This document discusses diabetic ketoacidosis (DKA). It defines DKA as a metabolic acidosis caused by the accumulation of ketones from severely low insulin levels. Key characteristics of DKA include hyperglycemia, low bicarbonate, acidosis, and ketonemia/ketonuria. The document outlines the pathophysiology of DKA, including how low insulin and high glucagon levels lead to increased ketone production and acidosis. Clinical presentation of DKA is also described.

1. DIABETICDIABETIC
KETOACIDOSISKETOACIDOSIS
DISHAN LOWEDISHAN LOWE
Consultant EndocrinologistConsultant Endocrinologist
General HospitalGeneral Hospital
KandyKandy

2. Diabetic KetoacidosisDiabetic Ketoacidosis
 Metabolic acidosis from the accumulationMetabolic acidosis from the accumulation
of ketones due to severely depressedof ketones due to severely depressed
insulin levelsinsulin levels
 Typically characterized by;Typically characterized by;
 Hyperglycemia (blood glucoseHyperglycemia (blood glucose>25>250 mg/dL)0 mg/dL)
 Low bicarbonate (<15 mEq/L)Low bicarbonate (<15 mEq/L)
 Acidosis (pH <7.30)Acidosis (pH <7.30)
 Ketonemia and ketonuriaKetonemia and ketonuria

3.  In the US:In the US:
 DKA seen primarily in type 1 DMDKA seen primarily in type 1 DM
 Incidence is roughly 2/100 patient years ofIncidence is roughly 2/100 patient years of
diabetes, with about 3% of type 1 diabeticdiabetes, with about 3% of type 1 diabetic
patients initially presenting with DKApatients initially presenting with DKA
 Mortality <5% in experienced centers .Mortality <5% in experienced centers .
Before the discovery of insulin in 1922,Before the discovery of insulin in 1922,
mortality rate was 100%mortality rate was 100%
 Mortality in HHS still remains high at 15%Mortality in HHS still remains high at 15%

4.  DKA tends to occur in individuals youngerDKA tends to occur in individuals younger
than 19 years, the more brittle type 1than 19 years, the more brittle type 1
diabetic patientsdiabetic patients
 May occur in type 1 and type 2 diabeticMay occur in type 1 and type 2 diabetic
patients of any agepatients of any age
 Most serious acute metabolicMost serious acute metabolic
complications of diabetes mellituscomplications of diabetes mellitus

5. Copyright ©2003 CMA Media Inc. or its licensors
Chiasson, J.-L. et al. CMAJ 2003;168:859-866
Schematic of the pathogenesis of diabetic ketoacidosis (DKA) and the hyperglycemic
hyperosmolar state (HHS)

6.  Diabetic ketoacidosis (DKA) and theDiabetic ketoacidosis (DKA) and the
Hyperglycemic Hyperosmolar State (HHS)Hyperglycemic Hyperosmolar State (HHS)
appear as 2 extremes in the spectrum ofappear as 2 extremes in the spectrum of
Diabetic DecompensationDiabetic Decompensation

7. Overlap of DKA/HHSOverlap of DKA/HHS
Findings in 612 patients admitted with hyperglycemia
0
20
40
60
DKA HHS Mixed
Wachtel et al. J Gen Int Med 6:495, 1991
%

8. Copyright ©2003 CMA Media Inc. or its licensors
Chiasson, J.-L. et al. CMAJ 2003;168:859-866

9. Pathophysiology of DKAPathophysiology of DKA
Relative/absolute insulin deficiencyRelative/absolute insulin deficiency
Elevations of insulin counterregulatoryElevations of insulin counterregulatory
hormones (ICRH)hormones (ICRH)
GlucagonGlucagon
Catecholamines (epinephrine, norepinephrine)Catecholamines (epinephrine, norepinephrine)
CortisolCortisol
Growth hormoneGrowth hormone

10. Pathogenesis of DKAPathogenesis of DKA
What causes hyperglycemia?What causes hyperglycemia?
What causes ketogenesis?What causes ketogenesis?

