Iterative assessment of a sports rehydration beverage containing a novel amino acid formula on water uptake kinetics.

PURPOSE: Rapid gastric emptying and intestinal absorption of beverages is essential for rapid rehydration, and certain amino acids (AA) may augment fluid delivery. Three sugar-free beverages, containing differing AA concentrations (AA + PZ), were assessed for fluid absorption kinetics against commercial sugar-free (PZ, GZ) and carbohydrate-containing (GTQ) beverages. METHODS: Healthy individuals (n = 15-17 per study) completed three randomised trials. Three beverages (550-600 mL) were ingested in each study (Study 1: AA + PZ [17.51 g/L AA], PZ, GZ; Study 2: AA + PZ [6.96 g/L AA], PZ, GZ; Study 3: AA + PZ [3.48 g/L AA], PZ, GTQ), containing 3.000 g deuterium oxide (D2O). Blood samples were collected pre-, 2-min, 5-min, and every 5-min until 60-min post-ingestion to quantify maximal D2O enrichment (Cmax), time Cmax occurred (Tmax) and area under the curve (AUC). RESULTS: Study 1: AUC (AA + PZ: 15,184 ± 3532 δ‰ vs. VSMOW; PZ: 17,328 ± 3153 δ‰ vs. VSMOW; GZ: 17,749 ± 4204 δ‰ vs. VSMOW; P ≤ 0.006) and Tmax (P ≤ 0.005) were lower for AA + PZ vs. PZ/GZ. Study 2: D2O enrichment characteristics were not different amongst beverages (P ≥ 0.338). Study 3: Cmax (AA + PZ: 440 ± 94 δ‰ vs. VSMOW; PZ: 429 ± 83 δ‰ vs. VSMOW; GTQ: 398 ± 81 δ‰ vs. VSMOW) was greater (P = 0.046) for AA + PZ than GTQ, with no other differences (P ≥ 0.106). CONCLUSION: The addition of small amounts of AA (3.48 g/L) to a sugar-free beverage increased fluid delivery to the circulation compared to a carbohydrate-based beverage, but greater amounts (17.51 g/L) delayed delivery.

Effectiveness of ORSL® Variants as an Adjuvant along with Standard-of-care Treatment in the Restoration of Oral Fluid, Electrolytes, and Energy in Patients with Fever and/or General Weakness in Indian Patients in an Outpatient Setting.

BACKGROUND: Dehydration due to reduced intake or increased losses including insensible losses in patients with acute nondiarrheal diseases may lead to fluid, electrolytes, and energy (FEE) deficits. The impact of oral FEE supplementation adjuvant to standard of care (SOC) treatment on recovery in patients with acute nondiarrheal diseases is yet to be evaluated. AIM: To determine the effectiveness of ORSL® variants (ORSL® Apple Drink and ORSL® PLUS Orange Drink), fruit juice-based electrolyte drinks as an adjuvant along with SOC in the restoration of oral FEE in patients with acute nondiarrheal disease with fever and/or general weakness who attended an outpatient department (OPD). MATERIALS AND METHODS: This was a prospective, interventional, open-label, multicenter, real-world, study conducted at eight sites across India. Patients with fever and/or general weakness due to an acute nondiarrheal illness were given either ORSL® Apple Drink or ORSL® PLUS Orange Drink as an adjuvant along with SOC treatment per physician's discretion. The primary endpoint of the study was to assess improvement from baseline in energy or hydration levels after ORSL® variants consumption at 6, 24, and 48 hours measured by a new aided recovery scale (ARS). Secondary endpoints were to assess the improvement in energy and hydration levels at 20, 40, and 60 minutes, as well as energy levels and hydration levels at 20, 40, and 60 minutes, 6, 24, and 48 hours after the consumption of ORSL® Apple Drink or ORSL® PLUS Orange Drink. The patient's consumption of ORSL® variants and treatment experience, physician's experience of recommending ORSL® variants, and product safety were evaluated. RESULTS: In total, 612 patients were enrolled with mean age 38.3 years, of whom 62.9% were male. The mean baseline level of energy and hydration was 1.59 (range 1.0-2.0) on ARS. Statistically significant (p < 0.0001) improvements were observed in energy or hydration 6 hours after first consumption of ORSL formulations. Furthermore, improvement was observed from 40 minutes, and in levels of energy, hydration, and both energy and hydration from 60 minutes. Patients and physicians reported a positive experience with ORSL® variants. CONCLUSION: ORSL® Apple Drink and ORSL® PLUS Orange Drink are clinically proven to provide hydration and/or energy to patients with fever and/or general weakness.

