Severe electrolyte- and acid-base disorders. GIC oktober 2013

Transcription

1 Severe electrolyte- and acid-base disorders GIC oktober 2013

2 Case (1) 19-year-old male, 60 kg Fever persisting for 1 month Cough and chest congestion for 10 days Lethargy for 1 week Admitted with diagnosis of chest infection No edema - stable hemodynamics

3 Case (2) Sodium 115 Potassium 1.0 Chloride 87 Urea 1.8 Creatinine 88 ph 7.56 PCO2 26 PO2 92 HCO3-24 Urine potassium 45 Calcium 2.05 Phosphorus 0.32 Urine phosphorus Urine calcium < 32 mmol/24 hrs 18 mmol/24 hrs Magnesium 0.58 TSH 5.05 Urine osmolality 261 Urine sodium 41 Cortisol 34 and 54 μg/dl

4 Life-threatening Severe hypokalemia Severe hyponatremia (Severe hypophosphatemia) Admission to ICU

5 Normal K + intake? mmol/day

6 Potassium physiology Potassium TMG - 2% 98% Intracellular shift Renal excretion

7 Without IC shift... Many people would die World record bananas eaten in 1 hour = 81 That is = 972 mmol potassium Without shift extracellular (16 L) potassium would increase with 61 mmol/l!!! What is essential for an IC shift to occur?

8 Potassium shift Na + Na + 3 Na + H + Na + -K + - ATPase 2 K + KATP KCa Insulin K + Kvg β-mimetics Potassium enters cell because of - TMG

9 Potassium excretion Flow rate CCT [K + ] CCT

10 Normally mmol of potassium reaches the CCT To increase potassium excretion we need to [K + ]CCT or increase flow rate CCT To increase [K + ]CCT (excretion) we need open K + channels and a - TMG for the tubule lumen

11 Late distal convoluted tubule Connecting segment Cortical collecting duct T CC

12 Severe hypokalemia? Insufficient intake Intracellular shift Renal loss Extrarenal loss

13 Severe hypokalemia? Insufficient intake Intracellular shift Renal loss Extrarenal loss

14 First diagnostic step with hypokalemia Spot urine K + measurement 24-hour urine K + measurement (< mmol/day) Urine potassium : creatinine ratio (< 1.5) Transtubular potassium gradient (TTKG) Spot urine K + 28 and 45 mmol/l (> 30 mmol/l usually means a urinary potassium loss)

15 TTKG CCT TTKG K + H2O but... K + TTKG = K+ urine Osm blood K+ blood Osm urine Normal 4-8

16 Severe hypokalemia? Insufficient intake Intracellular shift Renal loss Extrarenal loss TTKG 25:1

17 Renal K + loss Diuretics Hyperaldosteronism Hypomagnesemia (0.58) Renal tubular acidosis (types 1 and 2) Drugs (amphotericin, aminoglycosides)

18 Hypomagnesemia Mg blocks ROMK and blocks K + efflux Huang CL. JASN 2007;18:

19 Case (3) Hypokalaemia (urinary loss) Metabolic alkalosis Expected [HCO3 - ] = [(PCO2-40)/5] + 24 acute Expected [HCO3 - ] = [(PCO2-40)/2] + 24 chronic Expected [HCO3 - ] = [(26-40)/2] + 24 = 17

20 Differential diagnosis Bartter syndrome Gitelman syndrome

21 Upregulated by Inhibited or blocked by Thiazides Gitelman syndrome K + depletion Cotransporter Cl - depletion alkalosis Cl - HCO3 - Early distal nephron Na + Cl - Connecting tubule PENDRIN Distal tubule Flow and alkali stimulation Thiazides Loop diuretics Gitelman Bartter GI Cl - loss Inhibited or blocked by Loop diuretics Bartter syndrome K + depletion Loop of Henle Na + K + 2Cl - Cotransporter Secondary to ENaC activity K + H + Secondary to K + depletion ROMK Maxi K H + - ATP-ase Collecting duct ENaC Na + Direct stimulation Conn GRA Cushing Liddle Congenital adrenal disease 11 β HS dehydrogenase K + H + /K + - H + ATP-ase

