Diabetic Ketoacidosis

Dr.P.Raja Kumar
PG in Internal Medicine
KIMS
 Definition
2009 ADA consensus statement on DKA
Diabetic ketoacidosis (DKA) is an acute metabolic
disorder characterized by markedly increased circulating
ketone bodies leading to ketoacidosis in the presence of
prolonged hyperglycemia due to an absence of insulin.
Life-threatening condition characterized by
hyperglycemia (glucose >250mg/dl)
Ketonemia or ketonuria
Arterial pH <7.3
Bicarb < 15mmol/L
Patients may sometime present with euglycemic
ketoacidosis (glucose <300 milligrams/dL or <16.6
mmol/L), such as those who present just after receiving
insulin, type 1 diabetics who are young and vomiting,
patients with impaired gluconeogenesis (alcohol abuse or
liver failure), patients with low caloric intake/starvation,
patients with depression, or pregnant patients. Euglycemic
DKA has recently been described as an adverse effect of
sodium-glucose cotransporter 2 (SGLT-2) inhibitors
(canaglifozin and others).

Check blood ketones, venous pH, bicarbonate levels and

anion gap) to avoid missing euglycemic DKA, because the
degree of hyperglycemia may not be significant.
 Epidemiology/Statistics

Annual incidence 5-8 episodes/1000 person-years

Mortality ~5% in adult DKA
Underlying precipitating illness
Annual hospitalizations for DKA 100,000
Annual hospitalization cost exceeds $1 billion.
 Pathogenesis

Insulin deficiency and/or resistance

Excess of counter-regulatory hormones (glucagon,
catecholamines, cortisol, GH)
Increased gluconeogenesis, glycogenolysis,
proteolysis, lypolysis
Decreased glucose utilization in peripheral tissues
 Pathophysiology

Unchecked gluconeogenesis Hyperglycemia

Osmotic diuresis Dehydration

Unchecked ketogenesis Ketosis

Dissociation of ketone bodies into Anion-gap metabolic

hydrogen ion and anions acidosis

Often a precipitating event is identified (infection, lack of

insulin administration)
Glucagon excess decreases the activity of pyruvate kinase, whereas insulin
deficiency increases the activity of phosphoenolpyruvate carboxykinase.
 Precipitating Factors
Infections (30-50%)
Medication non-compliance or inadequate
treatment (30%)
New onset diabetes (20%)
Others- CVA, MI, trauma, pancreatitis, alcohol
and drug abuse, pregnancy, thyrotoxicosis,
hypercortisolism, drugs
 History
Polyuria Nausea, vomiting
Polydipsia Abdominal pain
Polyphagia Weakness
Weight loss Clouding sensorium
 Physical Exam
Evidence of dehydration Fruity odor
dry mucus membrane Tachycardia
decreased skin turgor Hypotension
orthostatic hypotension
Kussmauls respiration
decreased Urinary Output
Altered mental status
Shock
Coma
 Diagnostic Studies
Blood work
Chemistry panel, including Mg, PO4
Serum ketones
UA with urine ketones
ABG/VBG
Serum Osmolality
Cbc with differential
Others: autoantibodies (anti-GAD, anti-islet cells), C-
peptide, A1c, fasting lipid
 Diagnostic Studies (contd)
K+, Mg++, PO4-- depletion are usually found.
Initial serum K+ can be high due to extracellular shift
of K+ secondary insulin deficiency and acidemia
Hyponatremia - osmotic pull of water into
intravascular space, vomiting with fluid loss and
free water replacement, or severe hyperlipidemia
(pseudohyponatremia)
 Diagnostic Studies (contd)
Cr may be falsely elevated due to acetoacetate interference
with measuring method
Leukocytosis is usually present, but usually wbc <25K and
no left shift
Amylase, lipase, and LFT can be elevated
In rare cases, patients can have severe hyperlipidemia,
requiring sample dilution, leading to factitiously
pseudohypo- or normoglycemia
 Diagnostic Studies (contd)
Ketones in DKA are acetoacetate, acetone and B
hydroxybutyrate (BHB is not detected by
nitroprusside reaction)
During treatment for DKA, B hydroxybutyrate is
converted to acetoacetate, so test for ketones may
become more strongly positive despite improvement
of DKA
 Diagnostic Studies (contd)
EKG
CXR if pneumonia present
Blood cx, urine cx, throat cx if indicated
 Diagnosis
Diagnostic criteria
BG >250, HCO3 <15, pH <7.3
Ketonemia or ketonuria

