PROTRACTED ACUTE HYPERVOLEMIC HYPERNATREMIA UNMASKED AFTER VASOPRESSIN THERAPY, A CASE REPORT, REVIEW OF LITERATURE, AND PROPOSED ALGORITHMIC APPROACH

Transcription

1 AACE Clinical Case Reports Rapid Electronic Articles in Press Rapid Electronic Articles in Press are preprinted manuscripts that have been reviewed and accepted for publication, but have yet to be edited, typeset and finalized. This version of the manuscript will be replaced with the final, published version after it has been published in the print edition of the journal. The final, published version may differ from this proof. Case Report ACCR PROTRACTED ACUTE HYPERVOLEMIC HYPERNATREMIA UNMASKED AFTER VASOPRESSIN THERAPY, A CASE REPORT, REVIEW OF LITERATURE, AND PROPOSED ALGORITHMIC APPROACH Michael Morkos, MD, MS 1, 2 ; Maria Fam, BHSc 1 ; Mishita Goel, MD 1 ; Peter Hart, MD 2 ; Rasa Kazlauskaite, MD, MSc 1 From: 1 Rush University Medical Center, Chicago, IL, USA. 2 John H. Stroger, Jr. Hospital of Cook County. Running title: Hypervolemic Hypernatremia Correspondence address: Rasa Kazlauskaite Associate Professor, Department of Medicine Division of Endocrinology and Metabolism Rush University Medical Center 1750 W. Harrison St. (Jelke) Ste. 604w Chicago, IL rasa_kazlauskaite@rush.edu

2 Abstract Objective: Acute hypervolemic hypernatremia is the most common form of hypernatremia in critical care settings. Previous reports implicated acute kidney injury and vasopressin withdrawal-induced central diabetes insipidus. Methods: We present a 52-year-old woman who developed hypervolemic hypernatremia after treatment of septic shock due to complicated bowel perforation. Results: After discontinuation of a 30-hour infusion of vasopressin analog, the patient manifested hypernatremia ( meq/l, equivalent to mmol/l) with hypo-natriuric (urine sodium 49 meq/l) hypo-osmolar (osmurine 163 mosm/l) polyuria (urine output 6.9 L/24h) in a setting of the cumulative positive fluid balance of 20.1 liters. A trial of desmopressin yielded incomplete urinary concentration suggestive of renal resistance to desmopressin likely due to fluid overload. Despite positive water balance, her urine sodium was low at meq/l compared to serum sodium = meq/l. The hypernatremia with polyuria persisted for 16 days and resolved after treatment of the positive cumulative water balance (with controlled diuresis prioritizing natriuresis). Conclusion: Hypervolemic hypernatremia may result in insufficient urine sodium clearance. We propose to modify the diagnostic/treatment algorithm by including hypervolemic hypernatremia in a critical care setting, and recommending judicious administration of loop diuretic to prioritize natriuria in hypernatremia with extreme cumulative fluid overload. Key Words: hypervolemia, hypernatremia Abbreviations: ADH = anti-diuretic hormone; DI = diabetes insipidus; HHN = hypervolemic hypernatremia; L= liters; Naurine = urine sodium; osmurine = urine osmolarity; POD = postoperative day. Introduction Hypernatremia is defined as a serum sodium concentration above 145 meq/l. Although hypernatremia most often occurs due to unreplaced water loss (dehydration), hypervolemic hypernatremia (HHN) can occur during intensive treatment of shock. HHN in the intensive care

3 settings most often is thought to occur due to iatrogenic sodium loading. The examples of iatrogenic sodium overload include infusion of hypertonic sodium bicarbonate to treat metabolic acidosis, administration of hypertonic saline to treat traumatic head injury or other conditions, normal saline use during the treatment of hyperosmolar hyperglycemic state, treatment of critically ill edematous patients with large volumes of saline followed by loop diuretics, and in intensive care of patients recovering from acute kidney injury (1). Regardless of the prevalent view that hypernatremia occurs due to dehydration (2), HHN is the most common cause of hypernatremia in the intensive care settings. There is a need for a systematic algorithms for evaluation and treatment of HHN. We report a case of HHN, illustrating the need for diagnostic and management approach in an acute care setting, different from that in dehydration (hypovolemic hypernatremia). Case Description A 51-year-old African American woman with a history of ulcerative colitis, hypertension, and of sleeve gastrectomy for morbid obesity 17 months prior to admission was treated for septic shock due to bowel perforation and abdominal abscess, complicating sigmoid diverticulitis with clostridium difficile infection. Upon admission, her serum sodium (Naserum) was 142 meq/l (reference range (ref): meq/l) and estimated glomerular filtration rate was (egfr) >90 ml/min/1.73 m 2. On the 2 nd day of intensive care hospitalization, her treatment required surgical drainage of abscess, partial small bowel resection, and a double-barrel ileostomy. During the first 30 hours post-operatively, she required mechanical ventilation and blood pressure support with normal saline boluses and vasopressin (0.01 to 0.03 units/min). The cumulative fluid balance and serum sodium levels are depicted in Figure 1. Hypernatremia manifested after 30 hours of discontinuing vasopressin. Her serum creatinine ranged from 0.35 to 0.77, e GFR >90 ml/min/1.73 m 2, from the beginning of her hospital admission till the resolution of hypernatremia. She didn t develop acute kidney injury all through her hospital stay and there was no prior history of lithium intake. Evaluation of hypernatremia (serum sodium peaking at 156 meq/l), revealed a positive fluid balance (with a cumulative positive fluid balance of 20.2 liters [L]) with bilateral upper and lower extremity edema, urine output reaching 6.9 L/24h, and urine osmolality (osmurine) of 183 mos/kg. Her random urine sodium (Naurine) ranged between 36 to 49 meq/l compared to