Restrictive versus Liberal Fluid Therapy for Major Abdominal Surgery.

BACKGROUND: Guidelines to promote the early recovery of patients undergoing major surgery recommend a restrictive intravenous-fluid strategy for abdominal surgery. However, the supporting evidence is limited, and there is concern about impaired organ perfusion. METHODS: In a pragmatic, international trial, we randomly assigned 3000 patients who had an increased risk of complications while undergoing major abdominal surgery to receive a restrictive or liberal intravenous-fluid regimen during and up to 24 hours after surgery. The primary outcome was disability-free survival at 1 year. Key secondary outcomes were acute kidney injury at 30 days, renal-replacement therapy at 90 days, and a composite of septic complications, surgical-site infection, or death. RESULTS: During and up to 24 hours after surgery, 1490 patients in the restrictive fluid group had a median intravenous-fluid intake of 3.7 liters (interquartile range, 2.9 to 4.9), as compared with 6.1 liters (interquartile range, 5.0 to 7.4) in 1493 patients in the liberal fluid group (P<0.001). The rate of disability-free survival at 1 year was 81.9% in the restrictive fluid group and 82.3% in the liberal fluid group (hazard ratio for death or disability, 1.05; 95% confidence interval, 0.88 to 1.24; P=0.61). The rate of acute kidney injury was 8.6% in the restrictive fluid group and 5.0% in the liberal fluid group (P<0.001). The rate of septic complications or death was 21.8% in the restrictive fluid group and 19.8% in the liberal fluid group (P=0.19); rates of surgical-site infection (16.5% vs. 13.6%, P=0.02) and renal-replacement therapy (0.9% vs. 0.3%, P=0.048) were higher in the restrictive fluid group, but the between-group difference was not significant after adjustment for multiple testing. CONCLUSIONS: Among patients at increased risk for complications during major abdominal surgery, a restrictive fluid regimen was not associated with a higher rate of disability-free survival than a liberal fluid regimen and was associated with a higher rate of acute kidney injury. (Funded by the Australian National Health and Medical Research Council and others; RELIEF ClinicalTrials.gov number, NCT01424150 .).

Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis.

BACKGROUND: Diabetic ketoacidosis in children may cause brain injuries ranging from mild to severe. Whether intravenous fluids contribute to these injuries has been debated for decades. METHODS: We conducted a 13-center, randomized, controlled trial that examined the effects of the rate of administration and the sodium chloride content of intravenous fluids on neurologic outcomes in children with diabetic ketoacidosis. Children were randomly assigned to one of four treatment groups in a 2-by-2 factorial design (0.9% or 0.45% sodium chloride content and rapid or slow rate of administration). The primary outcome was a decline in mental status (two consecutive Glasgow Coma Scale scores of <14, on a scale ranging from 3 to 15, with lower scores indicating worse mental status) during treatment for diabetic ketoacidosis. Secondary outcomes included clinically apparent brain injury during treatment for diabetic ketoacidosis, short-term memory during treatment for diabetic ketoacidosis, and memory and IQ 2 to 6 months after recovery from diabetic ketoacidosis. RESULTS: A total of 1389 episodes of diabetic ketoacidosis were reported in 1255 children. The Glasgow Coma Scale score declined to less than 14 in 48 episodes (3.5%), and clinically apparent brain injury occurred in 12 episodes (0.9%). No significant differences among the treatment groups were observed with respect to the percentage of episodes in which the Glasgow Coma Scale score declined to below 14, the magnitude of decline in the Glasgow Coma Scale score, or the duration of time in which the Glasgow Coma Scale score was less than 14; with respect to the results of the tests of short-term memory; or with respect to the incidence of clinically apparent brain injury during treatment for diabetic ketoacidosis. Memory and IQ scores obtained after the children's recovery from diabetic ketoacidosis also did not differ significantly among the groups. Serious adverse events other than altered mental status were rare and occurred with similar frequency in all treatment groups. CONCLUSIONS: Neither the rate of administration nor the sodium chloride content of intravenous fluids significantly influenced neurologic outcomes in children with diabetic ketoacidosis. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Health Resources and Services Administration; PECARN DKA FLUID ClinicalTrials.gov number, NCT00629707 .).

