An Amino Acid-Based Oral Rehydration Solution Regulates Radiation-Induced Intestinal Barrier Disruption in Mice.

BACKGROUND: Radiotherapy inadvertently affects gastrointestinal (GI) epithelial cells, causing intestinal barrier disruption and increased permeability. OBJECTIVE: We examined the effect of amino acid-based oral rehydration solution (AA-ORS) on radiation-induced changes of intestinal barrier function and epithelial tight junctions (TJs) in a randomized experimental study using a total-body irradiation (TBI) mouse model. METHODS: Eight-week-old male Swiss mice received a single-dose TBI (0, 1, 3, or 5 Gy), and subsequent gastric gavage with AA-ORS (threonine, valine, serine, tyrosine, and aspartic acid) or saline for 2 or 6 d. Intestinal barrier function of mouse ileum was characterized by electrophysiological analysis of conductance, anion selectivity, and paracellular permeability [fluorescein isothiocyanate (FITC)-dextran]. Ultrastructural changes of TJs were evaluated by transmission electron microscopy. Membrane protein and mRNA expression of claudin-1, -2, -3, -5, and -7, occludin, and E-cadherin were analyzed with western blot, qPCR, and immunohistochemistry. Nonparametric tests were used to compare treatment-dose differences for each time point. RESULTS: Saline-treated mice had a higher conductance at doses as low as 3 Gy, and as early as 2 d post-TBI compared with 0 Gy (P < 0.001). Paracellular permeability and dilution potential were increased 6 d after 5 Gy TBI (P < 0.001). Conductance decreased with AA-ORS after 2 d in 3-Gy and 5-Gy mice (P < 0.05 and P < 0.001), and on day 6 after 5 Gy TBI (P < 0.001). Anion selectivity and FITC permeability decreased from 0.73 ± 0.02 to 0.61 ± 0.03 pCl/pNa (P < 0.01) and from 2.7 ± 0.1 × 105 to 2.1 ± 0.1 × 105 RFU (P < 0.001) in 5-Gy mice treated with AA-ORS for 6 d compared with saline. Irradiation-induced ultrastructural changes of TJs characterized by decreased electron density and gap formation improved with AA-ORS. Reduced claudin-1, -3, and -7 membrane expression after TBI recovered with AA-ORS within 6 d, whereas claudin-2 decreased indicating restitution of TJ proteins. CONCLUSIONS: Radiation-induced functional and structural disruption of the intestinal barrier in mice is reversed by AA-ORS rendering AA-ORS a potential treatment option in prospective clinical trials in patients with gastrointestinal barrier dysfunction.

Osmolality of Commercially Available Oral Rehydration Solutions: Impact of Brand, Storage Time, and Temperature.

Oral rehydration solutions (ORS) are specifically formulated with an osmolality to optimize fluid absorption. However, it is unclear how many ORS products comply with current World Health Organization (WHO) osmolality guidelines and the osmotic shelf-life stability is not known. Therefore, the purpose of this investigation was to examine the within and between ORS product osmolality variation in both pre-mixed and reconstituted powders. Additionally, the osmotic stability was examined over time. The osmolality of five different pre-mixed solutions and six powdered ORS products were measured. Pre-mixed solutions were stored at room temperatures and elevated temperatures (31 °C) for two months to examine osmotic shelf stability. Results demonstrated that only one pre-mixed ORS product was in compliance with the current guidelines both before and after the prolonged storage. Five of the six powdered ORS products were in compliance with minimal inter-packet variation observed within the given formulations. This investigation demonstrates that many commercially available pre-mixed ORS products do not currently adhere to the WHO recommended osmolality guidelines. Additionally, due to the presence of particular sugars and possibly other ingredients, the shelf-life stability of osmolality for certain ORS products may be questioned. These findings should be carefully considered in the design of future ORS products.

A pectin-gelatin gel containing oral rehydration solution and the release of sodium chloride under simulated gastric conditions.