11. InsulinInsulin
Anabolic actionsAnabolic actions
Promotes glucose uptake in muscle and fatPromotes glucose uptake in muscle and fat
Stimulates glucose oxidationStimulates glucose oxidation
Regulates rates of hepatic glucose productionRegulates rates of hepatic glucose production
Stimulates glycogen formationStimulates glycogen formation
Stimulates protein synthesis and lipogenesisStimulates protein synthesis and lipogenesis
Increases lipoprotein lipase activityIncreases lipoprotein lipase activity
Inhibits catabolic processesInhibits catabolic processes
Inhibits glycogen breakdownInhibits glycogen breakdown
Inhibits gluconeogenesisInhibits gluconeogenesis
Inhibits protein breakdownInhibits protein breakdown
Inhibits lipolysisInhibits lipolysis
Inhibits ketogenesisInhibits ketogenesis

12. GlucagonGlucagon
 Inhibits insulin mediated glucoseInhibits insulin mediated glucose
uptakeuptake
 Stimulates gluconeogenesisStimulates gluconeogenesis
 Stimulates glycogenolysisStimulates glycogenolysis
 Inhibits lipogenesisInhibits lipogenesis
 Stimulates ketone formationStimulates ketone formation

13. Epi Increase EGP
Norepi Activates lipolysis
Inhibits insulin release
Decrease glucose uptake
Cortisol Increased EGP
Increase protein breakdown
Increase lipolysis
Growth Decrease glucose uptake
Hormone
Other Counterregulatory Hormones

14. Insulin deficiency
glucose uptake
(muscle/fat)
Glucagon excess
Proteolysis  Alanine
Lipolysis  glycerol
GNG
Hyperglycemia
Stimulates ketogenesis
Insulin deficiencyInsulin deficiency
glucose uptake
(muscle/fat)
Proteolysis  Alanine
Lipolysis  glycerol
Insulin deficiency

15. Pathogenesis of DKAPathogenesis of DKA
What causes acidosis?What causes acidosis?

16. Lipid and ketone metabolismLipid and ketone metabolism
Triglyceride
Activation of HSL
GlycerolMassive release
of FFA
Insulin deficiency
Increase ICRH
Glucagon
Substrate for GNG
Increase production
of ketone bodies by
the liver
Glucagon
+

17. Glucagon effect on ketoacid productionGlucagon effect on ketoacid production
Acetyl CoA Malonyl CoA FFAAcetyl CoA Malonyl CoA FFA
acetyl CoA carboxylaseacetyl CoA carboxylase
Low levels of malonyl CoA Increased CPT1Low levels of malonyl CoA Increased CPT1
Increase in CPT1 facilitates entry of FFA into theIncrease in CPT1 facilitates entry of FFA into the
mitochondria for oxidationmitochondria for oxidation
__

18. Outer Membrane
Inner Membrane
Mitochondrial matrix
Fatty Acyl CoA
CoASH
Carnitine Acyl carnitine
CPT1
CPT2
CoASH
Acetyl CoA
Fatty acid
β oxidation
Acyl CoA
Cytosol
Triglyceride synthesisMalonyl CoA
Ketone bodies

19. Keto-acidsKeto-acids
Beta-hydroxybutyrate and acetoacetatic acidBeta-hydroxybutyrate and acetoacetatic acid
 Weak acids that dissociate atWeak acids that dissociate at
physiologic pHphysiologic pH
 HH++ + HCO3- H2O and CO2+ HCO3- H2O and CO2
 Decrease in serum HCO3-Decrease in serum HCO3-
 Increase in Anion Gap approximatelyIncrease in Anion Gap approximately
equal to the decline in bicarbonateequal to the decline in bicarbonate
levelslevels

20. Keto-acidsKeto-acids
Beta-hydroxybutyrate and acetoacetatic acidBeta-hydroxybutyrate and acetoacetatic acid
Nitroprusside RXN:Nitroprusside RXN:
Acetest Test mainly forAcetest Test mainly for
Ketostix acetoacetateKetostix acetoacetate
Chemstrips UGKChemstrips UGK

21. MeasuringMeasuring
urine and serum ketonesurine and serum ketones
 Absence of a nitroprusside reaction does notAbsence of a nitroprusside reaction does not
eliminate the possibility of DKAeliminate the possibility of DKA
 Even a positive test can grossly underestimateEven a positive test can grossly underestimate
the severity of the DKAthe severity of the DKA
 Conversely, the persistence of or an increase inConversely, the persistence of or an increase in
ketones during therapy is not necessarily aketones during therapy is not necessarily a
manifestation of deteriorating clinical status, andmanifestation of deteriorating clinical status, and
may in fact be a sign of improvementmay in fact be a sign of improvement

