Fluid and Hyponatremia Management By Craig B. Whitman, Pharm.D., BCPS, BCCCP Reviewed by Serena A. Harris, Pharm.D., BCPS, BCCCP; Ohoud A. Aljuhani, Pharm.D., BCCCP; and Abigail D. Antigua, Pharm.D., BCCCP LEARNING OBJECTIVES 1. Evaluate intravascular volume status and administer intravenous fluids (IVFs) to a critically ill patient. 2. Develop a plan to administer the appropriate IVF choice in a critically ill patient according to evidence from the literature. 3. Justify the use of peripheral administration of hypertonic saline and vasopressin antagonists to correct hyponatremia in a critically ill patient. 4. Demonstrate the role of desmopressin in preventing sodium overcorrection when treating hyponatremia. INTRAVENOUS FLUID THERAPY ABBREVIATIONS IN THIS CHAPTER AKI Acute kidney injury Introduction IVC Inferior vena cava Intravenous fluid (IVF) therapy has been used in clinical medicine IVF Intravenous fluid since the 1830s during the European cholera epidemic (Severs 2015). LOS Length of stay Many indications exist for IVF therapy in the critically ill population. RRT Renal replacement therapy Intravascular volume replacement is the most common reason for SIADH Syndrome of inappropriate using large volumes of IVF in the ICU, with sepsis, trauma, burn, antidiuretic hormone and perioperative volume loss requiring replacement. Hypovolemia TBI Traumatic brain injury occurs with reduction of extracellular volume and requires replace- ment with IVF. Electrolyte repletion, management of acidosis, and Table of other common abbreviations. prevention and management of drug-induced toxicities are other examples of common indications for IVF (Severs 2015). Many IVFs have been developed to optimize composition and administration in patients requiring treatment. These solutions are classified as crys- talloids and colloids. Crystalloid solutions contain small solutes with various amounts of water. The prototypical crystalloid solution is 0.9% sodium chloride (normal saline), with lactated Ringer solution and other various “balanced crystalloid” solutions available for IVF therapy. Intravascular volume expansion from normal saline is main- tained for up to 6 hours, with close to one-half of the infusate located in the interstitium (Severs 2015). Colloid solutions contain large mole- cules that more effectively maintain intravascular volume by exerting an oncotic pressure. Available colloids include iso-oncotic (4%–5%) and hyperoncotic (20%–25%) albumin solutions, semisynthetic col- loids like hydroxyethyl starch, dextrans, gelatins, and blood products. Despite the longstanding use of available IVFs, considerable debate exists regarding the optimal fluid choice, dose, and method of administration in the critically ill population. This chapter aims to discuss recent advances in knowledge of IVF therapy and provide insight into optimal use of various fluid choices in this population. CCSAP 2018 Book 3 • Fluids and Nutrition/GI and Liver Disorders 7 Fluid and Hyponatremia Management Assessment of Volume Status or large body habitus. In general, static measurements of in the Critically Ill Patient intravascular blood volume (e.g., central venous or pulmo- Assessing intravascular volume status and fluid responsive- nary artery occlusion pressure) should be avoided as the ness in critically ill patients is one of the more challenging sole assessment method (Rhodes 2017; Kalantari 2013). To a s p e c t s o f m a n a g i n g I V F t h e r a p y i n t h i s p o p u l a t i o n . A p p r o p r i a t e optimize therapy, intravascular volume should continually be assessment is important because it may mitigate a positive assessed and reassessed in patients who receive IVF. fluid balance, which may be associated with increased mor- tality (Malbrain 2014). A variety of methods including physical IVF Administration in Critically Ill Patients examination, chest radiography, laboratory values, and inva- Fluid may be administered in a variety of ways in critically ill sive monitoring can be used to assess volume status. There patients. The 12th Acute Dialysis Quality Initiative Conference is no universally accepted method to assess intravascular workgroup has proposed definitions pertinent to fluid adminis- volume in critically ill patients. Physical examination findings tration (Hoste 2014). Fluid bolus is a rapid infusion to correct should be used during the initial evaluation of intravascular intravascular volume status in shock states that consists of at volume status and combined with dynamic measurements least 500 mL over a maximum of 15 minutes. A fluid challenge is of blood volume. The Surviving Sepsis Campaign guide- a rapid infusion to correct hemodynamic instability, administer- lines recommend using dynamic variables to assess fluid ing 100–200 mL over 5–10 minutes followed by reassessment responsiveness, including passive leg raises, pulse pres- (Hoste 2014). The Surviving Sepsis Campaign recommends sure variation, and stroke volume variation (Rhodes 2017). 