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Key Clinical Message: Generalized tetanus is still a global concern with a mortality rate of up to 50%, especially in low and middle‐income countries. We reported a 23‐year‐old man from Afghanistan admitted to emergency department, with the chief complaint of generalized severe spasms and lockjaw. The patient had skin lesions and had never been vaccinated against tetanus. He intubated and admitted to the intensive care unit (ICU) with diagnose of severe generalized tetanus. After receiving tetanus immunoglobulin and intravenous metronidazole, a combination therapy of midazolam, propofol, atracurium, and morphine was administered. Due to the refractory muscular spasms intravenous phenobarbital started and little by little recovery was achieved. The patient receiving the first two doses of the Td vaccine, and discharged on Day 42 of hospitalization with no symptom recurrence. This case management showed adding phenobarbital to severe tetanus treatment regimen could significantly reduce refractory spasm caused by tetanus, also decrease other medication requirement. [ABSTRACT FROM AUTHOR]

Background: Different virulence factors are involved in the pathogenesis of urinary tract infection (UTI) caused by Uropathogenic Escherichia coli (UPEC); hence, this study aimed to study the prevalence of biofilm formation, virulence factors, and phylogenetic groups and their correlation with biofilm formation among UPEC isolates through a systematic review and meta-analysis. Materials and Methods: A literature search was conducted from 1, 2000, to the end of 2021 in different databases for studies that reported biofilm together with virulence genes or phylogenetic groups in UPEC isolates from patients with UTI according to PRISMA protocol. Data were analyzed by Comprehensive meta-analysis software. Results: The pooled prevalence of biofilm formers was 74.7%. The combined prevalence of phylogenetic Groups A, B1, B2, and D (s) were reported at 19.6%, 11%, 50.7%, and 20.5%, respectively. The most common virulence genes reported worldwide were fimA, ecpA, and fimH, with a combined prevalence of 90.3%, 86.6%, and 64.9%, respectively. The pooled prevalence of biofilm formation in UPEC isolates with phylogenetic Groups A, B1, B2, D, C, and F were 12.4%, 8.7%, 33.7%, 12.4%, 2.6%, and 2.65%, respectively. Several studies showed a correlation between biofilm production and virulence genes, or phylogenetic groups. Conclusion: Regarding data obtained, the high level of combined biofilm formation (74.7%) and the presence of a positive correlation between biofilm production and virulence genes, or phylogenetic groups as reported by the most studies included in the present review, indicates an important role of biofilm in the persistence of UPEC in the UTI. [ABSTRACT FROM AUTHOR]

Remdesivir, an antiviral medication, became an early promising therapeutic candidate for coronavirus disease 2019 (COVID-19) due to its ability to inhibit the virus in vitro. Current evidence about remdesivir treatment has been very controversial, so we aim to evaluate remdesivir to improve our knowledge about COVID-19 management and its long-term effects. In this retrospective cohort study using registered data derived from the Sina Hospital COVID-19 Registry with a 9-month follow-up, we enrolled patients receiving remdesivir and then matched a "control group" which did not receive remdesivir based on age, gender, and severity using propensity score matching. We used multivariant Cox regression to evaluate the remdesivir effect on patients' 9-month and in-hospital survival. We enrolled 227 patients, 116 in remdesivir and 111 in the control group. 213(93.8%) patients developed the severe disease, 88(38.8%) died during the 9-month follow-up, and 84(37.0%) died during hospitalization. In multivariate analysis, remdesivir did not affect the 9-month all-cause mortality and in-hospital mortality. Remdesivir was associated with increased in-hospital survival only in severe patients with diabetes (HR: 0.32; 95% CI: 0.14-0.75; P:0.008), and there was a trend for better 9-month survival in severe patients with diabetes (HR: 0.47; 95% CI: 0.20-1.09; P:0.080). We concluded that remdesivir treatment did not increase the 9-month survival rate either in patients with COVID-19 or patients with severe disease and underlying diseases. On the other hand, we found that remdesivir treatment could increase inhospital survival only in patients with severe COVID-19 and a history of diabetes mellitus. [ABSTRACT FROM AUTHOR]

Byline: Elchin. Barzegar, Masoumeh. Nouri, Sarah. Mousavi, Arezoo. Ahmadi, Mojtaba. Mojtahedzadeh Background and Aims: Vasopressin (VP) in sepsis apart from vasoconstrictive effect may have some immunomodulatory effects. The aim of [...]

