This document provides information on diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic syndrome (HHS), two life-threatening emergencies that can occur in patients with diabetes. It defines DKA and HHS, describes their symptoms, causes, management including treatment goals, complications, and comparisons between the two conditions. The document emphasizes the importance of promptly diagnosing and treating these emergencies, closely monitoring patients, involving the diabetes care team, and considering all possible diagnoses including unusual presentations.

1. Diabetes Emergencies:
DKA & HHS
Rahul Nayar
Clinical Lead Diabetes: Northern Clinical Networks
Consultant in Diabetes & Endocrinology
RCP Northern Region: Medicine
16th September 2020

2. Definitions
Basic facts
Acute management
Aims of Rx
Key points
Audit/QI
Remember the
patients perspective
Unusual Aspects
Mixed picture
Content

3. Symptoms
• Glucose
• Dehydration
• Electrolyte imbalance
“To make a diagnosis you need to think of the diagnosis”
Consider it in any person with diabetes who is ill
Patients perspective
• Fear
• Judgement
Causes
• Relative insulin deficiency
• Infection
• New presentation
• Co-morbidities
The Basics

4. Diabetic Ketoacidosis
• Pathophysiology
• Complex metabolic state, occurs due to an absolute or relative
deficiency of insulin, accompanied by an increase in counter
regulatory hormones
• Definition
• Hyperglycaemia > 11mmol/l
• Ketonaemia/Ketosis > 3mmol/L or 2+ urinary ketones
• Acidaemia HCO3- < 15mmol/L and or Venous pH < 7.3

5. • Epidemiology
• 4.8 – 8 episodes per 1,000 patients
• NaDIA – HARMS: recognised that DKA occurring in-hospital is
a significant issue (medical & non-medical wards)
• Mortality & Morbidity
• Significant improvement over 20yrs in care but people with
diabetes are still dying because of poor management (0.67%)
Diabetic Ketoacidosis

6. DKA: Management
• Fluid administration (70kg patient = 7L fluid deficit)
• Aims:
• Restore circulating volume
• Clearance of ketones
• Correct electrolyte imbalance (potassium)
• Insulin Therapy
• A Fixed Rate Intravenous Insulin Infusion (FRIII) rate =
0.1units/kg body weight/hr
• Aims
• Suppression of ketogenesis
• Reduction in blood glucose
• Correction of electrolyte disturbance (watch potassium)

7. Monitoring & team work
• Venous pH not arterial
• Bedside monitoring – vital signs, ketones & capillary glucose
• Continuation of long acting (basal) s/c insulin alongside FRIII
• Monitor potassium levels frequently – at least 2hourly

8. Markers of Severity
One or more indicates severe DKA
• Blood ketones over 6mmol/L
• Bicarbonate level below 5mmol/L
• Venous/arterial pH below 7.0
• Hypokalaemia on admission (under 3.5mmol/L)
• GCS less than 12 or abnormal AVPU scale
• Oxygen saturation below 92% on air (assuming normal baseline
respiratory function)
• Systolic BP below 90mmHg
• Pulse over 100 or below 60bpm
• Anion gap above 16 [Anion Gap = (Na+ + K+) – (Cl- + HCO3-) ]

9. Metabolic targets
• Reduction of blood ketones by 0.5mmol/L/hour
• Increase Venous Bicarbonate by 3mmol/L/Hour
• Reduce capillary blood glucose by 3mmol/L/Hour
• If serum glucose < 14mmol/l and ketosis commence 10% dextrose
to avoid hypoglycaemia whilst continuing FRIII
• Maintain Potassium between 4 – 5.5mmol/L
• https://www.inpatientdiabetes.org.uk/diabetes-emergencies-dka-hhs
Resolution of DKA
Defined as
• pH > 7.3
• Bicarbonate > 15mmol/L
• Blood ketones < 0.6mmol/L

10. Complications
• Cerebral Oedema
• Hypokalaemia
• Hypoglycaemia
• Hyperchloraemic Acidosis
• Phosphate replacement
• Sodium Bicarbonate
Infusion

11. Unusual situations
• Euglycaemic Ketoacidosis
• Pregnancy (CSII)
• SGLT2 inhibitors
• Other drugs - Atypical anti-psychotics
• Mixed picture – make a decision and review
• Starvation / Alcohol
• Acute/Chronic Kidney
• Lactic acidosis
• Stress Hyperglycaemia vs new diagnosis with acid/base
imbalance

