DKA - The Canadian Association of Critical Care Nurses

Diabetic Ketoacidosis……when we are too sweet for our own good!

Brenda Morgan RN BScN MScClinical Nurse Specialist, CCTCLondon Health Sciences Centre

Pancreas

Endocrine�Alpha cells: glucagon�Beta cells: insulin �Delta: somatostatin�Delta: somatostatin�Pancreatic Polypeptide

Exocrine�Pancreatic juices

Physiology

Insulin

Glucagon

Insulin:Glucagon

Insulin Glucagon

Stimulated by: Stimulated by:Stimulated by:

�Increased BS

Stimulated by:

�decreased BS

�Exercise

�malnutrition

�increased AA

�SNS

Insulin Glucagon

Effects:

�Movement of glucose and K into cell

�Decreased fat mobilization

Effects:

�Raise blood sugar

�Gluconeogenesis

�Glycogenolysis�Decreased fat mobilization

�Decrease protein breakdown leaving protein available for cell growth

�Maintains serum osmolality

�Glycogenolysis

�Fat mobilization

�Protein mobilization

Fed State

� Insulin > Glucagon (insulin activity dominates)

� Movement of nutrients into cells

� Storage of nutrients for later use� Storage of nutrients for later use

Fasting State

� Glucagon > Insulin (glucagon activity dominates)

� Use of endogenous fuels to maintain blood sugar for energy and metabolismblood sugar for energy and metabolism

Fasting State

� Liver becomes major source for glucose

� Stored sugar in liver (glycogen) is converted to glucose (glycogenolysis)

� Decreased insulin causes lipolysis to � Decreased insulin causes lipolysis to increase free fatty acids (used for muscle fuel)

Fasting State

� Free fatty acids converted to ketones in liver by glucagon (another energy source for brain and muscle)– Beta-hydroxybutyrate vs acetoacetate– Beta-hydroxybutyrate vs acetoacetate

� Glycerol (released by lipolysis) and alanine (from protein catabolism) provides additional substrates for gluconeogenesis in liver

Other Triggers

� Cortisol

� Catecholamines

� Growth hormones

Renal Regulation

� Glucose filtered in glomerulus

� Filtered glucose reabsorbed in proximal tubules to maintain serum glucose

� Kidney removes excess glucose� Kidney removes excess glucose

� Decreased renal perfusion impairs glucose removal

Diabetic Complications

Effects of Diabetes� chronic complications develop in 75% of patients� magnitude and duration of hyperglycemia correlates to:

microvascular disease:� retinopathy� retinopathy� nephropathy

neuropathy� gastroparesis� diarrhea� impotence� resting tachycardia, bradyarrhythmias� postural hypotension� limb sensation

Diabetic Complications

Macrovascular diseases� coronary artery disease� peripheral vascular disease � cerebrovascular disease� hypertension� hypertension

Macrovascular and Neuropathy� foot disease

� risk increases with smoking, obesity, hyperglycemia, lipid abnormalities.

� increased lipid alterations increases with hyperglycemia� neuroglycopenia

Diabetic Ketoacidosis

� Primarily Type I DM risk

� Exaggerated expression of fasting state

� Little has changed in mortality� Little has changed in mortality

� Prevention of deaths through early detection

� Role for urine testing for ketones

DKA

Glucagon>Insulin

increased hepatic glucose production

Insufficient Insulin

LipolysisIncreased serum

osmolality

Ketosis

Anion Gap Acidosis

Osmotic Diuresis

Dehydration

Kushmaul breathing

Signs and SymptomsSigns and Symptoms

Key Features of DKA� Hyperglycemia� Anion gap metabolic acidosis� Ketonuria� Dehydration, secondary tachycardia and hypotensionhypotension

� Polyuria, polydipsia � Increased serum:urine osmolarity� Kussmaul's respiration; fruity acetone breath� Normal to low temperature� Hyperkalemia� Hyponatremia

Diabetic Ketoacidosis

� Hyperglycemia

� Metabolic acidosis with ketosis

� Fluid and electrolyte imbalance

� Altered mental state� Altered mental state� Only 10% in coma; 20% clear mentated

� Hypothermia may be present, but fever not due to DKA

� Look for precipitating event!