4 Naserum =152 to 156 meq/l. Based on hypernatremia and body weight (194.6 kg), her free water deficit pertaining to hypernatremia was calculated at 10.1 L.(2) Based on a traditional hypernatremia treatment algorithms, the 5% dextrose infusion was initiated after discontinuing sodium-based fluid replacement without improvement in hypernatremia. Her free water intake (through D5W) was consistently higher than the volume of her urinary output. The hypernatremia with polyuria persisted for 13 days despite positive cumulative water balance with dextrose 5% in water (D5W) infusion. The patient responded only partially to a trial of desmopressin with osmurine increasing from 163 mos/kg only to 237 mos/kg and serum sodium of 152 meq/l before and after the trial, suggestive of partial nephrogenic diabetes insipidus due to fluid overload. Considering the diagnosis of partial nephrogenic diabetes insipidus, Hydrochlorothiazide 25 mg daily trial was started on postoperative day (POD) 11, followed by Spironolactone on POD15 which was discontinued soon afterward due to hyperkalemia. Both medications failed to reverse hypernatremia. On POD 16, she received intravenous Furosemide 20 mg when her serum Na was 146 meq/l, followed by daily Amiloride 5 mg therapy. Hypernatremia persisted until her cumulative fluid balance was reduced from 27.7 L to 8.8 L when her serum sodium was 140 meq/l, 3 days after Furosemide administration. Dextrose infusion, Amiloride, and Hydrochlorothiazide were discontinued without recurrence of her hypernatremia. Discussion We report HHN after discontinuation of vasopressin therapy for blood pressure support, recognizing the other contributing factors for hypernatremia: substantial cumulative fluid overload, gastrointestinal loss of hypo-osmolar secretions, possible acute kidney injury due to septic shock, lack of voluntary access to oral water intake due to critical illness. The traditional algorithm for treatment of hypernatremia with free water replacement in this patient with hypervolemia failed to normalize the serum sodium levels despite ensuring adequate free water infusion to exceed her urine output. In fact, correcting positive cumulative fluid overload by withdrawing intravenous fluids and judicious use of loop diuretics facilitated resolution of HHN.

5 Hypernatremia after withdrawal of vasopressin therapy has been reported to occur in up to 3% of intensive care patients and has been typically ascribed to transient diabetes insipidus (DI) after withdrawal of vasopressin therapy (3-5). Traditionally diabetes insipidus refers to the euvolemic or hypovolemic state. However, inappropriate intravenous solute administration in the setting of diabetes insipidus may result in HHN. Moreover, HHN has been described in patients recovering from acute kidney injury due to hypotonic polyuria with the inability of the kidney to concentrate the urine (1, 6). Inability to normally concentrate the urine from kidney dysfunction, combined with high urine or stool output, large urea output from the high serum urea concentration and inability to drink water have been identified as a combination of factors contributing to HHN in patients recovering from kidney injury in critical care settings. As illustrated by the reported case, the hypernatremia evaluation algorithm should first include determination of the overall fluid balance (7): euvolemic/hypovolemic (dehydration) hypernatremia versus HHN. HHN in critical care can be diagnosed in the setting of persistent positive fluid balance of >3L/24h, hyponatric urinary/intestinal fluid loss, edema/weight increase, and lack of voluntary oral water intake. Intravenous fluid type becomes particularly important prior to and following discontinuation of vasopressin therapy used as a pressor therapy due to hypotension. This phenomenon can be explained by inappropriate water diuresis with hypo-osmolar polyuria (183 mos/kg) in the setting of hypernatremia suggestive of diabetes insipidus (DI). DI may develop due to resistance to intrinsic anti-diuretic hormone (ADH) at the level of the renal receptors (nephrogenic DI) or the inability to create or secrete ADH at the cerebral level (central DI). Desmopressin trial is indicated to distinguish nephrogenic versus central etiologies: the latter resolves with the administration (with an increase in osmurine of approximately 200mOs/kg) whereas the nephrogenic DI does not (7, 8). Traditionally, vasopressin withdrawalinduced hypernatremia resolves with the administration of vasopressin or desmopressin implying central DI as the cause (3). However, in a setting of HHN with large urine output (and cumulative intravenous fluid overload), desmopressin trial may fail to concentrate the urine adequately, as illustrated by our case. This may also happen whenever the kidneys lose the urine concentration capacity as in acute kidney injury or loop diuretics, neither was the situation in our case (4, 6, 9). Nevertheless, desmopressin may be useful in combination with judicious loop diuretic management of positive fluid balance in HHN prioritizing the rate of natriuria over the rate of urinary water loss.

