Presentation on theme: "Bicarbonate Therapy in Severe Metabolic Acidosis"— Presentation transcript:
1 Bicarbonate Therapy in Severe Metabolic Acidosis Neil A. Kurtzman, MDDepartment of Internal Medicine,Texas Tech University Health Sciences Center,Lubbock, Texas 79430
2 Metabolic acidosis: A primary fall in the bicarbonate concentration Due to either a gain of acid or a loss of base (usually HCO3)Acidemia refers solely to a fall in pH
3 Gain of Acid Exogenous (eg, NH4Cl) Endogenous Abnormal lipid metabolism DKAAbnormal CHO metabolism Lactic acidosisNormal protein metabolism Uremic acidosis
4 Kraut and Kurtz did an online (Clin Exp Neprol 10: , 2006) survey of how intensivists and nephrologists gave HCO3 to patients with metabolic acidosisForty percent of the intensivists would not give bicarbonate unless the pH was less than 7.0Only 6% of nephrologists wait until pH gets this low (p < 0.01)
5 More than 80% of nephrologists consider the pCO2 in making their decision to treat Only 59% of intensivists do (p<0.02)In patients with lactic acidosis, 86% of nephrologists treat with bicarbonateTwo-thirds of intensivists give bicarbonate (p< 0.05)
6 60% of nephrologists treat DKA with bicarbonate 28% of intensivists give bicarbonate to patients with DKA (p<0.01)Both would administer bicarbonate by constant infusion, targeting an arterial pH of 7.2Seventy-five percent of nephrologists calculate the amount of bicarbonate required, while only one-third of intensivists do so
7 Metabolic acidosis results from a loss of bicarbonate (eg diarrhea) Or from its titration to an anionic base that often can be converted back to bicarbonate (eg DKA or lactic acidosis)This non-bicarbonate base anion is commonly termed “potential” bicarbonate
8 Giving bicarbonate to a patient with a true bicarbonate deficit is not controversial Controversy arises when the decrease in bicarbonate concentration is the result of its conversion to another base which, given time, can be converted back to bicarbonate
9 In considering acute bicarbonate replacement four questions should be considered 1. What are the deleterious effects of acidemia and when are they manifest?2. When is acidemia severe enough to warrant therapy?
10 3. How much bicarbonate should be given and how is that amount calculated? 4. What are the deleterious effects of bicarbonate therapy?
11 Deleterious effects of acidemia Decreased myocardial contractilityFall in cardiac outputFall in BPPulmonary venoconstriction
12 Deleterious effects of acidemia Decreased binding of norepinephrine to its receptorsAcidemia may adversely affect cell functions such as enzymatic reactions, ATP generation, fatty acid biosynthesis, and bone formation/resorption
13 Deleterious effects of acidemia Drugs which are salts of weak acids are more active during acidemiaMore receptor bindingMore entry to cellsBest example is ASA
15 Optimal extracelluar pH 7.4 Optimal intracellular pH 7.1Deviations from normal pH will obviously decrease the efficiency of all reactions
16 Acidemia protects the central nervous system against seizures, it sensitizes the myocardium to arrhythmiasExtracellular pH is a surrogate for intracellular pH
17 When is acidemia severe enough to warrant therapy? Most authorities in acid-base physiology would give bicarbonate to a patient with an arterial pH < 7.1Not a hard and fast ruleMore on this later
18 How much bicarbonate should be given and how is that amount calculated? The volume of distribution of bicarbonate is approximately that of total body waterIn patients with metabolic acidosis it is said to vary from 50% to greater than 100%, depending on the severity of the acidemia
19 How much bicarbonate should be given and how is that amount calculated? Any calculated amount is approximateFernandez et al have derived a formula for calculating the bicarbonate space (KI 36: , 1989)( / pHCO3) (body weight)
20 How much bicarbonate should be given and how is that amount calculated? At a pCO2 of 13 mm Hg and HCO3 of 4 mEq/l, the arterial pH is 7.1Raise the HCO3 to only to 8 mEq/L the blood pH will increase to 7.4This assumes the pCO2 doesn’t change
21 How much bicarbonate should be given and how is that amount calculated? If the bicarbonate concentration rises only mEq/L the pH would be above 7.2Arterial pCO2 typically however does not remain the same after bicarbonate infusionIn severely acidotic patients it rises 6.7 ± 1.8 mm Hg when an infusion of sodium bicarbonate is given (1.5 mmol/kg over 5min)
