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Three Part Question

In [adults with diabetic ketoacidosis and significant acidaemia] is [the additional administration of iv bicarbonate better than standard fluid resuscitation] give [more rapid improvement of biochemical parameters and an increased survival]

Clinical Scenario

A 28 year old diabetic attends having been found unrusable by friends. Initial examination shows her to be GCS 5/15 with a BM measurement of high. Blood gases show her to have a pH of 7.02 and a blood sugar comes back at 41mmol/l and her urine shows three plus ketones. You begin treatment with insulin and IV fluids and contact ITU for an opinion on airway management and ventilation. The ITU registrar asks you to start a bicarbonate infusion while he is on the way down. You are unsure if this is beneficial and decide to find evidence on who is right.

Search Strategy

Medline 1966-November week 1 2003 using the OVID interface
[{exp DIABETIC KETOACIDOSIS/ OR keto-acidosis.af OR ketoacidosis.af. OR dka.af.} AND {exp BICARBONATES/ OR bicarbonate.af. OR nahco3.af. OR (hydrogen adj5 carbonate).af.}]LIMIT to human AND English language

Search Outcome

327 papers found 5 appeared relevant to the three part question

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Lutterman JA et al 1979 Netherlands	24 patients in DKA (ph<7.10). 12 recieved high dose insulin and 167 mmol bicarbonate plus iv fluid. 12 recieved low dose insulin and iv fluid.	PRCT	plasma glucose	No statistical difference at 8hours	Randomization by year of attendance= ?change in skills of staff small numbers results complicated by differing dose insulin
			pH	both groups all reached>7.3 within 10h.No significant difference in mean pH between 2 groups at an time
			Survival	1 patient in fluids group died. 69yo with 12 hour coma prior to treatment
Lever E Jaspan JB 1983 USA/UK	73 patients in two hospitals with 85 episodes DKA (pH<7.1) 73 episodes recieved a mean of 130 mmol of bicarbonate. 22 without. Otherwise standard treatment.	Retrospective case note review.	Mean change in pH/hour	bicarb 0.038+/-0.013 no bicarb 0.032 +/-0.005 (n/s)	Retrospective numbers small
			mean change glucose mmol/l/hr	bicarb 3.3 +/-1.1 no bicarb 4.1 +/- 1.2
			mean time to GCS 15 (hours)	bicarb 4+/-1 No bicarb 4+/- 1.5 (n/s)
			mean change bicarbonate mmol/l/hr	bicarb 0.9+/-0.3 no bicarb 1.1 +/- 0.3
Hale et al 1984 UK	38 patients with DKA (pH<7.2).16 bicarbonate 150meq + fluid/insulin.16 fluid only. 6 excluded due to starting glucose.	PRCT	Mean rise in pH at 120 mins	bicarb 7.06 to 7.23 no bicarb 7.05 to 7.12 (p<0.01)	small numbers study lasted only 120 minutes
			Level of ketones,pyruvate and lactete	Significantly lower (p<0.05) in no bicarb group
Morris RL et al 1986 USA	21 patient is DKA (pH 6.9-7.14). 10 bicarbonate/fluids/insulin. 11 fluids/insulin	PRCT	time for PH to reach 7.3	bicarb 13.1+/-2.5h no bicarb 15.6+/-2.5h(n/s)	small numbers control group sicker at baseline
			rate of change in pH, ketones,bicarbonate levels	no significant difference at 8 hours
Viallon et al 1999 France	39 DKA pts (pH<7.1).24 bicarbonat/fluid/insulin. 15 fluid/insulin	Retrospective review of case notes	Time to pH>7.3	Bicarb 8+/-1h No bicarb 8+/-1.2h	Small retrospective study
			PaCO2,lactate,chloride,creatinine,urea,osmolality,respiratory rate,heart rate,GCS arterial pressure	No significant difference

Comment(s)

All the studies are small which may explain the lack of statistical significance. However all contain graphs showing the variables under investigation over time all of which are similar in pattern. The impression these give is that bicarbonate gives an initial rise in pH as one would expect from it's buffer properties, however the use of bicarbonate seems to have a detrimental affect on the breakdown of the fatty acids causing the acidosis hence initially treating symptom but not cause. In all groups rehydration/insulin seem to settle the source of acidosis over time.

Editor Comment

BF

Clinical Bottom Line

There appears to be no advantage to the use of intravenous bicarbonate in diabetic ketoacidosis.

References

1. Lutterman JA, Adriaansen AAJ & van't Laar A Treatment of Severe Diabetic Ketoacidosis A Comparative Study of Two Methods Diabetologia 17, 17-21 (1979)
2. Lever E & Jaspan JB Sodium Bicarbonate Therpy in Severe Diabetic ketoacidosis American Journal of Medicine Aug 83, 75,263-268
3. Hale PJ, Crase J, Nattrass M Metabolic effects of bicarbonate in the treatment of diabetic ketoacidosis BMJ 289,20 Oct 84,1035-8
4. Morris LR, Murphy MB, Kitabchi AE Bicarbonate therapy in Severe Diabetic Ketoacidosis Annals of Internal Medicine 1986;105:836-840
5. Viallin A,Zeni F,Lafond P, Venet C, Tardy B, Pages Y, Bertrand JC Does bicarbonate therapy improve the management of severe diabetic ketoacidosis Critical care medicine 1999;27(12):2690-2693