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23 Case (4) Bartter syndrome - Mg (N), Ur Ca 2+ (N) Gitelman syndrome - Mg (L), Ur Ca 2+ (L) Mg 0.58 and Ur Ca 2+ /24 hrs 1.8 mmol (N > 2.5) Gitelman

24 Hyponatremia = Na+ + K e + e PNa TBW Can we explain this hyponatremia with a water gain?

25 Probably not First estimate amount of total body H2O In this patient kg = 36 L Total water gain = 115 New TBW New TBW = 43.8 L Water gain 7.8 L

26 Hyponatremia = Na+ + K e + e PNa TBW Can we explain this hyponatremia with a sodium deficit?

27 Probably not First estimate amount of total body H2O In this patient kg = 36 L Total Na + loss ( ) 36 Na + loss = 900 mmol Severe hyponatremia usually is a combination of both

28 Can TBW be reliably estimated? Child 0.6 weight Young male 0.6 weight Young female 0.5 weight Old male 0.5 weight Old female 0.45 weight

29 Why calculate with total body water? H Plasma Interstitium Extracellular Intracellular Hyponatremia indicates general cell swelling

30 Medical emergency? Weak and lethargic No coma No seizures Probably not but what would you do if this patient arrived in the ER with a seizure?

31 Low sodium Do not correct more than 8 mmol/day Severe symptoms Mild symptoms Asymptomatic Mental changes/seizures NaCl 3% i.v. Correct 6 meq in 6 hours or until severe symptoms resolve - recalculate NaCl 3% and go to mild symptoms Rahman M. Neurosurgery 2009;65:

32 Overgaard-Steensen C. Crit Care 2013;17:206

33 Questions What is the influence of dysnatremia on ICU outcome? Discuss potential underlying explanations

34 Incidence (%) Hospital mortality (%) ,2 2,7 13,8 75,4 < > ,6 32,9 21,2 14,6 < > 155 5,1 28,5 [Na+] at the time of ICU admission (mmol/l) N = Retrospective 1,2 45,3 0,6 57,8 Funk GC. Intensive Care Med 2010

35 Multivariate analysis 5 Hospital Mortality Odds ratio (95% CI) < > 155 [Na+] at the time of ICU admission (mmol/l) Funk GC. Intensive Care Med 2010

36 Surgical patients Incidence (%) ,1 2,5 59,4 Na+ admission Na+ admission ICU stay Na+ during ICU stay Na+ during ICU stay Both / during ICU stay 13,6 9,1 N = Retrospective 4,3 Hospital mortality (%) 22 16,5 11 5,5 16,5 18,8 4,6 6, ,8 0 Na+ admission Na+ admission ICU stay Na+ during ICU stay Na+ during ICU stay Both / during ICU stay Sakr Y. Crit Care Med 2013

37 Multivariate analysis 5 Hospital Mortality Odds ratio (95% CI) Na+ admission Na+ admission Na+ during ICU stay Na+ during ICU stay / during ICU stay Sakr Y. Crit Care Med 2013

38 [Na + ] changes during ICU stay Sakr Y. Crit Care Med 2013

39 Hypernatremia Increases peripheral insulin resistance Impairs hepatic gluconeogenesis Impairs lactate clearance Decreases left ventricular contractility Muscle weakness Neurologic impairment

40 6 Normal response? 5 Plasma vasopressin (pg/ml) Plasma Osmolality (mosm/kg) Robertson GL. Kid Intern 1976;10:25-37

41 Urine osmolality Urine osmolality (mosm/kg) Plasma vasopressin (pg/ml) Robertson GL. Kid Intern 1976;10:25-37

42 Diuresis Amount of osmoles to be excreted Urine osmolality [Normal diet mosmol/day] Think: beer potomania and tea and toast diet

43 200 L 15 L

44 Factors that hinder excretion diluted urine Low GFR Increased proximal tubule reabsorption Drugs interfering with Na and Cl reabsorption (diuretics) Presence ADH (appropriate/inappropriate)