Can an amino acid mixture alleviate gastrointestinal symptoms in neuroendocrine tumor patients?

BACKGROUND: Neuroendocrine tumors, although relatively rare in incidence, are now the second most prevalent gastrointestinal neoplasm owing to indolent disease biology. A small but significant sub-group of neuroendocrine tumor patients suffer from diarrhea. This is usually secondary to carcinoid syndrome but can also be a result of short gut syndrome, bile acid excess or iatrogenic etiologies. Recently, an amino acid based oral rehydration solution (enterade® Advanced Oncology Formula) was found to have anti-diarrheal properties in preclinical models. METHODS: A retrospective chart review of all NET patients treated with enterade® AO was performed after IRB approval. RESULTS: Ninety-eight NET patients who had received enterade® AO at our clinic from May 2017 through June 2019 were included. Patients (N = 49 of 98) with follow up data on bowel movements (BMs) were included for final analysis. Eighty-four percent of patients (41/49) had fewer BMs after taking enterade® AO and 66% (27/41) reported more than 50% reduction in BM frequency. The mean number of daily BMs was 6.6 (range, 3-20) at baseline before initiation of therapy, while the mean number of BMs at 1 week time point post enterade® AO was 2.9 (range, 0-11). CONCLUSIONS: Our retrospective observations are encouraging and support prospective validation with appropriate controls in NET patients. This is first published report of the potential anti-diarrheal activity of enterade® AO in NET patients.

Carbohydrate hastens hypervolemia achieved through ingestion of aqueous sodium solution in resting euhydrated humans.

PURPOSE: Ingesting beverages containing a high concentration of sodium under euhydrated conditions induces hypervolemia. Because carbohydrate can enhance interstitial fluid absorption via the sodium-glucose cotransporter and insulin-dependent renal sodium reabsorption, adding carbohydrate to high-sodium beverages may augment the hypervolemic response. METHODS: To test this hypothesis, we had nine healthy young males ingest 1087 ± 82 mL (16-17 mL per kg body weight) of water or aqueous solution containing 0.7% NaCl, 0.7% NaCl + 6% dextrin, 0.9% NaCl, or 0.9% NaCl + 6% dextrin under euhydrated conditions. Each drink was divided into six equal volumes and ingested at 10-min intervals. During each trial, participants remained resting for 150 min. Measurements were made at baseline and every 30 min thereafter. RESULTS: Plasma osmolality decreased with water ingestion (P ≤ 0.023), which increased urine volume such that there was no elevation in plasma volume from baseline (P ≥ 0.059). The reduction in plasma osmolality did not occur with ingestion of solution containing 0.7% or 0.9% NaCl (P ≥ 0.051). Consequently, urine volume was 176-288 mL smaller than after water ingestion and resulted in plasma volume expansion at 60 min and later times (P ≤ 0.042). In addition, net fluid balance was 211-329 mL greater than after water ingestion (P ≤ 0.028). Adding 6% dextrin to 0.7% or 0.9% NaCl solution resulted in plasma volume expansion within as little as 30 min (P ≤ 0.026), though the magnitudes of the increases in plasma volume were unaffected (P ≥ 0.148). CONCLUSION: Dextrin mediates an earlier hypervolemic response associated with ingestion of high-sodium solution in resting euhydrated young men. (247/250 words).

Balanced Crystalloids Versus Saline in Critically Ill Adults: A Systematic Review and Meta-analysis.

Background: The optimal resuscitative fluid remains controversial. Objective: To assess the association between crystalloid fluid and outcomes in critically ill adults. Methods: Cumulative Index to Nursing and Allied Health Literature, Scopus, PubMed, and Cochrane Central Register for Controlled Trials were searched from inception through July 2019. Cohort studies and randomized trials of critically ill adults provided predominantly nonperioperative fluid resuscitation with balanced crystalloids or 0.9% sodium chloride (saline) were included. Results: Thirteen studies (n = 30 950) were included. Balanced crystalloids demonstrated lower hospital or 28-/30-day mortality (risk ratio [RR] = 0.86; 95% CI = 0.75-0.99; I2 = 82%) overall, in observational studies (RR = 0.64; 95% CI = 0.41-0.99; I2 = 63%), and approached significance in randomized trials (RR = 0.94; 95% CI = 0.88-1.02; I2 = 0%). New acute kidney injury occurred less frequently with balanced crystalloids (RR = 0.91; 95% CI = 0.85-0.98; I2 = 0%), though progression to renal replacement therapy was similar (RR = 0.91; 95% CI = 0.79-1.04; I2 = 38%). In the sepsis cohort, odds of hospital or 28-/30-day mortality were similar, but the odds of major adverse kidney events occurring in the first 30 days were less with balanced crystalloids than saline (OR = 0.78; 95% CI = 0.66-0.91; I2 = 42%). Conclusion and Relevance: Resuscitation with balanced crystalloids demonstrated lower hospital or 28-/30-day mortality compared with saline in critically ill adults but not specifically those with sepsis. Balanced crystalloids should be provided preferentially to saline in most critically ill adult patients.

