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Coma in diabetes (DM) may be related to many metabolic changes. The most commonly encountered clinical situation is diabetic ketoacidosis. In addition to this a diabetic can become unconscious due to hyperosmolar coma, lactic acidosis, hypoglycemia and associated nephropathy leading to uremic coma. Non metabolic complications like myocardial infarction with cardiogenic shock, cerebrovascular accident leading to cerebral haemorrhage and gram negative septicemia can also alter sensorium of diabetics.
In our country diabetic ketoacidosis (DKA) accounts for 3-8% hospital admissions. 20% of IDDM for the first time come in DKA ir, UK. In cases under 20 years of age DKA is the commonest cause of death. Clinical spectrum of DKA can be pure ketoacidosis where there is marked insulin deficiency. It can be ketosis with hyperosmolar state where insulin lack is less marked.
Pathophysiology of DKA
Three cardinal features of DKA are a) insulin deficiency b) increased counterregulatory hormones c) dehydration. First two factors contribute to hyperglycemia.
In DKA there is decreased insulin secretion or increased insulin resistance or both. Other anti-insulin hormones like cortisone, growth hormone, glucagon and catecholamine levels in blood are increased. These hormonal changes lead to increased glycogenolysis, gluconeogenesis, ketogenesis and excessive triglyceride synthesis.
In the muscle there is decreased glucose utilisation, aminoacid uptake is also reduced and there is reduced protein synthesis.
In adipose tissue there is increased lipolysis and decreased glucose uptake and triglyceride synthesis. The net effect of all these changes leads to hyperglycemia, ketosis and triglyceridemia.
Precipitating factors of DKA and hyper osmolar coma
Infection, omission or inadequate insulin, diuretic induced hypokalaemia, acute pancreatics, can precipitate ketoacidosis. DKA may be seen in diabetics when there is additional endocrine problem like hyperthyroidism, pheochromocytoma and steroid use. Stress in DM can precipitate DKA as it is seen in diabetics getting myocardial infarction.
There are many drugs which can aggravate DKA or hyperosmolar coma; to name few: hydrochlorthiazide, betablockers, dilantin, alcohol, calcium channel blocker, cortisone. They affect insulin secretion, increased insulin resistance and aggravate hyperglycemia and ketosis.
Sites of Ketogenesis
80% of ketone formation occurs in liver and 20% is formed in kidney. Ketosis can be seen in the absence of hyperglycemia like alcoholic and starvation ketosis,. When free insulin level is less than 15mu/litre in IDDM is often associated with DKA. But rarely with this level NIDDM get ketosis, due to attenuated ketogenesis state.
Clinical presentation of diabetic ketoacidosis
Patients get abdominal pain, nausea and vomiting. Dehydration is marked. Patient's breathing is acidotic - Kussmaul's breathing. Nausea is due to hyperketonaemia. Vomiting occurs in the presence of gastric dilatation. Muscle cramps and abdominal pain are related to potassium deficit and associated ileus and gastric dilatation. Hypotension and orthostatic hypotension are due to volume depletion. There is tachycardia related to volume depletion. Dehydration is related to osmotic diuresis rnd vomiting. Patient has warm skin as a result of peripheral vasodilation due ketosis. Hyperosmolarity leads to coma, patient may have hyperventilation due to ketosis.
Hypotension and volume depletion may lead to oliguria.
Investigations
There are glycosuria and hyperglycemia, ketonuria and ketonaemia. pH of blood is low. Bicarbonates are low around 15 mEq. There is leucocytosis even without infection-haematocrit is elevated due to dehydration. Usually sodium is low and potassium is low. With poor renal function potassium may go up.
Complications of DKA
Following complications are seen in DKA. Electrolyte imbalance in the form of hypo-or hyperkalemia, hyponatraemia can be seen. Aspiration pneumonia, thromboembolic manifestation, ARDs, pulmonary oedenia, cerebral oedema and hypoglycernia can occur.
Management
In the management of DKA following points are to be kept in mind.
a) Care of unconscious patient
b) Correction of dehydration
c) Insulin replacement therapy
d) Potassium replacement
e) Bicarbonate - when to give?
f) Correcting and managing the precipitating factors.
g) Use of antibiotics for control of infection.
Fluid replacement:
On an average loss of blood and electrolytes in an adult with DKA of moderate severity are as follows:
Water 6 litres
Sodium 500 mmol
Chloride 400 mmol
Potassium 350 mmol
About half the deficit of total body water is derived from the intracellular compartment and occurs early in the development of acidosis with few clinical features, the remainder represents loss of extracellular fluid later on. It is at this time there is marked contraction of the size of extracellular space, with hematocrit concentration, decreased blood volume and fall in blood pressure.