Both gelatin and pectin have the ability to trap salt and facilitate its release under simulated gastric conditions. The objective of this study was to develop a pectin-gelatin gel fortified with oral rehydration solution/s (ORS) that can maintain a more rigid structure to limit salt mobility (potentially less salty taste), yet allow rapid release in simulated gastric conditions. Two gels containing both pectin and gelatin were developed: (1) low salt (LS) containing 2.6 g/L salt and 13.5 g/L sugar and (2) high salt (HS) containing 5.2 g/L salt and 27.0 g/L sugar. The ORS-fortified gels were compared with commercially available gelatin gels and a control pectin-gelatin gel without added salt or sugar. A stronger gel network (higher G') and higher viscosity was noted for HS compared to other samples. HS had slower salt release (80.70 ±â€¯1.92%) than LS (95.95 ±â€¯3.82%) at 1 min in simulated gastric conditions. After 120 min, HS showed up to 99.38 ±â€¯1.08% release of salt, while LS had 95.95 ±â€¯3.82% release. HS had a favorable textural profile, having values more similar to the ready-to-eat commercial cup gel than did the LS formulation. The HS formulation resulted in a stable structure for ORS delivery and beneficial release properties.

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 .).

Insidious Harm of Medication Diluents as a Contributor to Cumulative Volume and Hyperchloremia: A Prospective, Open-Label, Sequential Period Pilot Study.

OBJECTIVES: Although the potential dangers of hyperchloremia from resuscitation fluids continue to emerge, no study to date has considered the contribution of medication diluents to cumulative volume and hyperchloremia. This study compares saline versus dextrose 5% in water as the primary medication diluent and the occurrence of hyperchloremia in critically ill patients. DESIGN: Prospective, open-label, sequential period pilot study. SETTING: Medical ICU of a large academic medical center. PATIENTS: Adult patients admitted to the medical ICU were eligible for inclusion. Patients who were admitted for less than 48 hours, less than 18 years old, pregnant, incarcerated, or who had brain injury were excluded. INTERVENTIONS: Saline as the primary medication diluent for 2 months followed by dextrose 5% in water as the primary medication diluent for 2 months. MEASUREMENTS AND MAIN RESULTS: A total of 426 patients were included, 216 in the saline group and 210 in the dextrose 5% in water group. Medication diluents accounted for 63% of the total IV volume over the observation period. In the saline group, 17.9% developed hyperchloremia compared with 10.5% in the dextrose 5% in water group (p = 0.037), which was statistically significant in multivariable analysis (odds ratio, 0.50; 95% CI, 0.26-0.94; p = 0.031). In the saline group, 34.2% developed acute kidney injury versus 24.5% in the dextrose 5% in water group (p = 0.035); however, this was not statistically significant when adjusting for baseline covariates. No other significant differences in dysnatremias, insulin requirements, glucose control, ICU length of stay, or ICU mortality were observed. CONCLUSIONS: This study identified that medication diluents contribute substantially to the total IV volume received by critically ill patients. Saline as the primary medication diluent compared with dextrose 5% in water is associated with hyperchloremia, a possible risk factor for acute kidney injury.

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 .).

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.

Amino Acid Hydration Decreases Radiation-Induced Nausea in Mice: A Pica Model.

Nausea and diarrhea are common yet inconsistent side effects of abdominal and pelvic irradiation. Their frequency, chronicity, and severity vary greatly, and the reasons for inter-subject variability are unknown. We studied the potential for radiation-induced changes in amino acid absorption and mucosal barrier function to lead to gastrointestinal toxicity. We found profound and prolonged changes in the absorption and secretion of several electrolytes and nutrients, caused by changes in transporter function, after radiation doses as low as 1 to 3 Gy. After identifying absorbed and non-absorbed amino acids, we demonstrated the role of a beneficial amino acid drink to alleviate radiation-related gastrointestinal symptoms in a mouse model.

Chloride Content of Fluids Used for Large-Volume Resuscitation Is Associated With Reduced Survival.