Oral rehydration solution coverage in under 5 children with diarrhea: a tri-country, subnational, cross-sectional comparative analysis of two demographic health surveys cycles.

BACKGROUND: More than 3 million children under 5 years in developing countries die from dehydration due to diarrhea, a preventable and treatable disease. We conducted a comparative analysis of two Demographic Health Survey (DHS) cycles to examine changes in ORS coverage in Zimbabwe, Zambia and Malawi. These surveys are cross-sectional conducted on a representative sample of the non-institutionalized individuals. METHODS: The sample is drawn using a stratified two-stage cluster sampling design with census enumeration areas, typically, selected first as primary sampling units (PSUs) and then a fixed number of households from each PSU. We examined national and sub-regional prevalence of ORS use during a recent episode of diarrhea (within 2 weeks of survey) using DHSs for 2007-2010 (1st Period), and 2013-2016 (2nd Period). Weighted proportions of ORS were obtained and multivariable- design-adjusted logistic regression analysis was used to obtain Odds Ratios (aORs) and 95% confidence intervals (CIs) and weighted proportions of ORS coverage. RESULTS: Crude ORS coverage increased from 21.0% (95% CI: 17.4-24.9) in 1st Period to 40.5% (36.5-44.6) in 2nd Period in Zimbabwe; increased from 60.8% (56.1-65.3) to 64.7% (61.8-67.5) in Zambia; and decreased from 72.3% (68.4-75.9) to 64.6% (60.9-68.1) in Malawi. The rates of change in coverage among provinces in Zimbabwe ranged from 10.3% over the three cycles (approximately 10 years) in Midlands to 44.2% in Matabeleland South; in Zambia from - 9.5% in Eastern Province to 24.4% in Luapula; and in Malawi from - 16.5% in the Northern Province to - 3.2% in Southern Province. The aORs for ORS use was 3.95(2.66-5.86) for Zimbabwe, 2.83 (2.35-3.40) for Zambia, and, 0.71(0.59-0.87) for Malawi. CONCLUSION: ORS coverage increased in Zimbabwe, stagnated in Zambia, but declined in Malawi. Monitoring national and province-level trends of ORS use illuminates geographic inequalities and helps identify priority areas for targeting resource allocation.. Provision of safe drinking-water, adequate sanitation and hygiene will help reduce the causes and the incidence of diarrhea. Health policies to strengthen access to appropriate treatments such as vaccines for rotavirus and cholera and promoting use of ORS to reduce the burden of diarrhea should be developed and implemented.

Abomasal emptying rate of diarrhoeic and healthy suckling calves fed with oral rehydration solutions.

The aim of the study was to determine the abomasal emptying rate (AER) of calves suffering from naturally occurring diarrhoea compared with that of healthy calves. Furthermore, the effects of an oral rehydration solution (ORS) mixed into milk replacer on the AER were determined. Acetaminophen absorption test (APAT) was performed to estimate the AER. Sixty Holstein-Frisian calves (age < 14 days) were included in the study and divided into groups as follows: healthy calves (H; n = 16), healthy calves fed with ORS (HORS; n = 14), diarrhoeic calves (D; n = 15) and diarrhoeic calves fed with ORS (DORS; n = 15). For the APAT, the calves were fed 2 L of milk replacer containing 50 mg acetaminophen (AP)/kg body weight. Venous blood samples were collected before and after milk replacer and AP intake in 30-60 min intervals for 12 hr. During the APAT, no significant differences in median maximum acetaminophen concentration (Cmax ) were observed among all groups. Time to reach maximum acetaminophen concentration (Tmax ) in DORS (median 390 min, 25/75 quartiles: 300/480 min) was significantly higher compared with that in H (median: 270 min 25/75 quartiles: 210/315 min) and HORS (median: 300 min (25/75 quartiles: 240/360 min). Non-linear regression revealed that the calculated abomasal half-life (AP t1/2 ) tended to be delayed in DORS (median: 652 min, 25/75 quartiles: 445/795 min, p = .10). The area under the AP curve values (AUC) from 0 to 120 min and 0 to 240 min of the observation period were significantly higher in H than D and DORS. In conclusion, significant differences in the AER indices reflected delayed abomasal emptying in diarrhoeic calves. Furthermore, the hypertonic ORS tended to have an additive delaying impact on the AER, which needs attention for the feeding management of diarrhoeic calves.