6 A general algorithm modification for the approach to hypernatremia in a critical care setting is proposed in Figure 2. Our patient manifested chronic HHN in the setting of vasopressin-induced transient diabetes insipidus which did not respond to desmopressin trial. Hypervolemic status was established and 9.5 kg weight gain. Given the algorithm, dextrose 5% solution should be administered for free water replacement concomitantly with a loop diuretic in a setting of hypervolemic hypernatremia. D5W is an isosmotic solution which becomes hypotonic upon infusion due to glucose metabolism thereby diluting the serum solution (10). Despite administration of D5W alone, the patient s body continued to retain sodium despite positive fluid balance which suggests prevailing impaired renal regulation of sodium and water balance. Loop diuretics cause natriuresis thereby eliminating excess sodium gain. The patient in this case report responded appropriately to the loop diuretic. The trend of Na urine was not monitored to confirm natriuresis but can be inferred given the resolution of hypernatremia. Hydrochlorothiazide can also be used as it decreases excretion of pure water thereby increasing total body water (9), however, in extreme cumulative fluid overload may prove inadequate. Of note, clinical judgement should be used for treatment of hypervolemic hypernatremia in the diuretic phase of acute tubular necrosis, as loop diuretics may result in exaggerated diuresis and worsening of the hypernatremia. In summary, acute HHN can develop following vasopressin administration and positive cumulative fluid balance with large urinary output in the setting of septic shock. Management of hypernatremia in the critical care setting merits a systemic approach to overall fluid balance as illustrated in the proposed algorithm.

7 References 1. Sarahian S, Pouria MM, Ing TS, Sam R. Hypervolemic hypernatremia is the most common type of hypernatremia in the intensive care unit. Int Urol Nephrol. 2015;47: Adrogue HJ, Madias NE. Hypernatremia. N Engl J Med. 2000;342: Bohl MA, Forseth J, Nakaji P. Transient Diabetes Insipidus After Discontinuation of Vasopressin in Neurological Intensive Care Unit Patients: Case Series and Literature Review. World Neurosurg. 2017;97: Ferenchick H, Ferguson N, Dicpinigaitis P. Incidence of Diabetes Insipidus After Cessation of Vasopressin Infusion for Treatment of Shock. C103 Critical care: sepsis and shock-what we are supposed to do, what is actually done, and what can we do better: American Thoracic Society, 2018: A6008-A Kristeller JL, Sterns RH. Transient diabetes insipidus after discontinuation of therapeutic vasopressin. Pharmacotherapy. 2004;24: Sam R, Hart P, Haghighat R, Ing TS. Hypervolemic hypernatremia in patients recovering from acute kidney injury in the intensive care unit. Clin Exp Nephrol. 2012;16: Al-Absi A, Gosmanova EO, Wall BM. A clinical approach to the treatment of chronic hypernatremia. Am J Kidney Dis. 2012;60: Overgaard-Steensen C, Ring T. Clinical review: practical approach to hyponatraemia and hypernatraemia in critically ill patients. Crit Care. 2013;17: Mahoney JH, Goodman AD. Hypernatremia due to hypodipsia and elevated threshold for vasopressin release. Effects of treatment with hydrochlorothiazide, chlorpropamide and tolbutamide. N Engl J Med. 1968;279:

8 10. Rasouli M. Basic concepts and practical equations on osmolality: Biochemical approach. Clin Biochem. 2016;49: Legends Figure 1: Serum Sodium Concentration and Cumulative Fluid Balance Figure 2: Diagnostic algorithm for hypernatremia

9 Serum Sodium > 145 meq/l Hypovolemic Euvolemic Hypervolemic Clinical Uosm>600 mosm/kg Urine Na< 20 meq/l Uosm mosm/kg Urine Na> 20 meq/l Uosm>300mOsm/kg Urine Na variable EFWC is negative Uosm<300mOsm/kg Urine Na variable EFWC is positive Sodium Gain>0 [Na+K]infused-[Na+K]excreted Lab tests EFWC (Electrolyte Free Water Clearance): Urine volume X (1-[Naurine+Kurine])/Naserum EFWC positive: Renal causes EFWC negative: Extra-Renal causes Calculate water deficit Total body water X (Naserum/[140-1]) 0.45% saline 0.9% saline 5% Dextrose (Free Water Replacement) If Uosm normalizes (Central DI) Administer Desmopressin Exogenous ADH (Desmopressin Trial) If Uosm does not normalize: Nephrogenic DI 5% Dextrose ± Loop diuretics 1. Stop Sodium based IV fluids 2. Loop diuretic with/without D5W to prioritize natriuria over water excretion. * 3. Consider monitoring of urine and serum Na and K 4. Desmopressin (expecting partial response) 5. Hemodialysis if resistant Treatment * In the diuretic phase of an acute tubular necrosis (ATN), loop diuretic use must be judicious and only in cases of persistently positive cumulative fluid overload (water and sodium retention). Loop diuretic therapy in the diuretic phase of ATN can result in massive diuresis and worsening of the hypernatremia.