OBJECTIVE: We sought to investigate if the chloride content of fluids used in resuscitation was associated with short- and long-term outcomes. DESIGN: We identified patients who received large-volume fluid resuscitation, defined as greater than 60 mL/kg over a 24-hour period. Chloride load was determined for each patient based on the chloride ion concentration of the fluids they received during large-volume fluid resuscitation multiplied by the volume of fluids. We compared the development of hyperchloremic acidosis, acute kidney injury, and survival among those with higher and lower chloride loads. SETTING: University Medical Center. PATIENTS: Patients admitted to ICUs from 2000 to 2008. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 4,710 patients receiving large-volume fluid resuscitation, hyperchloremic acidosis was documented in 523 (11%). Crude rates of hyperchloremic acidosis, acute kidney injury, and hospital mortality all increased significantly as chloride load increased (p < 0.001). However, chloride load was no longer associated with hyperchloremic acidosis or acute kidney injury after controlling for total fluids, age, and baseline severity. Conversely, each 100 mEq increase in chloride load was associated with a 5.5% increase in the hazard of death even after controlling for total fluid volume, age, and severity (p = 0.0015) over 1 year. CONCLUSIONS: Chloride load is associated with significant adverse effects on survival out to 1 year even after controlling for total fluid load, age, and baseline severity of illness. However, the relationship between chloride load and development of hyperchloremic acidosis or acute kidney injury is less clear, and further research is needed to elucidate the mechanisms underlying the adverse effects of chloride load on survival.

Polymer-based oral rehydration solution for treating acute watery diarrhoea.

BACKGROUND: Acute diarrhoea is one of the main causes of morbidity and mortality among children in low-income countries. Glucose-based oral rehydration solution (ORS) helps replace fluid and prevent further dehydration from acute diarrhoea. Since 2004, the World Health Organization (WHO) has recommended the osmolarity of less than 270 mOsm/L (ORS ≤ 270) versus greater than 310 mOsm/L formulation (ORS ≥ 310). Polymer-based ORS (for example, prepared using rice or wheat) slowly releases glucose and may be superior to glucose-based ORS. OBJECTIVES: To compare polymer-based oral rehydration solution (polymer-based ORS) with glucose-based oral rehydration solution (glucose-based ORS) for treating acute watery diarrhoea. SEARCH METHODS: We searched the following sources up to 5 September 2016: the Cochrane Infectious Diseases Group (CIDG) Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 9), MEDLINE (1966 to 5 September 2016), EMBASE (1974 to 5 September 2016), LILACS (1982 to 5 September 2016), and mRCT (2007 to 5 September 2016). We also contacted researchers, organizations, and pharmaceutical companies, and searched reference lists. SELECTION CRITERIA: We included randomized controlled trials (RCTs) of people with acute watery diarrhoea (cholera and non-cholera associated) that compared polymer-based and glucose-based ORS (with identical electrolyte contents). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the search results and risk of bias, and extracted data. In multiple-treatment arms with two or more treatment groups, we combined outcomes as appropriate and compared collectively with the control group. MAIN RESULTS: Thirty-five trials that included 4284 participants met the inclusion criteria: 28 trials exclusively included children, five included adults, and two included both adults and children. Polymer-based ORS versus glucose-based ORS (osmolarity ≤ 270) Eight trials (752 participants) evaluated this comparison, and seven trials used rice as a polymer source. Polymer-based ORS may decrease mean stool output in the first 24 hours by 24 mL/kg (mean difference (MD) -24.60 mL/kg, 95% CI -40.69 to -8.51; one trial, 99 participants, low quality evidence). The average duration of diarrhoea may be reduced by eight hours (MD -8.24 hours, 95% CI -13.17 to -3.30; I² statistic = 86%, five trials, 364 participants, low quality evidence) with polymer ORS but results are heterogeneous. Limited trials showed no observed difference in the risk of unscheduled use of intravenous fluid (RR 0.66, 95% CI 0.43 to 1.02; I² statistic = 30%; four trials, 376 participants, very low quality evidence), vomiting (very low quality evidence), and hyponatraemia (very low quality evidence). Polymer-based ORS versus glucose-based ORS (osmolarity ≥ 310) Twenty-seven trials (3532 participants) evaluated this comparison using a variety of polymers. On average, polymer ORS may reduce the total stool output in the first 24 hours by around 65 mL/kg (MD -65.47 mL/kg, 95% CI -83.92 to -47.03; 16 trials, 1483 participants, low quality evidence), and may reduce the duration of diarrhoea by around eight hours (MD -8.57 hours; SD -13.17 to -4.03; 16 trials, 1137 participants, low quality evidence) with substantial heterogeneity. The proportion of participants that required intravenous hydration was low in most trials with fewer in the polymer ORS group (RR 0.75, 95% CI 0.57 to 0.98; 19 trials, 1877 participant, low quality evidence) . Subgroup analysis by type of pathogen suggested an effect on unscheduled intravenous fluid in those infected with mixed pathogens (RR 0.63, 95% CI 0.41 to 0.96; 11 trials, 928 participants, low quality evidence), but not in participants positive for Vibrio cholerae (RR 0.94, 95% CI 0.66 to 1.34; 7 trials, 535 participants, low quality evidence). No difference was observed in the number of patients who developed vomiting (RR 0.91, 95% CI 0.72 to 1.14; 10 trials, 584 participants, very low quality evidence), hyponatraemia (RR 1.82, 95% CI 0.52 to 6.44; 4 trials, 385 participants, very low quality evidence), hypokalaemia (RR 1.29, 95% CI 0.74 to 2.25; 2 trials, 260 participants, low quality evidence), or persistent diarrhoea (RR 1.28, 95% CI 0.68 to 2.41; 2 trials, 885 participants, very low quality evidence). AUTHORS' CONCLUSIONS: Polymer-based ORS shows advantages compared to glucose-based ORS (at ≥ 310 mOsm/L). Comparisons favoured polymer-based ORS over ORS ≤ 270 but analysis was underpowered.