Oral Rehydration in Children with Acute Diarrhoea and Moderate Dehydration-Effectiveness of an ORS Tolerance Test.

Oral rehydration solution (ORS) is the mainstay of treatment of acute watery diarrhoea, but it is underutilized in many hospitals, resulting in children with moderate degrees of dehydration being unnecessarily hospitalized and receiving intravenous fluids. We aimed to assess the utility of an ORS tolerance test on initial presentation to an emergency department, and determine the volume of ORS a child with diarrhoea and moderate dehydration needed to tolerate to be successfully managed at home. One hundred and twenty-nine children with acute watery diarrhoea and moderate dehydration were given ORS and observed in a Children's Emergency Department (CED) over a period of 2-4 h. Patients were admitted, kept in the CED for further management or discharged, based on the assessment of oral intake and the clinical judgement of the treating health workers. Seventy-nine (61.2%) patients tolerated ORS well. They drank a median [interquartile range (IQR)] of 24.4 ml (IQR 12.5-28.8) ml/kg, were judged to have passed the ORS test and were discharged to continue oral rehydration treatment at home. At follow-up on days 2 and 5, 63/79 (79.7%) children had improved, were adequately hydrated and the diarrhoea had reduced. Sixteen of the 79 (20.3%) failed oral home treatment, with persisting diarrhoea, vomiting, hypokalaemia and/or weakness. The 63 who succeeded had tolerated a median of 25.8 (IQR 18.4-30.0) ml/kg of ORS in the CED, whilst the 16 who failed oral home treatment had tolerated 11.1 (IQR 9.1-23.0) ml/kg ORS (p < 0.001).

Hyaluronidase-Assisted Resuscitation in Kenya for Severely Dehydrated Children.

BACKGROUND: Dehydration, mainly due to diarrheal illnesses, is a leading cause of childhood mortality worldwide. Intravenous (IV) therapy is the standard of care for patients who were unable to tolerate oral rehydration; however, placing IVs in fragile, dehydrated veins can be challenging. Studies in resource-rich settings comparing hyaluronidase-assisted subcutaneous rehydration with standard IV rehydration in children have demonstrated several benefits of subcutaneous rehydration, including time and success of line placement, ease of use, satisfaction, and cost-effectiveness. METHODS: A single-arm trial assessing the feasibility of hyaluronidase-assisted subcutaneous resuscitation for the treatment of moderately to severely dehydrated individuals in western Kenya was conducted. Children aged 2 months or older who presented with moderately to severely dehydration clinically warranting parenteral rehydration and had at least 2 failed IV attempts were eligible. Study staff received training on standard dehydration management and hyaluronidase infusion processes. Children received all other standards of care. They were monitored from presentation and through discharge, with a 1-week phone follow-up. Predischarge surveys were completed by caregivers, and semistructured interviews with providers were performed. RESULTS: A total of 51 children were enrolled (median age, 13.0 months; interquartile range of 18 months). Fifty-one patients (100%) had severe dehydration. The median length of subcutaneous infusion was 3.0 hours (interquartile range [IQR], 2.95). The median total subcutaneous infusion was 700.0 mL (IQR, 420 mL). Median time to resolution of moderate to severe dehydration symptoms was 3.0 hours (IQR, 2.95 hours). There were no significant complications. CONCLUSIONS: Hyaluronidase-assisted subcutaneous resuscitation is a feasible alternative to IV hydration in moderately to severely dehydrated children with difficult to obtain IV access in resource-limited areas.

Effects of Intraoperative Fluid Management on Postoperative Outcomes: A Hospital Registry Study.

