A quantitative approach to intravenous fluid therapy in the syndrome of inappropriate antidiuretic hormone secretion

Abstract

Background A wide range of interesting mathematical models has been derived to predict the effect of intravenous fluid therapy on the serum sodium concentration (most notably the Adrogué–Madias equation), but unfortunately, these models cannot be applied to patients with disorders characterized by aberrant antidiuretic hormone (ADH) release, such as the syndrome of inappropriate ADH secretion (SIADH). The use of intravenous fluids in these patients should prompt caution, as the inability of the kidneys to properly dilute the urine can easily result in deterioration of hyponatremia. Methods In this report, a transparent and clinically applicable equation is derived that can be used to calculate the estimated effect of different types and volumes of crystalloid infusate on the serum sodium concentration in SIADH patients. As a “proof of concept”, we discuss five SIADH patient cases from our clinic. Alternatively, our mathematical model can be used to determine the infusate volume that is required to produce a certain desired change in the serum sodium concentration in SIADH patients. Conclusion The presented model facilitates rational intravenous fluid therapy in SIADH patients, and provides a valuable addition to existing prediction models.

Comparing the Voets equation and the Adrogue-Madias equation for predicting the plasma sodium response to intravenous fluid therapy in SIADH patients

“…The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is one of the most common causes of hypotonic hyponatremia, which is defined as a plasma sodium concentration below 135 mmol/L in the context of plasma hypotonicity [ 1 – 4 ]. This condition is characterized by the feedback-independent–and often tonic–release of antidiuretic hormone (ADH) or arginine vasopressin, an oligopeptide hormone that stimulates the translocation of aquaporin 2 water channels in the collecting ducts and promotes pure water retention by the kidneys [ 1 , 2 , 4 ]. ADH can be secreted in this feedback-independent fashion by the posterior pituitary gland, often provoked by certain drugs or pain, or by malignant cells in the case of paraneoplastic SIADH, especially in patients with small-cell lung cancer [ 1 , 2 , 4 ].…”

“…This condition is characterized by the feedback-independent–and often tonic–release of antidiuretic hormone (ADH) or arginine vasopressin, an oligopeptide hormone that stimulates the translocation of aquaporin 2 water channels in the collecting ducts and promotes pure water retention by the kidneys [ 1 , 2 , 4 ]. ADH can be secreted in this feedback-independent fashion by the posterior pituitary gland, often provoked by certain drugs or pain, or by malignant cells in the case of paraneoplastic SIADH, especially in patients with small-cell lung cancer [ 1 , 2 , 4 ]. Furthermore, SIADH can be mimicked by the exogenous administration of vasopressin analogues, such as desmopressin, in the treatment of–among other afflictions–enuresis nocturna or certain types of Von Willebrand disease [ 1 , 4 ].…”

“…ADH can be secreted in this feedback-independent fashion by the posterior pituitary gland, often provoked by certain drugs or pain, or by malignant cells in the case of paraneoplastic SIADH, especially in patients with small-cell lung cancer [ 1 , 2 , 4 ]. Furthermore, SIADH can be mimicked by the exogenous administration of vasopressin analogues, such as desmopressin, in the treatment of–among other afflictions–enuresis nocturna or certain types of Von Willebrand disease [ 1 , 4 ]. Because the ADH release in SIADH patients is not governed by physiological osmotic stimuli, their renal ability to excrete water is greatly diminished–which is reflected by concentrated urine with a relatively elevated and fixed urine osmolality–whereas their renal ability to excrete sodium remains fairly unaffected [ 1 , 2 , 4 ].…”

“…Furthermore, SIADH can be mimicked by the exogenous administration of vasopressin analogues, such as desmopressin, in the treatment of–among other afflictions–enuresis nocturna or certain types of Von Willebrand disease [ 1 , 4 ]. Because the ADH release in SIADH patients is not governed by physiological osmotic stimuli, their renal ability to excrete water is greatly diminished–which is reflected by concentrated urine with a relatively elevated and fixed urine osmolality–whereas their renal ability to excrete sodium remains fairly unaffected [ 1 , 2 , 4 ]. As a result, it has classically been accepted by clinicians that administering normal saline infusate to a SIADH patient will exacerbate hypotonic hyponatremia and should thus be considered an inappropriate treatment strategy for these patients [ 1 – 3 ].…”

“…that normal saline can in fact be effective in treating SIADH-induced hypotonic hyponatremia, as long as the urine is not concentrated beyond approximately 530 mOsmol/L [ 4 – 8 ]. Based on the electrolyte-free water balance of intravenous fluid input versus urine output, we have previously derived a novel model–hereafter referred to as the Voets equation for clarity–that can be used to predict the effect of various volumes of crystalloid infusate with various tonicities on the plasma sodium concentration in SIADH, taking into account patient characteristics, such as the total body water, the urine osmolality, and the initial plasma sodium concentration [ 4 ]. Using a retrospective chart review, we have experimentally validated our previously presented mathematical model in SIADH patients by comparing the plasma sodium response to crystalloid intravenous fluid therapy of varying volumes and tonicities as predicted by our model to the measured plasma sodium change.…”