of hydrocortisone used in this study showed that the combination of glucocorticoids and AVP had a significant effect on Angs level which eventually causes less endothelial permeability and higher MAP in this group of patients.
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http://dx.doi.org/10.4103/ijccm.IJCCM_258_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5613609PMC
September 2017