12. SGLT2i’s
HbA1c, glycated haemoglobin;
SGLT2, sodium–glucose co-transporter 2
Increased glucose excretion
Increased sodium excretion
Reduced glycaemia HbA1c reduction
Loss of energy
(calories)
Weight loss
Reduced sodium
load
Blood pressure
reduction
• Oral glucose lowering agent for people with type 2 diabetes
• Expected clinical effects of SGLT2 inhibition based on the mode of action
• Mechanism of action via kidney tubules
• Increasing evidence in reduction of risk – Heart Failure and Nephropathy
Risks:
• Euglycaemic or DKA, Lower Limb Amputation, Osteoporosis, Acute Kidney
injury, Post Operative Ketosis

13. Technology
Free Style Libre Device
“Flash” glucose monitoring systems
Continuous
Subcutaneous Insulin
Infusion (CSII)
“insulin pump”

14. Hyperosmolar Hyperglycaemia Syndrome (HHS)
• HHS can be a complex condition to manage and is
associated with a significant mortality.
• Approximately 10%
• Diagnosis must be made promptly, treatment
intensively monitored and the specialist diabetes
team informed & involved.

15. Hyperosmolar Hyperglycaemia Syndrome (HHS)
• has no precise definition, but characteristic features that
differentiate it from other hyperglycaemic states such as
Diabetic ketoacidosis (DKA) are:
• Hypovolaemia
• Marked hyperglycaemia (30mmol/L or more)
• Without significant hyperketonaemia (< 3mmol/L) or ketonuria
(2+ or less) or acidosis (pH>7.3, bicarbonate> 15mmol/L)
• Osmolality usually 320mosmol/kg or more

17. Aims of Treatment:
Are to treat the underlying cause and to gradually
and safely:
• Normalise the osmolality
• Replace fluid and electrolyte losses
• Normalise blood glucose
• Other goals include prevention of:
• Arterial or venous thrombosis
• Other potential complications e.g. cerebral
oedema/central pontine myelinolysis
• Foot ulceration

18. Remember
• Calculated Serum osmolality =
2Na+ + glucose + urea:
(normal range 280 - 295mosmol/kg)
• A mixed picture of HHS and DKA may occur.
Metabolic acidosis may be present in patients who
are critically unwell.

19. Severity
• The presence of one or more may indicate severe HHS and HDU/Level 2 care
a) Pulse < 60 OR > 100 bpm
b) Systolic BP < 90 mmHg
c) SaO2 < 92% on air (assuming normal baseline)
d) Hypothermia
e) GCS < 12 (or abnormal AVPU score)
f) Serum sodium >160mmol/L
g) Venous or arterial pH < 7.1
h) Hypokalaemia (< 3.5mmol/L) on admission
i) Osmolality > 350mosmol/kg
j) Decompensated heart or renal disease
k) Macrovascular event such as acute MI or CVA
l) Other serious Co-morbidity

20. Treatment
• Immediate
• Commence IV 0.9% sodium chloride – 1 litre over 1 hour
• Consider more rapid replacement if SBP below 90 mmHg
• Caution in the elderly where too rapid rehydration may
precipitate heart failure but insufficient may fail to reverse
acute kidney injury
• Only commence insulin infusion (0.05 units/kg/hr) IF there is
significant ketonaemia (blood ketone level) greater than 1
mmol/L) or ketonuria 2+ or more (i.e., mixed DKA and HHS
picture)
• Establish appropriate monitoring of patient (hourly capillary
blood glucose, Na+, K+, urea and calculated osmolality)

21. Additional considerations
• Assess degree of dehydration, insert urinary catheter to
monitor hourly urine output and calculate fluid balance
• Examine for source of sepsis or evidence of vascular event
• Commence prophylactic LMWH
• Consider IV antibiotics if sepsis identified or suspected
• Ensure your patients’ heels are off - loaded
• Assessment of fluid balance, aiming to achieve positive fluid
balance of 2 - 3L by 6 hours, should be part of the on-going
management in all patients

22. Additional considerations
• Maintain potassium within normal range
• If capillary blood glucose falls to < 14mmol/L then commence 10%
glucose at 62.5ml/hr in addition to sodium chloride +/- potassium
infusion.
• Aim to keep capillary blood sugar between 10 - 15mmol/L in first 24hrs
and avoid hypoglycaemia.
• Commence IV insulin infusion at presentation ONLY if significant
ketonaemia (blood ketone >1mmol/L or ketonuria >2+)
• Commence IV insulin if blood glucose level falling at rate < 5 mmol/L/hr
despite adequate fluid replacement
• IV insulin rate in unit/hour (based on 0.05unit/kg/hr)