OBJECTIVE: Evaluate the dose-response relationship between intraoperative fluid administration and postoperative outcomes in a large cohort of surgical patients. BACKGROUND: Healthy humans may live in a state of fluid responsiveness without the need for fluid supplementation. Goal-directed protocols driven by such measures are limited in their ability to define the optimal fluid state during surgery. METHODS: This analysis of data on file included 92,094 adult patients undergoing noncardiac surgery with endotracheal intubation between 2007 and 2014 at an academic tertiary care hospital and two affiliated community hospitals. The primary exposure variable was total intraoperative volume of crystalloid and colloid administered. The primary outcome was 30-day survival. Secondary outcomes were respiratory complications within three postoperative days (pulmonary edema, reintubation, pneumonia, or respiratory failure) and acute kidney injury. Exploratory outcomes were postoperative length of stay and total cost of care. Our models were adjusted for patient-, procedure-, and anesthesia-related factors. RESULTS: A U-shaped association was observed between the volume of fluid administered intraoperatively and 30-day mortality, costs, and postoperative length of stay. Liberal fluid volumes (highest quintile of fluid administration practice) were significantly associated with respiratory complications whereas both liberal and restrictive (lowest quintile) volumes were significantly associated with acute kidney injury. Moderately restrictive volumes (second quintile) were consistently associated with optimal postoperative outcomes and were characterized by volumes approximately 40% less than traditional textbook estimates: infusion rates of approximately 6-7 mL/kg/hr or 1 L of fluid for a 3-hour case. CONCLUSIONS: Intraoperative fluid dosing at the liberal and restrictive margins of observed practice is associated with increased morbidity, mortality, cost, and length of stay.

Pyruvate in reduced osmolarity oral rehydration salt corrected lactic acidosis in sever scald rats.

BACKGROUND: A novel pyruvate-based oral rehydration salt (Pyr-ORS) was demonstrated of superiority over bicarbonate- or citrate-based one to preserve organ function and correct lactic acidosis in rehydration of lethal shock in animals. This study further compared these effects between low-osmolar Pyr-ORS and equimolar citrate-based counterpart. METHODS: Eighty rats, using a fatal burn shock model, were randomized into four groups (two subgroups per group: n = 10): the sham group (group SR), Pyr-ORS group (group PR), WHO-ORS III group (group CR), and no rehydration group. ORS was delivered by manual gavage during 24 h following burns. Oral administration consisted of half of counted volume in the initial 8 h plus the rest in the later 16 h. Systemic hemodynamics, visceral organ surface blood flow, organ function, and metabolic acidosis were determined at 8 h and 24 h after burn. Another set of rats with identical surgical procedures without tests was observed for survival. RESULTS: Survival was markedly improved in the groups PR and CR; the former showed a higher survival rate than the latter at 24 h (40% versus 20%, P < 0.05). Systemic hemodynamics, visceral blood flow, and function of heart, liver, and kidney were greatly restored in group PR, compared with group CR (all P < 0.05). Hypoxic lactic acidosis was efficiently reversed in group PR, instead of group CR, (pH 7.36 versus 7.11, base excess 2.1 versus -9.1 mmol/L, lactate 4.28 versus 8.18 mmol/L; all P < 0.05) at 24 h after injury. CONCLUSIONS: Pyruvate was advantageous over citrate in low-osmolar ORS for protection of organs and survival; pyruvate, but not citrate, in the ORS corrected hypoxic lactic acidosis in rats subjected to lethal burn shock in 24 h.

HYDration and Bicarbonate to Prevent Acute Renal Injury After Endovascular Aneurysm Repair With Suprarenal Fixation: Pilot/Feasibility Randomised Controlled Study (HYDRA Pilot Trial).

OBJECTIVE/BACKGROUND: Up to 25% of patients undergoing elective endovascular aneurysm repair (EVAR) develop acute kidney injury (AKI), which is associated with short and long-term morbidity and mortality. There is no high quality randomised evidence regarding prevention of EVAR related AKI. METHODS: A novel AKI prevention strategy for EVAR was devised, based on best evidence and an expert consensus group. This included a bolus of high dose sodium bicarbonate (NaHCO3) immediately before EVAR (1 mL/kg of 8.4% NaHCO3) and standardised crystalloid based hydration pre- and post-EVAR. A pilot/feasibility randomised controlled trial (RCT) was performed in two centres to assess the safety of the intervention, potential impact on AKI prevention, and feasibility of a national RCT; the primary end point was the proportion of eligible patients recruited into the study. AKI was defined using "Kidney Disease Improving Global Outcomes" and "Acute Kidney Injury Network" criteria based on National Institute for Health and Clinical Excellence AKI recommendations, using serum creatinine and hourly urine output. RESULTS: Fifty-eight patients (84% of those screened; median age 75 years [range 57-89 years], 10% female) were randomised to receive the standardised intravenous hydration with (intervention) or without (control) NaHCO3. Groups were comparable in terms of AKI risk factors; 56 of 58 participants had a device with suprarenal fixation. Overall, 33% of patients in the control arm developed AKI versus 7% in the intervention arm (as treated analysis). None of the patients receiving NaHCO3 developed a serious intervention related adverse event; five patients did not attend their 30 day follow-up. CONCLUSION: Bolus high dose NaHCO3 and hydration is a promising EVAR related AKI prevention method. This trial has confirmed the feasibility of delivering a definitive large RCT to confirm the efficacy of this novel intervention, in preventing EVAR related AKI.