45 Back to our patient... Na 115 Urine osmolality 261 Urine sodium 41

46 X X X X X X 261 vs 241 UNa 41 Note: Due to metabolic alkalosis UNa is unrealible to exclude ineffective circulating volume However Ucl 86 TSH 5.05 Cortisol 54 μg/dl Overgaard-Steensen C. Crit Care 2013;17:206

47 Final conclusion Probably SIADH (secondary to critical illness - pneumonia) Gitelman (thiazide effect) not completely excluded Treatment with fluid restriction - slow recovery

48 Overgaard-Steensen C. Crit Care 2013;17:206

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50 Pathophysiology and treatment of CPM Liquid diet + DDAVP Na + < 120 mmol Correction 25 mmol/24 h Correction gradient from 29 to 14 mmol/l Kengne FG. Kidney International 2009;76:

51 Correction Dexamethason Reinduction hyponatremia % Dexamethason Reinduction Correction Control Day 5 CPM Day 10 Mortality Kengne FG. Kidney International 2009;76:

52 Blood-brain barrier permeability Microglial activation Control Correction Dexamethason Reinduction Kengne FG. Kidney International 2009;76:

53 Last issue... Hypophosphataemia (0.32) Decreased intake, intestinal loss, redistribution, renal loss Urinary phosphorus 1 and 1.49 mmol/l (very low) No intestinal loss Probably redistribution (respiratory alkalosis)

54 Conclusion Gitelman syndrome Hyponatremia due to SIADH Hypophosphatemia due to respiratory alkalosis

55 Where does the acid come from?

56 Medical history Female, 51 Previous suicide attempt Possible alcohol abuse No history of diabetes (recent glucose 5.6) Nausea and vomiting for 4 days EMS warning for husband but female on the floor and hyperventilating admission

57 Physical examination Stable hemodynamics Hyperventilation No fruity odor Normal consciousness Looks dehydrated Further physical examination normal

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59 Lab results Na 123, K 2.4, Ca 2+ ion 1.04, Mg 0.74 Cl - 86, P , lactate 3.2 Albumin 43 Glucose 17.3, urea 6.9, creatinine 177 ph 7.22, PaO2 17.2, PaCO2 1.1, HCO3 3.4, BE Serum osmolarity 284 Urine: ph 5.5, Gluc 0.4, ketones +, Na 54, K 52, Cl < 20

60 Acid-base diagnosis Metabolic acidosis Appropriate respiratory compensation Expected PaCO 2 = [1.5*HCO 3 - ] + 8 ± 4 = 9, mm Hg Increased anion gap [Na + + K + ] - [Cl - + HCO 3 - ] = = 36 Increase in anion gap 24 = decrease in HCO 3 - no delta gap

61 Strong Ion Difference Electrical neutrality Apparent SID Effective SID Na + Cl Lact Total negative charges of K + HCO Ca 2+ Mg 2+ Alb - P SIDa meq/l Strong Ion Gap = = 22.24

62 Effective SID HCO3 - HCO3 - [Alb - ] [Alb] (0.123 ph ) [P - ] [P] (0.309 ph )

63 Relation corrected Anion Gap - Strong Ion Gap SIG (meq/l) y = 0,8494x + 2,1877 R 2 = 0, Corrected AG -12 (meq/l) Moviat M. Crit Care 2003;7:R41-R45

64 N = 935 Do we make a more accurate diagnosis? HCO3 / BE Stewart approach HCO3 / BE / Anion gap corrected 120 patients undetected All detected by SID 108 detected by AGcor Metabolic acidosis Dubin A. Crit Care Med 2007;35:

65 Is there a difference? ph = pk1 + log HCO3 - αpco2 = [SID+ ]-Kα[ATOT]/Kα+10 -ph αpco2 No HH is a limited form of the more general Stewart-Figge equation Derksen R. Eur J Intern Med 2006;17:

66 Increased anion gap metabolic acidosis Lactate acidosis (insufficient explanation) Ketoacidosis AKI (insufficient explanation) Intoxication with methanol, ethylene glycol, paraldehyde, aspirin, paracetamol (screening negative)

