Modulation of oxidative and nitrosative stress attenuates microvascular hyperpermeability in ovine model of Pseudomonas aeruginosa sepsis

In sepsis, microvascular hyperpermeability caused by oxidative/nitrosative stress (O&NS) plays an important role in tissue edema leading to multi-organ dysfunctions and increased mortality. We hypothesized that a novel compound R-107, a modulator of O&NS, effectively ameliorates the severity of microvascular hyperpermeability and preserves multi-organ function in ovine sepsis model. Sepsis was induced in twenty-two adult female Merino sheep by intravenous infusion of Pseudomonas aeruginosa (PA) (1 × 1010 CFUs). The animals were allocated into: 1) Control (n = 13): intramuscular injection (IM) of saline; and 2) Treatment (n = 9): IM of 50 mg/kg R-107. The treatment was given after the PA injection, and monitored for 24-h. R-107 treatment significantly reduced fluid requirement (15–24 h, P < 0.05), net fluid balance (9–24 h, P < 0.05), and water content in lung/heart/kidney (P = 0.02/0.04/0.01) compared to control. R-107 treatment significantly decreased lung injury score/modified sheep SOFA score at 24-h (P = 0.01/0.04), significantly lowered arterial lactate (21–24 h, P < 0.05), shed syndecan-1 (3–6 h, P < 0.05), interleukin-6 (6–12 h, P < 0.05) levels in plasma, and significantly attenuated lung tissue 3-nitrotyrosine and vascular endothelial growth factor-A expressions (P = 0.03/0.002) compared to control. There was no adverse effect in R-107 treatment. In conclusion, modulation of O&NS by R-107 reduced hyperpermeability markers and improved multi-organ function.

Modulation of Oxidative and Nitrosative Stress Attenuates Microvascular Hyperpermeability in Ovine Model of Pseudomonas Aeruginosa Sepsis

In sepsis, microvascular hyperpermeability caused by oxidative/nitrosative stress (O&NS) plays an important role in tissue edema leading to multi-organ dysfunctions and increased mortality. We hypothesized that a novel compound R-107, a modulator of O&NS, effectively ameliorates the severity of microvascular hyperpermeability and preserves multi-organ function in ovine sepsis model. Sepsis was induced in twenty-two adult female Merino sheep by intravenous infusion of Pseudomonas aeruginosa (PA) (1x1010 CFUs). The animals were allocated into: 1) Control (n = 13): intramuscular injection (IM) of saline; and 2) Treatment (n = 9): IM of 50 mg/kg R-107. The treatment was given after the PA injection, and monitored for 24-hour. R-107 treatment significantly reduced fluid requirement (15–24 hours, p < 0.05), net fluid balance (9–24 hours, p < 0.05), and water content in lung/heart/kidney (p = 0.02/0.04/0.01) compared to control. R-107 treatment significantly decreased lung injury score/modified sheep SOFA score at 24-hour (p = 0.01/0.04), significantly lowered arterial lactate (21–24 hours, p < 0.05), shed syndecan-1 (3–6 hours, p < 0.05), interleukin-6 (6–12 hours, p < 0.05) levels in plasma, and significantly attenuated lung tissue 3-nitrotyrosine and vascular endothelial growth factor-A expressions (p = 0.03/0.002) compared to control. There was no adverse effect in R-107 treatment. In conclusion, modulation of O&NS by R-107 reduced hyperpermeability markers and improved multi-organ function.