An amino acid-based oral rehydration solution (AA-ORS) enhanced intestinal epithelial proliferation in mice exposed to radiation.

Destruction of clonogenic cells in the crypt following irradiation are thought to cause altered gastrointestinal function. Previously, we found that an amino acid-based oral rehydration solution (AA-ORS) improved gastrointestinal function in irradiated mice. However, the exact mechanisms were unknown. Electrophysiology, immunohistochemistry, qPCR, and Western blot analysis were used to determine that AA-ORS increased proliferation, maturation, and differentiation and improved electrolyte and nutrient absorption in irradiated mice. A single-hit, multi-target crypt survival curve showed a significant increase in crypt progenitors in irradiated mice treated with AA-ORS for six days (8.8 ± 0.4) compared to the saline-treated group (6.1 ± 0.3; P < 0.001) without a change in D0 (4.8 ± 0.1 Gy). The Dq values increased from 8.8 ± 0.4 Gy to 10.5 ± 0.5 Gy with AA-ORS treatment (P < 0.01), indicating an increased radiation tolerance of 1.7 Gy. We also found that AA-ORS treatment (1) increased Lgr5+, without altering Bmi1 positive cells; (2) increased levels of proliferation markers (Ki-67, p-Erk, p-Akt and PCNA); (3) decreased apoptosis markers, such as cleaved caspase-3 and Bcl-2; and (4) increased expression and protein levels of NHE3 and SGLT1 in the brush border membrane. This study shows that AA-ORS increased villus height and improved electrolyte and nutrient absorption.

Oral Rehydration Therapy and Feeding Replaces Total Parenteral Nutrition: A Clinical Vignette.

A 27-year-old patient with spina bifida and a high output loss of water and electrolytes from her ileostomy was successfully liberated from dependency on total parenteral nutrition and intravenous fluid and electrolyte replacement by the use of a rice-based oral rehydration therapy (ORT). This allowed her to return home to the care of her mother. We suggest that ORT can be effective in the context of modern high-technology settings, as well as in resource-poor situations.

