1. PRINCIPLES OF SURGERY FLUID AND ELECTROLYTE BALANCE PART 1: DISORDERS OF WATER AND SALT BALANCE January 2010 Dr. Bob Richardson, Toronto General Hospital

2. Objectives (1) 1. Understand how humans maintain water balance Role of ADH and thirst 2. Understand the role of sodium in body fluid homeostasis Manifestations of sodium depletion

3. Objectives (2) 3. Know the mechanisms for postoperative hyponatremia  How to prevent it  How to treat it 4. Know some of the literature on perioperative IV fluid therapy 5. Understand the mechanisms and treatment of surgically induced diabetes insipidus and hypernatremia

4. Case 1: 84 year old woman admitted for knee replacement. On thiazide diuretic for hypertension. Preoperative serum sodium 134 mmol/L (135-145). Postoperatively had frequent vomiting. Given 6 litres of 5% dextrose in saline for 2 days (i.e. 2/3-1/3 at 125 ml/h). After 48 hours became comatose, serum sodium was 115 mmol/L. Sodium concentration was corrected over 5 days but patient was left with permanent cognitive deficit. (Reported in BMJ 1999)

5. Question 1 She developed hyponatremia because she received: A. Too much IV fluid B. Too much of the wrong IV fluid C. The wrong IV fluid D. Hydrochlorthiazide

6. Question 2 How should she have been treated after 48 h? A. Water restriction B. Isotonic saline C. Hypertonic saline D. Hypertonic saline + furosemide

7. Water Physiology What protects us from hyponatremia or hypernatremia?

8. PHYSIOLOGY OF ADH AND WATER Q: How would you make someone hyponatremic? A: Give ___________________ and ________________________ ADH (vasopressin) causes collecting duct to reabsorb water HYPONATREMIA = WATER EXCESS (relative to sodium) Usually need water intake and ADH action to get hyponatremic water ADH

9. Q: What prevents normals from developing hyponatremia? A: suppress pituitary secretion of ADH Allows the kidney to excrete large volumes of hypotonic fluid In young healthy adults, in the absence of ADH, urine flow could be close to 1 L/h with an osmolality < 100 mosmol/kg)

10. Normal ADH physiology ADH is secreted in response to an increasing serum sodium concentration Exhibits a threshold and a slope: normal threshold is about 135 mmol/L below this value for serum sodium, ADH should be totally suppressed. Most common reason for hyponatremia = failure to suppress ADH when the serum sodium is < 135 mmol/L

11. ADH vs Serum Sodium: Threshold and Slope Thirst

12. Q: What prevents normals from developing hypernatremia even when fluid losses are high? A: Thirst Drinking water lowers serum sodium concentration back toward normal. Commonest cause of hypernatremia is failure to drink fluid when water depleted. Note that increased ADH during hypernatremia prevents excessive urine loss of water but does not replace water deficits.

13. Water Pathophysiology How do things go wrong?

14. HYPONATREMIA Non-osmotic stimulation of ADH Reduced effective circulating volume Nausea Pain, psychological stress Pregnancy Drugs Cortisol deficiency, hypothyroidism Surgery Tumours (SCLC), intracranial disorders, intrathoracic disorders (SIADH)

15. EFFECTIVE CIRCULATING VOLUME Definition: the adequacy of arterial filling; depends on cardiac output and peripheral vascular resistance. Reduced when: Cardiac output is reduced ( low intravascular volume or cardiac failure) Peripheral arterial vasodilatation which is not matched by an equivalent increase in cardiac output (cirrhosis with ascites, distributive shock)

16. Characteristics of Low Effective Circulating Volume  low BP, postural fall in BP, low JVP  signs of CHF: edema, pulmonary edema,  JVP  ascites, edema  tachycardia   renin, angiotensin II, aldosterone, noradrenaline, adrenaline, cortisol and ADH

17. ADH and Effective Circulating Volume ADH = vasopressin Important regulator of peripheral vascular resistance Not surprising that ADH secretion is stimulated by low ECV Primarily baroreceptor (carotid sinus to brain stem to hypothalamus)

18. Kidney response to low effective circulating volume low sodium excretion and low urinary sodium concentration (< 20 mmol/L) low urine flow with concentrated urine (osmolality > 500 mosmol/kg) may be low GFR with high creatinine

19. What factors could increase ADH levels in the perioperative state? 1. Reduced effective circulating volume 2. Nausea (surgery, narcotics) 3. Pain, stress 4. Surgery itself 5. Ectopic secretion by tumours (SCLC) 6. Release from damage to hypothalamus, posterior pituitary