Byline: Legese. Chelkeba, Arezoo. Ahmadi, Mohammad. Abdollahi, Atabak. Najafi, Mohammad. Ghadimi, Reza. Mosaed, Mojtaba. Mojtahedzadeh Introduction: Severe sepsis and septic shock is characterized by inflammation and oxidative stress. Selenium levels [...]

Phenobarbital is still one of the drugs of choice in managing patients with brain injury in the intensive care unit (ICU). However, the impact of acute physiological changes on phenobarbital pharmacokinetic parameters is not well studied. This study aimed to evaluate the pharmacokinetic parameters of parenteral phenobarbital in critically ill patients with brain injury. Patients with severe traumatic or nontraumatic brain injury at high risk of seizure were included and followed for seven days. All patients initially received phenobarbital as a loading dose of 15 mg/kg over 30-minutes infusion, followed by 2 mg/kg/day divided into three doses. Blood samples were obtained on the first and fourth day of study at 1, 2, 5, 8, and 10 hours after the end of the infusion. Serum concentrations of phenobarbital were measured by high-pressure liquid chromatography (HPLC) with an ultraviolet (UV) detector. Pharmacokinetic parameters, including the volume of distribution (Vd), half-life (t1/2), and the drug clearance (CL), were provided by MonolixSuite 2019R1 software using stochastic approximation expectation-maximization (SAEM) algorithm and compared with previously reported parameters in healthy volunteers. Data from seventeen patients were analyzed. The mean value±standard deviation of pharmacokinetic parameters was calculated as follows: Vd: 0.81±0.15 L/kg; t1/2: 6.16±2.66 days; CL: 4.23±1.51 ml/kg/h. CL and Vd were significantly lower and higher than the normal population with the value of 5.6 ml/kg/h (P=0.002) and 0.7 L/kg (P=0.01), respectively. Pharmacokinetic behavior of phenobarbital may change significantly in critically ill brain-injured patients. This study affirms the value of early phenobarbital therapeutic drug monitoring (TDM) to achieve therapeutic goals. [ABSTRACT FROM AUTHOR]

Experimental studies have suggested the beneficial effects of curcuminoids as natural polyphenols against traumatic brain injury (TBI). The aim of this study was to investigate the effects of supplementation with curcuminoids on inflammatory and oxidative stress biomarkers, clinical outcomes and nutritional status in critically ill patients with TBI. A total of 62 ICU‐admitted adult patients with TBI were randomly allocated to receive either a daily dose of 500 mg curcuminoids or matched placebo via enteral nutrition for 7 consecutive days based on stratified block randomization by age and sex. Inflammatory and oxidative stress as well as clinical outcomes and nutritional status of the patients were measured at baseline and at the end of the study. There were no overall group effects regarding to all dependent variables. Compared with baseline, serum levels of IL‐6, TNF‐α, MCP‐1 and CRP were significantly reduced in patients receiving curcuminoids (p <.05) without any significant changes in placebo group; however, changes in the activities of GPx and SOD in serum were not significant between two groups. Moreover, APACHEII and NUTRIC score were significantly improved following curcuminoids consumption in comparison with placebo (p <.05). The findings of this study suggest that short‐term supplementation with curcuminoids may have beneficial effects on inflammation, clinical outcomes and nutritional status of critically ill patients with TBI. [ABSTRACT FROM AUTHOR]

Byline: Legese. Chelkeba, Arezoo. Ahmadi, Mohammad. Abdollahi, Atabak. Najafi, Mojtaba. Mojtahedzadeh Introduction: Survival sepsis campaign guidelines have promoted early goal-directed therapy (EGDT) as a means for reduction of mortality. On [...]

