DIABETES KETOACIDOSIS

AND HYPEROSMOLAR
NONKETOTIC STATE
Dr. Paul Ngugi
Consultant Endocrinologist
Kenyatta National Hospital
 Diabetes Ketoacidosis
Definition
• Hyperglycemia-blood sugar level greater
than or equal 14meq/l
• Acidosis with pH usually less than 7.3
• Bicarbonate less than 15meq/l
• Ketosis-ketonuria greater than +++
Historical Background, Incidence
and Mortality Rate
• 1886 Dreschfeld described two types of fatal diabetic
complications with coma.
• One had a fruity smell in the patients breath a strong
reducing agent in the urine
• The other insidious in onset and seen in older patients
• Incidence of DKA 3-8 periods per 100 diabetic
patients
• Mortality has improved with the discovery of insulin.
Initially before 1922was at 100%. Studies done
recently shows mortality at 2%-10%
 Precipitating Factors
• Infections
• Omissions of or inadequate insulin
• Newly diagnosed diabetes mellitus
• Unknown
• others e.g alcohol abuse, pulmonary
embolism, emotional stress, pancreatitis,
surgery
• CSII devices
 Pathogenesis
• Insulin deficiency
• Increased counter regulatory hormones such as
glucagon, catecholamines and growth hormones. This
phenomena is however is impaired in those who have
had diabetes for more than 15 years and hhence the
severity of DKA may be less. In mild DKA the counter
regulatory hormones levels are not raised. In severe
DKA these hormones exaggerate the state of metabolic
decompensation
• Dehydration
 Glucose Metabolism
• DKA is a catabolic state
• Increased gluconeogenesis
• Increased glucogenolysis
• High glucose levels
• Decreased glucose uptake by insulin
sensitive tissues such as muscles, fat and
liver
 Ketone Body Metabolism
• Low insulin levels
• High counter regulatory hormones
• Favour lypolysis increased fatty acids
• Glucagon also lowers hepatic levels of malony CoA
increased production of beta-hydroxybutyric acid and
acetoaceticacid.
• CAmp+glucagon excess+insulin deficiency=direct
positive effect in ketogenesis that is independent of an
increased substrate supply from adipose tissue
• Clearance of ketone is also decreased in DKA
 Protein And Aminoacid
Metabolism
• Negative nitrogen balance-gluconeogenic
amino acid(glutamine, alanine, threonine,
serine, glutamate, glycine) decreased
• Ketogenic amino acids like leucine,
isoleucine and valine increased
• The above is due to increased cortisol and
glucagon levels in DKA
 Lipid Metabolism
• High triglyceride levels due to increased
secretions of VLDL by the liver in case of
insulin deficiency
• High fatty acid levels leads to increased
synthesis of triglycerides
• Decreased clearance of VLDL. HDL lower
in DKA and improves with treatment
 Water And Acid Base
• Water loss 5-8litres
• Sodium loss 400-700meq
• Potassium loss 250-700meq
• Acidosis ranges from anion gap acidosis-
hyperchloremic metabolic acidosis
• The contributing factors in the development of
hyperchloremic metabolic acidosis is higher
intravascular volume and lower initial insulin
levels during initial therapy
 Diagnosis
• History-most times from relatives as most
patients have decreased mental ability
• Polyuria
• Polydipsia
• Weight loss
• Vomiting
• Abnormal discomfort
 Examination
• kussmaul breathing
• Dehydration with loss of skin turgor
• Soft eyeballs
• Weakness
• Acetone(fruity) smell
• Signs of vascular collapse
• Coma usually in patients whose osmolarity is than
330mosm/kg
 Laboratory Data
• Blood glucose >14mmol/l
• Bicarbonate <15meq/l
• pH <7.3
• Ketonuria >+++
• Ketonemia present at dilution 1:2
• Sodium may be fictiously low due to hyperglycemia or
hyperlipedemia
• Potassium low, high or normal
• High wbc count up to 25000
• Amylase levels high
 Hyperglycemic, Hyperosomolar
Nonketotic State
• First described in 1957 by Samerit and Schwantz.
Characterised by extreme hyperglycemia,
increased serum osomolarity(2Na+
+glucose+BUN), severe dehydration without
significant ketosis or acidosis
• Bicarbonate is greater than 20meq/l and arterial
pH is greater than 7.3
• Most times patients have depressed sensorium
• Patients elderly
 Precipitating Factors
• Infection
• Gastroenteritis
• New onset diabetes
• Discontinued insulin
• Miscellaneous
 Pathogenesis
• Higher levels of counter regulatory hormones and
free fatty acids in DKA vs. HHNS
• Relatively higher levels of endogenous insulin
reserve in HHNS adequate to prevent lypolysis but
inadequate to inhibit hepatic glucose production
• Inhibition of lypolysis by the hyperosmolar state
thus decreasing ketogenesis
• Coma due to hyperosmolarity
 Diagnosis
• Blood glucose >33mmol/l
• Serum osmolarity >330mosmol/kg.
Absence or minimal levels of serum ketone
• Arterial pH >7.3
• Bicarbonate >20mmol/l
• Moderate to severe mental obtudation
• Ketonuria less than ++
 Guidelines for the treatment of
diabetic coma (ketoacidosis and
hyperosmolar
• Initial therapy:
non-ketogenic)
Insulin
 Start with 16 units regular i.m., continue with
infusion of insulin at 4 units/hr (infusion pump)
 If blood glucose decreases <10% during 2hr
increase insulin dose to 8 units/hr
Preparation of the insulin infusion: add 50 units
insulin to 500ml NaCl 0.9%. Discard the first
50ml
Water And Sodium Replacement
The composition of the infusion fluid is dependent on the
serum sodium concentration:
Composition
Serum-sodium (mmol/l) Infusion solution
>165 2.5% glucose
145-165 0.45%NaCl
<145 0.9%NaCl
Infusion rate:
1st hour- 1litre
2nd –7th hour- 0.5l/hr
After 8th hour- 0.2l/hr
Infusion rate in patients with cardiac failure or with hypotension: fluid administration according
to central venous pressure (CVP) or pulmonary artery pressure (PAP):