22. Renal threshold for glucose ~ 180-200Renal threshold for glucose ~ 180-200
mg/dlmg/dl
Renal threshold for ketones is very lowRenal threshold for ketones is very low

23. Differential diagnosisDifferential diagnosis
 Starvation ketosisStarvation ketosis
 Alcoholic ketoacidosis (AKA)Alcoholic ketoacidosis (AKA)
 Other causes of high-anion gap metabolicOther causes of high-anion gap metabolic
acidosis;acidosis;
 lactic acidosislactic acidosis
 ingestion of drugs such as salicylate,ingestion of drugs such as salicylate,
methanol, ethylene glycol, and paraldehydemethanol, ethylene glycol, and paraldehyde
 chronic renal failurechronic renal failure

24. Precipitating factors forPrecipitating factors for
DKA/HHSDKA/HHS
New onset DM (8%)New onset DM (8%)
Omission of orOmission of or
inadequate dose ofinadequate dose of
insulin (21%)insulin (21%)
Any acute illnessAny acute illness
MI (5%)MI (5%)
Pancreatitis (5%)Pancreatitis (5%)
Infection (37%)Infection (37%)
Drugs/alcohol (10%)Drugs/alcohol (10%)
Insulin pumpInsulin pump
malfunctionmalfunction
Luteal phase decreaseLuteal phase decrease
in insulin sensitivityin insulin sensitivity
HypovolemiaHypovolemia
Unknown (14%)Unknown (14%)

25. Clinical presentation
 Ketoacidosis usually evolve in <24 hrsKetoacidosis usually evolve in <24 hrs
 May evolve or develop more acutelyMay evolve or develop more acutely
 May present in DKA with no prior clues orMay present in DKA with no prior clues or
symptomssymptoms

26.  For both DKA and HHS, the classicalFor both DKA and HHS, the classical
clinical picture includesclinical picture includes;;
 a history of polyuria, polydipsia, polyphagia,a history of polyuria, polydipsia, polyphagia,
 weight loss,weight loss,
 vomiting,vomiting,
 abdominal pain (only in DKA),abdominal pain (only in DKA),
 dehydration,dehydration,
 weakness,weakness,
 clouding of sensoria, and finally comaclouding of sensoria, and finally coma

27.  Physical findings may include poor skin turgor,Physical findings may include poor skin turgor,
Kussmaul respirations (in DKA), tachycardia,Kussmaul respirations (in DKA), tachycardia,
hypotension, alteration in mental status, shock,hypotension, alteration in mental status, shock,
and ultimately coma (more frequent in HHS).and ultimately coma (more frequent in HHS).
 A normal or elevated temperature may indicateA normal or elevated temperature may indicate
underlying infectionunderlying infection primarily because ofprimarily because of
peripheral vasodilationperipheral vasodilation
 Hypothermia, if present, is a poor prognosticHypothermia, if present, is a poor prognostic
sign*sign*
* Matz R: Hypothermia in diabetic acidosis. Hormones 3:36–41, 1972

28.  Up to 25% of DKA patients have emesis,Up to 25% of DKA patients have emesis,
which may be coffee-ground inwhich may be coffee-ground in
appearance.appearance.
 Endoscopy has related this finding to theEndoscopy has related this finding to the
presence of hemorrhagic gastritispresence of hemorrhagic gastritis

29. Abdominal PainAbdominal Pain
in Decompensated DMin Decompensated DM
Infrequent with HCO3- > 10 meq/LInfrequent with HCO3- > 10 meq/L
No correlation with degree ofNo correlation with degree of
hyperglycemia or dehydrationhyperglycemia or dehydration
May be related to precipitating eventMay be related to precipitating event
Campbell et al. JAMA 233:66, 1975Campbell et al. JAMA 233:66, 1975

30. Level of consciousness is related to theLevel of consciousness is related to the
severity of the serum osmolarity inseverity of the serum osmolarity in
DKA/HHSDKA/HHS
250
300
350
400
1 2 3 4
Fulop et al. Lancet 2:635, 1973
Glasgow Coma scale

