When is urine hypotonic

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Reprints and Permissions. Our study had certain limitations. First, to be able to measure the effect size as precisely as possible, we designed the study as a crossover experiment including only healthy volunteers rather than patients.

Although we attempted to counteract this issue by selecting broad inclusion criteria, mimicking real life as closely as possible, the applicability of our findings to certain patients is unclear. In particular, the management of maintenance fluids in patients who are already fluid expanded or have renal failure requires exploration. The role of essential hypertension also remains unclear, as exaggerated natriuresis was clearly present in one of our subjects who had not previously been diagnosed with hypertension.

Finally, it is difficult to assess the definitive clinical impact of our findings, because the exact mechanisms behind the deleterious effect of fluid and salt overload require elucidation in many patient populations, including the critically ill.

Only a set of well-designed clinical trials, performed in different subgroups, will be able to clarify this issue. At the guideline-recommended dose, isotonic v s hypotonic maintenance solutions caused the retention of a potentially clinically relevant amount of fluid, characterized by decreased serum aldosterone concentrations that indicate volume expansion, which is not the intent of maintenance fluid therapy.

The use of NaCl 0. In view of the widespread use of maintenance fluids, trials with carefully chosen end points are needed to address their safety in different clinical settings. Advice on the physiological explanation behind the findings: T. All authors have read and approved the final draft. All authors had full access to all of the data. Supplementary material is available at British Journal of Anaesthesia online. We are indebted to Petra Vertongen for essential logistical support before, during, and after the two extremely intense study periods and to our subjects for their endurance.

We also wish to thank our laboratory staff, Nina Jansoone, Gwladys Verstraete, Jan Van Den Bossche, and Laurence Roosens, for their expert handling of countless serum and urine samples. The other authors declare no conflicts of interest. British Association for Parenteral and Enteral Nutrition British Consensus Guidelines on intravenous fluid therapy for adult surgical patients Dietary reference values for food energy and nutrients for the United Kingdom.

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First and foremost, we set out to investigate whether, how and how much fluid retention could be induced by isotonic compared to hypotonic maintenance fluid therapy[1]. All prior studies focused almost exclusively on the occurrence of hyponatraemia, thereby systematically neglecting this potential side effect.

Although the clinical impact remains to be judged in dedicated trials, fluid retention of the size we observed in our experiment will not be regarded as trivial by most physicians dealing with postoperative or critical care[]. The effect size after being exposed to salt-rich solutions for more than 48 hours, as frequently encountered in clinical practice, can be expected to be even more substantial. There is no reason to suppose that our findings on fluid retention would be different in a situation of non-osmotic stimulation of antidiuretic hormone ADH.

We fully acknowledge that iatrogenic hyponatraemia is an important phenomenon, at least when viewed in the right perspective. The largest of the mentioned trials, of which we do not seek to minimize the findings, reported a significant difference in symptomatic hyponatraemia: it was encountered in 0.

The question that needs to be answered urgently is whether it is clinically acceptable to induce unnecessary salt and fluid overload in the vast majority of patients This is especially true when putting non-osmotic ADH-stimulation and subsequent hyponatraemia in perioperative or critical care into their right context by regarding them as markers of an underlying problem rather than an issue with the fluid itself.

This is illustrated by the fact that hyponatremia was repeatedly found to be associated with worse outcomes, while symptoms of fluid-induced hyponatraemia are rarely encountered, especially in adults. Also in this debate, association seems to have been confused with causality. Regular assessments of serum and urine sodium are key to identify patients at risk and protect them from harm by treating the underlying problem.

Together with others, we believe the most important cause of non-osmotic stimulation of antidiuretic hormone is hypovolemia, occurring sometimes very subtly and thus remaining frequently undetected[7]. This situation prompts treatment with isotonic resuscitation fluids before even considering the administration of maintenance fluids.

One of the other concerns raised is the challenge imposed by the injudicious extrapolation of findings in healthy individuals to the clinical setting, thereby overlooking the issue of non-osmotic stimuli of ADH-production. In our view, our study setting resembles at least part of the stress level of certain clinical situations in which maintenance fluids are prescribed. Being a study subject in an elaborate hour, intensively supervised experiment, spending a total of four sleep-deprived nights in a research facility with noisy volumetric pumps and bothersome infusion catheters in both arms, experiencing hunger, thirst and weight loss, being venepunctured and weighed every few hours, all the while having to precisely collect every drop of urine, is not what many would regard as a normal, unstressful situation.

Nevertheless, we agree with this limitation of our study and therefore designed the double blind randomized controlled TOPMAST-trial clinicaltrials. Currently, half of the subjects are recruited and the first results are to be expected in the beginning of Regarding our choice of study solutions, Drs. Leroy and Hoorn consider NaCl 0. It should be considered that, besides commonly not containing glucose or dextrose, not one of these solutions contains more than mmol litre-1 of potassium.

This is far less than recommended by guidelines and necessary to protect patients from hypokalaemia. To prevent or treat this important electrolyte disorder, most clinicians will choose to administer extra potassium chloride, thereby renouncing the advantages of these low-chloride solutions. We would like to point out that only fluids for resuscitation were evaluated in this study, while the prescription of maintenance fluids remained at the discretion of the treating clinicians.

This was reflected in the overall very low volumes of the study solutions median mL during the whole ICU stay. In these amounts, it is unlikely that the slightly different chloride content would have caused a detectable difference in harm, especially since over two litres of isotonic fluids were already administered prior to enrolment.

Editor - Sick patients who are unable to ingest oral fluids usually receive intravenous maintenance fluid therapy IVMFT. Despite its routine application, IVMFT is still often based on dogmatic principles rather than high quality empirical research. Fortunately, well-designed high quality studies performed over the last decade have substantially improved our insights in what is safe and effective IVMFT.

Recently, Van Regenmortel and colleagues contributed additional data to this growing body of evidence by comparing the effects of isotonic and hypotonic IVMFT in healthy adult volunteers. In line with a previous report by this group, the authors argue that IVMFT should be hypotonic in order to avoid fluid overload.

We fully concur that fluid overload can negatively impact on outcomes and should be avoided at all times. The study findings are, however, in strong contradiction with the rapidly growing evidence that favours the use of isotonic balanced solutions for IVMFT in sick patients. The study findings are not a surprise. Basic physiological principles explain that the distribution volume of isotonic fluids is limited to the extracellular fluid compartment ECF which includes the intravascular space , whereas hypotonic solutions will diffuse over the extracellular and intracellular compartments.

This change, sensed by hypothalamic osmoreceptors, switches off antidiuretic hormone ADH release and hence decreases water reabsorption in the renal collecting ducts. As a consequence free water excretion will increase and osmotic homeostasis is maintained.