Hyperglycemic Hyperosmolar Non-Ketotic Syndrome (HONK, HHNS)

� Similar to DKA except hepatic ketogenesis is inhibited (insulin presence)

� Symptoms similar to DKA without ketosis and acidosis

� Hyperglycemia (and hyperosmolality) often � Hyperglycemia (and hyperosmolality) often worse (syndrome usually persists longer before seeking treatment; +/- renal impairment)

� Mortality higher than DKA� Larger volume deficit

Hypo or Hyper?

� Coma may occur in either

� Cold, clammy and shaky vs volume depleted, acidotic

� When in doubt?� When in doubt?

� Coma…look for other causes

Fluid and Electrolyte Impairment

� Dry, dry, dry

� Overall loss of sodium, potassium, chloride, phosphate and magnesium but serum levels often elevated due to serum levels often elevated due to hypovolemia or shifts

Management of DKA

� ABC’s with fluid resuscitation

� Insulin

� Electrolyte replacement

� Lab monitoring� Lab monitoring

Critical Lab Monitoring

• Glucose

• Sodium

• Bicarbonate

• Anion Gap• Anion Gap– Albumin

– Chloride

Osmolality

Calculated Osmolality

= (2 X Na + urea + Glucose + [EtoH])

Increased blood sugar, ketones

Water moves from cells to plasma

Increased serum

osmolality

Hyperosmolar diuresis leads to dehydration and dilutional reduction in sodium

Sodium

� High or low

� Mild dilutional hyponatremia common

� High sodium in severe dehydration

� Net sodium deficit due to urinary loss � Net sodium deficit due to urinary loss (bound to ketones)

� Sodium can be falsely low with hyperglycemia

� Recalculate prior to changing IV infusion

Sodium Correction

� Several methods used

� Correction of sodium for hyperglycemia to identify underlying sodium deficit

� For every 10 mmol/L rise in blood glucose > 8 � For every 10 mmol/L rise in blood glucose > 8 mmol/L, upwardly correct Na by 3 mmol/L

Sodium Correction

Glucose-8 X 3 + Na10

Sodium Correction

Na = 138

Glucose = 49

What is the corrected sodium?

Sodium Correction

Na = 138

Glucose = 49

Glucose-8 X 3 + Na10

Sodium Correction

Na = 138

Glucose = 49

49-8 X 3 + 13810

Corrected Sodium

Na = 150

Chloride

� Net chloride loss is often less than sodium (not bound to ketones)

� Hyperchloremia commonly develops following fluid resuscitation with 0.9% following fluid resuscitation with 0.9% NaCl

� Vomiting causes loss of chloride ions (favouring alkalosis)� Mixed picture

Potassium� May have normal, hyper or hypokalemia (20%)

� Deficit usual present due to diuresis, GI loss and dehydration induced aldosterone releaserelease

Potassium� Insulin deficit causes shift from cells:

� May present with hyperkalemia despite overall deficit

� Renal impairment may be associated with hypekalemiahypekalemia

Ketones

• In DKA, beta hydroxybutyrate to acetacetate ratio is 3:1

• Most labs measure acetoacetate (nitroprusside reagent test strip)

• Ketonuria may be under-detected in early DKA• Ketonuria may be under-detected in early DKA• Insulin converts beta-hydroxybutyrate to acetoacetate, increasing ketonuria during recovery

• Ketonuria detection ~36 hours post stabilization; poor marker of resolution

Anion gap is calculated when metabolic acidosis is diagnosed, to help narrow down the possible cause.