31.  Occurrence of coma in diabetic patients in theOccurrence of coma in diabetic patients in the
absence of definitive elevation of effectiveabsence of definitive elevation of effective
osmolality ≥320 mOsm/kg demandsosmolality ≥320 mOsm/kg demands
immediate consideration of other causes ofimmediate consideration of other causes of
such change.such change.
 Effective osmolality may be calculated by theEffective osmolality may be calculated by the
following formula:following formula:
2[measured Na (mEq/l)] + glucose (mg/dl)/182[measured Na (mEq/l)] + glucose (mg/dl)/18

32. Initial laboratory evaluation of patients withInitial laboratory evaluation of patients with
suspected DKA or HHS should includesuspected DKA or HHS should include
 plasma glucoseplasma glucose
 blood urea/creatinineblood urea/creatinine
 serum ketonesserum ketones
 electrolytes (withelectrolytes (with
calculated anion gap)calculated anion gap)
 osmolalityosmolality
 UrinalysisUrinalysis
 urine ketones byurine ketones by
dipstickdipstick
 arterial blood gasesarterial blood gases
 complete blood countcomplete blood count
with differentialwith differential
 electrocardiogram.electrocardiogram.

33.  Bacterial culturesBacterial cultures of urine, blood, and throat,of urine, blood, and throat,
etc., should be obtained and appropriateetc., should be obtained and appropriate
antibiotics given if infection is suspected.antibiotics given if infection is suspected.
 CXRCXR should also be obtained if indicated.should also be obtained if indicated.
 HbA1cHbA1c may be useful in determiningmay be useful in determining
◊◊culmination of an evolutionary process inculmination of an evolutionary process in
previously undiagnosed or poorly controlledpreviously undiagnosed or poorly controlled
diabetesdiabetes
◊◊truly acute episode in an otherwisetruly acute episode in an otherwise well-well-
controlled patientcontrolled patient

34. FINDINGFINDING CAUSE/SCAUSE/S
LeukocytosisLeukocytosis Proportional to blood ketone bodyProportional to blood ketone body
concentration, Infectionconcentration, Infection
Hyponatraemia*Hyponatraemia* Osmotic flux of water from theOsmotic flux of water from the
intracellular to the extracellular space,intracellular to the extracellular space,
Severe hypertriglyceridemiaSevere hypertriglyceridemia
HypokalaemiaHypokalaemia Extracellular shift of potassium caused byExtracellular shift of potassium caused by
insulin deficiency, hypertonicity, andinsulin deficiency, hypertonicity, and
acidemiaacidemia
Elevated AmylaseElevated Amylase Non-pancreatic sources, such as theNon-pancreatic sources, such as the
parotid glandparotid gland
* Serum Na should be corrected for hyperglycemia (for each 100 mg/dl
glucose >100 mg/dl, add 1.6 mEq to sodium value for corrected Na value)

35. TreatmentTreatment
 The success of treatment of DKA andThe success of treatment of DKA and
HHS depends on;HHS depends on;
 Adequate correction ofAdequate correction of dehydrationdehydration,,
hyperglycemiahyperglycemia,, ketoacidosisketoacidosis andand electrolyteelectrolyte
deficitsdeficits
 Identification & treatment of anyIdentification & treatment of any comorbidcomorbid
precipitating eventsprecipitating events
 Frequent patientFrequent patient monitoringmonitoring

37. Fluid therapyFluid therapy
 Objective is to expand extracellularObjective is to expand extracellular
volume and restore renal perfusionvolume and restore renal perfusion
 Start with infusion of isotonic salineStart with infusion of isotonic saline
 (0.9% NaCl) at a rate of 15–20 mL/kg per hour(0.9% NaCl) at a rate of 15–20 mL/kg per hour
during the first hour (1–1.5 L in the averageduring the first hour (1–1.5 L in the average
adult)adult)

38.  Subsequent choice of fluid replacementSubsequent choice of fluid replacement
depends on the state of hydration,depends on the state of hydration,
electrolyte levels and urinary output.electrolyte levels and urinary output.
 InfuseInfuse 0.45% Nacl0.45% Nacl at a rate of 4–14 mL/kgat a rate of 4–14 mL/kg
per hour if theper hour if the correctedcorrected serum Na isserum Na is
normal or elevatednormal or elevated..
 0.9% NaCl0.9% NaCl at a similar rate is appropriateat a similar rate is appropriate
if correctedif corrected serum Na is lowserum Na is low