23. Aims
• To achieve gradual decline in osmolality
(3 - 8 mosmol/kg/hr)
• To maintain potassium in normal range
• To avoid hypoglycaemia, aim to keep blood glucose 10-
15 mmol/L in first 24 hrs with 10% Dextrose
• Important aspects for continuous review
• Monitor vital signs and chart Early Warning Score (EWS)
• Maintain accurate fluid balance chart (minimum urine
output 0.5ml/kg/hr)
• Biochemical assessment to calculate osmolarity

24. What to do if .....
• Measure glucose, urea and electrolytes hourly and calculate osmolality
(2Na+ + glucose + urea) and record on HHS prescription chart.
• If plasma Na+ increasing but osmolality declining at appropriate rate,
continue 0.9% sodium chloride
• If plasma Na+ increasing AND osmolality increasing (or declining at less
than 3 mosmol/kg/hr) check fluid balance. If positive balance is
inadequate increase rate of infusion of 0.9% sodium chloride
• If osmolality increasing and fluid balance is adequate, consider
switching to 0.45% sodium chloride at the same rate
• If osmolality falling at rate exceeding 8 mosmol/kg/hr consider
reducing infusion rate of IV fluids and/or insulin (if already commenced)

25. • If blood glucose falling less than 5mmol/L check fluid
balance
• If positive balance is inadequate, increase rate of infusion
of 0.9% sodium chloride
• If positive fluid balance is adequate, commence low dose
IV insulin (0.05 units/kg/hr) or if already running, increase
rate to 0.1 units/kg/hr
What to do if .....

26. Things to consider in a deteriorating
patient with HHS
• Serious complications may arise during the
management of HHS as a result of treatment. These
include:
a) Hypo or hyperkalaemia
b) Hypoglycaemia
c) Cerebral oedema
d) Pulmonary Oedema
e) Central pontine myelinolysis

27. Comparison of DKA and HHS
Factor Diabetic ketoacidosis Hyperosmolar
Hyperglycaemic syndrome
Volume status Usually dehydrated Hypovolaemic
Glucose (mmol/L) >11 or known diabetes > 30
Urine ketones +++ or more ++ or less
Capillary blood ketones
(mmol/L)
> 3 < 3
pH < 7.3 > 7.3
Bicarbonate (mmol/L) < 15 > 15
Osmolarity (mosmol/kg) Variable > 320
Intravenous fluids Immediately Immediately
Insulin Immediately at fixed
rate infusion of 0.1
units/kg/hr
Immediately only if capillary
ketones >1 mmol/L or urine
ketones >2+
(at 0.05 units/kg/hr);
otherwise withhold insulin
until fluid resuscitated

28. Summary
• Two serious life threatening complications of diabetes
• ALL regional hospitals have guidelines, but implementing and
following these can be a challenge
• To make a diagnosis you need to think of the diagnosis, this
includes the rare or unusual causes, detecting complications, and the
reasons for not responding to standard treatment plans
• Recognise the signs of severity and escalate
• Monitoring (clinical & biochemical parameters) with a ‘team
approach’ and regular timely review is vital
• Understand the patients’ perspective

29. Thank you

30. Distinguishing type 1 & type 2
• History: weight loss
• Ketones – check blood or urine
• Severity of symptoms
• Family history
• Age

31. Auto-Antibody Testing
Autoantibody Abbreviation Target Specificity
Anti-glutamic acid
decarboxylase
Anti-GAD Measures specific antibody to an
enzyme present in pancreatic β
cells
85%
Insulin
autoantibodies
IAA This test measures antibodies
targeted against the insulin
molecule
Age & Gender
dependent
60 – 80%
Insulinoma-
associated - 2
autoantibodies
IA-2 detects antibodies mounted
against pancreatic β cells
60%
Islet cell
cytoplasmic
autoantibodies
ICA Infrequent test: reaction between
human islet cell antibodies
and islet cell proteins from animal
pancreas
70 – 80% new
onset type 1
Zinc transporter 8
autoantibodies
ZnT8Ab Newest test, detects antibodies
targeting a β cell specific enzyme
80%