Differential diagnoses
Diagnosis (contd)
 TREATMENT
RECOMMENDATIONS
 Treatment With IV Fluids and
Dextrose
For severe hypovolemia, during the first 1-2 hours (in absence
of cardiac compromise), give 1-1.5 L 0.9% NaCl
After initial volume resuscitation, or for more mild
dehydration, use intravenous fluid rate of 250-500 mL/hr
Compute corrected serum Na
For every 100 mg/dL BG elevation, add 1.6 mEq/L to Na value
Use 0.45% NaCl if corrected Na normal
Use 0.9% NaCl if corrected Na <135
When BG reaches 200 mg/dL (DKA) or 300 mg/dL (HHS),
change to 5% dextrose with 0.45% NaCl at
150-250 mL/hr (ie, clamping blood glucose until anion gap
has closed in DKA)
 Conventional Insulin Guidelines
Initiate the correction of hypovolemic shock with
fluids, and correct hypokalemia if present, before
starting insulin
When starting insulin, initially infuse 0.1 to 0.14
units/kg/h
If plasma glucose does not decrease by 50-75 mg in
the first hour, increase the infusion rate of insulin
Continue insulin infusion until anion gap
closes
Initiate subcutaneous insulin at least 2 h before
interruption of insulin infusion
Kitabchi AE, et al. Diabetes Care. 2009;32:1335-1343.
30
 Rationale for a Dynamic Insulin
Protocol for DKA and HHS
Even with low-dose insulin therapy1,2
Hypokalemia and hypoglycemia may continue to
occur
Failure to reduce insulin infusion rate as the blood
glucose approaches target may lead to hypoglycemia
There is a lag between the change in intravenous
insulin infusion rate and the resulting effects3

1. Umpierrez GE, et al. Arch Intern Med. 1997;157:669-675.

2. Burghen GA, et al. Diabetes Care. 1980;3:15-20.
3. Mudaliar S, et al. Diabetes Care. 2002;25:1597-1602.
 A Dynamic Insulin Protocol for
DKA
Physician orders for DKA: target blood glucose 150-199 mg/dL until recovery

Default is
Column 1 Column 2 Column 3 Column 4 Column 5
column 3
Insulin Insulin Insulin Insulin Insulin
BG mg/dL
units/h units/h units/h units/h units/h
<90 0.1 0.1 0.1 0.1
90-129 0.2 0.3 0.3 0.4
130-149 0.4 0.6 0.8 1.0
150-169 0.6 1.1 1.5 1.8 2.5
170-179 0.8 1.6 2.3 3.0 4.3
180-199 1.0 2.0 3.0 4.0 6.0
200-229 1.1 2.2 3.3 4.4 6.5
230-259 1.3 2.5 3.8 5.0 7.5
260-289 1.4 2.8 4.2 5.6 8.4
290-319 1.5 3.1 4.6 6.2 9.3
320-359 1.7 3.4 5.1 6.8 10.2
360-399 1.8 3.7 5.5 7.4 11.1
400 2.0 4.0 6.0 8.0 12.0
Devi R, et al. Diabetes Manage. 2011;1:397-412.
 A Dynamic Insulin Protocol for
HHS
Physician orders for HHS: target blood glucose 200-299 mg/dL until recovery