Previous studies have shown a beneficial effect of curcuminoids supplementation on serum concentrations of adipokines; however, there are no published studies that have examined this effect among critically ill patients. We aimed to assess the effects of supplementation with curcuminoids on serum concentrations of leptin and adiponectin in critically ill patients with traumatic brain injury (TBI). In this trial, 62 critically ill patients with TBI, aged 18-65 years, were randomly allocated to receive either 500 mg/day curcuminoids (co-administered with 5 mg/day piperine) or matched placebo for 7 days. Patients in both intervention groups received routine treatments for TBI as well as enteral nutrition. Serum concentrations of leptin and adiponectin were measured at baseline and at the end of trial. We found a significant reduction in serum levels of leptin in both curcuminoids (47.1%) and placebo (22.8%) groups; though the magnitude of reduction was greater in the former (p < .05). Supplementation with curcumioinds was not found to alter serum concentrations of adiponectin (p > .05). Supplementation with curcumioinds significantly reduced serum levels of leptin but had no significant effect on adiponectin levels in critically ill patients with TBI. Further clinical trials, particularly those with a long-term period, are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Diazinon (DZN) causes serious liver damage in both humans and animals. In the present study, the hepatoprotective effects of Cynara scolymus L. leaf extract against DZN-induced liver injury were examined. Methods: Forty male rats were divided into five groups. The control group received a normal diet. The DZN group received DZN only (25 mg/kg, po). The DZN + Syl group received DZN (25 mg/kg, po) and silymarin (Syl) (50 mg/kg, po). The DZN + Art group received DZN (25 mg/kg, po) and artichoke (Art) leaf extract (1500 mg/kg, po). The Art group received Art leaf extract only (1500 mg/kg, po). After 15 days, serum tumor necrosis factor α (TNF-α), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lipid profile, protein carbonyl content, serum and hepatic malondialdehyde (MDA), hepatic TNF-α gene expression, hepatic catalase (CAT), superoxide dismutase (SOD), and vitamin C (Vit C) were measured and histopathological examination was performed. Results: DZN caused a significant elevation in serum ALP, AST, ALT, MDA, TNF-α, protein carbonyl, hepatic MDA, and TNF-α gene expression in the DZN group as opposed to the control group. Also, DZN led to the reduction of hepatic CAT, SOD, and Vit C in the DZN group relative to the control group. The administration of Art extract resulted in not only a significant reduction in serum ALP, AST, ALT, MDA, TNF-α, and protein carbonyl but also an improvement of liver histopathological changes and hepatic CAT and SOD activities as opposed to the DZN group. Conclusions: This study confirmed that Art leaf extract has liver protective effects and causes downregulation of oxidative stress in acute DZN-induced liver injury in rats. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abdominal aortic aneurysm (AAA) is widely considered as the disease of elderly white men. Inflammation is one of the most well-known mechanisms involved in the pathogenesis of AAA. Magnesium is one of the most important minerals in the body with established antiinflammatory effects. In this study, we aimed to investigate the impact of Mg loading following AAA surgery on two inflammation markers, IL-6 and CRP, as well as patient's outcome. This study was conducted as a randomized clinical trial on 18 patients (divided into two groups) after surgical correction of Acute Aortic Aneurysm (AAA). All the patients admitted in ICU ward of Sina Hospital. In intervention group, 10 g of MgSO4 has been infused through 12 h. The control group has not received the intervention. IL-6 and CRP were measured and compared at times 0, 12, 24 and 36 h. The patients were monitored for 36 h. After intervention, the differences of heart rate and APACHE II score were not statistically significant between intervention and control groups (P = 0.097 and P = 0.472, respectively). IL-6 levels decreased consistently in both groups after inclusion in the study. However, IL-6 level was significantly less in intervention group early after the end of MgSO4 infusion comparing with control group (P = 0.01). Likewise, the CRP level decreased significantly after inclusion in the study (P = 0.005). However, these changes were not significant between intervention and control groups (P = 0.297). According to the results of this study, continuous infusion of MgSO4 after AAA surgery may provide IL-6 suppression. [ABSTRACT FROM AUTHOR]

