For several years after the introduction of insulin in 1922 ketoacidosis was usually treated with comparatively small doses determined by the level of the blood glucose and totalling less than 200 units in the first 24 hours of treatment. The steady improvement in outcome was due to the early and adequate use of intravenous fluid infusion. In about 1950 insulin dosage escalated, first in the USA and then in Britain, and doses of the order of one or two thousands of units in the first 24 hours, some given intravenously, became typical. The continuing fall in mortality which was associated with the rising dosage1 also coincided with improvements in the use of antibiotics, intravenous fluids and electrolytes, and general supportive care. Reports of circulating insulin antagonists in severe ketoacidosis2 provided scientific support for the use of very large insulin doses.
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