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

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

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

4. 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

5. WHY?

6. WhO?

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

8. 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

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

13. 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”

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

15. Framing the Question

16. 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

17. “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

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

20. 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

22. “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 ( )

23. “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

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

25. DKA

29. 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

30. - 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

31. “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.”

32. 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.”

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

34. 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:
Copyright © by SAGE Publications

35. 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

36. What about lactic acidosis in sepsis?

40. 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

41. “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.

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

43. 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

44. 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

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

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