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Diabetic ketoacidosis and hyperosmolar hyperglycaemic state

Table of Contents

Overview #

Definitions

  • Diabetic ketoacidosis (DKA) = acute metabolic complication of diabetes (usually T1DM, but occasionally T2DM) characterised by hyperglycaemia, hyperketonaemia and metabolic acidosis 
  • Hyperosmolar hyperglycaemic state (HHS) = acute metabolic complication of diabetes (usually T2DM) characterised by hyperglycaemic hyperosmolality and dehydration with little or no ketones
  • Euglycaemic DKA = DKA with no or mild hyperglycaemia; commonly associated with the use of SGLT2 inhibitors (e.g. empagliflozin, dapagliflozin) 

Key points

  • Symptom onset over hours for DKA, whereas more insidious over days for HHS
  • Refer to endocrinology ASAP +/- ICU consultation
  • General management points:
    • Fluid resuscitation
    • IV insulin +/- dextrose 
    • Potassium management

Triage #

Medical emergency requiring immediate attention

Causes #

  • Infection (30-40% in DKA; 32-60% in HHS)(1)
    • Pneumonia
    • Urinary tract infection
    • Diabetic foot ulcer
    • Other
  • Acute illness
    • Acute myocardial infarction (AMI)
    • Cerebrovascular accident (CVA)
    • Acute pancreatitis
  • Medication-related
    • Insufficient insulin
    • Omission of insulin 
    • Other drugs 
  • New-onset diabetes (20-25% in DKA)

Clinical features #

Aim of clinical assessment is to identify potential precipitants, assess severity and identify any complications

History

  • Symptoms of hyperglycaemia
    • Early symptoms: polydipsia, polyuria
    • Increased degree/duration of hyperglycaemia: neurological symptoms, weight loss
    • Other: nausea, vomiting, abdominal pain, dyspnoea, headache
  • Symptoms of a precipitant
    • Assess for infective source 
    • Assess for acute illness (e.g. AMI, CVA, pancreatitis) 
  • Medications/other drugs
    • Regular insulin regime
    • Recent omission of insulin
    • Other diabetic drugs 
    • Other drugs (e.g. glucocorticoids including intra-articular glucocorticoids, second generation antipsychotics) 

Examination

  • ABCD approach
    • Breathing: ketotic breath, Kussmaul respiration
    • Circulation: volume status
    • Disability: mental status
  • Identify precipitating event (e.g. source of infection, AMI, CVA) 
  • Identify any focal neurological deficits

Diagnosis #

DKA 

  • Serum glucose >13.9 mmol/L
  • Venous pH <7.3 or HCO3– <18 mmol/L
  • Ketonaemia (>0.6 mmol/L) or ketonuria 

HHS

  • Serum glucose >30 mmol/L
  • Hyperosmolality >320 mOsm/kg 
  • Minimal or undetectable ketones

Investigations #

Initial investigations

InvestigationSignificance
Urinalysis +/- MCSIdentify any ketonuriaIf any suspicion of UTI on urinalysis, send sample for formal urine MCS 
Finger prick glucoseNote that usually any reading >33.3 mmol/L will be unrecordable
Finger prick ketones<0.6: normal≥0.6: abnormal
ECGAssess for features of AMI as a precipitant and ECG abnormalities due to electrolyte derangement
VBGIdentifies serum glucose level (note that upper limit of detection is variable depending on blood gas analyser)Determine any metabolic acidosis and calculate anion gap (DKA results in high anion gap metabolic acidosis) 
FBENote leukocytosis may occur in the absence of infection due to stress response, however higher suspicion of infection if WCC severely elevated
UECNa+ concentration is variablePatients have a total body deficit of K+, but hypokalaemia is seen in only 5% of cases. Note that at presentation hyperkalaemia is often present, however once fluid resuscitation and insulin is commenced, K+ often rapidly decreases (2)AKI may occur due to hypovolaemia 
CMPPatients have a total body deficit of PO4–, but PO4– levels are usually normal or even high (3, 4)
Serum osmolality(mOsm/kg)Can also be calculated using formula (5)(2 x [Na+ concentration + K+ concentration]) + glucose + urea)