Default is
Column 1 Column 2 Column 3 Column 4 Column 5
column 3
Insulin Insulin Insulin Insulin Insulin
BG mg/dL
units/hr units/hr units/hr units/hr units/hr
<100 0.1 0.1 0.1 0.1
100-149 0.2 0.2 0.3 0.3
150-199 0.3 0.5 0.6 0.7
200-219 0.5 0.8 1.1 1.3 1.7
220-239 0.6 1.1 1.5 1.9 2.6
240-259 0.8 1.5 2.1 2.7 3.9
260-299 1.0 2.0 3.0 4.0 6.0
300-329 1.1 2.1 3.2 4.2 6.3
330-359 1.1 2.3 3.4 4.6 6.9
360-399 1.3 2.5 3.8 5.0 7.5
400-449 1.4 2.8 4.2 5.6 8.3
450-599 1.6 3.3 4.9 6.6 9.9
600 2.0 4.0 6.0 8.0 12.0

Devi R, et al. Diabetes Manage. 2011;1:397-412.

 Continuation of physician orders for DKA and HHS
Initiation of insulin drip, monitoring of BG, and termination of insulin drip
Initiate IV insulin infusion using selected or default column assignment. Reassignment to a higher column before
4 hours of treatment requires an MD order. If BG fails to fall each hour during hrs 1-4, notify MD
Adjust column assignment for DKA or HHS based on column change rules, and adjust drip rate based on BG
level
Measure BG every 1 hour ( fingerstick or capillary blood sample using point-of-care glucose monitor)
If BG is within target range x 4hrs, then measure BG q 2 h. If column reassignment occurs, measure q 1 h
Record BG results, insulin drip rate changes, and column reassignments on the ICU flow sheet
Obtain order for SQ insulin to be administered q 1-2 h before discontinuing IV insulin
Algorithm for order to treat patient if BG <70 mg/dL
If BG is <70 mg/dL, administer 25 ml of D50 by IV
Adjust column assignment to next lower column and use pretreatment BG to assign row
Recheck BG in 5 minutes. If BG is <70 mg/dL, repeat administration of 25 ml of D50 by IV
Column change rules after 4 hours of treatment of DKA
If BG 200 mg/dL and not falling after 3 successive hourly tests (or for 2 h) on the same column, move to next
higher column
If BG <180 mg/dL after 3 successive hourly tests (or for 2 h) on the same column during infusion of fluids
containing D5W, or if any BG <150 mg/dL, move to next lower column
Column change rules after 4 hours of treatment of HHS
If BG 300 mg/dL and not falling after 3 successive hourly tests (or for 2 h) on the same column, move to next
higher column
If BG <280 mg/dL after 3 successive hourly tests (or for 2 h) on the same column during infusion of fluids
containing D5W, or if any BG <200 mg/dL, move to next lower column

Devi R, et al. Diabetes Manage. 2011;1:397-412.

34
When and how do you switch insulin
infusion to sc?
Once blood glucose reaches 250 mg/dl reduce insulin infusion
rate to 0.05 U/kg/h to maintain blood glucose between 150-
200 mg/dl for DKA till acidosis is resolved (S .Bicarbonate
>18 meq/L,Anion gap<12,venous PH>7.3).
Once acidosis is resolved administer short acting insulin s/c and
continue insulin infusion for 1-2 hrs.If insulin infusion
discontinued before s/c insulin has taken effect,ketoacidosis may
recur.
If patient remains NPO despite resolution of DKA, insulin
infusion is to be continued.
Once DKA resolved, patient taking orally, start previous
s/c regimen or 0.6-0.7 U/kg as basal bolus regimen.
 Cerebral Edema
Cerebral edema is a dreaded complication of DKA
in childhood1
Mortality may be 24%, with significant morbidity
among survivors2
One pediatric study found that rates of fluid
administration and insulin administration were not
associated with cerebral edema3
In another case control pediatric study, insulin dose
in first 2 h was significantly associated with the risk
of cerebral edema4
1. Muir AB, et al. Diabetes Care. 2004;27:1541-1546. 2. Edge JA, et al. Arch Dis Child. 2001;85:16-22.
3. Glaser N, et al. N Engl J Med. 2001;344:264-269. 4. Edge J, et al. Diabetologia. 2006;49:2002-2009.
39
 Bicarbonate therapy in DKA?
Bicarbonate and metabolic acidosis
administer bicarbonate if the arterial pH is less
than 6.90.
Give 100 mEq of sodium bicarbonate in 400
mL sterile water(200 ml/Hr) with 20 mEq
of potassium chloride, if the serum potassium is
less than 5.3 mEq/L, administered over two
hours.
Repeat the same therapy if Ph<7.0
Uptodate-online
How do you calculate Bicarbonate
deficit?
How do you calculate Bicarbonate
deficit?

