Diabetic Ketoacidosis(DKA)
Definition
DKA - acidosis accompanied by the accumulation of ketone bodies in diabetes patient. (1) Consist of the biochemical triad of ketonemia, hyperglycemia, and acidemia. (2) Most patients with DKA have autoimmune type 1 diabetes , however patients with type 2 diabetes are also at risk during catabolic stress of acute illness. (3)
Pathophysiology
Absolute or relative insulin deficiency accompanied by an increase in counter-regulatory hormones which enhances hepatic gluconeogenesis , glycogenolysis , and lipolysis. (3,4)
Absolute insulin deficiency may occur in certain condition such as undiagnosed type 1 diabetes and patient who miss their insulin doses. (5) Relative insulin deficiency may occur when concentrations of counterregulatory hormones increase in response to stress conditions. (5)
Gluconeogenesis and glycogenolysis will increase the blood glucose level and causing hyperglycemia.(3) Lipolysis increase serum fatty acids which will undergo oxidation as an alternative energy source to produce ketone bodies resulting ketonemia and metabolic acidosis. (3) Fluid depletion can occur due to hyperglycemia induce osmotic diuresis, vomiting due to ketoacidosis and inability to take in fluid due to diminished level of consciousness. (2)
Sign and symptoms
Dry skin Characteristic acetone (ketotic) breath odor Nausea, vomiting, or abdominal pain Tachypnea Hypotension Tachycardia Hypothermia Polyuria, polydipsia, and nocturia
Diagnostic criteria (3)
DIABETES CARE, VOLUME 32, NUMBER 7, JULY 2009
Goals of therapy
Expansion of the intravascular volume.
Correction of deficit in fluids, electrolyte & acid base status.
Initiation of intravenous insulin infusion therapy. Assessment and monitoring of therapy. Treatment of concurrent infection if present.
General management issues
1. Fluid administration and deficits
the most important initial therapeutic intervention to restore circulatory volume, clearance of ketones and correction of electrolytes imbalance. Typical deficits in DKA:
Water (ml/kg) Sodium (mmol/kg) Chloride (mmol/kg) Potassium (mmol/kg) 100 7-10 3-5 3-5
2. Insulin therapy Insulin has the effects of suppression of ketogenesis, reduction of blood glucose and correction of electrolyte imbalance Administration of intravenous insulin infusion at a fixed rate of 0.1 units/kg is recommended Priming dose of insulin is not necessary provided if the insulin infusion is started promptly at a dose of at least 0.1 unit/kg/hr . (Kitabchi 2008)(2)
3. Metabolic treatment targets The recommended targets are
Reduction of blood ketone concentration by 0.5 mmol/L/hr Increase in venous bicarbonate by 3 mmol/L/hr Reduce capillary blood glucose by 3 mmol/L/hr Serum potassium level should be maintain between 4-5 mmol/L
If these rates are not achieved then the fixed rate of intravenous insulin infusion should be increased.
4. Intravenous glucose concentration
Administration of intravenous infusion of 10% glucose is necessary in order to avoid hypoglycemia and to allow the continuation of a fixed rate IVII to suppress ketogenesis.
Introduction of 10 % glucose is recommended when the blood glucose falls below 14mmol/L IVII should not be discontinued until the patient is eating and drinking normally.
Management pathway
Joint British Diabetes Societies Inpatient Care Group. The Management of Diabetic Ketoacidosis in Adults (March 2010).
1. Immediate management upon diagnosis at the first hour
Aims
Start IV 0.9% sodium chloride solution Start a fixed rate IVII after starting fluid therapy Established monitoring regime hourly blood glucose, ketone measurement and at least 2 hourly serum potassium for the 1st 6 hours Clinical and biochemical assessment of the patient
Actions 1.Intravenous access and initial investigation
ABC, IV fluid replacement, clinical assessment, lab investigation, and consider precipitating causes and treat appropriately.
2.Restoration of circulating volume
SBP below 90 mmHg give 500ml of 0.9% Nacl over 10-15 minutes. Once SBP above 90 mmHg follow fluid replacement as in table 1
Table 1
Fluid replacement (Sarawak handbook 3rd ed)
1 liter NS in 1 hour Then 1 liter in 2 hour Then 1 liter in 4 hour Then 1 liter in 6 hour Then 1 liter in 8 hour
Potassium replacement More than 5 mmol/L no need add KCl 4.5 5.0 mmol/L add 1 g KCl each liter 3.5 4.5 mmol/L add 2 g KCl each liter 3 3.5 mmol/L add 3 g KCl each liter Less than 3 add 4 g KCl each liter
3. Potassium replacement
Serum K is often high on admission (although total body potassium is low) but falls precipitously upon treatment with insulin. To maintain K level at 4-5 mmol/L with 20-40 mmol/L K.
4. Starting a fixed rate intravenous insulin infusion
50 units of insulin made up to 50 ml of NS and infused at a fixed rate of 0.1 unit/kg/hr Only give stat dose of insulin if there is a delay in setting up a fixed rate of IVII.
2. 60 minutes to 6 hours
Aims
Clear the ketones from blood and suppress ketogenesis Achieve a rate of fall of ketones of at least 0.5 mmol/L/hr Or bicarbonate should rise by 3 mmol/L/hr and blood glucose should fall by 3 mmol/L/hr Maintain serum K and avoid hypoglycemia
Actions 1.Reassess patient and monitor vital signs
Consider urinary catheterisation isfincontinent or anuric Accurate fluid balance chart, minimum urine output 0.5ml/kg/hr
2.Review metabolic parameters
Assess the resolution of ketoacidosis Calculate the rate of change of ketone level fall or glucose or rise in bicarbonate Ketone falling at least 0.5mmol/L/hr, bicarbonate rise at least 3 mmol/L/hr or glucose falling at least 3 mmol/L/hr
Increase the rate of intravenous insulin infusion if the ketone or glucocose level did not fall or bicarbonate level did not increase as above. Continue the IVII until ketones less than 0.3 mmol/L, venous pH over 7.3 and/or venous bicarbonate over 18 mmol/L If glucose falls below 14 mmol/L, 10% glucose should be given at 125ml/hr with 0.9% Nacl solution.