Further investigations

InvestigationIndication
General
HbA1CDetermine if acute episode in previously undiagnosed diabetes or poorly controlled diabetes vs acute episode in well-controlled diabetes
Septic screen (callout box)
Sputum cultureIf productive sputum and suspicious for chest infection
Stool cultureIf diarrhoea present and suspicious for gastroenteritis
Blood cultures
CXRIf suspicious for chest infection
Other
TroponinIf chest pain and suspicious for AMI as precipitant
LipaseIf suspicious for pancreatitis, although note is often elevated in DKA without clinical or radiological features of pancreatitis. Hence, diagnosis is primarily based upon clinical and radiological features
CT brain +/- stroke protocolIf suspicious for cerebral oedema as a complicationConsider CT brain stroke protocol if suspicious for CVA as a precipitant 
CT abdomenIf suspicious for pancreatitis

Classification (6) #

DKAHHS
MildModerateSevere
Glucose (mmol/L)>13.9>13.9>13.9>33.3
pH7.25 – 7.307.0 – 7.24<7.0>7.30
HCO3–  (mmol/L)15 – 1810 – 14<10>18
KetonesPresentPresentPresentMinimal/normal
Serum osmolality (mOsm/kg)VariableVariableVariable>320
Anion gap>10>12>12Variable
Mental statusAlertAlert/drowsyStupor/comaStupor/coma

Management #

General principles

  • Refer to local hospital protocol if available
  • Requires very close monitoring until stable
    • Hourly serum glucose
    • 2-4 hourly VBG, electrolytes (and osmolality if HHS) 
    • 4 hourly finger prick ketones (in DKA) 
    • Fluid balance +/- IDC insertion
  • EARLY referral to endocrinology (ideally prior to or if not possible, then as soon as possible following commencement of IV insulin infusion)
  • Never withhold basal insulin

ICU consultation (7)

Refer to ICU if any of the following:

  • pH <7.1
  • Altered conscious state
  • Severe hypokalaemia (<3.0 mmol/L)
  • Severe hyponatraemia (<125 mmol/L)
  • Haemodynamic instability
  • Severe AKI or anuria
  • Pregnancy

Overview of management (5, 7-12)

*Please note that this is an example only and may not reflect local hospital guidelines*

DKAHHS
Correction of fluid loss
Fluid resuscitation with crystalloid fluid (sodium chloride 0.9% or CSL)Give 1 L as rapidly as possible and then reassess Fluid resuscitation with crystalloid fluid (sodium chloride 0.9% or CSL)Replace ~50% of estimated fluid loss in first 12 hours and the remainder in the following 12-36 hours Adjust fluid replacement so that there is a gradual decline in osmolality (3 mOsm/hr)Overall, slower correction of fluid losses compared to DKAAfter fluid resuscitation with ~3 L of sodium chloride 0.9% or CSL and if osmolality not declining → give sodium chloride 0.45%
Correction of hyperglycaemia
InitialIf K+ >3.5 mmol/L → commence short-acting insulin IV bolus 0.1 unit/kg followed by short-acting insulin IV infusion at 0.1 unit/kg/hr (maximum starting dose 10 units/hr; example of short-acting insulin is Actrapid)If K+ <3.5 mmol/L → replace K+, recheck levels and commence short-acting insulin IV infusion once K+ >3.5 mmol/L
OngoingRate of short-acting IV insulin infusion is titrated depending on serum glucose as per local hospital protocol  When serum glucose <15 mmol/L → commence 10% glucose 100 mL/hr to maintain serum glucose 10-15 mmol/L		Insulin is not absolutely necessary to correct hyperglycaemia. Fluid replacement alone (without insulin) will lower serum glucoseCommence insulin IV infusion once serum glucose is not decreasing with fluid replacement alone or if significant ketonaemiaIf serum glucose decreasing <5 mmol/L/hr or ketonaemia >1 mmol/L and K+ >3.5 mmol/L → commence insulin IV infusion at 0.05 units/kg/hrIf serum glucose decreasing <5 mmol/L/hr or ketonaemia >1 mmol/L and K+ <3.5 mmol/L → replace K+, recheck levels and commence insulin IV infusion once K+ >3.5 mmol/LAim: lower serum glucose at a rate of 4-6 mmol/L/hr with target of 10-15 mmol/LWhen serum glucose <15 mmol/L → give 10% glucose, aiming to keep serum glucose at 10-15 mmol/L for the first 24 hours
Transition to subcutaneous insulin when:Glucose <12 mmol/LPatient well and eating/drinkingAcidosis resolved Ketones <0.6 mmol/L
Ensure long-acting insulin given at least 2 hours prior to ceasing IV insulin infusion 
Correction of electrolyte abnormalities
PotassiumIf K+ >5.0 mmol/L or patient anuric → withholdIf K+ 3.5-5.0 mmol/L → give KCl 10 mmol/hr (only while hyperglycaemic, acidaemic and receiving IV insulin infusion)If K+ <3.5 mmol/L → give KCl 20 mmol/hr (ED or ICU only) 
Bicarbonate#If pH <6.90 → give NaHCO3