The Washington Manual of Critical Care 2nd e

Harmful effects of Bicarbonate
therapy?
 Harmful effects of Bicarbonate
therapy?
Neurologic deterioration
The administration of alkali may slow the rate of
recovery of the ketosis
Hypokalemia

The indications for bicarbonate therapy in DKA are

controversial and evidence of benefit is lacking In a randomized
trial of 21 DKA patients with an admission arterial pH between
6.90 and 7.14 (mean 7.01), bicarbonate therapy did not change
morbidity or mortality
Bicarbonate therapy in severe diabetic ketoacidosis.
Morris LR, Murphy MB, Kitabchi AE
 Potassium Balance in DKA
Potassium is dominantly intracellular
Urinary losses occur during evolution of DKA (due to
glycosuria)
Total body potassium stores are greatly reduced in any patient
with DKA
Potassium moves from inside the cell to the extracellular space
(plasma)
During insulin deficiency
In presence of high blood glucose
As cells buffer hydrogen ions
Blood levels of potassium prior to treatment are usually high but
may drop precipitously during therapy

46
 Potassium Repletion in DKA
Life-threatening hypokalemia can develop
during insulin treatment
Potassium reenters cells with insulinization and
correction of acidosis
The small extracellular compartment experiences
a precipitous drop of potassium concentration
Anticipatory potassium replacement during
treatment of DKA is almost always required

47
 Potassium Repletion in DKA
K+ >5.2 mEq/L
Do not give K+ initially, but check serum K+ with
basic metabolic profile every 2 h
Establish urine output ~50 mL/hr

K+ <3.3 mEq/L
Hold insulin and give K+ 20-30 mEq/hr until
K+ >3.3 mEq/L
K+ = 3.3-5.2 mEq/L
Give 20-30 mEq K+ in each L of IV fluid to
maintain serum K+ 4-5 48mEq/L
 Phosphorus Repletion in DKA
A sharp drop of serum phosphorus can also
occur during insulin treatment
Treatment is usually not required
Caregiver can give some K+ as K- phos

49
 Disposition
Discharge from ER
Mild DKA
Alert
Able to tolerate oral intake
Compliant
Good social support

Admission
All other cases, including those with comorbidities and
poor social support
 Complications
Cardiac arrhythmias
From electrolyte abnormalities or acidosis
Hypoglycemia
From overzealous insulin dosage
Hypokalemia
Due to administration of insulin and bicarbonate
Hyperglycemia/DKA recurrence
Due to discontinuation of IV insulin prematurely or
failure to cover with SC insulin
 Complications (contd)
Hyperchloremic metabolic acidosis
Excessive Cl- from IV fluid
Loss of HCO3- due to excretion of ketoanions as Na and K salts
Cerebral edema
Due to osmotically-driven movement of water into CNS
Occurs primarily in children
When plasma osmolality decreases too rapidly
Suspect when patients sensorium deteriorates or remains impaired
despite resolution of DKA
 Complications (contd)

Pulmonary edema
Patients with widened A-a gradients, wet crackles on lung
exam
Frequently monitor patients with cardiac disease or renal
insufficiency
Venous and arterial thrombosis
DKA is a hypercoagulable state from endothelia injury,
hypofibrogenolysis, and platelet hyperaggregation
DVT prophylaxis
 Clinical Presentation of
Hyperglycemic Hyperosmolar State
Compared to DKA, in HHS there is greater
severity of:
Dehydration
Hyperglycemia

