Diabetic Keto Acidosis Dr Jeremy Turner MRCP D.Phil Consultant Physician, Elsie Bertram Diabetes Centre Norfolk and Norwich University Hospital What is the definition of DKA? Diabetic ketoacidosis is defined as the presence of a metabolic acidosis (venous bicarbonate less than 15 mmol/l or ph less than 7.3) and significant ketosis (plasma beta hydroxybutyrate greater than 3 mmol/l or ketonuria greater than 2+ on standard urinalysis sticks) in the presence of a random plasma glucose greater than 11 mmol/l or known diabetes. The latter criterion is important as the entity of normoglycaemic DKA is well recognized and is a diagnostic pit fall for the unwary, especially in pregnancy. New national guidelines on management of DKA were released in the UK in March 2010 (http://www.diabetes.nhs.uk/publications_and_resources/reports_and_guidanc e/). History Is the patient vomiting? Vomiting is a classical presenting symptom of DKA. Does the patient have abdominal pain? Abdominal pain is a classical presenting symptom of DKA and usually resolves as the acidosis resolves. However sometimes it is mistakenly diagnosed as a surgical emergency. This is avoidable by performing urinalysis. Once the diagnosis of DKA is made it should be treated first unless there is unequivocal evidence of a surgical emergency mandating urgent laparotomy. When did the patient last take insulin? Omission of doses of insulin is the commonest precipitant of DKA. This may be intentionally or may occur mistakenly when the patient has an intercurrent illness causing vomiting or anorexia. Under these circumstances patients understandably miss insulin to avoid hypoglycaemia. Educate patients assiduously about sick day rules to avoid this. Is the patient known to have diabetes? DKA is still the presenting feature of diabetes in a small proportion of cases and thus there may not necessarily be a past medical history of diabetes. What type of diabetes does the patient have? While DKA is classically regarded as the hyperglycaemic emergency of T1DM, ketosis prone T2DM is increasingly recognized and DKA has also been reported in gestational diabetes. Has the patient had a distinct intercurrent illness? Infection is a common precipitant of DKA. Created on 5/16/2011 1:00:00 PM 1
Is the patient pregnant? Pregnancy is an inherently ketosis-prone state and is a high-risk time for DKA in women with T1DM. Has there been any technical difficulty with insulin delivery? Not infrequently patients develop DKA without an apparent cause and despite their best efforts to combat the rising glycaemia and progressing ketosis. In such cases it later transpires that the vial of insulin in their insulin pen was broken, or the pen itself was defective. Thus, reviewing these aspects of management after DKA has resolved is important. Has the patient been drinking alcohol to excess? Alcoholic binges are another common precipitant of DKA Examination A thorough general and systemic examination is an essential part of the assessment of the patient with DKA or any other diabetic emergency. However, particular attention should be paid to certain areas: Is the patient shocked? A systolic blood pressure less than 100 mm Hg (less than 90 mm Hg in a previously young fit healthy adult) with tachycardia, cold peripheries and poor urine output is a marker of severity. The usual cause of shock in DKA is severe fluid depletion secondary to osmotic diuresis and vomiting. However, alternative explanations should be considered including septic shock and cardiogenic shock in severe acidosis. Is the patient conscious? The obtunded/unconscious patient is a marker of severity and while mental obtundation is usually related to the severity of the metabolic derangement, consideration should still be given to alternative explanations such as CNS infection, intra-cranial catastrophe, or toxin ingestion. Is the patient febrile? Infection is a common precipitant of DKA and potential signs of infection should be sought. Abdominal Examination A thorough abdominal examination is important to seek signs of a surgical abdomen that may be the precipitant for DKA. Note should also be made of areas of lipohypertrophy at injection sites during abdominal examination. However, a painful abdomen with some tenderness on palpation (and often a raised amylase as well) is actually a common finding in DKA and will normally resolve as the DKA is treated this should be kept under regular review as the DKA is treated. Created on 5/16/2011 1:00:00 PM 2
Investigations Assessment of ketosis Traditionally, this is by urinalysis giving a result on a 0 4+ scale. Urinalysis however has technical short-comings including the fact that the sodium nitropruside reaction does not pick up the main ketone body in DKA (beta hydroxy-butyrate), it only detects acetone and aceto acetate. Further more, urinalysis necessarily provides a somewhat retrospective look at what ketosis was like when the urine in the bladder was made rather than a real-time readout. For these reasons, there is a move towards blood ketone assessment in many hospitals which may be performed with near-patient testing apparatus not unlike BM machines using a capillary blood sample. Results are given in mmol/l, > 3 mmol/l is indicative of significant ketosis, < 0.3 mmol/l is indicative of complete resolution of ketosis. Acid base status Conventionally, arterial blood gasses were used, however, the most recent national guidelines on management of DKA advocate use of venous blood gasses. This is preferable from the patient s point of view as it is less painful, carries significantly less risk from the procedure itself and unless the patient also has a gas exchange problem as well as DKA (eg pneumonia, PE, etc) provides no additional useful information. Most blood gas analysers will also give a reasonable estimate of serum K+. FBC NB: Leukocyte count rises in direct proportion to the degree of ketosis. Glucose Laboratory glucose is an essential baseline investigation. Amylase Measure this only if you are seriously concerned that the patient may have pancreatitis, it can often be elevated as much as x5 upper limit of normal due to the DKA itself. CXR This is usually performed as part of the septic screen but should be omitted in the frequent flyer where there is no suspicion of sepsis and insulin omission is more likely. This is to reduce the total life time exposure to X- irradiation Urinary hcg This should be performed in all female patients between menarche and menopause presenting with DKA. Urinalysis The presence of nitrites, leukocytes, protein and blood should prompt a sample being sent for microscopy, culture and sensitivity. Created on 5/16/2011 1:00:00 PM 3