#Seek senior clinician advice prior to use

References #

  1. Hirsh IB, Emmett M. Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Clinical features, evaluation, and diagnosis. In: Nathan DM, Mulder JE, editors. UpToDate. [Internet]. Waltham (MA): UpToDate Inc; 2020. [updated 2020 Mar 29; cited 2021 Oct 1]. Available from: https://www.uptodate.com/contents/diabetic-ketoacidosis-and-hyperosmolar-hyperglycemic-state-in-adults-clinical-features-evaluation-and-diagnosis?topicRef=1795&source=see_link 
  2. Arora S, Cheng D, Wyler B, Menchine M. Prevalence of hypokalemia in ED patients with diabetic ketoacidosis. Am J Emerg Med. 2012 Mar;30(3):481-4.
  3. Kebler R, McDonald FD, Cadnapaphornchai P. Dynamic changes in serum phosphorus levels in diabetic ketoacidosis. Am J Med. 1985;79(5):571.
  4. Shen T, Braude S. Changes in serum phosphate during treatment of diabetic ketoacidosis: predictive significance of severity of acidosis on presentation. Intern Med J. 2012 Dec;42(12):1347-50. 
  5. eTG complete [Internet]. Melbourne (Vic): Therapeutic Guidelines Ltd; 2019. Hyperosmolar hyperglycaemia in adults; [updated 2021 Mar; cited 2021 Oct 1]. Available from: https://tgldcdp.tg.org.au.acs.hcn.com.au/viewTopic?topicfile=hyperosmolar-hyperglycaemia-in-adults#toc_d1e236 
  6. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009 Jul;32(7):1335-43.
  7. Queensland Government. Management of diabetic ketoacidosis in adults (age 16 years and over) [Internet]. Queensland: The State of Queensland (Queensland Health); 2015 [updated 2015 Sep; cited 2021 Oct 1]. Available from:  https://www.health.qld.gov.au/__data/assets/pdf_file/0019/621640/diabetic-ketoacidosis.pdf
  8. Hirsh IB, Emmett M. Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Treatment. In: Nathan DM, Mulder JE, editors. UpToDate. [Internet]. Waltham (MA): UpToDate Inc; 2021. [updated 2021 Sep 24; cited 2021 Oct 1]. Available from: https://www.uptodate.com/contents/diabetic-ketoacidosis-and-hyperosmolar-hyperglycemic-state-in-adults-treatment?topicRef=1792&source=see_link 
  9. eTG complete [Internet]. Melbourne (Vic): Therapeutic Guidelines Ltd; 2019. Diabetic ketoacidosis; [updated 2021 Mar; cited 2021 Oct 1]. Available from: https://tgldcdp.tg.org.au.acs.hcn.com.au/viewTopic?topicfile=diabetic-ketoacidosis 
  10. Nickson C. Hyperosmolar Hyperglycaemic State [Internet]. Melbourne: Life In The Fast Lane; 2020 [updated 2020 Nov 3; cited 2021 Oct 1]. Available from: https://litfl.com/hyperosmolar-hyperglycemic-state/
  11. Diabetic Ketoacidosis (DKA) Adult Treatment Pathway. Peninsula Health Prompt. 
  12. Hyperosmolar Hyperglycaemic State (HONK / HHS) Adult Treatment Pathway. Peninsula Health Prompt.

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