39.  Successful progress with fluidSuccessful progress with fluid
replacement is judged by;replacement is judged by;
 hemodynamic monitoring (improve BP)hemodynamic monitoring (improve BP)
 measurement of fluid input/outputmeasurement of fluid input/output
 clinical examinationclinical examination
 Fluid replacement should correctFluid replacement should correct
estimated deficits within the first 24 h.estimated deficits within the first 24 h.
 Induced change in s osmolality should notInduced change in s osmolality should not
exceed 3 mOsm · kg-1 H2O · h-1exceed 3 mOsm · kg-1 H2O · h-1

40.  When the plasma glucose level reachesWhen the plasma glucose level reaches
250mg/dl, change to250mg/dl, change to 5% dextrose5% dextrose withwith
0.45% Nacl infused at 150-250 ml/hr0.45% Nacl infused at 150-250 ml/hr

41. Paediatric patients (<20 yrs of age)Paediatric patients (<20 yrs of age)
 The 1st hr of fluids should be isotonicThe 1st hr of fluids should be isotonic
saline at 10–20 ml · kg-1 · h-1.saline at 10–20 ml · kg-1 · h-1.
 Initial reexpansion should not exceed 50Initial reexpansion should not exceed 50
ml/kg over the first 4 h of therapy.ml/kg over the first 4 h of therapy.
 Replace fluid deficit evenly over 48 hReplace fluid deficit evenly over 48 h
 In general, 0.45–0.9% NaCl (dependingIn general, 0.45–0.9% NaCl (depending
on serum Na ) infused at a rate of 1.5on serum Na ) infused at a rate of 1.5
times the 24-h maintenancetimes the 24-h maintenance
requirements ( 5 ml · kg-1 · h-1) willrequirements ( 5 ml · kg-1 · h-1) will
accomplish a smooth rehydrationaccomplish a smooth rehydration

42. Potassium therapyPotassium therapy
 The treatment of DKA and HHS withThe treatment of DKA and HHS with
rehydration and insulin is typicallyrehydration and insulin is typically
associated with a rapid decline in theassociated with a rapid decline in the
plasma K concentration, particularly duringplasma K concentration, particularly during
the first few hours of therapythe first few hours of therapy

43. Causes of hypokalaemiaCauses of hypokalaemia
 insulin-mediated re-entry of potassium intoinsulin-mediated re-entry of potassium into
the intracellular compartmentthe intracellular compartment
 extracellular fluid volume expansionextracellular fluid volume expansion
 correction of acidosiscorrection of acidosis
 continued potassium loss owing tocontinued potassium loss owing to
osmotic diuresis and ketonuriaosmotic diuresis and ketonuria

44.  Because treatment will rapidly induceBecause treatment will rapidly induce
decreased serum K concentrations, Kdecreased serum K concentrations, K
replacement must be initiated as soon asreplacement must be initiated as soon as
levels falllevels fall below 5.0 mmol/Lbelow 5.0 mmol/L, assuming, assuming
urine output is adequateurine output is adequate
 It is recommended thatIt is recommended that 20–30 mmol of K20–30 mmol of K
be added to each litrebe added to each litre of infusion fluid toof infusion fluid to
maintainmaintain K concentration 4 - 5 mmol/LK concentration 4 - 5 mmol/L

45.  If serum K level isIf serum K level is << 3.3 mmol/L3.3 mmol/L, K, K
replacement should be startedreplacement should be started
immediately with fluid therapyimmediately with fluid therapy
 Initiation of insulin should be delayed untilInitiation of insulin should be delayed until
K is restored toK is restored to >>3.3 mmol/L, in order to3.3 mmol/L, in order to
avoid arrhythmia, cardiac arrest andavoid arrhythmia, cardiac arrest and
respiratory muscle weaknessrespiratory muscle weakness

46.  Initially, the serum K level should beInitially, the serum K level should be
measured every 1–2 hrs because the mostmeasured every 1–2 hrs because the most
rapid change occurs during the first 5 hrsrapid change occurs during the first 5 hrs
of treatment.of treatment.
 After that, it should be measured every 4–After that, it should be measured every 4–
6 hrs as indicated clinically6 hrs as indicated clinically