CVP (cmH2O) PAP (mmHg) Infusion rate (l/hr)

<3 10 1

3-8 10-18 0.5-1

8-12 18-24 0.5

>12 >14 0.25

Limitations:
Total amount of fluids in the first 12hr should not exceed 10% of body weight.
If hypovolemia persists after 6 litres of fluids, administer colloid-containing solutions (e.g.
albumin)
 Potassium

Infusion rate according to serum-K+ and to pH

Serum K+ Amount of K+ (mmol/hr)
(mmol/l) pH <7.1 pH >7.1
<3 30 20
3-3.9 20 15
4.0-4.9 15 10
5.0-5.9 10 5
>6.0 0 0
 Correction of acidosis (only if
blood pH<7.0).
• Bicarbonate (mmol/l)=base deficitbody
weight(kg)0.1(as sodium bicarbonate, infuse
during 2hr)
• Potassium and magnesium replacement: if serum
phosphate decreases <0.5mmol/l infuse 33-
66mmol phosphate as sodium phosphate buffer
over 8hr. If serum magnesium decreases
<0.6mmol/l infuse 20-40mmol magnesium
sulphate over 8hr
Monitoring of serum parameters
• Glucose, Na, K, urea, every 2hr, phosphate
and magnesium every 6-12hr during the
first 48hr, thereafter daily
 Treatment after blood glucose
concentration has decreased
below 14mmol/l
 Infuse 1litre of glucose 5% during
5hr,containing 20-80mmol potassium
(according to serum potassium) and 10-
30units insulin
 Alternatively, administer insulin separately
as continuous infusion (2-6units/hr)
 Replace phosphate and magnesium if their
serum concentrations are decreased
Height:
Weight: DKA FLOWSHEET
0hr:_
12hr:
24hr:
24hr:

Physical
examinati
on
Electrolytes

A.G.B.

Insulin

Intake
fluid/meta
bolites

Output
 Complications Of Therapy
• Cerebral Edema-occurs rarely and mostly in
children and adolescents.
Causes(suggestive)-too rapid administration of fluids
and correction of osmotic imbalance between the
brain and its extracellular fluid.
-excessive use of bicarbonate
-rapid decrease in blood glucose levels below
200mg/dl
During DKA it lack overt clinical signs though can
be suspected by severe headaches,
changes in arousal/behavior, pupillary
changes, bradycardia, disturbed temperature
regulation
Therapy is empiric but suspect is given
1-2g/kg body weight of Mannitol.
Intubation with hyperventilation for
comatose patients
• Hyperchloremic Acidosis-common in patients
recovering from DKA.
Causes-ketonuria loss of much of the ketone that
would be use for bicarbonate regeneration
-amount of bicarbonate in the proximal tubule is
limited thus increased chlorine reabsorption
-decreased total buffering capacity due to low
bicarbonate levels
Incomplete treated ketoacidosis treated by
continued vigorous administration of
insulin
Clinically treated patients are given oral
administration and decreased insulin
administration.
 Other Complications
• Pulmonary edema-rare diabetic pulmonary
vascular microangiopathy with altered
alveolocapillary permeability
• Aspiration of gastric contents leading to
pneumonia and respiratory or cardiac arrest