Hypernatremia

Hyperosmolality

Because some insulin typically persists in HHS,

ketogenesis is absent to minimal and is
insufficient to produce significant acidosis
 Clinical Presentation of
Hyperglycemic Hyperosmolar State
Patient Profile Disease Characteristics
Older More insidious development

More comorbidities than DKA (weeks vs

History of type 2 diabetes,
hours/days)
which may have been Greater osmolality and

unrecognized mental status changes than

DKA
Dehydration presenting with
a shock-like state
 Electrolyte and Fluid Deficits in
DKA and HHS
Parameter DKA* HHS*

Water, mL/kg 100 (7 L) 100-200 (10.5 L)

Sodium, mmol/kg 7-10 (490-700) 5-13 (350-910)

Potassium, mmol/kg 3-5 (210-300) 5-15 (350-1050)

Chloride, mmol/kg 3-5 (210-350) 3-7 (210-490)

Phosphate, mmol/kg 1-1.5 (70-105) 1-2 (70-140)

Magnesium, mmol/kg 1-2 (70-140) 1-2 (70-140)

Calcium, mmol/kg 1-2 (70-140) 1-2 (70-140)

* Values (in parentheses) are in mmol unless stated otherwise and refer to the total body
deficit for a 70 kg patient.
Chaisson JL, et al. CMAJ. 2003;168:859-866.
63
 Laboratory Diagnostic Criteria of
DKA and HHS
Parameter Normal range DKA HHS

Plasma glucose, mg/dL 76-115 250 600

Arterial pH* 7.35-7.45 7.30 >7.30

Serum bicarbonate, mmol/L 22-28 15 >15

Effective serum osmolality, mmol/kg 275-295 320 >320

Anion gap, mmol/L <12 >12 Variable

Serum ketones Negative Moderate to high None or trace

Urine ketones Negative Moderate to high None or trace

* If venous pH is used, a correction of 0.03 must be made.

Calculation: Na+ - (Cl- + HCO3-).

Chaisson JL, et al. CMAJ. 2003;168:859-866.

 Fluid and Electrolyte
Management in HHS
Treatment of HHS requires more free water and
greater volume replacement than needed for
patients with DKA
To avoid heart failure, caution is required in the
elderly with preexisting heart disease
Potassium
Usually not significantly elevated on admission
(unless in renal failure)
Replacement required during treatment
 Causes of Morbidity and
Mortality in DKA
Shock Acute renal failure
Hypokalemia during Adult respiratory distress
treatment syndrome
Hypoglycemia during Vascular thrombosis
treatment Precipitating illness,
Cerebral edema during including MI, stroke,
treatment sepsis, pancreatitis,
Hypophosphatemia pneumonia
 DKA Management Pitfalls
Not assessing for and/or treating underlying cause
of the DKA
Not watching K+ closely enough and/or not
replacing K+ aggressively enough
Following serial serum ketone concentrations
Following serum bicarbonate instead of the anion
gap, with misinterpretation of expansion acidosis as
persistent ketoacidosis
Interrupting IV insulin too soon (eg, patient not yet
eating, anion gap not yet closed)
 DKA Management Pitfalls
Occurrence of rebound ketosis consequent to
inadequate insulin dosing at transition (eg,
failure to give SC insulin when glucose is low
or injudicious use of sliding scale insulin)
Inappropriate extension of hospitalization to
fine-tune an outpatient regimen
Inadequate patient education and training
Inadequate follow-up care
FINDING THE CAUSE AND
PREVENTING RECURRENCE
Possible Precipitating Causes or
Factors in DKA: Type 1 Diabetes
Nonadherence to insulin regimen or psychiatric
issues
Insulin error or insulin pump malfunction
Poor sick-day management
Infection (intra-abdominal, pyelonephritis, flu)
Myocardial infarction
Pancreatitis
Other endocrinopathy (rare)
Steroid therapy, other drugs or substances
73
Possible Precipitating Causes or
Factors in DKA: Type 2 Diabetes
Nonadherence to medication regimen
Poor sick-day management
Dehydration
Renal insufficiency
Infection (intra-abdominal, pyelonephritis, flu)
Myocardial infarction, stroke
Other endocrinopathy (rare)
Steroid therapy, other drugs or substances
Predischarge Checklist
Diet information
Glucose monitor and strips (and
associated prescription)
Medications, insulin, needles
(and associated prescription)
Treatment goals
Contact phone numbers
Medic-Alert bracelet
Survival Skills training
 Education in Type 1 Diabetes
to Prevent DKA
Recognize symptoms and findings that require
contact with a healthcare provider
Prevent ketoacidosis through self-management
skills:
Glucose testing
Appropriate use of urine acetone testing