To correct dehydration give i.v. 0.9% N saline one litre in 30 mts. in next 30 mts. 0.51 is given, subsequent 0.51 of N. Saline is given in the next one hour. When the blood glucose comes around 250 mgm start 5% glucose solution to avoid hypoglycemia. In elderly with CAD or CCF monitor CVP line, reduce the saline infusion if there is danger of CCF. Early rapid rehydration is essential; otherwise insulin will not reach poorly perfused tissues.
If the plasma sodium is 155 mmol, 0.45% saline to be given utially instead of 0.9% N. saline. In children 10.20 ml/Kg saline is be given in 2 hrs.
Isulin therapy
Always use unmodified, clear, regular insulin in DKA. Never use long acting insulin, start IV insulin infusion 5 units/hr. or alternatively 10-20 unit intramuscular, followed by 5 units/hr intramuscularly. The blood glucose concentration should fall by 3-6 mmol per hour. If there is no fall of blood glucose by 2 hrs. after treatment then the dose of insulin should be doubled until satisfactory response is obtained. Ketosis, dehydration, acidaemia and stress all produce severe insulin resistance.
Potassium replacement
Before treatment of DKA potassium level in serum is high. This is because of acidosis, hyperglycemia and oliguria. But once DKA is treated with insulin and body deficit of fluid corrected serum potassium becomes low. With potassium level over 5.5 mmol/1 no potassium to be given. If potassium is 3.5 mmol to 5 mmol, 20 mmol and give 40 mmol if potassium is below 3.5 mmol/1. If there is oliguria avoid potassium chloride supplement. Start only when urine output is maintained.
Use of bicarbonate in DKA
Bicarbonate is not rountinely indicated. Only to be given if pH is below 7.0. One ampoule of sodium bicarbonate containing 44mEq will increase 4-5 meq/1 of Na, will relieve Kussmaul breaming. In comatose patients as there is risk of increasing osmoolarity, sodium bicarbonate is to be avoided.
Acidosis below 7pH has a few hazards
It has negative inotropic effect on heart, causes peripheral vasodilatation, produce cerebral depression, insulin resistance and also causes enzyme depression. Overenthusiastic correction of acidosis with sodabicarb carries the following risks.
a) Hypokalaemia
b) Increased anaerobic glycolysis
c) Impaired tissue oxygen supply
d) Paradoxical fall in CSF pH leading to cerebral oedema
e) Rebound alkalosis and sodium overload. Because of these inherent risk with sodium
bicarbonate, alkali therapy to correct DKA is not rountinely used unless the acidosis
is severe and pH is below 7.
Phosphate therapy in DKA
It is said that in DKA there is hypophosphataemia. This leads to decrease in levels of 2.3 diphosphoglycerate level in RBC, which in turn leads to more O2 affinity and is not released at the tissue level, leading to tissue hypoxia. To correct this, potassium hydrogen phosphate is used, if serum phosphate is less than 1 mEq/m2. Therapy carries the risk of soft tissue calcification and hence phosphate replacement is not routinely done.
Assessment of therapy in DKA
Clinically assessed by seeing blood pressure urine output, tongue hydration and pulse volume; urine acetone and blood glucose are to be checked every hourly.
Prevention of DKA
Major emphasis should be given to prevent DKA in IDDM. This can be done by diabetic clinics, physician or general practitioners who take care of diabetics. Patients are to be told that during illness due to infection or if they have loss of appetite and are not eating they should never omit insulin. The dose may be reduced but not completely omitted. During sick days diabetics should check urine 'frequently for glycosuria and ketonuria'. Diabetic ketoacidosis should be diagnosed early and treatment to be started early after hospitalization. If an IDDM patient is already taking two doses of long acting insulin during his illness he may switch over to short acting regular insulin and take frequently at every 4-6 hours.
REFERENCES
1. Saul Genuth - Diabetic ketoacidosis Page 173-176 in : Clinical Diabetes - Modern
management by Stephen Podolsky 1980 Published Appleton Century - Crofts, New
York.
2. Robert Bradley - "Diabetic ketoacidosis and coma" Page 368-369 in Joslin's diabetes
mellitus Alexander Marble, Priscilia White, llth edition Lea and Febiger, Philadelphia,
1971.
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