First do no harm: making oral rehydration solution safer in a cholera epidemic.
Oral rehydration solution (ORS) is lifesaving therapy for cholera and pediatric diarrhea. During a cholera epidemic in Guinea-Bissau, we evaluated the microbiologic quality of ORS prepared at a hospital and tested a simple intervention using special vessels for disinfecting tap water with bleach and for preparing, storing, and dispensing ORS. Few coliform bacteria and Escherichia coli were recovered from tap water; however, pre-intervention ORS contained numerous bacteria including E. coli and toxigenic Vibrio cholerae O1. In contrast, ORS samples from intervention vessels had few or no coliform bacteria, no E. coli, and no V. cholerae. Mean pre-intervention counts of coliform bacteria (3.4 x 10(7) colony-forming units [cfu]/100 ml) and E. coli (6.2 x 10(3) cfu) decreased significantly during the intervention period to 3.6 x 10(2) cfu and 0 cfu, respectively (P < 0.001). This simple system using bleach disinfectant and special storage vessels prevents bacterial contamination of ORS and reduces the risk of nosocomial transmission of cholera and other enteric pathogens. (+info)
Effect of hypervolemic therapy on cerebral blood flow after subarachnoid hemorrhage : a randomized controlled trial.
BACKGROUND AND PURPOSE: Cerebral blood flow (CBF) is reduced after subarachnoid hemorrhage (SAH), and symptomatic vasospasm is a major cause of morbidity and mortality. Volume expansion has been reported to increase CBF after SAH, but CBF values in hypervolemic (HV) and normovolemic (NV) subjects have never been directly compared. METHODS: On the day after aneurysm clipping, we randomly assigned 82 patients to receive HV or NV fluid management until SAH day 14. In addition to 80 mL/h of isotonic crystalloid, 250 mL of 5% albumin solution was given every 2 hours to maintain normal (NV group, n=41) or elevated (HV group, n=41) cardiac filling pressures. CBF ((133)xenon clearance) was measured before randomization and approximately every 3 days thereafter (mean, 4.5 studies per patient). RESULTS: HV patients received significantly more fluid and had higher pulmonary artery diastolic and central venous pressures than NV patients, but there was no effect on net fluid balance or on blood volume measured on the third postoperative day. There was no difference in mean global CBF during the treatment period between HV and NV patients (P=0.55, random-effects model). Symptomatic vasospasm occurred in 20% of patients in each group and was associated with reduced minimum regional CBF values (P=0.04). However, there was also no difference in minimum regional CBF between the 2 treatment groups. CONCLUSIONS: HV therapy resulted in increased cardiac filling pressures and fluid intake but did not increase CBF or blood volume compared with NV therapy. Although careful fluid management to avoid hypovolemia may reduce the risk of delayed cerebral ischemia after SAH, prophylactic HV therapy is unlikely to confer an additional benefit. (+info)
Input rate as a major determinant of furosemide pharmacodynamics: influence of fluid replacement and hypoalbuminemia.
To investigate how the response to a bolus and an infusion of furosemide is modulated by the rate of fluid replacement and by hypoalbuminemia, rabbits received 5 mg/kg of furosemide as a bolus or infused over 60 min, whereas diuresis was replaced with 13, 121, or 238 ml/h NaCl 0.9%/glucose 5% (50:50). Natriuretic and diuretic efficiencies were greater with the infusion than with the bolus of furosemide. Fluid replacement increased natriuretic and diuretic efficiency of furosemide bolus but only diuretic efficiency of furosemide infusion. Furosemide net fluid depletion reached a plateau when fluid replacement increased beyond 121 ml/h. Repeated plasmapheresis decreased plasma albumin by 30% (P <.05) and increased furosemide unbound fraction (P <.05). Compared with control rabbits, hypoalbuminemia decreased the natriuresis of the bolus (22.7 +/- 1.5-16.6 +/- 1.3 mmol, P <.05) but not that elicited by furosemide infusion (26.2 +/- 1.8 mmol). Given as a bolus, furosemide natriuretic and diuretic response as a function of its urinary rate of excretion exhibited an hyperbolic relationship, and after its infusion a clockwise hysteresis, denoting tolerance. Plasma renin activity was increased by the bolus and the infusion of furosemide, even in the presence of 121 ml/h of fluid replacement. It is concluded that: 1) the increase in natriuretic/diuretic efficiency of the bolus induced by fluid replacement is greater than when furosemide is infused, 2) furosemide net effect does not increase proportionally to fluid replacement, and 3) the infusion of furosemide prevents the hypoalbuminemia-induced decrease in response of furosemide given as a bolus. (+info)
Effects of anion substitution on hydration behavior and water uptake of the red-spotted toad, Bufo punctatus: is there an anion paradox in amphibian skin?
Amphibians absorb water osmotically across their skins and rely on chemosensory information from the skin to assess the suitability of hydration sources. The time spent with skin in contact with a moist surface provides a quantitative measure of their ability to perceive the ionic and osmotic properties of aqueous solutions. Dehydrated toads given hyperosmotic (250 mM) solutions of NaCl or Na-gluconate showed significantly longer periods of hydration behavior on the gluconate solution, but they lost water osmotically when immersed in either solution. Similarly, dehydrated toads given 250 mM solutions of NaCl, Na-acetate, Na-phosphate or Na-gluconate showed a progressively greater length of hydration time on solutions with the larger mol. wt anions. These results are consistent with the chemosensory phenomenon previously described in mammalian tongue as 'anion paradox'. On dilute (50 mM) solutions of NaCl or Na-gluconate, the hydration time was not different between anions, despite toads gaining water more rapidly when immersed in dilute NaCl than in Na-gluconate solutions. The differing behavioral results with hyperosmotic and hypoosmotic salt solutions suggest that chemosensory transduction through toad skin involves both transcellular and paracellular pathways. (+info)
Double blind, randomised controlled clinical trial of hypo-osmolar oral rehydration salt solution in dehydrating acute diarrhoea in severely malnourished (marasmic) children.
