diabetic ketoacidosis
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DIABETIC DIABETIC KETOACIDOSISKETOACIDOSIS
DISHAN LOWEDISHAN LOWEConsultant EndocrinologistConsultant Endocrinologist
General HospitalGeneral HospitalKandyKandy
Diabetic Ketoacidosis Diabetic Ketoacidosis
Metabolic acidosis from the accumulation Metabolic acidosis from the accumulation of ketones due to severely depressed of 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
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 of Incidence is roughly 2/100 patient years of
diabetes, with about 3% of type 1 diabetic diabetes, 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%
DKA tends to occur in individuals younger DKA tends to occur in individuals younger than 19 years, the more brittle type 1 than 19 years, the more brittle type 1 diabetic patientsdiabetic patients
May occur in type 1 and type 2 diabetic May occur in type 1 and type 2 diabetic patients of any agepatients of any age
Most serious acute metabolic Most serious acute metabolic complications of diabetes mellituscomplications of diabetes mellitus
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)
Diabetic ketoacidosis (DKA) and the Diabetic ketoacidosis (DKA) and the Hyperglycemic Hyperosmolar State (HHS) Hyperglycemic Hyperosmolar State (HHS) appear as 2 extremes in the spectrum of appear as 2 extremes in the spectrum of Diabetic DecompensationDiabetic Decompensation
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
%
Copyright ©2003 CMA Media Inc. or its licensors
Chiasson, J.-L. et al. CMAJ 2003;168:859-866
Pathophysiology of DKAPathophysiology of DKA
Relative/absolute insulin deficiency Relative/absolute insulin deficiency
Elevations of insulin counterregulatory Elevations of insulin counterregulatory hormones (ICRH)hormones (ICRH)
GlucagonGlucagonCatecholamines (epinephrine, norepinephrine)Catecholamines (epinephrine, norepinephrine)
CortisolCortisol
Growth hormoneGrowth hormone
Pathogenesis of DKAPathogenesis of DKA
What causes hyperglycemia?What causes hyperglycemia?
What causes ketogenesis?What causes ketogenesis?
InsulinInsulinAnabolic actionsAnabolic actions
Promotes glucose uptake in muscle and fatPromotes glucose uptake in muscle and fatStimulates glucose oxidationStimulates glucose oxidationRegulates rates of hepatic glucose productionRegulates rates of hepatic glucose productionStimulates glycogen formationStimulates glycogen formationStimulates protein synthesis and lipogenesis Stimulates protein synthesis and lipogenesis Increases lipoprotein lipase activityIncreases lipoprotein lipase activity
Inhibits catabolic processesInhibits catabolic processesInhibits glycogen breakdownInhibits glycogen breakdownInhibits gluconeogenesisInhibits gluconeogenesisInhibits protein breakdownInhibits protein breakdownInhibits lipolysisInhibits lipolysisInhibits ketogenesisInhibits ketogenesis
GlucagonGlucagon
Inhibits insulin mediated glucose Inhibits insulin mediated glucose uptakeuptake
Stimulates gluconeogenesisStimulates gluconeogenesis Stimulates glycogenolysisStimulates glycogenolysis Inhibits lipogenesisInhibits lipogenesis Stimulates ketone formationStimulates ketone formation
Epi Increase EGP Norepi Activates lipolysis
Inhibits insulin release
Decrease glucose uptake Cortisol Increased EGP
Increase protein breakdownIncrease lipolysis
Growth Decrease glucose uptakeHormone
Other Counterregulatory Hormones
Insulin deficiency
glucose uptake (muscle/fat)
Glucagon excess
Proteolysis Alanine
Lipolysis glycerol GNG
Hyperglycemia
Stimulates ketogenesis
Insulin deficiency Insulin deficiency
glucose uptake (muscle/fat)
Proteolysis Alanine
Lipolysis glycerol
Insulin deficiency
Pathogenesis of DKAPathogenesis of DKA
What causes acidosis?What causes acidosis?