Meta-analysis of high- versus low-chloride content in perioperative and critical care fluid resuscitation.

BACKGROUND: The objective of this systematic review and meta-analysis was to assess the relationship between the chloride content of intravenous resuscitation fluids and patient outcomes in the perioperative or intensive care setting. METHODS: Systematic searches were performed of PubMed/MEDLINE, Embase and Cochrane Library (CENTRAL) databases in accordance with PRISMA guidelines. Randomized clinical trials, controlled clinical trials and observational studies were included if they compared outcomes in acutely ill or surgical patients receiving either high-chloride (ion concentration greater than 111 mmol/l up to and including 154 mmol/l) or lower-chloride (concentration 111 mmol/l or less) crystalloids for resuscitation. Endpoints examined were mortality, measures of kidney function, serum chloride, hyperchloraemia/metabolic acidosis, blood transfusion volume, mechanical ventilation time, and length of hospital and intensive care unit stay. Risk ratios (RRs), mean differences (MDs) or standardized mean differences (SMDs) and confidence intervals were calculated using fixed-effect modelling. RESULTS: The search identified 21 studies involving 6253 patients. High-chloride fluids did not affect mortality but were associated with a significantly higher risk of acute kidney injury (RR 1.64, 95 per cent c.i. 1.27 to 2.13; P < 0.001) and hyperchloraemia/metabolic acidosis (RR 2.87, 1.95 to 4.21; P < 0.001). High-chloride fluids were also associated with greater serum chloride (MD 3.70 (95 per cent c.i. 3.36 to 4.04) mmol/l; P < 0.001), blood transfusion volume (SMD 0.35, 0.07 to 0.63; P = 0.014) and mechanical ventilation time (SMD 0.15, 0.08 to 0.23; P < 0.001). Sensitivity analyses excluding heavily weighted studies resulted in non-statistically significant effects for acute kidney injury and mechanical ventilation time. CONCLUSION: A weak but significant association between higher chloride content fluids and unfavourable outcomes was found, but mortality was unaffected by chloride content.

The addition of whey protein to a carbohydrate-electrolyte drink does not influence post-exercise rehydration.

The addition of whey protein to a carbohydrate-electrolyte drink has been shown to enhance post-exercise rehydration when a volume below that recommended for full fluid balance restoration is provided. We investigated if this held true when volumes sufficient to restore fluid balance were consumed and if differences might be explained by changes in plasma albumin content. Sixteen participants lost ~1.9% of their pre-exercise body mass by cycling in the heat and rehydrated with 150% of body mass lost with either a 60 g · L(-1) carbohydrate drink (CHO) or a 60 g · L(-1) carbohydrate, 20 g · L(-1) whey protein isolate drink (CHO-P). Urine and blood samples were collected pre-exercise, post-exercise, post-rehydration and every hour for 4 h post-rehydration. There was no difference between trials for total urine production (CHO 1057 ± 319 mL; CHO-P 970 ± 334 mL; P = 0.209), drink retention (CHO 51 ± 12%; CHO-P 55 ± 15%; P = 0.195) or net fluid balance (CHO -393 ± 272 mL; CHO-P -307 ± 331 mL; P = 0.284). Plasma albumin content relative to pre-exercise was increased from 2 to 4 h during CHO-P only. These results demonstrate that the addition of whey protein isolate to a carbohydrate-electrolyte drink neither enhances nor inhibits rehydration. Therefore, where post-exercise protein ingestion might benefit recovery, this can be consumed without effecting rehydration.

Fluid resuscitation in sepsis: a systematic review and network meta-analysis.