AIMS: To compare the clinical efficacy of hypo-osmolar oral rehydration salt (ORS) solution (224 mmol/l) and standard ORS solution (311 mmol/l) in severely malnourished (marasmic) children having less than 60% Harvard standard weight for age with dehydrating acute watery diarrhoea. METHODS: In a double blind, randomised, controlled trial, 64 children aged 6-48 months were randomly assigned standard (n = 32) or hypo-osmolar ORS (n = 32). RESULTS: Stool output (52.3 v 96.6 g/kg/day), duration of diarrhoea (41.5 v 66.4 hours), intake of ORS (111.5 v 168.9 ml/kg/day), and fluid intake (214.6 v 278.3 ml/kg/day) were significantly less in the hypo-osmolar group than in the standard ORS group. Percentage of weight gain on recovery in the hypo-osmolar group was also significantly less (4.3 v 5.4% of admission weight) than in the standard ORS group. A total of 29 (91%) children in the standard ORS group and 32 (100%) children in the hypo-osmolar group recovered within five days of initiation of therapy. Mean serum sodium and potassium concentrations on recovery were within the normal range in both groups. CONCLUSION: Our findings suggest that hypo-osmolar ORS has beneficial effects on the clinical course of dehydrating acute watery diarrhoea in severely malnourished (marasmic) children. Furthermore, children did not become hyponatraemic after receiving hypo-osmolar ORS. (+info)
Comparison of abomasal emptying in neonatal calves with a nuclear scintigraphic procedure.
The purpose of the present study was to demonstrate that nuclear medicine technology allows observation of the effect that milk clotting has on abomasal emptying in the living neonatal calf. Scintigraphic evaluation of abomasal emptying was carried out in 6 healthy male Holstein calves. The calves were fed 10% of their body weight daily as whole cow's milk that was divided equally and consumed as 2 feedings via a nipple bottle. One day before the nuclear scintigraphic procedure, the calves were randomly fed whole cow's milk, or an oral rehydration solution (ORS) containing bicarbonate and high levels of soluble fibre was fed for 3 consecutive feedings an hour before the portion of milk. For each calf, both feeding programs were repeated twice at a one-week interval. Immediately following administration of the 99mTC-sulfur-colloid-containing milk, the calves were imaged with the gamma camera positioned lateral and ventral to the abomasum. Additional right lateral and ventral views of the abomasum were collected at 15, 30, 45, 60, 90, 120, 150, 180, 210, and 240 min after administration of the radionuclide. Blood glucose determination were performed at one-hour intervals for 7 h after feeding milk to evaluate milk digestibility in both feeding programs. No significant differences in the results of the glucose absorption test or in the radionuclide counts of the abomasum were found between both feeding programs. Scintigraphic evaluation of abomasal emptying was found to be a useful technique for visualization of milk clotting and to test the effect of an ORS on milk digestibility. (+info)
Issues in contemporary fluid management.
Fluid management strategies need to be guided by an understanding of the pathophysiologic mechanisms underlying fluid imbalance. In the hypovolaemic patient, reduced circulating blood volume and venous return and, in severe cases, altered tissue perfusion may initiate a cascade of pathophysiologic processes culminating in multiple organ failure. The objectives of fluid management are to maintain adequate blood pressure, tissue oxygenation and intravascular fluid volume. Both crystalloids and colloids can be useful for these purposes. In the hypovolaemic patient with normal pulmonary function, the use of colloids to maintain colloid osmotic pressure can limit the development of peripheral as well as pulmonary oedema. However, choice of fluid is less important in states of increased lung capillary permeability. Further evidence is needed to broaden understanding of the optimal roles for particular fluid management strategies. Experimental models can make an important contribution in gathering such evidence. Rigorous pharmacoeconomic studies are also needed to define the benefits and costs of differing fluid regimens. (+info)
An alternative pathway for preclinical research in fluid management.
Recent meta-analyses have created uncertainties regarding the appropriate clinical role of colloid resuscitation fluids in critically ill patients and prompted changes in fluid management practice. Such changes may not be justified in view of methodological limitations inherent in the meta-analyses. Further research is nevertheless needed to resolve the questions raised concerning the relationship between choice of resuscitation fluid and patient outcome. Animal studies can play an important part by reliably indicating whether particular fluids are likely to prove effective and safe in clinical trials. It is important to avoid costly large-scale clinical trials that fail to demonstrate the clinical utility of the tested therapy, as resources expended in failed trials raise overall development costs and thereby restrict the range of therapies meeting criteria of commercial feasibility. Promising therapies may thus not be pursued, even though an urgent clinical need may exist. An alternative pathway of preclinical research may be of value in avoiding some of the major clinical trial failures of recent years, particularly in the area of sepsis. This alternative pathway commences with the formulation of hypotheses by therapeutics developers. Independent preclinical investigators are challenged, by means of a competitive request for proposals, to test the hypotheses in rigorous randomized studies employing clinically relevant animal models. Promising proposals would then be selected for further development with the aid of peer review. The results of the randomized animal studies, along with other preclinical data, could also be evaluated using accepted principles of 'critical appraisal' commonly applied to clinical trial results. This critical appraisal might, where appropriate, include meta-analysis of animal study findings. This alternative preclinical pathway to new product evaluation should be completed before the commencement of large-scale clinical trials. (+info)