Lipid and ketone metabolismLipid and ketone metabolism
Triglyceride
Activation of HSL
GlycerolMassive release of FFA
Insulin deficiency Increase ICRH
Glucagon
Substrate for GNGIncrease production of ketone bodies by
the liver
Glucagon+
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 the Increase in CPT1 facilitates entry of FFA into the mitochondria for oxidationmitochondria for oxidation
__
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 synthesis Malonyl CoA
Ketone bodies
Keto-acidsKeto-acidsBeta-hydroxybutyrate and acetoacetatic acidBeta-hydroxybutyrate and acetoacetatic acid
Weak acids that dissociate at Weak 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 approximately Increase in Anion Gap approximately
equal to the decline in bicarbonate equal to the decline in bicarbonate levelslevels
Keto-acidsKeto-acidsBeta-hydroxybutyrate and acetoacetatic acidBeta-hydroxybutyrate and acetoacetatic acid
Nitroprusside RXN:Nitroprusside RXN:
Acetest Test mainly for Acetest Test mainly for Ketostix acetoacetateKetostix acetoacetate
Chemstrips UGKChemstrips UGK
Measuring Measuring urine and serum ketonesurine and serum ketones Absence of a nitroprusside reaction does not Absence of a nitroprusside reaction does not
eliminate the possibility of DKAeliminate the possibility of DKA Even a positive test can grossly underestimate Even a positive test can grossly underestimate
the severity of the DKAthe severity of the DKA Conversely, the persistence of or an increase in Conversely, the persistence of or an increase in
ketones during therapy is not necessarily a ketones during therapy is not necessarily a manifestation of deteriorating clinical status, and manifestation of deteriorating clinical status, and may in fact be a sign of improvementmay in fact be a sign of improvement
Renal threshold for glucose ~ 180-200 Renal threshold for glucose ~ 180-200 mg/dlmg/dl
Renal threshold for ketones is very lowRenal threshold for ketones is very low
Differential diagnosisDifferential diagnosis
Starvation ketosis Starvation ketosis Alcoholic ketoacidosis (AKA)Alcoholic ketoacidosis (AKA) Other causes of high-anion gap metabolic Other 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 paraldehyde methanol, ethylene glycol, and paraldehyde chronic renal failure chronic renal failure
Precipitating factors for Precipitating factors for DKA/HHSDKA/HHS
New onset DM (8%)New onset DM (8%)
Omission of or Omission of or inadequate dose of inadequate 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 pump Insulin pump malfunctionmalfunction
Luteal phase decrease Luteal phase decrease in insulin sensitivityin insulin sensitivity
HypovolemiaHypovolemia
Unknown (14%)Unknown (14%)
Clinical presentation
Ketoacidosis usually evolve in <24 hrs Ketoacidosis usually evolve in <24 hrs May evolve or develop more acutelyMay evolve or develop more acutely May present in DKA with no prior clues or May present in DKA with no prior clues or
symptoms symptoms
For both DKA and HHS, the classical For 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 coma clouding of sensoria, and finally coma
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 indicate A normal or elevated temperature may indicate underlying infection underlying infection primarily because of primarily because of peripheral vasodilation peripheral vasodilation
Hypothermia, if present, is a poor prognostic Hypothermia, if present, is a poor prognostic sign* sign*
* Matz R: Hypothermia in diabetic acidosis. Hormones 3:36–41, 1972
Up to 25% of DKA patients have emesis, Up to 25% of DKA patients have emesis, which may be coffee-ground in which may be coffee-ground in appearance. appearance.
Endoscopy has related this finding to the Endoscopy has related this finding to the presence of hemorrhagic gastritispresence of hemorrhagic gastritis
Abdominal Pain Abdominal Pain in Decompensated DMin Decompensated DM
Infrequent with HCO3- > 10 meq/LInfrequent with HCO3- > 10 meq/L
No correlation with degree of No 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
Level of consciousness is related to the Level of consciousness is related to the severity of the serum osmolarity in severity 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
Occurrence of coma in diabetic patients in the Occurrence of coma in diabetic patients in the absence of definitive elevation of effective absence of definitive elevation of effective osmolality ≥320 mOsm/kg demands osmolality ≥320 mOsm/kg demands immediate consideration of other causes of immediate consideration of other causes of such change.such change.