BACKGROUND: Fluid resuscitation is the cornerstone of sepsis treatment. However, whether balanced or unbalanced crystalloids or natural or synthetic colloids confer a survival advantage is unclear. PURPOSE: To examine the effect of different resuscitative fluids on mortality in patients with sepsis. DATA SOURCES: MEDLINE, EMBASE, ACP Journal Club, CINAHL, HealthSTAR, the Allied and Complementary Medicine Database, and the Cochrane Central Register of Controlled Trials through March 2014. STUDY SELECTION: Randomized trials that evaluated different resuscitative fluids in adult patients with sepsis or septic shock and death. No language restrictions were applied. DATA EXTRACTION: Two reviewers extracted data on study characteristics, methods, and outcomes. Risk of bias for individual studies and quality of evidence were assessed. DATA SYNTHESIS: 14 studies (18916 patients) were included with 15 direct comparisons. Network meta-analysis at the 4-node level showed higher mortality with starches than with crystalloids (high confidence) and lower mortality with albumin than with crystalloids (moderate confidence) or starches (moderate confidence). Network meta-analysis at the 6-node level showed lower mortality with albumin than with saline (moderate confidence) and low-molecular-weight starch (low confidence) and with balanced crystalloids than with saline (low confidence) and low- and high-molecular-weight starches (moderate confidence). LIMITATIONS: These trials were heterogeneous in case mix, fluids evaluated, duration of fluid exposure, and risk of bias. Imprecise estimates for several comparisons in this network meta-analysis contribute to low confidence in most estimates of effect. CONCLUSION: Among patients with sepsis, resuscitation with balanced crystalloids or albumin compared with other fluids seems to be associated with reduced mortality. PRIMARY FUNDING SOURCE: The Hamilton Chapter of the Canadian Intensive Care Foundation and the Critical Care Medicine Residency Program and Critical Care Division Alternate Funding Plan at McMaster University.

Oral rehydration therapy in the second decade of the twenty-first century.

Oral rehydration solution (ORS) was established as the cornerstone of therapy for dehydration secondary to acute infectious diarrhea approximately 40 years ago. The efficacy of ORS is based on the ability of glucose to stimulate Na and fluid absorption in the small intestine via a cyclic AMP-independent process. Despite the establishment that ORS is the primary reason for the substantial reduction in morbidity and mortality from diarrhea in children in developing countries, the use of ORS has lagged for many reasons. This review highlights efforts to establish a major reformulation of ORS following the demonstration that short-chain fatty acids (SCFA) stimulate colonic Na and fluid absorption by a cyclic AMP-independent mechanism. The addition of high-amylose maize starch (HAMS), a microbially-fermentable (or 'resistant') starch, to ORS results in delivery of non-absorbed carbohydrate to the colon where it is fermented to SCFA. To date, three randomized controlled trials with a HAMS-ORS in south India have demonstrated a substantial decrease in diarrhea duration in both adults and children hospitalized for acute diarrhea. Significant efforts are now underway to establish this dual-action, modified HAMS-hypoosmolar ORS solution as the standard ORS for the treatment of dehydration from acute diarrhea.

[Volume replacement therapy; what is the solution?]. / Volumeresuscitatie, wat is de oplossing?

2 types of infusion solutions are used for volume replacement: crystalline fluids (such as NaCl 0.9% and lactated Ringer's solution) and colloidal fluids made of hydroxyethyl cellulose, albumin or gelatine. The choice of fluids used appears to be determined by the personal preference of the physician or the department. Infusion of colloidal solutions results in rapid recovery of the circulating volume but can cause anaphylaxis, renal insufficiency and an increased bleeding tendency. The use of hydroxyethyl cellulose (HEC) is associated with higher mortality and renal impairment, and is therefore not very justifiable. Albumin-based infusions appear to be predominantly indicated for septic patients with hypoalbuminaemia. Gelatin-based infusion fluids have not yet been extensively studied. The balanced lactated Ringer's solution, the composition of which is closer to plasma than that of NaCl 0.9%, is being used with ever-increasing frequency. Lactated Ringer's infusion solution does not cause hyperchloremic acidosis and probably less often leads to renal insufficiency than when NaCl 0.9% is infused.