20. Why Reduced Effective Circulating Volume?  Sodium loss: vomiting, ileus, pancreatitis, NG suction, ileostomy, bile drainage, hemorrhage, diarrhea  congestive heart failure (MI, tamponade, arrhythmia)  cirrhosis/ascites  sepsis (vasodilatation)  epidural anesthesia

21. Effect of Surgery on ADH Secretion  ADH increases from 2 uU/ml to 25 uU/ml after manipulation of viscera during cholecystectomy.  ADH levels stay elevated following most types of surgery for 1.5 to 4 days  Abdominal and cardiothoracic surgery stimulate ADH more than others  ADH levels > 5-10 cause a maximally concentrated urine

22. Relationship of Sodium and Hyponatremia Why does sodium loss cause hyponatremia? Even isotonic sodium loss can lead to hyponatremia Loss of isotonic sodium (diarrhea, burns, pancreatitis etc.) lowers effective circulating volume: ↑ ADH If hypotonic fluid is given, water is retained - hyponatremia

23. POSTOPERATIVE HYPONATREMIA CAUSE: stimulation of ADH secretion by surgery (or other factors) with use of either hypotonic fluid intravenously, or excessive amounts of isotonic fluid. Patients at greatest risk are women and elderly, probably because they have smaller initial total body water due to low body weight and higher body fat

24. Incidence of Postoperative Hyponatremia About 3-5%  about one half have normal effective circulating volume  about one quarter have edema state  the rest are hypovolemic or have renal failure

25. Complications of Hyponatremia  Acute severe hyponatremia (serum sodium < 120 mM developing in less than 48 hours) causes brain cell swelling  coma, seizures, hypoxia, death  Chronic hyponatremia usually asymptomatic unless very severe (< 110 mM) Brain volume can adapt to normal with chronic hyponatremia Rapid correction of chronic severe hyponatremia may cause myelinolysis of brain resulting in severe irreversible brain injury

26. Case 1: 84 year old woman admitted for knee replacement. On thiazide diuretic for hypertension. Preoperative serum sodium 134 mmol/L (135-145). Postoperatively had frequent vomiting. Given 6 litres of 5% dextrose in saline for 2 days (i.e. 2/3-1/3 at 125 ml/h). After 48 hours became comatose, serum sodium was 115 mmol/L. Sodium concentration was corrected over 5 days but patient was left with permanent cognitive deficit. (Reported in BMJ 1999)

27. Why Did This Happen?  ADH from low ECFV, nausea, surgery Thiazides impair free water excretion Excessive amount of dilute fluid Small elderly female Probably low GFR

28. Question 1 She developed hyponatremia because she received: A. Too much IV fluid B. Too much of the wrong IV fluid C. The wrong IV fluid D. Hydrochlorthiazide

29. Question 1 She developed hyponatremia because she received: A. Too much IV fluid B. Too much of the wrong IV fluid C. The wrong IV fluid D. Hydrochlorthiazide

30. Question 2 How should she have been treated after 48 h? A. Water restriction B. Isotonic saline C. Hypertonic saline D. Hypertonic saline + furosemide

31. Question 2 How should she have been treated after 48 h? A. Water restriction B. Isotonic saline C. Hypertonic saline D. Hypertonic saline + furosemide (Plus urgent nephrology consult)

32. POSTOPERATIVE HYPONATREMIA: SPECIAL SITUATIONS

34. Q3 She became hyponatremic because of: A. Large volume of ringer’s lactate B. Absorption of irrigating solution C. Hemolysis D. ADH release by reduced ECV

35. Hyponatremia with Hypotonic Irrigating Solutions (eg. TURP, Hysteroscopy) Absorption of electrolyte- free water with either sorbitol or glycine through vascular bed of prostate or uterus. Hyponatremia, brain cell swelling Pulmonary edema  IVV and  se. albumin Encephalopathy from metabolism of glycine to ammonium. Incidence 1-4% Prevention: limit duration of procedure, limit pressure, monitor positive fluid balance

36. Q3 She became hyponatremic because of: A. Large volume of ringer’s lactate B. Absorption of irrigating solution C. Hemolysis D. ADH release by reduced ECV

37. Q3 She became hyponatremic because of: A. Large volume of ringer’s lactate B. Absorption of irrigating solution C. Hemolysis D. ADH release by reduced ECV

38. 24 year old woman undergoes resection of suprasellar craniopharyngioma. Normal pre- op serum sodium (141). During first hour of surgery passes 700 ml of urine.