47. Insulin therapyInsulin therapy
 Consensus is that, in DKA & HHS, regularConsensus is that, in DKA & HHS, regular
insulin should be administered byinsulin should be administered by
continuous iv infusion in small dosescontinuous iv infusion in small doses
through an infusion pumpthrough an infusion pump
 Low-dose insulin provides;Low-dose insulin provides;
 More physiologic insulin concentrationsMore physiologic insulin concentrations
 More gradual and steady fall in plasmaMore gradual and steady fall in plasma
glucose levelsglucose levels
 Decreased risk of hypoglycemia andDecreased risk of hypoglycemia and
hypokalemiahypokalemia

48.  As soon as hypokalemia (K < 3.3 mmol/L)As soon as hypokalemia (K < 3.3 mmol/L)
excluded, continuous infusion of regularexcluded, continuous infusion of regular
insulin can be started at a dose of 0.1insulin can be started at a dose of 0.1
U/kg per hourU/kg per hour
 This should produce a gradual decreaseThis should produce a gradual decrease
in the plasma glucose level of 3–4 mmol/Lin the plasma glucose level of 3–4 mmol/L
per hourper hour

49.  There is evidence that an iv bolus ofThere is evidence that an iv bolus of
insulin is not necessary. However, a bolusinsulin is not necessary. However, a bolus
may be used at the start of insulin therapy,may be used at the start of insulin therapy,
particularly if insulin treatment has beenparticularly if insulin treatment has been
delayed.delayed.
 In unusual circumstances where ivIn unusual circumstances where iv
administration is not possible, the im or scadministration is not possible, the im or sc
route has been used effectively. However,route has been used effectively. However,
poor perfusion will impair absorption ofpoor perfusion will impair absorption of
insulin.insulin.

50.  If the glucose level does not decline by 3If the glucose level does not decline by 3
mmol/L in the first hour, the hydrationmmol/L in the first hour, the hydration
status should be checked;status should be checked;
 if it is acceptable, the insulin dose shouldif it is acceptable, the insulin dose should
bebe doubled every hourdoubled every hour until a decrease ofuntil a decrease of
3–4 mmol/L per hour3–4 mmol/L per hour in the plasmain the plasma
glucose level is observedglucose level is observed

51.  When the plasma glucose level reachesWhen the plasma glucose level reaches
12–14 mmol/L, the12–14 mmol/L, the insulin infusion rateinsulin infusion rate
may be decreased by 50%may be decreased by 50% as 5%as 5%
dextrose is addeddextrose is added
 Thereafter, the insulin infusion dose mustThereafter, the insulin infusion dose must
be adjusted to maintain the plasmabe adjusted to maintain the plasma
glucose value in the range of 150 –glucose value in the range of 150 –
200mg/dl until the acidosis in DKA (or the200mg/dl until the acidosis in DKA (or the
clouded consciousness andclouded consciousness and
hyperosmolality in HHS) have beenhyperosmolality in HHS) have been
resolvedresolved

52.  It takes longer to correct ketonuria thanIt takes longer to correct ketonuria than
hyperglycemia.hyperglycemia.
 Because ß-hydroxybutyric acid is theBecause ß-hydroxybutyric acid is the
prevalent ketoacid and is graduallyprevalent ketoacid and is gradually
converted to acetoacetic acid, theconverted to acetoacetic acid, the
correction of ketonuria is underestimatedcorrection of ketonuria is underestimated
when measured by the nitroprussidewhen measured by the nitroprusside
methodmethod

53.  Measurement ofMeasurement of serum ß-hydroxybutyricserum ß-hydroxybutyric
acid levels using a reagent strip and aacid levels using a reagent strip and a
reflectance meter has been validatedreflectance meter has been validated
 Offers the possibility of bedside diagnosisOffers the possibility of bedside diagnosis
with better follow-up parameters ofwith better follow-up parameters of
hyperketonemia during treatmenthyperketonemia during treatment

54.  Once the ketoacidosis in DKA has beenOnce the ketoacidosis in DKA has been
correctedcorrected (plasma glucose level < 11.0(plasma glucose level < 11.0
mmol/L, serum bicarbonate level ≥18mmol/L, serum bicarbonate level ≥18
mmol/L, venous pH > 7.3 and anion gap <mmol/L, venous pH > 7.3 and anion gap <
12 mmol/L), the clouded consciousness12 mmol/L), the clouded consciousness
and hyperosmolality in HHS haveand hyperosmolality in HHS have
resolved, and patients are able to takeresolved, and patients are able to take
fluids orally)fluids orally),, a multidose insulin regimena multidose insulin regimen
may be initiated based on the patient'smay be initiated based on the patient's
treatment before DKA or HHS developedtreatment before DKA or HHS developed