30 mL/kg as the initial fluid challenge in patients with sep- Esophageal Doppler monitoring and ultrasound measure- sis (Rhodes 2017). Fluid infusion is the continuous delivery of ment of the inferior vena cava (IVC) can also be considered IVF to maintain homeostasis, replace losses, or prevent organ if the equipment is available and the operator has expertise injury. Maintenance infusion is administration to provide flu- in its use. Esophageal Doppler monitoring may be limited ids for patients who cannot maintain their needs by the oral or because it requires the patient to be sedated (Kalantari 2013). enteral route. For individuals without ongoing losses, a maxi- The accuracy of IVC ultrasonography may be affected by mum rate of 1–2 mL/kg/hour is recommended (Hoste 2014). elevated intra-abdominal pressure (e.g., post-laparotomy) Four distinct phases of fluid therapy in resuscitation have been proposed: rescue, optimization, stabilization, and de-escalation (Rewa 2015). The rescue phase occurs with hemodynamic instability and associated impaired organ perfusion, resulting BASELINE KNOWLEDGE STATEMENTS in life-threatening shock. Intravenous fluids are administered Readers of this chapter are presumed to be familiar using boluses in the rescue phase. Optimization is when the with the following: patient is no longer at imminent risk of life-threatening shock • Understanding of intravascular fluid composition, but requires fluid therapy to optimize cardiac function, sus- mechanism of action, and toxicities tain tissue perfusion, mitigate organ dysfunction, and achieve • Understanding of sodium and water physiology physiologic end points. Methods of fluid administration in this and homeostasis phase vary between bolus, fluid challenge, and continuous • General knowledge of pathophysiology and infusion. During the stabilization phase, the goals of fluid ther- differentiation of sodium disorders apy are to provide ongoing organ support, prevent worsening • Knowledge of modes of renal replacement therapy organ dysfunction, and avoid further complications. The need used in critically ill patients for fluid during this phase is directed toward maintaining intra- Knowledge of standard treatment approaches for • vascular volume homeostasis and replacing ongoing losses. sodium abnormalities Fluid challenge and continuous infusion are the methods of IVF Table of common laboratory reference values. administration during stabilization. The de-escalation phase occurs with mobilization and removal of accumulated fluid. ADDITIONAL READINGS With recovery and decreasing illness severity, a negative fluid balance is typically targeted and may be achieved by sponta- The following free resources have additional back- neous or active diuresis of the patient (Rewa 2015). ground information on this topic: • Surviving Sepsis Campaign: international guide- lines for management of sepsis and septic shock: CONTROVERSIES IN FLUID 2016. Crit Care Med 2017;45:486-552. RESUSCITATION • Verbalis JG, Goldsmith SR, Greenberg A, et al. Crystalloids vs. Colloids Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Theoretical advantages exist for using one type of IVF versus Am J Med 2013;126:s1-s42. another. Colloids may more effectively maintain intravascu- lar volume status, leading to potentially less total volume CCSAP 2018 Book 3 • Fluids and Nutrition/GI and Liver Disorders 8 Fluid and Hyponatremia Management administered, which may reduce significant edema (Rewa the first ICU week: 2 L (interquartile range [IQR] 1–3.5) com- 2015). However, albumin costs as much as 30 times more pared with 3 L (IQR 0.5–3.2) (p<0.001). Despite equivalent than normal saline or lactated Ringer solution (Severs 2015). outcomes, this study had many significant limitations. About Meta-analyses of small studies evaluating the difference 25% of subjects received open-label fluid administration. The between crystalloid and colloid solutions have had mixed study duration extended over 9 years, which may also reflect results, leading to questionable effects of colloids on mortal- inconsistencies in practice over that time and changes in ity (Finfer 2004). guideline recommendations. Finally, the study allowed a vari- The Saline versus Albumin Fluid Evaluation (SAFE) study ety of fluids to be chosen at the clinician’s discretion, making was the first large, multicenter, double-blind, controlled trial it extremely difficult to ascertain any difference between the to evaluate differences in clinical outcomes between