IV crystalloid fluid for acute alcoholic intoxication prolongs ED length of stay.

OBJECTIVES: Acute alcohol intoxication is often treated in emergency departments by intravenous crystalloid fluid (IVF), but it is not clear that this shortens the time to achieving sobriety. The study aim was to investigate the association of IVF infusion and length of stay in the ED. METHODS: This single-center retrospective cohort study was conducted in Japan and included patients aged ≥20years of age and treated for acute alcohol intoxication without or with IVF. The primary outcome was the length of the ED stay and the treatments were compared by time-to-event analysis. RESULTS: A total of 106 patients, 42 treated without IVF and 64 with IVF. The baseline characteristics of the two groups were similar. Kaplan-Meier analysis and the generalized Wilcoxon test found no significant difference between the two treatments in the time to ED discharge. The median time was 189 (IQR 160-230) minutes without IVF and 254.5 (203-267 minutes with IVF; p=0.052). A Cox proportional hazards regression model adjusted for potential confounding variables found that patients treated with IVF were less likely to be discharged earlier than those treated without IVF (HR 0.54, 95% CI: 0.35-0.84, p=0.006). CONCLUSIONS: IVF for treatment of acute alcoholic intoxication prolonged ED length of stay even after adjustment for potential confounders. Patients given IVF for acute alcohol intoxication should be selected with care.

Comparison of Sports Drink Versus Oral Rehydration Solution During Exercise in the Heat.

INTRODUCTION: This study compared 2 commercially available beverages, an oral rehydration solution (ORS; 60.9 mM Na+; 3.4% carbohydrate) and a sports drink (SDS; 18.4 mM Na+; 5.9% carbohydrate), on hydration and metabolism during submaximal exercise in the heat. METHODS: Ten male subjects completed two 90-min exercise trials (39ºC, 30%) of walking at 50% VO2max followed by a 30-min rest period in the heat while wearing wildland firefighter personal protective clothing. After 45 min of exercise, fluid delivery by either ORS or SDS replaced 150% of sweat loss. Subjects continued the exercise for 45 additional minutes followed by a 30-min rest period. Blood samples were collected pre-exercise (0 min), post-exercise (90 min), and post-trial (120 min) to measure plasma volume (%) and blood glucose (mg·dL-1). Expired gases were collected twice for 3 min for substrate oxidation. RESULTS: The sweat rate and percent dehydration did not differ between the groups (P=0.86 and P=0.79, respectively). Changes in plasma volume did not differ (P=0.55). Hemoglobin levels significantly increased in both groups post-trial (P=0.009). Blood glucose was significantly greater post-trial in SDS versus ORS (116±19 vs 103±13 mg·dL-1, respectively; P=0.01). Fat oxidation was lower post-exercise in SDS vs ORS (0.38±0.1 vs 0.47±0.2 g·min-1, respectively; P=0.049). CONCLUSIONS: These data indicate no difference in fluid retention between ORS or SDS when supplemented during exercise in the heat. This implies that fluid volume, and not drink contents, may be more important when ingested during exercise in a hot environment.

Hemodynamic Effect of Different Doses of Fluids for a Fluid Challenge: A Quasi-Randomized Controlled Study.