6 to 12 hours
Aims
Ensure that clinical and biochemical parameters are improving Continue IV fluid replacement and IVII Assess for complications of treatment example fluid overload or cerebral edema Avoid hypoglycemia
Actions
1. Reassess and monitor patient vital sign 2. Review of biochemical and metabolic parameters
Resolution of DKA is defined as ketones less than 0.3 mmol/L, and venous pH over 7.3
12 to 24 hours
By 24 hours the ketonemia and acidosis should have resolved. Aims
Ensure all parameters are improving or have normalised. Continue iv fluids if not eating or drinking Reassess for complications of treatment Transfer to subcutaneous insulin if patient eating and drinking normally
Actions
1. Reassess and monitor patient vital sign 2. Review of biochemical and metabolic parameters
Resolution is defined as ketones < 0.3 mmol/L, venous pH > 7.3
3. Subcutaneous insulin is started before IV insulin is discontinued. Ideally give subcutaneous fast acting insulin and a meal and discontinue IV insulin one hour later.
Complication of DKA treatment
Hypokalemia and hyperkalemia
Potentially life threatening Risk of acute renal failure associated with severe dehydration and therefore recommend that no potassium should be given with initial fluid resuscitation K will always falls as the DKA is treated with insulin and recommended that 0.9% Nacl solution with potassium 40 mmol/L is given as long K level below 5.5 mmol/L and patient is passing urine.
Joint British Diabetes Societies Inpatient Care Group. The Management of Diabetic Ketoacidosis in Adults (March 2010).
Hypoglycemia
Blood glucose may fall very rapidly as ketoacidosis is corrected and is a common mistake to allow the blood glucose drop to hypoglycemic levels This may result a rebound ketosis by counter regulatory hormones. Severe hypoglycemia can associate with cardiac arrhythmias brain injury and death. Once blood glucose drops to 14 mmol/L intravenous glucose 10% should be given to patient
Joint British Diabetes Societies Inpatient Care Group. The Management of Diabetic Ketoacidosis in Adults (March 2010).
Cerebral edema
More common in children Exact cause is unknown but recent studies suggest that cerebral hypoperfusion with subsequent reperfusion may be the mechanism operating.
Pulmonary edema
Rapid infusion of crystalloids over a short period of time increase the risk of complication Elderly and impaired cardiac function patient also at the risk of developing pulmonary edema
Joint British Diabetes Societies Inpatient Care Group. The Management of Diabetic Ketoacidosis in Adults (March 2010).
Recommendation and discussion
1. Arterial vs venous measurement? Difference btw arterial and venous pH is 0.020.15 units and bicarbonate is 1.88mmol/L Not really affect the diagnosis or management of DKA Venous blood are easily obtained Measure venous rather than arterial bicarbonate and pH
Joint British Diabetes Societies Inpatient Care Group. The Management of Diabetic Ketoacidosis in Adults (March 2010).
2. Colloid vs crystalloid Many guideline suggest that in hypotensive patients initial fluid resuscitation should use colloid. However hypotension results from a loss of electrolyte solution and it is more physiological to replace with crystalloid fluid. It is recommended that 0.9% sodium chloride solution should be the fluid of choice for resuscitation in all clinical areas as it supports safe practice and is available ready to use.
Joint British Diabetes Societies Inpatient Care Group. The Management of Diabetic Ketoacidosis in Adults (March 2010).
0.9% Nacl vs compound sodium
Joint British Diabetes Societies Inpatient Care Group. The Management of Diabetic Ketoacidosis in Adults (March 2010).
3. Initiating treatment with a priming dose of insulin? Is not really necessary if the insulin infusion is started promptly at a dose of at least 0.1 unit/kg/hr 4. Intravenous phosphate? No evidence of benefit of phosphate replacement However, in the presence of respiratory and skeletal muscle weakness, phosphate replacement should be considered.
Joint British Diabetes Societies Inpatient Care Group. The Management of Diabetic Ketoacidosis in Adults (March 2010).
5. Intravenous bicarbonate? Is not indicated Adequate fluid and insulin therapy will resolve the acidosis Acidosis is an adaptive response to improve oxygen delivery to the tissue causing a right shift to the oxygen dissociation curve . Excessive bicarbonate may cause a rise in CO2 partial pressure in CSF and may lead to a CSF acidosis. Use of bicarbonate may increase the risk of cerebral edema in children and young adults
Joint British Diabetes Societies Inpatient Care Group. The Management of Diabetic Ketoacidosis in Adults (March 2010).
Thank you
References
1. http://medicaldictionary.thefreedictionary.com/keto acidosis 2. Joint British Diabetes Societies Inpatient Care Group. The Management of Diabetic Ketoacidosis in Adults (March 2010). 3. Abbas E. Kitabchi, Guillermo e. Umpierrez, John m. Miles, Joseph n. Fisher. Hyperglycemic crises in adult patients with diabetes. Diabetes care, volume 32, number 7, july 2009. 4. http://emedicine.medscape.com/article/118361overview#aw2aab6b2b3aa 5. Shereen Abdelghaffar. Diabetic Ketoacidosis: Clinical Practice Guidelines. 2013 Abdelghaffar; licensee InTech