22 What are the deleterious effects of bicarbonate therapy? Bicarbonate therapy is associated with an increase in mortalityTrue in humans and experimental animals under a variety of acidemic conditionsFall in blood pressure and cardiac output
23 What are the deleterious effects of bicarbonate therapy? Shifts in ionized calciumIn strong acid acidosis potassium also shifts out of the cellSensitizes the heart to abnormal electrical activity and subsequent arrhythmias
24 What are the deleterious effects of bicarbonate therapy? “Paradoxical” intracellular acidosis – CO2 shifts into cellsBoth volume expansion and hypernatremia can occurFulminate congestive heart failure with flash pulmonary edema may result
25 What are the deleterious effects of bicarbonate therapy? In vitro studies show that intracellular alkalinization hastens cell death following anoxiaStimulates superoxide formation, increases pro-inflammatory cytokine release, and enhances apoptosisRelationship to human disorders unknown
26 What are the deleterious effects of bicarbonate therapy? Rebound alkalemia – especially with low arterial pCO2Blood lactate and ketone bodies increaseThis “potential” bicarbonate will be converted back to actual bicarbonate unless it lost in the urine
28 DKAAcetoacetate and beta-hydroxybutyrate are lost in the urine before the patient arrives at the hospitalThe patient is truly bicarbonate deficientMore urinary loss of ketone bodies occurs following fluid administration and volume repletion
29 DKAHyperchloremic metabolic acidosis the day after insulin therapyAlmost never necessary to give bicarbonate even though the patient is bicarbonate deficient unless renal function is permanently impairedBicarbonate therapy markedly increases blood acetoacetate and beta-hydroxybutyrate levels
30 DKABicarbonate therapy delays the removal of ketone bodies from the bloodBicarbonate therapy markedly increases blood acetoacetate and beta-hydroxybutyrate levels
31 Lactic AcidosisMortality greater than 80%Outcome depends on the treatment of its causeCardiogenic or hemorrhagic shockExogenous toxins such as cyanide or metformin
32 CASE #1: A 20 year-old man with a five-year history of type 1 diabetes mellitus was admitted for the ninth time in diabetic ketoacidosis. He was poorly responsive and had Kussmaul respirations. Before any therapy he had a plasma Na of 140 mEq/L, K 4 mEq/L, Cl 109 mEq/L, CO2 3 mEq/L, and his creatinine was 1 mg/dL. The arterial pH was 6.95, pCO2 14 mm Hg, and the calculated HCO3 was 3 mEq/L.
33 Urine and blood ketones were strongly positive Urine and blood ketones were strongly positive. He was treated with insulin and appropriate fluid and electrolyte replacement. He was not given bicarbonate. The next day he was fully oriented. His plasma Na was 142, K 4, Cl 114 and his CO2 was 18 mEq/L. The remainder of his clinical course was unremarkable.
34 CASE #2: An 80 year old man was admitted with severe congestive heart failure. He was hypotensive and oliguric. He had both pulmonary and peripheral edema. His baseline creatinine was known to be 1.6 mg/dL. On arrival at the emergency room his plasma Na was 135 mEq/L, K 4 mEq/L, Cl 97 mEq/L, CO2 7 mEq/L, and his creatinine was 2.5 mg/dl. His arterial pH was 7.1, pCO2 20 mm Hg, and the calculated HCO3 was 6 mEq/l. The blood lactate level was 20 mmol/L.
35 The patient was intubated and placed on a respirator keeping his pCO2 at 20 mmHg. CVVHD was begun with a bath containing 14 mEq/L of bicarbonate. He was given an infusion of 300 mEq of bicarbonate over two hours; with a total body water of 43 liters, one would aim for a HCO3 of 14 mEq/L: (7 mEq/L X 43 L = 301 mEq). At the end of that time his pH was 7.2 and the HCO3 was 13 mEq/L. Five days later he was transferred out of the intensive care unit, his lactic acidosis resolved.
36 Case #1 got no bicarbonate even though his pH was < 7.0 Case #2 received bicarbonate though he had a higher pHBicarbonate therapy must be individualized
37 Desired HCO3 – observed HCO3 Use total body waterAssume pCO2 will not changeGive that amount which will raise the pH to 7.2
38 Reevaluate in two hours Make new plan based on the new dataCorrect the underlying cause(s)
39 Sandra Sabatini and Neil A Sandra Sabatini and Neil A. Kurtzman: Bicarbonate Therapy in Severe Metabolic Acidosis, JASN in press.