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Table 3 Key studies on resolution of acidosis and ketosis with bicarbonate therapy in DKA

From: Bicarbonate in diabetic ketoacidosis - a systematic review

References Trial design No. of patients (bicarb vs. control) Mean age (yr) and initial pH Bicarbonate infusion Control Acidosis and ketosis
Hale et al. [13] RCT 16 vs. 16 47 vs. 41 (1st hr: 1 L isotonic saline for all) Higher pH and bicarb levels at 2 hr
Br Med J 1984 (single center)   6.85 vs. 6.85 2nd hr: 1 L isotonic bicarb vs. 1 L isotonic saline in bicarb arm vs. control, p < 0.01
       BUT
     (3rd hr: 1 L isotonic saline for all) Slower decline in blood ketone in 1st hr in bicarb arm
Morris et al. [14] RCT 10 vs.11 34 vs. 28 133.8 mmol if pH 6.9-6.99 no alkali No difference in rate of change of pH, bicarb, ketones
Ann Intern Med 1986 (single center)    OR 89.2 mmol if pH 7.0-7.09   OR time to reach pH 7.3
    7.03 vs. 7.00 OR 44.6 mmol if pH 7.1-7.14   OR bicarb levels to reach 15 mmol/L
     (over 30 min, 2 hourly until pH ≥ 7.15)   
Gamba et al. [15] RCT 9 vs. 11 29 vs. 28 133.5 mmol/150 ml (pH 6.9-6.99) 0.9% saline, also Higher pH at 2 hr in bicarb arm, p < 0.02
Rev Inves Clin 1991 double-blind    89 mmol/100 ml (pH 7.0-7.09) in similar aliquots AND higher bicarb in bicarb arm, p < 0.01
  (single center)   7.05 vs. 7.04 44.8 mmol/50 ml (pH 7.1-7.14)   
     (over 30 min, repeated at 2 hr   Change in pH and bicarb larger in bicarb arm at 2 hr,
     if pH increase by < 0.05)   p < 0.01
Okuda et al. [19] Prospective 3 vs. 4 24 vs. 34 50 mmol/hr over 4 hr No alkali Paradoxical increase in plasma acetoacetate in 1st 3 hr
J Clin Endocrinol Metab 1996 nonrandomized      in bicarb arm vs. control
  nonblinded   6.98 vs. 7.27 (IV insulin 0.1 U/kg/hr + 0.9% saline) Increase in plasma 3-hydroxybutyrate level after bicarb
  (single center)   (p < 0.05)    ceased vs. steady decline throughout in control
Lutterman et al. [17] Retrospective 12 vs. 12 41 vs. 34 167 mmol/L in 1 L Low-dose insulin No difference in mean pH rise in 1st 2 hr
Diabetologia 1979 (single center)    over 1 hr (if pH ≤ 7.0) IV 8 U/hr OR mean time to reach pH ≥ 7.30
    6.89 (with high dose insulin   OR rate of decline of ketosis
     mean 260 U in 1st 6 hrs)   
Lever et al. [18] Retrospective 52 (73 cases) 22.5-37.4 vs. mean 130-135 mmol No alkali No difference in mean change in bicarb level per hr
Am J Med 1983 (2 centers) vs 24.5-48.0 (majority slow infusion)   OR mean change in pH per hr
   21 (22 cases) 6.94-7.00 vs.    
    6.89-7.07   
Viallon et al. [20] Retrospective 24 vs. 15 45 vs. 47 mean 120 mmol (88-166) No alkali No difference in variation of mean pH, bicarb level, AG
Crit Care Med 1999 (single center)    1.4% over 1 hr infusion   anion gap in 1st 24 hr
    6.93 vs. 7.00    OR mean time to reach pH > 7.30
      OR urine ketone clearance
Green et al[24] Retrospective 57 (90 cases) 9.6 vs. 10.1 mean 2.08 mmol/kg (0.53- No alkali Unadjusted rate of bicarb rise faster in bicarb arm at
Ann Emerg Med 1998 (single center) vs   7.37 mmol/kg)   24 hr, p = 0.033
(pediatric)   49 (57 cases) 7.02 vs. 7.06    No difference in bicarb rise at 12 and 24 hr, or time to reach
       bicarb of 20 mmol/L (matched pair and multivariate analysis)
  1. cases: DKA episodes; IV: intravenous; hr: hour; min: minutes; bicarb: bicarbonate