COMPARISON OF LOW OSMOLAR ORAL REHYDRATION SOLUTION VERSUS STANDARD ORAL REHYDRATION SOLUTION IN CHILDREN WITH ACUTE DIARRHOEA IN RELATION TO UNSCHEDULED INTRAVENOUS FLUID REQUIREMENT

Objective: To determine requirement of unscheduled I/V fluid in children treated with low osmolar oral rehydration solution as compare to standard oral rehydration solution. Study Design: Case control study. Place and Duration of Study: Department of Paediatrics, Lahore General Hospital, Lahore, from Sep 2018 to Feb 2019. Methodology: Sample size of 400 patients was calculated using WHO calculator. Patients were recruited through non probability consecutive sampling. Patients were randomly divided into two groups. For each patient detailed history was taken including demographic information. Group A patients (controls) receive standard oral rehydration solution and Group B patients will receive low osmolar oral rehydration solution (Cases). Each group was followed for 6 hours after the treatment. Data analysis was done using SPSS version 24. Chi-square test applied and p-value ≤0.05 found significant. Results: A total of 400 cases were enrolled in the study. There were 220 (55%) male and 180 (45%) female in our study. Mean weight of patients was 9.46 Kg ± 5.9 SD. In group A, 8 patients showed unscheduled fluid requirement while 192 did not showed unscheduled fluid requirement. In group B, 32 patients showed unscheduled fluid requirement while 168 did not showed unscheduled fluid requirement (p=0.000). Conclusions: Incidence of or need of, unscheduled I/V fluid in children treated with low osmolar oral rehydration solution is less as compare to standard oral rehydration solution for management of acute diarrhea with some dehydration. And hence low osmolar oral rehydration solution shows better acceptance in management of acute diarrhea.

535 Vitamin C in the Management of Burn Patients: A Review of Benefits and Risks

Introduction Burns are global public health problem. Micronutrients play an essential role in defense mechanisms and immunity. Vitamin C has fostered a growing interest. We reviewed current evidence regarding the effects of Vitamin C on management of burn patients and aims to understand its benefits and risks. Methods A narrative review was performed from January 2000 through September 2020 via PubMed by searching the terms “vitamin C”, “ascorbic acid” and “burns”. The search yielded a total of 170 journal articles. The following were excluded: commentaries, experimental research and studies on non-human subjects. Ultimately, 20 articles qualified for review. Results A total of 924 patients were studied. The literature collectively endorsed a difference in patient outcomes when vitamin C is administered on the first day of admission. The average age across the studies was 15–45 years old. Only 10% of studies included vulnerable age groups (2–15 years old). The Mean Total Body Surface Area (TBSA) of patients was 31%. Most of the studies excluded patients with co-morbidities. The benefits of vitamin C in various aspects of burn management were documented in 70% of studies. Patients who were given vitamin C exhibited a decrease in fluid requirement in 42% of the studies when compared to controls. Additionally, a decrease in wound healing time was reported in 35% of studies, a decreased rate of post-burn infections was reported in 28%, and 14% of studies state that patients given vitamin C had reduced edema. The effect of vitamin C dosing methods on outcomes was also examined. It was reported by 14% of Studies that low-dose Vitamin C infusion does not improve outcomes, while 50% of studies that used high-dose infusion revealed improved results. Additionally, when comparing oral route of administration 20 % of studies used high-dose with favorable results. In regards to risk, oxalate nephropathy, acute kidney injury, and renal failure was documented by six studies. Conclusions Our review concludes that there is decreased fluid requirement, improvement in edema, healing time and post burn infections when high-dose vitamin C (66mg/kg/hr) is given to adults on first day of admission and continuously infused for 24 hours in 1st and 2nd degree burn involving 10 to 40% TBSA. However, there is an associated risk of acute kidney injury and renal failure.

Fluid requirement in adult dengue haemorrhagic fever patients during the critical phase of the illness: an observational study

