All Things Sodium & the Brain in the PICU

Welcome to PICU Doc On Call, A Podcast Dedicated to Current and Aspiring Intensivists.I'm Pradip Kamat and I'm Rahul Damania. We are coming to you from Children's Healthcare of Atlanta - Emory University School of Medicine.Here's the case:A 6-year-old child with a known h/o craniopharyngioma who has been endocrinologically intact with exception of needing thyroid replacement was admitted to the PICU prior to craniotomy to proceed with further tumor resection as well as the removal of a secondary cyst impacting his brainstem. The patient is receiving Keppra for seizures and per mother, he has recently been significantly more sleepy at school.On POD Op day 5: the PICU the bedside nurse notices increased urine output (6cc/kg/hr to as high as 10cc/kg/hr). Initially, there was an increase in Na to 157mEq/L within 48-72 hours the serum Na dropped to 128mEq/LTo summarize key elements from this case, this patient has:Increase UOPRapidly increasing Na initially followed by a dropAll of which brings up a concern for Na abnormality post craniotomyIn today’s episode, we will be breaking down all things Sodium & the Brain. We will discuss diagnostic & management frameworks related to three pathologies:Central Diabetes InsipidusSyndrome of inappropriate Anti-Diuretic Hormone or SIADHCerebral Salt WastingThese diagnoses can certainly be seen individually inpatients or as a spectrum of diseases — as we go through each of these diagnoses, pay particular attention to patient characteristics and lab abnormalities. Namely, serum sodium, serum osm, and urine osm.To build the fundamentals, lets first start with classic nephrology saying: Serum Na represents HydrationThis takes us into a brief review of normal physiology — talking about three important hormones:ADHAldosteroneAtrial Natriuretic Peptide (ANP)Let’s go through a quick multiple-choice question.A patient is recently started on DDAVP for pan-hypopituitarism. The medication acts similarly to a hormone that is physiologically synthesized in which of the following from which are in the body?A. Paraventricular Nucleus of the HypothalamusB. Supraoptic Nucleus of the HypothalamusC. Anterior PituitaryD. Vascular EndotheliumThe correct answer here is B the Supraoptic Nucleus of the Hypothalamus. Remember that ADH is synthesized in the hypothalamus and released from the posterior pituitary.What are the physiologic actions of ADH?ADH Increases H2O permeability by directing the insertion of aquaporin 2 (AQP2) H2O channels in the luminal membrane of the principal cells. Thus, as we will see with Central Diabetes insipidus, in the absence of ADH, the principal cells are virtually impermeable to water.Let's talk about our next hormone, aldosterone. What are the important physiologic considerations?Aldosterone is secreted from the adrenal cortex as a byproduct of the RAAS.Aldosterone increases Na+ reabsorption by the renal distal tubule, thereby increasing extracellular fluid (ECF) volume, blood volume, and arterial pressure.It also helps in secreting K and H. This physiology is applied directly at the bedside when we have patients in the ICU who have a contraction alkalosis secondary to diuretics. The increase in aldosterone as these patients lose free water from their Lasix administration results in hypokalemia and metabolic alkalosis.Alright, what about the third hormone, ANP?Atrial natriuretic peptide (ANP) is released from the atria in response to an increase in blood volume and atrial pressure.ANP causes relaxation of vascular smooth muscle, dilation of arterioles, and decreased TPR.causes increased excretion of Na+ and water by the kidney, which reduces blood volume and attempts to bring arterial pressure down to normal.As ANP causes natriuresis, diuresis, and inhibition of renin, you can consider this hormone as having a complementary & opposite effect to ADH and aldosterone.Alright, now that we have the basics, let's talk about our index case presentation, central diabetes insipidus, can you illustrate the key diagnostic features of this disease?Central diabetes insipidus (CDI) is an important cause of hypernatremia in the intensive care setting and can be seen in primary brain lesions, traumatic brain injury, or as a harbinger of brain death.CDI results from inadequate ADH secretion. Children in the intensive care setting typically present with abrupt polyuria and free water diuresis.What are common triggers for CDI?Traumatic brain injury, brain tumors, pituitary surgery (i.e. postoperative craniopharyngioma resection), central nervous system infections, and cerebral hemorrhages or infarcts.CDI occurs most commonly in the setting of brain death. Because patients with CDI can conserve sodium appropriately, they typically do not manifest signs of volume depletion unless the diagnosis is delayed. Thus CDI is a cause of euvolemic hypernatremia.Absolutely, actually, in CDI the urine osmolality is typically less than the plasma osmolality. These patients have about >4 mL/kg/hr of urine output.What is the management of CDI?CDI includes the correction of free water deficit and the administration of the ADH synthetic analog desmopressin acetate (dDAVP). In a critically-ill patient, a vasopressin infusion may be needed for the rapid increase in UOP and serum Na. An advantage of vasopressin is the “quick on-off effect”Desmopressin can be administered subcutaneously, intranasally, or intravenously. The dosing varies by the route of administration and can be thought of as the 1-10-100 rule.IV 1mcgIN 10mcg (one puff = 10mcg)PO 100mcgIn critically ill patients, edema and peripheral vasoconstriction may preclude effective subcutaneous administration therefore intravenous administration of dDAVP or a continuous vasopressin infusion may be required.Alright, so you gave the patient with presumed CDI a dose of DDAVP. What will you expect?Patients with central diabetes insipidus will typically have a reduction in urinary output and a greater than 50% increase in urine osmolality in response to the first dose of dDAVP.At times we are measuring their urine output in mL/kg/hr so if a patient is on a continuous vasopressin infusion for DI, titrating to a UOP of 1-2 mL/kg/hr can be appropriate.Rahul why do you think in our patient with high UOP and a high serum Na, the serum Na suddenly dropped in 48 hours?There are two possibilities. Either patient has received DDAVP or