OBJECTIVE: The objectives of this study are to determine what is the minimal volume required to perform an effective fluid challenge and to investigate how different doses of IV fluids in an fluid challenge affect the changes in cardiac output and the proportion of responders and nonresponders. DESIGN: Quasi-randomized controlled trial. SETTING: Cardiothoracic ICU, tertiary university hospital. PATIENTS: Eighty postcardiac surgery patients. INTERVENTION: IV infusion of 1, 2, 3, or 4 mL/Kg (body weight) of crystalloid over 5 minutes. MEASUREMENTS AND MAIN RESULTS: Mean systemic filling pressure measured using the transient stop-flow arm arterial-venous equilibrium pressure, arterial and central venous pressure, cardiac output (LiDCOplus; LiDCO, Cambridge, United Kingdom), and heart rate. The groups were well matched with respect to demographic and baseline physiologic variables. The proportion of responders increased from 20% in the group of 1 mL/kg to 65% in the group of 4 mL/kg (p = 0.04). The predicted minimal volume required for an fluid challenge was between 321 and 509 mL. Only 4 mL/Kg increases transient stop-flow arm arterial-venous equilibrium pressure beyond the limits of precision and was significantly associated with a positive response (odds ratio, 7.73; 95% CI, 1.78-31.04). CONCLUSION: The doses of fluids used for an fluid challenge modify the proportions of responders in postoperative patients. A dose of 4 mL/Kg increases transient stop-flow arm arterial-venous equilibrium pressure and reliably detects responders and nonresponders.

Arterial Pressure and the Rate of Elimination of Crystalloid Fluid.

Excretion of crystalloid fluid is slow during general anesthesia. The distribution and elimination of buffered Ringer's solution were analyzed to determine whether the rate of elimination correlates with a hemodynamic factor, consciousness, patient posture, or the type of general anesthesia. Data were derived from 4 separately published studies in which 30 volunteers and 48 anesthetized patients had received 0.833 (1 series 0.667) mL/kg/min of lactated or acetated Ringer's solution over 30 minutes. Frequent measurements of the blood hemoglobin and mean urinary excretion were used as input in a kinetic analysis according to a 2-volume model and covariates, using microconstants and mixed-effects modeling software.The results show that rate of elimination of crystalloid fluid decreased with the mean arterial pressure (MAP) and patient age, but was unaffected by consciousness and inhalational or intravenous anesthesia. The elimination rate constant was 6.5 (95% confidence interval, 5.2-7.9) × 10 × (MAP/mean MAP) × (Age/mean Age). The mean MAP for the 2108 data points was 81.3 mm Hg and the mean age was 40 years. The central fluid space that was expanded by infused fluid (Vc, plasma volume) increased with body weight but decreased with general anesthesia and with reductions of MAP.Simulations revealed a more than 10-fold difference in the excreted fluid volume after a theoretical 30-minute infusion, depending on whether the MAP was 50 or 100 mm Hg.In conclusion, the rate of elimination of crystalloid fluid decreased in proportion to MAP but was independent of general anesthesia and moderate-sized surgery.

Use of the Fluid Challenge in Critically Ill Adult Patients: A Systematic Review.

The fluid challenge (FC) aims at identifying patients in whom fluid administration improves hemodynamics. Although the FC has been extensively studied, the implementation and definition of improvement are not standardized. This systematic review of studies published between January 1, 1994 and December 31, 2014 characterizes these key components of the FC for critically ill adult patients, as described in the medical literature in the last 20 years. A literature search was performed using MEDLINE, Embase, and Cochrane. For each study, data were collected on study design, study size, study setting, patient population, and how the FC was administered. Eligibility criteria for FC were (1) the infusion of a definite quantity of fluid, (2) of a specific type, (3) in a fixed time period (expressed as either span or infusion rate), (4) with a defined hemodynamic variable as the target, and (5) for a predetermined threshold. One hundred fifty-seven full-text manuscripts were extracted from 870 potentially relevant studies. The inclusion criteria were met by 71 studies including 3617 patients. Sixty-six studies were from a single center and 45 were prospective observational in format. The most common amount infused was 500 cc, used by 55 (77.5%) studies. The most commonly infused fluids were colloids (62.0%). In 43 (60.5%) studies, the FC was administered between 20 and 30 minutes. A positive response to fluid administration was defined as an increase ≥15% of cardiac index or cardiac output in 44 (62.6%) studies. Static or dynamic physiologic indices were utilized in a minority of studies (16.9%) and safety limits for interrupting the FC are adopted in 4 (5.6%) studies only. This systematic review indicates that the FC most commonly consists in infusing 500 mL of crystalloids or colloids in 20-30 minutes, and considered an increase in cardiac index ≥15% as a positive response. However, definite standards for FC administration and evaluation remain undefined.