Arginine vasopressin as a supplementary vasopressor in septic shock restores vascular tone and mean arterial pressure, meanwhile decreases dose and exposure time to catecholamines. The objective of this study was to evaluate the effect of vasopressin on lactate and lactate clearance as markers of tissue perfusion during septic shock. In this prospective, randomized, controlled trial, 30 patients with septic shock were enrolled in two groups. One group received norepinephrine infusion (titrated to reach the target MAP of ≥65 mm Hg) and the other group in addition to norepinephrine, received vasopressin at a constant rate of 0.03 u/min. Serum lactate levels were assessed at baseline, 24 and 48 hours after randomization. Lactate clearance was estimated for each patient at 24 and 48 hours. Venous lactate was measured in both groups. Despite a tendency toward higher venous lactate at 24 and 48 hours in the norepinephrine group (3.1 vs. 2.5, P = 0.67 and 1.7 vs. 1.1, P = 0.47), the conflict was not statistically significant among them. While lactate clearance after 24 hours was significantly higher in vasopressin treatment group (46% vs. 20%, respectively; P = 0.048), the 48-hour lactate clearance did not differ from statistic viewpoints despite their clinical values (66% vs. 40%, P = 0.17). Although lactate levels did not significantly differ between treatment groups, lactate clearance at 24 hours was significantly higher in vasopressin group. This may be the effect of vasopressin effect on microcirculation and tissue hypoperfusion or its catecholamine sparing effect. [ABSTRACT FROM AUTHOR]

The empiric antibiotic therapy can result in antibiotic overuse, development of bacterial resistance and increasing costs in critically ill patients. The aim of the present study was to evaluate the effect of procalcitonin (PCT) guide treatment on antibiotic use and clinical outcomes of patients admitted to intensive care unit (ICU) with systemic inflammatory response syndrome (SIRS). A total of 60 patients were enrolled in this study and randomly divided into two groups, cases that underwent antibiotic treatment based on serum level of PCT as PCT group (n=30) and patients who undergoing antibiotic empiric therapy as control group (n=30). Our primary endpoint was the use of antibiotic treatment. Additional endpoints were changed in clinical status and early mortality. Antibiotics use was lower in PCT group compared to control group (P=0.03). Current data showed that difference in SOFA score from the first day to the second day after admitting patients in ICU did not significantly differ (P=0.88). Patients in PCT group had a significantly shorter median ICU stay, four days versus six days (P=0.01). However, hospital stay was not statistically significant different between two groups, 20 days versus 22 days (P=0.23). Early mortality was similar between two groups. PCT guidance administers antibiotics reduce antibiotics exposure and length of ICU stay, and we found no differences in clinical outcomes and early mortality rates between the two studied groups. [ABSTRACT FROM AUTHOR]

According to limitations in blood product resources and to prevent unnecessary transfusions and afterwards complications in perioperative period of total hip arthroplasty, authors administered fibrinogen concentrate in a pilot randomized clinical trial to evaluate bleeding and need to blood transfusion in preoperative period. Thirty patients (3-75 years old) with ASA physical status class I or II and candidate for total hip arthroplasty consequently enrolled in this study and randomly assigned into two groups: taking fibrinogen concentrate and control. Two groups were similar in serum concentration of fibrinogen, hemoglobin, and platelet preoperatively. After induction of general anesthesia 30mg/kg fibrinogen concentrate was administered in the fibrinogen group. Blood loss, need to blood transfusion and probable complications were compared between two groups. The mean operation time was 3.3 ± 0.8 hours in the fibrinogen group and 2.8 ± 0.6 hours in the placebo group, and this difference was statistically significant (P=0.04). There was a significant correlation between operation time and blood loss during surgery (P=0.002). The mean transfused blood products in the fibrinogen and control group was 0.8 ± 1.01 units and 1.06 ± 1.2 units respectively (P=0.53). The mean of perioperative blood loss was 976 ± 553 ml in the fibrinogen group and 1100 ± 350 ml in the control group, but this difference was not significant between two groups. By adjusting time factor for two groups, we identified that the patients in fibrinogen group had lower perioperative bleeding after adjusting time factor for two groups (P=0.046). None of the patients had complications related to fibrinogen concentrate administration. The prophylactic administration of fibrinogen concentrate was safe and effective in reducing bleeding in the perioperative period of total hip arthroplasty. [ABSTRACT FROM AUTHOR]