55. PhosphatePhosphate
 Despite whole-body phosphate deficits inDespite whole-body phosphate deficits in
DKA , serum phosphate is often normal orDKA , serum phosphate is often normal or
increased at presentation. Phosphateincreased at presentation. Phosphate
concentration decreases with insulinconcentration decreases with insulin
therapy.therapy.
 Prospective randomized studies haveProspective randomized studies have
failed to show any beneficial effect offailed to show any beneficial effect of
phosphate replacement on the clinicalphosphate replacement on the clinical
outcome in DKAoutcome in DKA

56.  However, to avoid cardiac and skeletalHowever, to avoid cardiac and skeletal
muscle weakness and respiratorymuscle weakness and respiratory
depression due to hypophosphatemia,depression due to hypophosphatemia,
careful phosphatecareful phosphate replacement mayreplacement may
sometimes be indicated in patients withsometimes be indicated in patients with
cardiac dysfunction, anemia, or respiratorycardiac dysfunction, anemia, or respiratory
depression and in those with serumdepression and in those with serum
phosphate concentration <1.0 mg/dl.phosphate concentration <1.0 mg/dl.

57.  When needed, 20–30 mEq/l potassiumWhen needed, 20–30 mEq/l potassium
phosphate can be added to replacementphosphate can be added to replacement
fluids.fluids.
 Overzealous phosphate therapy canOverzealous phosphate therapy can
causecause severe hypocalcemiasevere hypocalcemia with nowith no
evidence of tetanyevidence of tetany

58. BicarbonateBicarbonate
 Bicarbonate use in DKA remains controversial.Bicarbonate use in DKA remains controversial.
 At a pH >7.0, reestablishing insulin activityAt a pH >7.0, reestablishing insulin activity
blocks lipolysis and resolves ketoacidosisblocks lipolysis and resolves ketoacidosis
without any added bicarbonate.without any added bicarbonate. Studies failed toStudies failed to
show either beneficial or deleterious changes inshow either beneficial or deleterious changes in
morbidity or mortality with bicarbonate therapy inmorbidity or mortality with bicarbonate therapy in
DKA patients with pH between 6.9 - 7.1DKA patients with pH between 6.9 - 7.1
 No studies concerning the use of bicarbonate inNo studies concerning the use of bicarbonate in
DKA with pH values <6.9 have been reported.DKA with pH values <6.9 have been reported.

59. Severe acidosis may lead to adverseSevere acidosis may lead to adverse
vascular effectsvascular effects
RECOMMENDATIONS
PH HCO3 Infusion Rate
>7 No HCO3
6.9 - 7 50 mmol in 200ml water 200ml/hr
<6.9 100 mmol in 400ml water 200ml/hr
---

60.  Venous pH should be assessed every 2 hVenous pH should be assessed every 2 h
until the pH rises to 7.0, & treatmentuntil the pH rises to 7.0, & treatment
should be repeated every 2 h if necessaryshould be repeated every 2 h if necessary
 In the paediatric patient, If pH remainsIn the paediatric patient, If pH remains
<7.0 after the initial hour of hydration, it<7.0 after the initial hour of hydration, it
seems prudent to administer 1–2 mEq/kgseems prudent to administer 1–2 mEq/kg
HCO3 over the course of 1 h. This HCO3HCO3 over the course of 1 h. This HCO3
can be added to NaCl, with any requiredcan be added to NaCl, with any required
K, to produce a solution that does notK, to produce a solution that does not
exceed 155 mEq/l sodium.exceed 155 mEq/l sodium.