Background Dengue fever prevalence is rising globally and it causes significant morbidity and mortality. Fluid extravasation during the critical phase of dengue haemorrhagic fever (DHF) leads to shock, multi-organ failure and death if not resuscitated appropriately with fluids. The mainstay of management is judicious fluid replacement using a guideline based, calculated fluid quota of maintenance (M) fluid plus 5% deficit (M + 5% deficit) to prevent organ hypoperfusion. Methods We conducted an observational follow-up study in Sri Lanka from January–July 2017 to identify the fluid requirements of DHF patients and to identify whether features of fluid overload are present in patients who exceeded the fluid quota. Patients who developed DHF following admission to the place of study, were recruited and the amount of fluid received during the critical phase was documented. Results A total of 115 DHF patients with a mean age of 30.3 (SD 12.2) years were recruited to the study. There were 65 (56.5%) males and the mean fluid requirement was 5279.7 ml (SD 735) over the 48 h. Majority of the study participants (n = 80, 69.6%) received fluid in excess of the recommended maintenance + 5% deficit and this group had higher body mass index (22.75 vs 20.76, p0.03) and a lower white cell count at the onset of the critical phase (3.22 × 103 vs 4.78 × 103, p < 0.001). The highest fluid requirement was seen within the first 12 and 24 h of the critical phase in patients requiring fluid M + 5%–7.5% deficit and ≥ M + 7.5% deficit respectively. Patients exceeding M + 5% deficit had narrow pulse pressure and hypotension compared to the rest. DHF grades III and IV were seen exclusively in patients exceeding the fluid quota indicating higher amount of fluid was given for resuscitation. Fluid overload was detected in 14 (12.1%) patients and diuretic therapy was required in 6 (5.2%) patients. Conclusions The majority of patients received fluid in excess of the recommended quota and this group represents patients with narrow pulse pressure and hypotension. Although, fluid overload was infrequent in the study population, clinicians should be cautious when administering fluid in excess of M + 7.5% deficit.

A New Resuscitation Formula Based on Burn Index Provides More Reliable Prediction for Fluid Requirement in Adult Major Burn Patients

The Third Military Medical University (TMMU) formula is widely used in fluid resuscitation in China. However, the actual volume needs usually exceed the prediction provided by the TMMU formula in major burn patients with a high proportion of full-thickness burn wounds. This retrospective study included 149 adult major burn patients (≥40% TBSA) who were admitted to the Burn Department, Southwest Hospital from 2014 to 2020 and received appropriate fluid resuscitation by the TMMU protocol. The actual volume infused in the first 48 hours postburn was compared to the estimation by the TMMU formula. A new fluid volume prediction formula was developed by multivariate linear regression analysis. The mean fluid requirements were 2.35 ml/kg/% TBSA and 1.75 ml/kg/% TBSA in the first and second 24 hours postburn, respectively. The TMMU formula underestimated the fluid requirement, and its prediction accuracy was 54.1% and 25.8% for the first and second 24 hours, respectively. The proportion of full-thickness burn wound was found to be associated with the fluid requirements postburn. A revised multifactorial formula consisting of the burn index, body weight, and inhalation injury was developed. Using the revised formula, the prediction reliability of resuscitation fluid volume improved to 65.3% and 61.1% in the first and second 24 hours, respectively. The TMMU formula showed low accuracy in predicting fluid requirements among major burn patients. A revised formula based on burn index was developed to provide better guidance for initiative fluid resuscitation for major burns by the TMMU protocol.

A comparison of efficacy and tolerablity of epidural Levobupivacaine 0.5% with 0.5% Racemic mixture Bupivacaine for lower abdominal surgery

This study was performed to compare the efficacy and tolerability of 0.5% racemic Bupivacaine and 0.5% Levobupivacaine, in patients undergoing lower abdominal surgery.56 patients, ASA grade 1 and 2, were randomized to receive an epidural injection of study drug (17 ml 0.5% racemic Bupivacaine in group R and 17 ml of 0.5% Levobupivacaine in group L). The time to onset of adequate sensory block (T10 dermatome), maximum dermatome reached, time taken to reach maximum dermatome, time for 2 segment regression, time taken to regress to T10 were comparable. Although the onset of motor block was comparable in both the groups, Group L showed earlier commencement of motor block at 5 min after zero time. (P value 0.002). The regression of motor block was faster in group L (p value 0.042). The time to obtain maximum level of motor blockade was found to be faster in L group. (p value of 0.043). The number of patient obtaining MBS score of 3 was 62.5% in R group and 37.5% in L group. The grade of motor block showed that, the L group had lesser grade than that of Racemic group (p value of 0.016). The duration of motor block was similar in both the groups. The need for rescue analgesics, total IV fluid requirement and ephedrine usage, MAP,HR and the time of request for post-operative analgesia were similar. Both local anaesthetics were well tolerated and effective in producing epidural anaesthesia for patients undergoing lower abdominal surgery.