High-dose extended-interval dosage (HDED) regimen of aminoglycosides is now considered as the standard dosage strategy in sepsis. Although safety and efficacy of this dosing regimen is well studied, but new experiments show increased the risk of resistance development associated with %T>MIC less than 60% of the dosing interval following extended interval dosing. Moreover, limited information is available about safety of more frequent administration of high dose aminoglycosides. Authors studied nephrotoxicity following seven days' exposure to more frequent administration of higher doses of amikacin comparing with HDED regimen. In addition to Serum Creatinine (SrCr) and estimated glomerular filtration rate (eGFR), nephrotoxicity was studied with Neutrophil gelatinase-associated lipocalin (NGAL), a direct marker of tubular injury. A total of 40 patients with sepsis were quasi-randomized in two groups. Seven days' course of treatment with a moderate dose of amikacin (12.5 mg/Kg) was administered every 12 hours, known as the moderate-dose non-liberal-interval dosage (MDNLD) regimen compared with the high-dose extended-interval dosage (HDED) regimen (25mg/Kg every 24 hours). The pharmacokinetic/pharmacodynamic (PK/PD) goal of the MDNLD regimen was the Cmax>40 and the %T>MIC more than 60% during the PK/PD goal for the HDED regimen was the Cmax>60. The eGFR change from the baseline was the primary outcome of the study with a minimum clinical significance of 20ml/min (estimated SD of 20, Power>90%, P<0.05). No difference was observed between groups for the values of eGFR change and the SrCr percent change from the baseline (P=0.359 and P=0.114, respectively). Frequency of acute kidney injury also did not differ between groups (P=0.342). Serum NGAL level values' change from the baseline was more in the HDED regimen in comparison with the MDNLD regimen at third day and fifth day of the treatment (P=0.001 and P =0.002, respectively). This indicates a safer pattern of moderate doses with more frequent administration of amikacin at the tubular injury level. Higher doses of amikacin could be safely administered to achieve PK/PD goal of Cmax>40 and %T>MIC more than 60% of the dosing interval. This dosing regimen would be considered as an alternative to minimize the resistance development associated with the extended-interval dosing in septic patients with multi-drug resistant gram-negative organisms. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress processes play an important role in the pathogenesis of secondary brain injury after traumatic brain injury (TBI). Hypertonic saline (HTS) has advantages as being preferred osmotic agent, but few studies investigated oxidant and antioxidant effects of HTS in TBI. This study was designed to compare two different regimens of HTS 5% with mannitol on TBI‑induced oxidative stress. Materials and Methods: Thirty‑three adult patients with TBI were recruited and have randomly received one of the three protocols: 125 cc of HTS 5% every 6 h as bolus, 500 cc of HTS 5%as infusion for 24 h or 1 g/kg mannitol of 20% as a bolus, repeated with a dose of 0.25-0.5 g/kg every 6 h based on patient's response for 3 days. Serum total antioxidant power (TAP), reactive oxygen species (ROS) and nitric oxide (NO) were measured at baseline and daily for 3 days. Results: Initial serum ROS and NO levels in patients were higher than control (6.86± [3.2] vs. 1.57± [0.5] picoM, P = 0.001, 14.6± [1.6] vs. 7.8± [3.9] mM, P = 0.001, respectively). Levels of ROS have decreased for all patients, but reduction was significantly after HTS infusion and mannitol (3. 08 [±3.1] to 1.07 [±1.6], P = 0.001, 5.6 [±3.4] to 2.5 [±1.8], P = 0.003 respectively). During study, NO levels significantly decreased in HTS infusion but significantly increased in mannitol. TAP Levels had decreased in all patients during study especially in mannitol (P = 0.004). Conclusion: Hypertonic saline 5% has significant effects on the oxidant responses compared to mannitol following TBI that makes HTS as a perfect therapeutic intervention for reducing unfavorable outcomes in TBI patients. [ABSTRACT FROM AUTHOR]