Appropriate maintenance of insulin on sick days

Use of supplemental insulin during illness

Address social factors

 Please remember..
Alteration of consciousness has been reported to
correlate better with elevated serum osmolality (>320
mOsm/L or >320 mmol/kg) than with severity of
metabolic acidosis.

DKA leads to a wide-anion-gap metabolic acidosis.

Venous pH has essentially replaced arterial blood gases

in the assessment of the acid-base status of the DKA
patient. Venous pH is about 0.03 lower than arterial
pH. Venous pH obtained during routine phlebotomy
should be used to avoid arterial puncture, which is
painful and may cause arterial vascular complications.
 The decrease in serum potassium during therapy is
reported to be about 1.5 mEq/L (1.5 mmol/L) and
parallels the drop in glucose and the dose of insulin.

Standard teaching is that 1.6 mEq (1.6 mmol) should be

added to the reported sodium value for every 100
milligrams (5.55 mmol) of glucose >100 milligrams/dL
(>5.5 mmol/L). However, the correction factor is
probably 2.4, especially for blood glucose levels >400
milligrams/dL (>22.2 mOsm/L).

Serum creatinine frequently may be elevated factitiously

if the laboratory assay for creatinine is interfered with by
the nitroprusside assay.
 The order of therapeutic priorities is volume first and
foremost, correction of potassium deficits, and then
insulin administration.

The goal of treatment is glucose <200 milligrams/dL

(<11.1 mmol/L), bicarbonate 18 mEq/L (18 mmol/L),
and venous pH >7.3 .

In general, the first 2 L are administered rapidly over 0 to 2

hours, the next 2 L over 2 to 6 hours, and then an
additional 2 L over 6 to 12 hours.
 For each 0.1 decrease in pH, serum potassium
concentration rises approximately 0.5 mEq/L(0.5mmol/L).

The rapid development of severe hypokalemia is

potentially the most life-threatening electrolyte
derangement during the treatment of DKA.

Obtain an electrocardiogram immediately and check for

signs of hyperkalemia once DKA is suspected.

Continue the insulin infusion until the resolution of

DKAglucose <200 milligrams/dL (<11 mmol/L) and
two of the following:a serum bicarbonate level
>15mEq/L, a venous pH >7.3, and/or a normal calculated
anion gap.
 A transition from the IV insulin infusion to SC insulin
is necessary to avoid relapse to hyperglycemia or DKA
when the insulin infusion is stopped.

There is no established role for initiating IV K2PO4 for

DKA in the ED.

Give bicarbonate if the initial pH is 6.9, but do not give

bicarbonate if the pH is 7.0.

Patients with severe acidosis may be at higher risk for

clinical deterioration, so adults with a pH <6.9 can be given
100 mEq (100 mmol) of sodium bicarbonate in 400 mL of
water with 20 mEq (20 mmol) KCl at 200 mL/h for 2
hours until the venous pH >7.0 .
 Summary
DKA and HHS are life-threatening emergencies
Management involves
Attention to precipitating cause
Fluid and electrolyte management
Insulin therapy
Patient monitoring
Prevention of metabolic complications during recovery
Transition to long-term therapy
Patient education and discharge planning should
aim at prevention of recurrence