Base Treatment for Metabolic Acidosis due to DKA and Sepsis Nicholas Busch Henry Ford Hospital Emergency Medicine Grand Rounds September 17th, 2015

So who should get an AMP or two? 24 yo male with DKA pH 6.90 pCO2 45 HCO3 8

So who should get an AMP or two? 65 yo with septic shock pH 7.10 pCO2 42 HCO3 10

Objectives Quick Acid-Base review Discuss the hemodynamic effects of base therapy Discuss evidence for base therapy in: DKA Lactic acidosis/sepsis Not covered: Pediatrics, respiratory acidosis, toxic ingestions, RTA and other non-AG acidosis

WHY?

WhO?

Who gives sodium bicarb therapy? About 100 surveys completed by critical care and nephrology program directors throughout the nation.

Patient’s with lactic acidosis -67% of critical care physicians -86% of nephrologists Patient’s with ketoacidosis -28% of critical care physicians -60% of nephrologists

VERY Quick Acid-Base Review CO2 + H20  H2CO3  HCO3 + H+ Henderson Hasselbalch pK curve Using white board

Also what’s an AMP?? Ampule (amp, ampoule) NOT standardized unit of measure “Single dose of medication pre-packaged in an injectable glass or plastic vessel”

An “amp” of Bicarb 8.4% Sodium Bicarbonate 50 mEq Na+, 50 mEq HCO3- pH 8.0 1 mL is 84 mg

Framing the Question

Proposed Rationale for Base Therapy Use: 1. A low pH, in and of itself, is harmful (most notably by impairing cardiovascular function). 2. Sodium bicarbonate can increase the pH when infused IV. 3. Raising the pH with sodium bicarbonate improves cardiovascular function or some other relevant outcome. 4. Any adverse effects of sodium bicarbonate are outweighed by its benefits

“A low pH, in and of itself, is harmful (most notably by impairing cardiovascular function)” -Isolated animal heart muscle - acidosis generally reduces contractile function Human ventricular tissue showed modest reduction in contractility Whole animal models: contractility constant, decrease slightly or rise and then fall ARDS treatment : permissive hypercapnia tolerated to 7.15 and below Protective effect? – reduced cell death in hepatocytes exposed to anoxia

“Sodium bicarbonate can increase the pH when infused IV” Most animal studies show arterial pH will rise

What about the intracellular pH? Multiple compartments with different degrees of permeability Cerebral spinal fluid Bicarb shown in dog models to LOWER CSF pH Intracellular Space

“Raising the pH with sodium bicarbonate improves cardiovascular function or some other relevant outcome” 2 studies in humans with lactic acidosis and getting continuous vasoactive infusions No change in hemodynamics or catecholamine responsiveness HR, CVP, PAP, ScVo2, wedge pressure, or CO Still negative results with most acidotic (6.9-7.2)

“Any adverse effects of sodium bicarbonate are outweighed by its benefits” Negative side effects Fluid and sodium overload Lowers pO2 and oxygen delivery Increased lactate concentrations Lowers calcium LV contractility varies directly with ionized calcium concentration Clinical significance has not been demonstrated

More direct question… Does Sodium Bicarbonate improve outcomes for patients with severe DKA or lactic acidosis from sepsis?

DKA

24 patients received 120+/-40 mmol sodium bicarbonate. Two groups were similar at admission with regard to clinical and biological parameters Prospective, randomized trial No difference could be demonstrated between the two groups

- 21 adult patients, DKA with pH 6.9 to 7.14 No significant differences in Glucose or ketone levels Increase in pH orHCO3 in blood or CSF Time to glucose 250, pH 7.3, bicarb to 15

“We conclude that in severe diabetic ketoacidosis (arterial pH 6 “We conclude that in severe diabetic ketoacidosis (arterial pH 6.9 to 7.14), the administration of bicarbonate does not affect recovery outcome variables as compared with those in a control group.”

No Significant Difference: Hospitalization Mortality 12 case control studies 3 RCT with 73 patients No Significant Difference: Hospitalization Mortality No studies had any patients with pH <6.85 “The evidence to date does not support the use of bicarbonate administration for the emergent treatment of DKA” “There also is insufficient evidence to justify the recommendation of bicarbonate administration in more extreme acidemia of pH < 6.90.”

Retrospective cohort study 86 adult patients, DKA, pH <7.0

Table 2. Outcome Comparison. “…the use of sodium bicarbonate therapy did not improve time to resolution of acidosis or hospital length of stay in severe DKA.” Bryson Duhon et al. Ann Pharmacother 2013;47:970-975 Copyright © by SAGE Publications

Conclusions on DKA in adults: No data on pH <6.9 ADA recommends use No indication for routine use in pH greater than 6.9

What about lactic acidosis in sepsis?

Double blind, RCT, 65 patients with septic shock 2 groups – staged and control Bicarbonate improved lactate, pH, ScVO2, CI Compared with control group, in "stage" group, lactic acid (Lac) was significantly lowered (1.50±1.08 mmol/L vs. 2.93±1.09 mmol/L), and pH, mixed venous oxygen saturation (SvO2), oxygen extraction ratio (O2ER), cardiac index (CI), oxygen delivery (DO2) were significantly increased Staged group given bicarb to pH 7.25, control to 7.15

“We recommend against the use of sodium bicarbonate therapy for the purpose of improving hemodynamics or reducing vasopressor requirements in patients with hypoperfusion-induced lactic acidemia with pH ≥ 7.15 (Grade 1B).” @2013 Society of Critical Care Medicine, European Society of Intensive Care Medicine. www.survivingsepsis.org

Surviving sepsis sources: 14 + 10 patients with PA Catheters Sodium Bicarbonate increased pH, HCO3, pCO2. Decreased Ca No difference in any hemodynamic measures HCO3 vs NaCl

Review article after surviving sepsis guidelines 2008 Similar data to previous Advocate no treatment “pH <7.0 or less” Plan for slow infusion and clearing CO2

Conclusions in lactic acidosis from Sepsis: Clinical outcomes not yet shown to be improved Surviving Sepsis Guidelines recommend considering when pH <7.15 Consider negative effects Increased pCO2, decreased calcium, decreased oxygen delivery

So how to give if you decide to: Bicarb deficit Half of deficit in 4 hours, rest over 24 hours

Questions? “IT’S ALL ABOUT THAT BASS” Sources available upon request.