Background: Sepsis complication is a major cause of death in multiple trauma critically ill patients. Defensin (cysteine rich anti-microbial peptides), as an important component of immune system, might play an important role in this process. There is also rising data on immunological effects of N-acetyl-cysteine (NAC), a commonly used anti-oxidant in oxidative stress conditions and glutathione (GSH) deficiencies. The aim of the present study was to evaluate the potential beneficial effects of NAC administration on multiple trauma patients with sepsis. Methods: In a prospective, randomized controlled study, 44 multiple trauma critically ill patients who were mechanically ventilated and met the criteria of sepsis and admitted to the intensive care unit (ICU) were randomized into two groups . Control group received all standard ICU therapies and NAC group received intravenous NAC 3 gr every 6 hours for 72 hours in addition to standard therapies. Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores, length of ICU stay, ICU mortality were recorded. Levels of serum Immunoglobulin M (IgM), Human β-Defensin 2 (HβD2) and GSH were assessed at baseline and 24, 72, 120 hours after intervention. Results: During a period of 13-month screening, 44 patients underwent randomization but 5 patients had to be excluded. 21 patients in NAC group and 18 patients in control group completed the study. For both groups the length of ICU stay, SOFA score and systemic oxygenation were similar. Mortality rate (40% vs. 22% respectively, p = 0.209) and ventilator days (Mean ± SD 19.82 ± 19.55 days vs. 13.82 ± 11.89 days respectively, p = 0.266) were slightly higher for NAC group. IgM and GSH levels were similar between two groups (p = 0.325, 0.125 respectively), HβD2 levels were higher for NAC group (at day 3). Conclusion: High dose of NAC administration not only did not improve patients' outcome, but also raised the risk of inflammation and was associated with increased serum creatinine. [ABSTRACT FROM AUTHOR]

Background: The importance of resting heart rate as a prognostic factor was described in several studies. An elevated heart rate is an independent risk factor for adverse cardiovascular events and total mortality in patients with coronary artery disease, chronic heart failure, and the general population. Also heart rate is elevated in the Multi Organ Dysfunction Syndrome (MODS) and the mortality due to MODS is highly correlated with inadequate sinus tachycardia. To evaluate the value of resting heart rate in predicting mortality in patients with traumatic brain injury along scoring systems like Acute Physiology and Chronic Health Evaluation(APACHE II), Sequential Organ Failure Assessment (SOFA) and Glasgow Coma Score (GCS). Method: By analyzing data which was collected from an open labeled randomized clinical trial that compared the different means of osmotherapy (mannitol vs bolus or infusion hypertonic saline), heart rate, GCS, APACHE II and SOFA score were measured at baseline and daily for 7 days up to 60 days and the relationship between elevated heart rate and mortality during the first 7 days and 60th day were assessed. Results: After adjustments for confounding factors, although there was no difference in mean heart rate between either groups of alive and expired patients, however, we have found a relative correlation between 60th day mortality rate and resting heart rate (P=0.07). Conclusion: Heart rate can be a prognostic factor for estimating mortality rate in brain injury patients along with APACHE II and SOFA scores in patients with brain injury. [ABSTRACT FROM AUTHOR]

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-1β, IL-6, IL-10 and TNF-α. Pantoprazole infusion have decreased the plasma IL-1β 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-1β 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. [ABSTRACT FROM AUTHOR]

Background and the purpose of the study: Blood contact with artificial surfaces of the extracorporeal circuit and ischemia-reperfusion injury in CABG with CPB, may lead to a systemic inflammatory response. Hypertonic saline have been recently investigated as a fluid in order to decrease inflammatory response and cytokines generation in patients undergo cardiac operations. Our purpose is to study the prophylactic effect of HS 5% infusion versus NS on serum IL-6 as an inflammatory & IL-10 as an anti-inflammatory biomarker in CABG patients. Methods: The present study is a randomized double-blinded clinical trial. 40 patients undergoing CABG were randomized to receive HS 5% or NS before operation. Blood samples were obtained after receiving HS or NS, just before operation, 24 and 48 hours post-operatively. Plasma levels of IL-6 and IL-10 were measured by ELISA. Results and major conclusion: Patients received HS had lower levels of IL-6 and higher level of IL-10 compared with NS group, however these differences were not statistically significant. Results of this study suggest that pre-treatment with small volume hypertonic saline 5% may have beneficial effects on inflammatory response following CABG operation. [ABSTRACT FROM AUTHOR]