Anion Gap =

Assessment of Metabolic Acidosis

Anion Gap =

Cations (+ charges) – Anions (- charges)

Measured Cations Measured Anions

Sodium

Potassium

chloride

bicarb

Total Cations:

135-145

3.5-5.0

98-107

22-29

Total Cations: Total Anions:

144 mmol/L 130 mmol/L

Normal = ~7-15 (if K is included)

-

Normal = ~3-11 (if K excluded)

Measured Charges:

Cations > Anions

Unmeasured Anions (-) Unmeasured Cations (+)protein 15 mmol/L potassium 4.5 mmol/LPO4 2 mmol/L calcium 5.0 mmol/LSO4 1 mmol/L magnesium 1.5 mmol/Lorganic acids 5 mmol/L

Total 23 mmol/L Total 11 mmol/L

Unmeasured Charges:

Anions > Cations

An increased anion (fewer measured negatives) usually indicates there are more unmeasured negatives.

Anion Gap AcidosisPossible sources for unmeasured anions (causes for increased anion gap acidosis > 15):

“MUDPILERS”�Methanol� Uremia� Uremia� Diabetic ketoacidosis� Paraldehyde� Isoniazide/iron� Lactate� Ethylene glycol� Rhabdomyolysis� Salicylates

Na 144

K 5.2

Cl 95

144

104

40

Is this an anion gap acidosis?

HCO3 9

Glucose 45

104

Na 144

K 3.2

Cl 118

144

136

8


HCO3 18136

Unmeasured Anions (-) Unmeasured Cations (+)protein 15 mmol/L potassium 4.5 mmol/LPO4 2 mmol/L calcium 5.0 mmol/LSO4 1 mmol/L magnesium 1.5 mmol/Lorganic acids 5 mmol/L

Total 23 mmol/L Total 11 mmol/L

6.5

What is the effect of a low albumin?

Na 144

K 3.2

Cl 118

144

136

8


HCO3 18

Albumin 11

136

Corrected:

8 + 2.5 (3) = 15.5

Decreased or Falsely Normal Anion Gap Acidosis

� Decreased measured cations (e.g., sodium)

� Low serum protein � Low serum protein � Causes decrease in number of unmeasured protein anions

� If anion gap is normal, other unmeasured anions must be present

In ketoacidosis:

• Insulin decreases ketosis

• Ketones excreted with hydrogen or ammonium reduce ketosis and acidosisammonium reduce ketosis and acidosis

• Ketones also excreted with sodium or potassium (causing loss of bicarb precursors); acidosis persists despite reduction in anion gap

In ketoacidosis:

� Hyperchloremia (0.9% NaCl administration) a common cause of non-anion gap acidosis

� Non-anion gap acidosis very common for day or two post resolution of DKA (due to potential two post resolution of DKA (due to potential bicarb loss and chloride administration)

• Anion gap increases by 1 for every decrease in bicarbonate with ketoacidosis

• An anion gap increase > fall in bicarb suggests additional organic acids present (e.g., lactate)

Na 144

K 4.6

Cl 114

HCO3 8

144

122

22


HCO3 8

Albumin 38

122

Normal bicarb (24) – Actual bicarb (10) = 14

Measured gap (22) – Normal gap (8) = 14

AG = bicarb deficit

Na 149

K 5.2

Cl 108

149

114

35

Is this anion gap due to ketoacidosis?

HCO3 6

Glucose 35

Albumin 38

114



AG > bicarb deficit

Na 142

K 4.0

Cl 119

142

136

6


HCO3 17

Glucose 12

136



Bicarb deficit > AG

Treatment Principles

� ABCs with fluid resuscitation� Rehydration reduces hepatic glucose production, promotes insulin action and renal glucose clearance.renal glucose clearance.