39. Q4 What should you do? A. Give DDAVP and replace urine with 2/3-1/3 B. Give DDAVP and replace urine with isotonic saline C. Replace urine with 2/3-1/3 D. Replace urine with isotonic saline E. Do nothing – this will resolve by itself

40. Pituitary surgery Classic triphasic pattern initial central DI due to interruption of hypothalamic-pituitary axis  period of SIADH due to leak of ADH from injured cells  chronic central DI This pattern is uncommon, seen in only 1% of patients

41. What Actually Happens After Transsphenoidal Pituitary Adenoma Resection – 57 patients 25% no abnormality 40% - diabetes insipidus Permanent in 10% 20% hyponatremia 15% DI then hyponatremia J Neurosurg 2009;111:555

42. Management of Central DI Patients with central DI who are awake and appreciate thirst do not become hypernatremic – they drink adequate water An anesthetized patient with central DI is at high risk of acute hypernatremia and brain injury DDAVP (IV, SC) for acute situations, IN or PO for chronic

43. Q4 What should you do? A. Give DDAVP and replace urine with 2/3-1/3 B. Give DDAVP and replace urine with isotonic saline C. Replace urine with 2/3-1/3 D. Replace urine with isotonic saline E. Do nothing – this will resolve by itself

44. Q4 What should you do? A. Give DDAVP and replace urine with 2/3-1/3 B. Give DDAVP and replace urine with isotonic saline C. Replace urine with 2/3-1/3 D. Replace urine with isotonic saline E. Do nothing – this will resolve by itself

45. Cerebral Salt Wasting Syndrome Syndrome of hyponatremia, high ADH, intravascular volume depletion, high urinary sodium loss in association with subarachnoid hemorrhage, trauma, neurosurgical procedures etc. Pathogenesis unclear; difficult to distinguish from SIADH sometimes

46. Prevention of Postoperative Hyponatremia  Avoid large volumes of hypotonic fluid unless the patient is hypernatremic  Limit volume of I.V. fluid given to meet patient’s needs  Adjust volume to patient’s body weight

47. Peri-operative IV Fluid Annals Surgery 2003;238:641 RCT of standard vs restricted IV fluid in patients undergoing colorectal resection Multicenter study from Denmark Powered to detect a 20% difference in complications with 80% power 86 patients per group

48. Peri-operative IV Fluid - Standard Intra-op 500 ml HAES 6% in NS Third space loss: NS 7 ml/kg/h X1 h, then 5 ml/kg/h X 2, then.3 ml/kg/h Blood loss: up to 500 ml: 1-1.5 L NS then HAES Post-op 1-2 L crystalloid/day

49. Peri-operative IV Fluid Restricted Intra-op: No preloading No replacement of third space loss Blood loss: volume/volume with HAES Post-op 1000 ml 5% D/W for remaining OR day Then oral fluid or IV if needed Furosemide if weight increased by 1 kg

50. Results StandardRestricted IV fluid OR day5.4 L2.7 L* IV fluid POD 11.5 L0.5 L* Max increase wt 0.9 kg3.5 kg* Complications4021* Compl -major188*

51. Complication frequency related to IV fluid and wt gain on operative day

52. Meta-analysis of Standard vs Restricted IV Fluid - Colorectal surgery only Restricted fluid strategy reduced morbidity: OR 0.41 (0.22-0.77) True for pre-operative and intra-operative restriction but not post-operative) British J Surg 2009;96:331

53. Actual Predicted By end of surgery

54. A Comparison of Albumin and Saline for Fluid Resuscitation in the Intensive Care Unit NEJM 2004;350:2247 Previous meta-analysis suggested albumin resuscitation increased mortality RCT in 7,000 ICU patients 4% albumin vs crystalloid for fluid No difference in mortality

55. HYPERNATREMIA Water deficiency: may be excessive water loss (eg sweating, hyperventilation, burns, polyuria) but inadequate intake is always present.

56. Causes of Poor Intake Coma Conscious but unable to speak or communicate (intubated in ICU, stroke, infants) Dementia, elderly (reduced thirst appreciation) Unable to gain access to water - bedridden elderly

57. Treatment of Hypernatremia Replace ongoing losses with similar fluid Restore water deficit with hypotonic fluid 5% D/W 1/2 normal saline (75 mmol/L) 2/3 - 1/3 Correct chronic hypernatremia slowly: rate of change of serum sodium < 0.5 mmol/L/h

58. Most Important Messages No hypotonic fluid perioperatively unless patient is hypernatremic Restrictive fluid therapy seems best approach for elective abdominal surgery Frequent serum electrolytes following pituitary/hypothalamic surgery Treat acute symptomatic hyponatremia urgently with hypertonic saline