DIABETIC METABOLIC EMERGENCIES

Diabetic ketoacidosis

CAUSES

Diabetic ketoacidosis is the hallmark of IDDM. Its main causes can be grouped as follows:
• Previously undiagnosed diabetes
• Interruption of insulin therapy
• The stress of intercurrent illness
The majority of cases reaching hospital could have been prevented by earlier diagnosis, better communication between patient and doctor, and better patient education. The most common error of management is for patients to reduce or omit insulin because they feel unable to eat owing to nausea or vomiting. This is a factor in at least 25% of all hospital admissions. Insulin should never be stopped.

PATHOGENESIS

Ketoacidosis is a state of uncontrolled catabolism associated with insulin deficiency. Insulin deficiency is a necessary precondition since only a modest elevation in insulin levels is sufficient to inhibit hepatic ketogenesis. Even so,  stable patients do not readily develop ketoacidosis when insulin is withdrawn. Other factors include counteriregulatory hormone excess and fluid depletion. The combination of insulin deficiency with excess of its hormonal antagonists leads to the parallel processes

In the absence of insulin, hepatic glucose production accelerates and peripheral uptake by tissues such as muscle is reduced. Rising glucose levels lead to an osmotic diuresis, loss of fluid and electrolytes, and dehydration. Plasma osmolality rises and renal perfusion falls. In parallel, rapid lipolysis occurs, leading to elevated circulating free fatty-acid levels. The free fatty acids are broken down to fatty acyl-CoA within the liver cells, and this in turn is converted to ketone bodies within the mitochondria.
Accumulation of ketone bodies produces a metabolic acidosis. This is typically associated with nausea and vomiting, leading to further loss of fluid and electrolytes. The excess ketones are excreted in the urine but also appear in the breath, producing a distinctive smell similar to that of acetone. Respiratory compensation for the acidosis leads to hyperventilation, graphically described as ‘air hunger’. Progressive dehydration impairs renal excretion of hydrogen ions and ketones, aggravating the acidosis. As the pH falls below 7.0 ([H+] >100 nmol Iitre “), pHdependent enzyme systems in many cells function less effectively. Untreated, severe ketoacidosis is invariably fatal.

CLINICAL FEATURES

The features of ketoacidosis are those of uncontrolled diabetes with acidosis, and include prostration, hyperventilation (Kussmaul respiration), nausea, vomiting and, occasionally, abdominal pain. The latter is sometimes so severe as to cause confusion with a surgical acute abdomen.

Some patients are mentally alert at presentation, but confusion and stupor are common. Up to 5% present in coma. Evidence of marked dehydration is present and the eyeball is lax to pressure in severe cases. Hyperventilation is present but becomes less marked in very severe acidosis owing to respiratory depression. The smell of ketones on the breath allows an instant diagnosis to be made by those able to detect the odour. The skin is dry and the body temperature is often subnormal, even in the presence of infection; in such cases, pyrexia may develop later.

DIAGNOSIS

This is confirmed by demonstrating hyperglycaemia with ketonaemia or heavy ketonuria, and acidosis. No time should be lost and treatment is started as soon as the first blood sample has been taken. Hyperglycaemia is demonstrated by dipstick, while a blood sample is sent to the laboratory for confirmation. Ketonaemia is confirmed by centrifuging a blood sample and testing the plasma with a dipstick that measures ketones. An arterial blood sample is taken for blood gas analysis.

Further investigations are detailed below.

MANAGEMENT

The principles of management are as follows.
REPLACE THE FLUID LOSSES.
REPLACE THE ELECTROLYTE LOSSES. Potassium levels need to be monitored with great care to avoid the cardiac complications of hypokalaemia or hyperkalaemia.
RESTORE THE ACID-BASE BALANCE. A patient with healthy kidneys will rapidly compensate for the metabolic acidosis once the circulating volume is restored. Bicarbonate is seldom necessary, although it is usual for this to be given as isotonic 1.26% bicarbonate solution (not 8.4% which is grossly hyperosmolar) if the pH is below 7.0 ([H+] >100 nmollitre-‘).
REPLACE THE DEFICIENT INSULIN. Modern treatment is with low doses of insulin, which lower blood glucose by suppressing hepatic glucose output rather than by stimulating peripheral uptake, and are therefore much less likely to produce hypoglycaemia. Soluble insulin is given as an intravenous infusion where facilities for adequate supervision exist, or as hourly intramuscular injections. The subcutaneous route is avoided because subcutaneous blood flow is reduced in shocked patients.
MONITOR BLOOD GLUCOSE CLOSELY. Hourly measurement is needed in the initial phases of treatment.
REPLACE THE ENERGY LOSSES. When plasma glucose falls to near-normal values (12 mrnol litre “), saline infusion should be replaced with 5% dextrose containing 20 mmol KCl litre “. The insulin infusion rate is reduced and adjusted according to blood glucose.
SEEK THE UNDERLYING CAUSE. Physical examination may reveal a source of infection, e.g. a perianal abscess. Two common markers of infection are misleading: fever is unusual even when infection is present and polymorpholeucocytosis is present even in the absence of infection. Relevant investigations include a chest Xray, urine and blood cultures, and an ECG (to exclude myocardial infarction). If infection is suspected, broadspectrum antibiotics are started once the appropriate cultures have been taken.