61. COMPLICATIONS OF THERAPYCOMPLICATIONS OF THERAPY
 HypoglycemiaHypoglycemia - overzealous Rx with insulin- overzealous Rx with insulin
 HypokalemiaHypokalemia due to insulin & treatment ofdue to insulin & treatment of
acidosis with bicarbonateacidosis with bicarbonate
 HyperglycemiaHyperglycemia secondary tosecondary to
interruption/discontinuance of iv insulin therapyinterruption/discontinuance of iv insulin therapy
after recoveryafter recovery
 HyperchloremiaHyperchloremia caused by the use of excessivecaused by the use of excessive
salinesaline
 Transient non-anion gap metabolic acidosisTransient non-anion gap metabolic acidosis asas
ClCl‾‾ from iv fluids replaces ketoanions lost as Nafrom iv fluids replaces ketoanions lost as Na
& K salts during osmotic diuresis& K salts during osmotic diuresis

62.  HypoxemiaHypoxemia
 noncardiogenicnoncardiogenic pulmonary oedemapulmonary oedema
 Cerebral OedemaCerebral Oedema
 Hypoxemia is attributed to a reduction in colloidHypoxemia is attributed to a reduction in colloid
osmotic pressure that results in increased lungosmotic pressure that results in increased lung
water content and decreased lung compliance.water content and decreased lung compliance.
Patients with DKA who have a widened alveolo-Patients with DKA who have a widened alveolo-
arteriolar oxygen gradient noted on initial bloodarteriolar oxygen gradient noted on initial blood
gas measurement or with pulmonary rales ongas measurement or with pulmonary rales on
physical examination appear to be at higher riskphysical examination appear to be at higher risk
for the development of pulmonary edemafor the development of pulmonary edema
COMPLICATIONS OF THERAPYCOMPLICATIONS OF THERAPY

63. Cerebral edema in DKACerebral edema in DKA
More common in children and young adultsMore common in children and young adults
Incidence ~ 1%Incidence ~ 1%
Accounts for 31% of deaths associated with DKAAccounts for 31% of deaths associated with DKA
Heralded by development of a headache andHeralded by development of a headache and
increasing lethargyincreasing lethargy
Develops 4-12 hours after initiation of treatmentDevelops 4-12 hours after initiation of treatment
Proposed risk factors:Proposed risk factors:
Low pCOLow pCO22 ( 15 mm Hg) and elevated urea nitrogen( 15 mm Hg) and elevated urea nitrogen
(>21 mg/dl) at presentation(>21 mg/dl) at presentation
Treatment with bicarbonateTreatment with bicarbonate
Too rapid correction of dehydrationToo rapid correction of dehydration

64. Once the clinical symptoms other thanOnce the clinical symptoms other than
lethargy and behavioural changes occur,lethargy and behavioural changes occur,
mortality is high (>70%)mortality is high (>70%)
Only 7–14% of patients recover withoutOnly 7–14% of patients recover without
permanent morbiditypermanent morbidity
Cerebral Oedema in DKACerebral Oedema in DKA

65. Mechanism of Cerebral OedemaMechanism of Cerebral Oedema
 Not knownNot known
 Likely results from osmotically drivenLikely results from osmotically driven
movement of water into the centralmovement of water into the central
nervous system when plasma osmolalitynervous system when plasma osmolality
declines too rapidly with the treatment ofdeclines too rapidly with the treatment of
DKA or HHS.DKA or HHS.
 There is a lack of information on theThere is a lack of information on the
morbidity associated with cerebral edemamorbidity associated with cerebral edema
in adult patientsin adult patients

66. Prevention and treatment of cerebralPrevention and treatment of cerebral
edemaedema
PreventionPrevention
Gradual replacement of Na & HGradual replacement of Na & H22 O deficitsO deficits
Once plasma glucose of 200-250 mg/dlOnce plasma glucose of 200-250 mg/dl
achieved, maintain at this level with 5%achieved, maintain at this level with 5%
dextrosedextrose
TreatmentTreatment
IV mannitol 1G/kg over 30 minutes, followedIV mannitol 1G/kg over 30 minutes, followed
by infusion to maintain plasma osmolalityby infusion to maintain plasma osmolality
and sustain osmotic diuresis of waterand sustain osmotic diuresis of water

67. Strategies to Prevent Diabetic Ketoacidosis
Diabetic education
Blood glucose monitoring
Sick-day management
Home monitoring of ketones or beta-hydroxybutyrate
Supplemental short-acting insulin regimens
Easily digestible liquid diets when sick
Reducing, rather than eliminating, insulin when patients are
not eating
Guidelines for when patients should seek medical attention
Case monitoring of high-risk patients
Special education for patients on pump management