Managing Electrolytes Abnormalities in the Donor Management Phase The Sodium-Glucose Shuffle

1. Managing ElectrolytesAbnormalities in the Donor Management PhaseThe Sodium-Glucose Shuffle Dan Lebovitz, MD – Critical Care Akron Children’s Hospital Medical Director – Lifebanc, NE Ohio OPO

2. Metabolic derangements • Among the many derangements that effect the brain dead organ donor, electrolyte abnormalities remain one of the most common. • Abnormalities of electrolytes may present as benign or may present with an acute arrhythmia or hypotension that may result in the loss of transplantable organs from a potential donor.

3. Metabolic derangements • With the limited numbers of donors and the increasing need for transplantable organs it is imperative that these potential derangements are anticipated and avoided or rapidly treated during the entirety of the donor management phase of care to avoid the potential loss of any transplantation potential.

4. Metabolic derangements • In addition, there have been some publications questioning donor metabolic derangements and their effect on recipient organ outcomes that will be discussed later in this presentation

5. Brief Review of Electrolytes and Fluids in Human Physiology (Sorry, has to be done) • Humans are composed of electrolytes dissolved in water • Water (Total body water – TBW) is divided • 60% Intracellular compartment (IC) • Self explanatory • 40% Extracellular compartment (EC) • 8% Intravascular space • 28% Interstitial – around cells/ outside capillaries • 4% Transcellular area

6. Brief Review of Electrolytes and Fluids in Human Physiology • Electrolytesand Glucose are dissolved throughout the TBW • Not evenly because of number of variably permeable membranes, ionic pumps, osmolar gradients, hormonal factors, etc • Electrolytes levels are quite different depending on which fluid compartment you are looking at

7. Brief Review of Electrolytes and Fluids in Human Physiology • Sodium, Chloride and Bicarbonate are predominantly in the EC space • Potassium, Calcium, Magnesium and Phosphorous are mostly in the IC space • All sampling of levels takes place from the EC – intravascular space • Reasonable estimate of total body EC based lytes • Poor estimate of stores of IC contained lytes

8. Brief Review of Electrolytes and Fluids in Human Physiology • When abnormalities of both water and electrolytes occur the predominate deficit needed to return the electrolyte value back to the normal range is treated • So, if hypernatremia is the issue then replacement of free water need occur • If hyponatremia is found then the correction is sodium replacement

9. Brief Review of Electrolytes and Fluids in Human Physiology • In general once correction occurs via the EC space (iv infusion) the correction distributes through the TBW within ~15-30 minutes so re-testing to reevaluate correction may take place at that time • Osmolality influences the movement of free water between spaces (from low osm to high) and can be estimated by the formula serum osm=(2 x Na)+(Glu/18)+(BUN/2.8)

10. Brief Review of Electrolytes and Fluids in Human Physiology • If the result of treatment of a patient is to increase or decrease EC osmolality then IC water changes as well with cells becoming either dehydrated or bloated with water • If the derangements are severe enough cellular dysfunction may occur resulting in organ damage/ injury that may effect post transplantation function of organs

11. Brief Review of Electrolytes and Fluids in Human Physiology • OK enough of that • Back to our patient/donor

12. Electrolyte Issues in Deceased Organ Donors • Electrolyte abnormalities may occur in the brain dead donor as a result of: • Treatment of the patient prior to determination of death • Or as a result of the brain herniation process • In addition these abnormalities may be primary or secondary to alterations in TBW

13. Electrolytes abnormalities and their estimated incidence of occurrence in Brain Dead Donors Condition • Hypernatremia • Hyponatremia • Hyperkalemia • Hypokalemia • Hypophosphatemia • Hyperglycemia Incidence • 59% • 38% • 39% • 91% • 66% • Common Powner et al, Prog in Transpl. 2000;10:88-96

14. Electrolyte Issues in Deceased Organ Donors : predeclaration • Current management of increased ICP may include : • Isotonic saline as the primary IVF • Osmotherapy to dehydrate patients in an attempt to decrease cerebral edema to avoid brain herniation and death. • This therapy includes the active IV infusion of either 3%NaCl or Mannitol • 3% NaCl more common in the US

15. Electrolyte Issues in Deceased Organ Donors: predeclaration • This 3% NaCl pre brain death delivers a large amount of Na to the patient while at the same time dehydrating them • Causes significant hypernatremia • Loss of free water • In addition as previously mentioned in numerous discussions already the brain herniation that begins pre-declaration may result in SIADH or DI so lead to hypo or hyper natremia

16. Sodium Issues • The most common abnormality seen with sodium is hypernatremia • This results from: • Iatrogenic treatment with osmotherapy • Volume depletion of free water due to osmotic diuresis from this as well as elevated glucose levels • Diabetes insipidus - decreased or absent ADH(vasopressin) following loss of hypothalamic/ pituitary interaction after brain death

17. Sodium Issues • The All of these causes are primarily related to free water volume loss in excess of sodium loss • Treatment is free water replacement • Estimated by formula

18. Sodium Issues • Post liver transplant graft failure • Controversial • Studies early suggested real phenomena • More recent studies suggest not a significant issue

19. Glucose • Majority of deceased donors have elevated glucose • Due to insulin resistance • Possibly from elevated stress hormone levels – cortisol, glucagon, catecholamines • increased glucose production, • infused glucose • corticosteroids

20. Glucose • Concerns about organ dysfunction post transplant due to poor glycemic control • Similar to concerns raised in critical care arena • Blasi-Ibenez et al. anesthesiology 2009;110:331-41 • Retrospective chart review CTDN donors from 2005-2006 • 458 donors

21. A Randomized Prospective Trial of Insulin Therapy in Deceased Organ Donors For Renal Protection HRSA, R380T10586 ClinicalTrials.gov Identifier: NCT01140035

22. Study in progress – thanks Claus for these slides • 174 hospitals in Northern California and Nevada • All deceased organ donors 18 years and older were considered for enrollment. There was no gender or ethnicity restriction. • Allocation was achieved centrally and study participants were randomly assigned to 2 glucose target concentrations, 110-130 mg/dl or 180-200 mg/dl, respectively.

23. In this single donor service area prospective randomized trial in deceased organ donors, intensive to moderate insulin therapy did not demonstrate beneficial effects on terminal creatinine or delayed graft function when compared to conventional glucose management.

24. Conclusion • The study demonstrated that glucose levels of less than 150 mg/dl do not influence terminal creatinine values in deceased donors and DGF in recipients when compared to glucose levels of 180-200 mg/dl. Significant hyperglycemia (> 200 mg/dl) should be avoided since associated renal injury cannot be entirely ruled out.

25. Other important lytes at the dance - Potassium • Potassium – clearly important as significant derangements can result in cardiac arrest and loss of a donor prior to recovery of organs • Commonly seen low in donors • Pay close attention in donors that are acidotic – when the acidosis resolves either due to rehydration or bicarb the EC potassium shifts IC and the donor is left with significant potassium depletion

26. Other important lytes at the dance - Calcium • Calcium while predominately intracellular is critical to adequate cardiac muscle function • Follow the Ionized Calcium and maintain in the upper range of normal for best inotropic support