67 Why do we make TG Low levels of insulin ketones? FFA ADP Ketones Energy supply for the brain when glucose levels are low ATP ADP Work CO2 H2O ATP Work CO2 H2O ADP ATP Secretion ketones with NH4 + Very low or absent insulin levels are a prerequisite

68 This means... That the rate of ketones production is limited by the ADP availability in the liver That severe acidosis usually comes from diminished removal in brain and kidney due to decreased ADP availability (coma/ sedatives and AKI/low GFR)

69 Ingested ethanol Fatty acids Acetic acid (from colonic fermentation of poorly absorbed sugars) Acetyl-CoA Insulin Long chain fatty acids ATP ADP H + + ketoacid anions Very low or absent insulin levels are a prerequisite

70 Fasting + alcohol NADH NAD+ Acetoacetate β-oh butyrate Diabetes False negative nitroprusside test Aceton

71 Differential diagnosis Diabetic ketoacidosis Alcoholic ketoacidosis Fasting ketoacidosis Fermentation of poorly absorbed CH

72 Final clues Ethanol - β-hydroxybutyrate +++ β-hydroxybutyrate (Quant) follows Osmol gap 13.8 Fasting in combination with recent onset DM?

73 Osmol gap Osmol gap (mmol/kg) Control Alcohol ketoacidosis Lactic acidosis Schelling JR. Ann Intern Med 1990;113:

74 Four days later... another patient Female, 19 Exchange student Diabetes Mellitus Defective insulin pump Found unconscious by roommate No drugs or alcohol abuse

75 Physical examination Blood pressure 70/40 - cold extremities Kussmaul - SpO2 100% (15L O2) Fruity odor E1M1V1 Looks dehydrated Further physical examination normal

76 Lab results Na 124, K 7.5, Ca 2+ ion 1.27, Mg 1.23 Cl - 84, P , lactate 6.0 Albumin 39 Glucose > 55, urea 22.7, creatinine 266 ph 6.60, PaO2 30.4, PaCO2 1.4, HCO3 1.0, BE Serum osmolarity 380 (osmol gap 49.3) Urine: ph 5.5, Gluc +, ketones +, Na 54,

77 Acid-base diagnosis Metabolic acidosis Appropriate respiratory compensation Expected PaCO2 = [HCO3 - ] + 8 ± 4 = mm Hg Increased anion gap [Na + + K + ] - [Cl - + HCO3 - ] = = 46.5 Increase in anion gap 34.5 = > decrease in HCO3 - no delta gap

78 Strong Ion Difference Electrical neutrality Apparent SID Effective SID Na + Cl Lact Total negative charges of K + HCO Ca 2+ Mg 2+ Alb - P SIDa 46.5 meq/l Strong Ion Gap = = 31.52

79 Major danger during therapy? Cerebral edema - 0.5% With severe metabolic derangement Usually 5-15 hours after start treatment Either due to an increase in intracellular or extracellular water

80 5 risk factors Fall in effective plasma osmolality Activation of Na + /H + exchanger by a bolus of insulin Increased permeability of BBB Excessive saline infusion with fall in COP Excessive saline infusion with in BP

81 Reasonable suggestions Avoid a large saline bolus early during therapy unless there is a hemodynamic emergency Administration of a large bolus of insulin early during therapy

82 Reasonable suggestions Plasma sodium should increase by a amount approximately half of the decrease in plasma glucose Pgluc 50 2 PNa 140 Therapy Pgluc 20 2 PNa

83 Reasonable suggestions After 5-10 hours the action of insulin results in a rapid decrease in ketoacid anions. Lower levels of ketoacid anion results in faster glucose oxidation Glucose infusion when Pgluc < 15 may reduce effective plasma osmolality (use higher [glucose] or mix with NaCl 0.9%) Water resorption from the stomach may reduce effective plasma osmolality

84 Final clues Ethanol - β-hydroxybutyrate +++ β-hydroxybutyrate (Quant) follows Acetoacetate follows Diabetic ketoacidosis