� Insulin (stop ketogenesis, liploysis and gluconeogenesis)

� Assess potassium or add to IV empirically if producing urine

Treatment Principles

� Fluid and electrolye replacement

� Correct blood pH

� Monitor glucose q 1 h and lytes q2h for patient in shockpatient in shock

� Monitor bicarbonate, anion gap and calculated osmolality

Osmolality:

2(Na) + urea + glucose2(Na) + urea + glucose

Rapid reduction in osmolality

(rapid reduction of Na or glucose)

Water moves from plasma to interstitium and cells

Decreased

osmolality

Cerebral edema can occur

Glucose Correction

� Insulin 0.1 unit/kg IV bolus plus� Insulin 0.1 unit/kg/h infusion

� Higher doses exceed insulin saturation capacitycapacity

� Q 1 H blood sugar checks (lab)

� Double infusion if glucose has not dropped after first hour

� Double again once if glucose has not dropped in second hour

Glucose Correction

� SC regimen with insulin Lispo for non-shock patients

� Requires hourly blood sugar measurementmeasurement

� 0.3 u/kg SC bolus, then 0.1 u/kg q 1h until glucose 13-15 mmol/L

Glucose Correction

� Goal: 3-5 mmol/L/hr reduction

� If glucose falls > 5 mmol/L, reduce infusion (do not stop)

� Add 5% dextrose to saline once glucose � Add 5% dextrose to saline once glucose ~15-16 mmol/l

Glucose Correction

� Correct to 10-12 mmol/L; avoid lower levels in first 24 hours

� DO NOT use Intensive Insulin protocol for DKAfor DKA

� When glucose <13-15 mmol/L, anion gap is < 12, bicarb > 18 and patient eating, return to usual insulin Rx

� Continue infusion 1-2 hours after initial sliding scale dose

Fluid Replacement

� 5-8 L average loss; aggressive replacement to maintain MBP >70 and adequate urine output

� Start with 0.9% NaCl (correct Na � Start with 0.9% NaCl (correct Na deficit, protects against rapid reduction in osmolality) � Hypernatremia usually volume deficit

� 4-15 mL/kg/hr; usually 1 L/hour for average adult

Fluid Replacement

� Conversion to 0.9% NaCl after volume deficit replaced

� Additional of 40 mmol KCl/L IV increases osmolality of solution and will increases osmolality of solution and will delay correction of hyperosmolality

� 0.45 % NaCl with 40 mmol KCl/L or Ringers following hemodynamic stabilization and correction of defict

Saline

� 0.9% � 154 mmol sodium and chloride/L, 300 mosmol

� 0.45%� 0.45%� 77 mmol sodium and chloride/L

� 0.25%� 39 mmol sodium and chloride/L

Saline

� Lactated Ringers� 130 mmol sodium and 109 mmol chloride/L

� 28 mmol lactate, 4 mmol potassium� 28 mmol lactate, 4 mmol potassium

Goals

� Slow downward correction in sodium if hypernatremic

� If sodium rising or not improving after rehydration, consider Ringers or 0.45% rehydration, consider Ringers or 0.45% NaCl

� Recheck corrected sodium before downscaling sodium

Potassium

� Insulin and rehydration will lower potassium

� Add 20 mmol/L if K < 5.5 and patient producing urine with initial producing urine with initial resuscitation; bolus prn

� Safer to add K if potassium value unknown

Phosphate

� May be low, treatment controversal except� If low at presentation should be treated (insulin will drop it further)(insulin will drop it further)

� Monitor phosphate and magnesium and treat according to usual protocol

Acidosis

� Corrects slowly, hours post glucose normalization

� Ketosis corrects faster than hyperchloremic acidosishyperchloremic acidosis� Acidosis may persist after anion gap is corrected

� Anion gap is best method of determining that ketosis is corrected

Acidosis

� Avoid bicarb, not usually given unless pH <7.00 or patient has life-threatening hyperkalemia

� Bicarb administration increase CO2 � Bicarb administration increase CO2 production with drop in cerebral pH as CO2 crosses blood brain barrier