Blood cultures These should also be sent if there is suspicion that there is a septic precipitant of the episode. Management Management should be based on the JBDS diabetes DKA algorithm (http://www.diabetes.nhs.uk/publications_and_resources/reports_and_guidanc e/) Immediate management Investigations listed above should be initiated and 1 liter of normal saline should be administered intravenously. If the patient is not shocked then the first liter should go in over 1 hour, otherwise, normal saline should be administered as a 500 ml bolus over 15 minutes. This can be repeated once, if the systolic BP is still below 90 mm Hg at the end, then senior help should be sought and the patient transferred to HDU/ITU. A fixed-dose intravenous insulin infusion should be initiated. 50 units of soluble insulin such as actrapid is diluted in 50 ml normal saline and given via a syringe driver at a rate of 0.1 units/kg body weight/hour. Subsequent fluid management This should always be performed according to clinical assessment but as a rough guide, it is reasonable to expect the average case of DKA to be in 6-7 liter negative fluid balance and most of this should normally be replaced in the first 24 hours. Thus, after the first liter, the next should go in over 2 hours, the next over 4, the next over 6, the next over 8. But it must be stressed that these figures are only a guide. If there is any significant circulatory compromise, a urinary catheter should also be passed in order to monitor urine output. After the first hour, serum K + should be re-assessed (no K + should be given in the first bag of fluid). If the serum K + is greater then 5.5 mmol/l then K + supplementation should be withheld, between 3.5 and 5.5, 40 mmol K + should go in to each bag and if less than 3.5 mmol/l, the patient should be transferred to a high dependency clinical area where strong IV K + can be administered centrally. Monitoring regimen It is essential that a monitoring regimen is instituted. The JBDS guidelines recommend hourly assessment of capillary blood glucose levels and blood ketones (if available in your hospital), 2 hourly assessment of venous blood gases and 4 hourly Us + Es and lab Glucose. In addition, the patient should be frequently clinically re-assessed, especially with respect to their volume status. Expectations during clinical management: If treatment is successful it can be expected that ketones will fall by roughly 0.5 mmol/l/hr and/or venous HCO3 - will rise by ~ 3mmol/L/hr. If these targets are not being met then consideration should be given to revising the rate of insulin infusion eg. Changing from 7u/hr (for a 70 Kg patient) to 9u/hr, Created on 5/16/2011 1:00:00 PM 4
reassessing in a further 2 hours and if necessary adding a further 2u/hr to the insulin infusion rate. If the patient is not improving at the anticipated rate or not improving at all, consideration should also be given to the possibility that there is a pump malfunction, line occlusion, cannula misplacement or other technical problem. What do I do when the blood glucose level starts to fall? The rationale of a fixed dose insulin infusion is that it provides more effective suppression of ketogenesis. However, the practical draw back is that eventually the blood glucose level will fall and the patient may become hypoglycaemic. This is avoided by running 10% dextrose (125 ml/hr) alongside the IV normal saline once blood glucose is less than 12 mmol/l. If the glucose level continues to fall then either the rate of glucose infusion is increased or the strength is increased to 20%. Continuation of long acting insulin It is recommended that the long acting insulin (for patients on a basal bolus regimen) should be continued throughout the management of their DKA. This increases safety by ensuring there is always some insulin onboard and also speeds up conversion back on to their usual sub cutaneous insulin. When should the patient be converted back on to their usual insulin regimen? This should be undertaken once DKA is resolved and they are eating and drinking normally. Resolution of DKA is judged to have happened once either the urine is clear of ketones or blood ketones are less than 0.3 mmol/l and venous ph is greater than 7.3. If the long acting sub cut insulin has been continued throughout then stopping IV insulin is a fairly straightforward process of waiting until a mealtime and giving the usual dose of prandial insulin with the meal, overlapping with the IV insulin for 2 hours and then turning off the IV insulin infusion. Should I give intravenous bicarbonate? The use of IV bicarbonate should be avoided except in extremis. phs greater than 6.9 will usually respond to fluid resuscitation and effective suppression of ketogenesis by insulin. However, once the ph is less than 6.8 the situation is dire and although there is very little evidence to support its use, many would give intravenous bicarbonate at this point. This should always be done on the ITU, under close monitoring. Should I worry about the risk of cerebral oedema? Cerebral oedema is a serious and not infrequent complication of paediatric DKA and this elevated risk extends in to the young adult age range (ie early 20s). In adults however it is a very rare complication thankfully. Is there any role for sliding scale intravenous insulin infusion? In a minority of cases, the ketoacidosis will resolve but the patient is still too unwell to resume eating and drinking normally and taking sub cut insulin. In these instances, the patient can then be switched from a fixed dose insulin infusion to sliding scale insulin. Created on 5/16/2011 1:00:00 PM 5
Is 0.9% NaCl really the best intravenous fluid for managing DKA? This question has been the basis of some debate/controversy recently and other fluids including Hartman s have been proposed as crystalloid of choice in DKA. However, the wide availability of normal saline, the fact that it comes with either 20 or 40 mmoles of pre-added K + (unlike Hartmans) and the very low incidence of hyperchloraemic acidosis (one of the theoretical advantages of Hartmans is a lower risk of hyperchloraemic acidosis) associated with its use mean that it is recommended as the first choice intravenous fluid for management of DKA. For more DKA advice and more diabetes advice in general, please see my website: http://www.diabetesbible.com Created on 5/16/2011 1:00:00 PM 6