Effective osmolality may be calculated by the Effective 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
Initial laboratory evaluation of patients with Initial laboratory evaluation of patients with suspected DKA or HHS should include suspected DKA or HHS should include plasma glucoseplasma glucose blood urea/creatinineblood urea/creatinine serum ketonesserum ketones electrolytes (with electrolytes (with
calculated anion gap)calculated anion gap) osmolalityosmolality
UrinalysisUrinalysis urine ketones by urine ketones by
dipstickdipstick arterial blood gasesarterial blood gases complete blood count complete blood count
with differentialwith differential electrocardiogram.electrocardiogram.
Bacterial culturesBacterial cultures of urine, blood, and throat, of urine, blood, and throat, etc., should be obtained and appropriate etc., 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 determining may be useful in determining
◊◊culmination of an evolutionary process in culmination of an evolutionary process in previously undiagnosed or poorly controlled previously undiagnosed or poorly controlled
diabetes diabetes ◊◊truly acute episode in an otherwise truly acute episode in an otherwise well-well-
controlled patientcontrolled patient
FINDINGFINDING CAUSE/SCAUSE/S
Leukocytosis Leukocytosis Proportional to blood ketone body Proportional to blood ketone body concentration, Infection concentration, Infection
Hyponatraemia*Hyponatraemia* Osmotic flux of water from the Osmotic flux of water from the intracellular to the extracellular space, intracellular to the extracellular space, Severe hypertriglyceridemia Severe hypertriglyceridemia
HypokalaemiaHypokalaemia Extracellular shift of potassium caused by Extracellular shift of potassium caused by insulin deficiency, hypertonicity, and insulin deficiency, hypertonicity, and acidemiaacidemia
Elevated Amylase Elevated Amylase Non-pancreatic sources, such as the Non-pancreatic sources, such as the parotid gland parotid 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)
Treatment Treatment
The success of treatment of DKA and The success of treatment of DKA and HHS depends on; HHS depends on; Adequate correction of Adequate correction of dehydrationdehydration, ,
hyperglycemiahyperglycemia, , ketoacidosisketoacidosis and and electrolyte electrolyte deficits deficits
Identification & treatment of any Identification & treatment of any comorbidcomorbid precipitating eventsprecipitating events
Frequent patient Frequent patient monitoringmonitoring
Fluid therapyFluid therapy
Objective is to expand extracellular Objective is to expand extracellular volume and restore renal perfusionvolume and restore renal perfusion
Start with infusion of isotonic saline Start 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 average during the first hour (1–1.5 L in the average adult) adult)
Subsequent choice of fluid replacement Subsequent 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.
Infuse Infuse 0.45% Nacl0.45% Nacl at a rate of 4–14 mL/kg at a rate of 4–14 mL/kg
per hour if the per hour if the correctedcorrected serum Na is serum Na is normal or elevatednormal or elevated . .
0.9% NaCl0.9% NaCl at a similar rate is appropriate at a similar rate is appropriate if corrected if corrected serum Na is lowserum Na is low
Successful progress with fluid Successful 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 correct Fluid replacement should correct estimated deficits within the first 24 h. estimated deficits within the first 24 h.
Induced change in s osmolality should not Induced change in s osmolality should not exceed 3 mOsm · kg-1 H2O · h-1exceed 3 mOsm · kg-1 H2O · h-1
When the plasma glucose level reaches When the plasma glucose level reaches 250mg/dl, change to 250mg/dl, change to 5% dextrose5% dextrose with with 0.45% Nacl infused at 150-250 ml/hr 0.45% Nacl infused at 150-250 ml/hr
Paediatric patients (<20 yrs of age)Paediatric patients (<20 yrs of age)
The 1st hr of fluids should be isotonic The 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 50 Initial 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 (depending In general, 0.45–0.9% NaCl (depending
on serum Na ) infused at a rate of 1.5 on serum Na ) infused at a rate of 1.5 times the 24-h maintenance times the 24-h maintenance requirements ( 5 ml · kg-1 · h-1) will requirements ( 5 ml · kg-1 · h-1) will accomplish a smooth rehydrationaccomplish a smooth rehydration
Potassium therapy Potassium therapy
The treatment of DKA and HHS with The treatment of DKA and HHS with rehydration and insulin is typically rehydration and insulin is typically associated with a rapid decline in the associated with a rapid decline in the plasma K concentration, particularly during plasma K concentration, particularly during the first few hours of therapythe first few hours of therapy