� Alkali administration may slow resolution of ketosis and/or cause alkalosis

Acidosis

� Insulin administration key

� Continue insulin infusion until anion gap corrected; give additional glucose if needed to maintain blood glucoseneeded to maintain blood glucose

� Monitor pH (venous pH acceptable) and anion gap for resolution

Cerebral Edema

� Highest risk in children

� Rapid reduction of osmolality poses risk, bicarb administration associated with more cerebral edemamore cerebral edema

� Monitor for headache, lethargy, altered LOC

Cerebral Edema

� Consider 0.25-1 g/kg mannitol or 5-10 ml/kg 3% saline

� 70% mortality; 7-14% good neurological recoveryrecovery

Case 1

• 25 year old woman, 26 weeks gestation

• Flu like symptoms, vomiting and diarrhea

• Felt too unwell to eat, withheld insulin

• Resumed eating and insulin on following • Resumed eating and insulin on following day

• Still feeling week

Case 1

In ED:

• Glucose 16.8

• Lytes: Na 145 K 4.9 Cl 109 Bicarb 15

• 3+ ketones• 3+ ketones

• “Resolving DKA, resume diabetic management”

Corrected Na: ~148

Anion Gap: 21

Case 1

• Labs following day:

• Na 148 K 4.9 Cl 111 Bicarb 12

• Glucose 22

• Sleepy• Sleepy

Corrected Na: ~153

Anion Gap: 25

Case 1

� Treated as DKA with IV insulin, 0.9% Nacl with potassium replacement

� The following day:� Na 143 K 3.9 Cl 118 Bicarb 18� Na 143 K 3.9 Cl 118 Bicarb 18

� Concern regarding persistent acidosis

Anion Gap: 7

Bicarb Gap: 6

Case 2

• 28 year old woman, DMI since childhood

• “poor control”

• Admitted in coma with DKA

• Lab on admission:• Lab on admission:Glucose: 42Lytes: Na 144 K 5.1 Cl 108 Bicarb 8

• Ketones: 1+

Anion Gap: 28

Corrected Sodium: 152

Case 2

• Blood glucose drops to 3.5 after 12 hours

• Insulin infusion stopped and D50 administeredadministered

• Over next 12 hours, glucose < 8 mmol/L

• Bicarb dropping; anion gap widening

Case 3• 81 year old woman, DMI since 27

• Admitted in coma

• Blood glucose 36

• Na 148 K 5.5 Cl 110 Bicarb 4• Na 148 K 5.5 Cl 110 Bicarb 4

• What is her anion gap?

• Is this DKA alone?

Anion Gap: 34

Corrected Sodium: 156

Bicarb Gap: 20

Case 4

� 18 year old woman, DMI since age 12

� Well controlled

� Celebration

� Admitted with DKA� Admitted with DKA

� Transferred to Level 3 on Day 2

� CT shows no differentiation between grey and white

Summary

� Rehydration to restore and maintain MBP

� Initial resuscitation with 0.9% NaCl

� Maintain renal perfusion� Maintain renal perfusion

� Insulin bolus 0.1 unit/kg and continuous infusion 0.1 unit/kg/hr with potassium to IV

� Add potassium to IV unless hyperkalemic; monitor lytes q 1h

Summary

� Avoid glucose reduction > 5 mmol/L/hr

� Add dextrose to IV once glucose < 16 mmol/L

� Treat with insulin until glucose < 13-15; � Treat with insulin until glucose < 13-15; AG < 12, bicarb > 18 and eating

� Continue IV insulin 1-2 hours after initial SC

Summary

� DO NOT STOP INSULIN

� DO NOT USE INSULIN PROTOCOL DURING ACUTE PHASE

References

� Kitabchi (2006). Hyperglycemic crisis in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. Diabetes Association. Diabetes Care. 29:2739.

� Kitabchi (2009). Treatment of diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults. Uptodate on-line. Last update: May 1, 2009.

Documents

DKA - The Canadian Association of Critical Care Nurses