BMJ  2007;334:1284-1285 (23 June), doi:10.1136/bmj.39237.661111.80

Editorials

Diabetic ketoacidosis

Saline should be used for fluid replacement rather than Hartmann's solution

Diabetic ketoacidosis is a life threatening condition caused by insulin deprivation or inadequate use of insulin in people with type 1 (or occasionally type 2) diabetes mellitus. Precipitants include deliberate insulin omission, intercurrent illness, surgery, trauma, alcohol, late presentation of previously undetected type 1 diabetes, and the use of drugs that alter carbohydrate metabolism.¹ People with diabetic ketoacidosis need swift intervention by specialists because of the substantial morbidity and mortality arising from the acid-base imbalance, profound fluid loss, and electrolyte disturbances.

Current guidelines written by diabetes specialists from the United States and the United Kingdom recommend initial replacement of fluids and electrolytes and intravenous insulin.^{1 2} The fluid advocated in these guidelines is 0.9% saline. However, people may be treated by emergency and intensive care doctors as well as diabetes specialists, and the type of fluid used can vary.

During the first few hours of hospital admission many people with diabetic ketoacidosis are treated by emergency or intensive care doctors who commonly prefer to use Hartmann's solution (sodium lactate intravenous infusion).³ Subsequent care is usually delivered by the diabetes team, who prefer to use 0.9% saline. The conflict arises because guidelines for fluid replacement in the acute setting are written by diabetes specialists,^{1 2} whereas no widely accepted guidelines have been written by emergency or intensive care doctors for fluid replacement in diabetic ketoacidosis.

For decades, 0.9% saline has been the fluid of choice for diabetic ketoacidosis, and its use continues to be advocated in modern textbooks on diabetes.⁴ Early studies on diabetic ketoacidosis in the 1970s used 0.9% saline,⁵ and this approach was reinforced a decade later.⁶ However, giving patients large amounts of chloride can cause a hyperchloraemic metabolic acidosis,^{3 7} so administration of 0.9% saline for diabetic ketoacidosis could potentially worsen the metabolic acidosis. Thus, 0.9% saline may be the fluid of choice simply because evidence for the efficacy of other fluids is lacking. The question of which fluid replacement is optimal in patients with acute diabetic ketoacidosis is, therefore, still unanswered.

Saline 0.9% contains 150 mmol/l of sodium and chloride. Hartmann's solution contains 131 mmol/l of sodium, 111 mmol/l of chloride, 29 mmol/l of bicarbonate (as lactate), 5 mmol/l of potassium, and 2 mmol/l of calcium. The pH of 0.9% saline and Hartmann's varies according to temperature. At 25^oC the pH of 0.9% saline is about 4.5 and that of Hartmann's solution is about 6.0. Although Hartmann's solution has a lower chloride concentration and higher pH, its routine use in diabetic ketoacidosis could be argued against for several reasons.

Firstly, people with diabetic ketoacidosis already have a high lactate to pyruvate ratio, and the 29 mmol/l of lactate in Hartmann's solution could potentially exacerbate this and lead to more adverse outcomes.⁸ Secondly, Hartmann's solution raises plasma lactate and generates more glucose from the lactate.⁹ Thirdly, giving a solution containing even 5 mmol/l potassium to a patient who may be hyperkalaemic could lead to potentially fatal cardiac arrhythmias, such as bradycardia and asystole. Fourthly, bicarbonate is not recommended for patients with pH greater than 7.0 because it could worsen the acidosis.¹⁰ Finally, because low serum sodium at presentation is a risk factor for developing cerebral oedema, initial treatment with a relatively hypotonic fluid could be harmful.¹¹ Thus, Hartmann's solution does not seem to be optimal for use in diabetic ketoacidosis, and Hartmann himself strongly argued against its use after some of his insulin deprived patients died.¹²

Diabetes specialists accept that acidosis caused by large volumes of 0.9% saline is mild and transient, and it is not associated with adverse outcomes or prolonged length of stay.¹ The low base deficit in the face of a normal pH may be a cause of concern and may lead to the perception of persistent hypoperfusion. However, this is a trap for the unwary, because if a high chloride concentration is found, then the base deficit can be safely ignored.

The primary treatment in diabetic ketoacidosis is replacement with large volumes of fluid. This in itself substantially reduces blood glucose and begins to correct the acidosis. Ideally, a randomised study comparing 0.9% saline and Hartmann's would provide information about the optimum type of fluid replacement. This is unlikely to happen, though, partly because of the potential dangers of Hartmann's solution discussed above. In the absence of such a trial and in view of the large body of supporting evidence that has led to the development of the guidelines,^{1 2} the fluid of choice in the initial resuscitation of people with diabetic ketoacidosis should remain 0.9% saline.

Norfolk and Norwich University Hospital NHS Trust, Elsie Bertram Diabetes Centre, Norwich NR4 7UY

---

Competing interests: None declared.

Provenance and peer review: Non-commissioned; externally peer reviewed.

References

1. Kitabchi AE, Umpierrez GE, Murphy MB, Kreisberg RA. Hyperglycemic crises in adult patients with diabetes: A consensus statement from the American Diabetes Association. Diabetes Care 2006;29:2739-48.[Free Full Text]
2. Savage MW, Kilvert A. ABCD guidelines for the management of hyperglycaemic emergencies in adults. Practical Diabetes Int 2006;23:227-31.[CrossRef]
3. Skellett S, Mayer A, Durward A, Tibby SM, Murdoch IA. Chasing the base deficit: hyperchloraemic acidosis following 0.9% saline fluid resuscitation. Arch Dis Child 2000;83:514-6.[Abstract/Free Full Text]
4. LeRoith D, Taylor SI, Olefsky JM. Diabetes mellitus. A fundamental and clinical text. Philadelphia: Lippincott Williams and Wilkins, 2000.
5. Page MM, Alberti KG, Greenwood R, Gumaa KA, Hockaday TD, Lowy C, et al. Treatment of diabetic coma with continuous low-dose infusion of insulin. BMJ 1974;2:687-90.[ISI][Medline]
6. Hillman K. Fluid resuscitation in diabetic emergencies—a reappraisal. Intensive Care Med 1987;13:4-8.[ISI][Medline]
7. Stewart PA. Modern quantitative acid-base chemistry. Can J Appl Physiol Pharmacol 1983;61:1444-61.
8. Suistomaa M, Ruokonen E, Kari A, Takala J. Time-pattern of lactate and lactate to pyruvate ratio in the first 24 hours of intensive care emergency admissions. Shock 2000;14:8-12.[ISI][Medline]
9. Thomas DJ, Alberti KG. Hyperglycaemic effects of Hartmann's solution during surgery in patients with maturity onset diabetes. Br J Anaesth 1978;50:185-8.[Abstract/Free Full Text]
10. Okuda Y, Adrogue HJ, Field JB, Nohara H, Yamashita K. Counterproductive effects of sodium bicarbonate in diabetic ketoacidosis. J Clin Endocrinol Metab 1996;81:314-20.[Abstract]
11. Edge JA, Jakes RW, Roy Y, Hawkins M, Winter D, Ford-Adams ME, et al. The UK case-control study of cerebral oedema complicating diabetic ketoacidosis in children. Diabetologia 2006;49:2002-9.[CrossRef][ISI][Medline]
12. Hartmann AF, Senn MJ. Studies in the metabolism of sodium r-lactate. II. Response of human subjects with acidosis to the intravenous injection of sodium r-lactate. J Clin Invest 1932;11:337-44.[ISI][Medline]

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