Personification of infusion therapy in patients with ischemic stroke depending on the severity of the violation of energy-structural status

Objective. To determine the tactics of infusion therapy in patients with ischemic stroke (IS) depending on the severity of the violation of energy-structural status (ESST). Materials and methods. A study of 32 patients with severe IS on the National Institutes of Health Stroke Scale (16,7±1,5), who were in the department of anesthesiology with intensive therapy units of the Municipal Non-Profit Enterprise «City Hospital № 9» Zaporizhzhia City Council. Of these, 11 were men (34,4 %; the average age – 68,2±2,5 years), 21 were women (65,6 %; average age – 72,1±1,6). Results and discussion. In patients with IS, disorders ESST were defined as hyperergic damage at values of cardiac index (CI) of 4,45-5,09 L×min-1×m-2 and oxygen consumption index (IVO2) 186-210 ml×min-1×m-2, and at values of CI ≥5,10 L×min-1×m-2 and IVO2 ≥211 ml×min-1×m-2 – as hyperergic insufficiency. While hypoergic damage ESST occurred at values of CI 2,33-1,82 L×min-1×m-2 and IVO2 104-85 ml×min-1×m-2, and at CI ≤1,81 L×min-1×m-2 and IVO2 ≤84 ml×min-1×m-2 hypoergic insufficiency of ESST was observed. The daily fluid requirement of a patient with IS was calculated according to the formula 4+2+1: for the first 10 kg of weight – 4 ml×kg-1×h-1; from 11 to 20 kg – 2 ml×kg-1×h-1; from 21 kg – on 1 ml×kg-1×h-1 (Park G.R., Roe P.G., 2005; Netyazhenko V.Z., Halushko O.A., 2012). Infusion therapy in patients with IS and hyperergic damage ESST was performed with 0,9 % sodium chloride solution according to the formula 4+2+1 on the background of the use of esmolol intravenously bolus 250 mg and subsequent administration of 50 mсg×kg-1×min-1, and in hyperergic insufficiency 500 mg of esmolol intravenously bolus and subsequent administration of 100 mсg×kg-1×min-1. While in hypoergic damage ESST on the background of infusion therapy used dopamine or dobutamine 1-5 mсg×kg-1×min-1, and in hypoergic insufficiency, the dose of dopamine or dobutamine was increased to achieve the desired effect. Conclusions. The personification of infusion therapy depending on the severity of the violation of ESST can improve the results of treatment of patients with IS in the most acute period.

Vitamin C as Prevention in Burn Sepsis

Background: Burns is a severe public health problem. Its poor treatment can lead to the worst complication called sepsis. Since sepsis decreases the immune system, the critical therapy management of burn sepsis ensures adequate end-organ perfusion. According to the Surviving Sepsis Campaign Bundle, immediate identification and management in the initial hours generate a better outcome. The inflammation of burn injury is known to increase ROS production, which causes cellular damage, sepsis, and MODS. This condition initiates the importance of ROS scavenger. Methods: This literature reviewed from relevant works of literature which searched from major journal databases of WHO, Pubmed, Elsevier, JAMA, Springer, NEJM, which published from 2013 until 2018 Results: Vitamin C is a cheap but effective antioxidant, which acts as a ROS scavenger and reduces the fluid requirement in burn resuscitation for the prevention of burn sepsis Conclusion: Vitamin C could be recommended as adjuvant therapy in the prevention of burn sepsis