Background: Septimeb is a new herbal-derived remedy, recently approved for its potential immunomodulatory effects. Regarding the key role of immune system in the pathogenesis of severe sepsis and lack of any standard treatment for improving survival of these patients; we evaluated the effect of Septimeb -as an adjutant to standard treatment-on inflammatory biomarkers and mortality rates in patients with severe sepsis. Methods: In this multicenter, randomized, single-blind trial, we assigned patients with severe sepsis and Acute Physiology and Chronic Health Evaluation (APACHE II) score of more than 20 to receive standard treatment of severe sepsis (control group) or standard treatment plus Septimeb. This group was treated with Septimeb for 14 days then followed up for another14 days. APACHE score, Sequential Organ Failure Assessment (SOFA) and Simplified Acute Physiology Score (SAPS) were calculated daily. Blood samples were analyzed for interleukin 2 tumor necrosis factor-á, total antioxidant power, platelet growth factor and matrix metalloproteinase 2. Results: A total of 29 patients underwent randomization (13 in control group and 16 in Septimeb group). There was significant difference between the Septimeb and control group in the 14 days mortality rate (18.8% vs. 53.85 respectively, P=0.048). Compared to control group, Septimeb was significantly effective in improving SAPS (P= 0.029), SOFA (P=0.003) and APACHE II (P=0.008) scores. Inflammatory biomarkers didn't change significantly between the two groups (P>0.05). Conclusion: Septimeb reduces mortality rates among patients with severe sepsis and it could be added as a safe adjutant to standard treatment of sepsis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Iran was one of the first countries to become an epicenter of the coronavirus disease 2019 (COVID-19) epidemic. However, there is a dearth of data on the outcomes of COVID-19 and predictors of death in intensive care units (ICUs) in Iran. We collected extensive data from patients admitted to the ICUs of the one of the tertiary referral hospitals in Tehran, Iran, to investigate the predictors of ICU mortality. Methods: The study population included 290 COVID-19 patients who were consecutively admitted to the ICUs of the Sina hospital from May 5, 2021, to December 6, 2021, a period that included the peak of the epidemic of the delta (δ) variant. Demographic data, history of prior chronic diseases, laboratory data (including markers of inflammation), radiologic data, and medication data were collected. Results: Of the 290 patients admitted to the ICUs, 187 (64.5%) died and 103 (35.5%) survived. One hundred forty-one (141, 48.6%) were men, and the median age (10th percentile, 90th percentile) was 60 (41, 80). Using logistic regression models, older age, history of hypertension, high levels of inflammatory markers, low oxygen saturation, substantial lung involvement in computed tomography (CT) scans, and gravity of the disease as indicated by the WHO 8-point ordinal scale were primary predictors of mortality at ICU. The use of remdesivir and imatinib was associated with a statistically non-significant reduction in mortality. The use of tocilizumab had almost no effect on mortality. Conclusion: The findings are consistent with and add to the currently existing international literature. The findings may be used to predict risk of mortality from COVID-19 and provide some guidance on potential treatments [ABSTRACT FROM AUTHOR]

Introduction: we report a 56-year-olds female with supraventricular arrhythmia due acute ischemic stroke without structural heart disease. Case Description: A patient presented with sudden onset of lethargy, right hemiplegia, and global aphasia. There was previous history of stroke 1 year ago presented with left hemiplegia that recovered completely during 10 days. There was no history of comorbid illness. The brain CT revealed extensive hypodensity in left temporoparietal region suggestive of infarct without midline shift. General examination revealed hypotension and bradycardia that treated with dopamine that gradually recovered during 5 days thus infusion of dopamine discontinued, and muscular power in paretic limbs and aphasia was recovered. In 6th day of admission electrocardiographic monitoring of patient showed a rapidly changing tachyarrhythmia including sinus tachycardia, atrial fibrillation, and atrial flutter that quickly interchanged to another, without hemodynamic instability and alteration in mental status. Laboratory tests and TEE study were normal. During 48 hour arrhythmia relived spontaneously. Discussion: Stroke can cause any type of cardiac arrhythmias that may not be constant. [ABSTRACT FROM AUTHOR]