Causes of hypokalaemiaCauses of hypokalaemia
insulin-mediated re-entry of potassium into insulin-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 to continued potassium loss owing to
osmotic diuresis and ketonuria osmotic diuresis and ketonuria
Because treatment will rapidly induce Because treatment will rapidly induce decreased serum K concentrations, K decreased serum K concentrations, K replacement must be initiated as soon as replacement must be initiated as soon as levels fall levels fall below 5.0 mmol/Lbelow 5.0 mmol/L, assuming , assuming urine output is adequate urine output is adequate
It is recommended that It is recommended that 20–30 mmol of K 20–30 mmol of K be added to each litrebe added to each litre of infusion fluid to of infusion fluid to maintain maintain K concentration 4 - 5 mmol/LK concentration 4 - 5 mmol/L
If serum K level is If serum K level is << 3.3 mmol/L 3.3 mmol/L, K , K replacement should be started replacement should be started immediately with fluid therapyimmediately with fluid therapy
Initiation of insulin should be delayed until Initiation of insulin should be delayed until K is restored to K is restored to >>3.3 mmol/L, in order to 3.3 mmol/L, in order to avoid arrhythmia, cardiac arrest and avoid arrhythmia, cardiac arrest and respiratory muscle weakness respiratory muscle weakness
Initially, the serum K level should be Initially, the serum K level should be measured every 1–2 hrs because the most measured every 1–2 hrs because the most rapid change occurs during the first 5 hrs rapid 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 clinically 6 hrs as indicated clinically
Insulin therapyInsulin therapy Consensus is that, in DKA & HHS, regular Consensus is that, in DKA & HHS, regular
insulin should be administered by insulin 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 plasma More gradual and steady fall in plasma
glucose levels glucose levels Decreased risk of hypoglycemia and Decreased risk of hypoglycemia and
hypokalemia hypokalemia
As soon as hypokalemia (K < 3.3 mmol/L) As soon as hypokalemia (K < 3.3 mmol/L) excluded, continuous infusion of regular excluded, continuous infusion of regular insulin can be started at a dose of 0.1 insulin can be started at a dose of 0.1 U/kg per hour U/kg per hour
This should produce a gradual decrease This should produce a gradual decrease in the plasma glucose level of 3–4 mmol/L in the plasma glucose level of 3–4 mmol/L per hour per hour
There is evidence that an iv bolus of There is evidence that an iv bolus of insulin is not necessary. However, a bolus insulin 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 been particularly if insulin treatment has been delayed.delayed.
In unusual circumstances where iv In unusual circumstances where iv administration is not possible, the im or sc administration is not possible, the im or sc route has been used effectively. However, route has been used effectively. However, poor perfusion will impair absorption of poor perfusion will impair absorption of insulin.insulin.
If the glucose level does not decline by 3 If the glucose level does not decline by 3 mmol/L in the first hour, the hydration mmol/L in the first hour, the hydration status should be checked; status should be checked;
if it is acceptable, the insulin dose should if it is acceptable, the insulin dose should be be doubled every hourdoubled every hour until a decrease of until a decrease of 3–4 mmol/L per hour3–4 mmol/L per hour in the plasma in the plasma glucose level is observed glucose level is observed
When the plasma glucose level reaches When the plasma glucose level reaches 12–14 mmol/L, the 12–14 mmol/L, the insulin infusion rate insulin 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 must Thereafter, the insulin infusion dose must be adjusted to maintain the plasma be 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 the 200mg/dl until the acidosis in DKA (or the clouded consciousness and clouded consciousness and hyperosmolality in HHS) have been hyperosmolality in HHS) have been resolvedresolved
It takes longer to correct ketonuria than It takes longer to correct ketonuria than hyperglycemia. hyperglycemia.
Because ß-hydroxybutyric acid is the Because ß-hydroxybutyric acid is the prevalent ketoacid and is gradually prevalent ketoacid and is gradually converted to acetoacetic acid, the converted to acetoacetic acid, the correction of ketonuria is underestimated correction of ketonuria is underestimated when measured by the nitroprusside when measured by the nitroprusside method method
Measurement of Measurement of serum ß-hydroxybutyricserum ß-hydroxybutyric acid levels using a reagent strip and a acid levels using a reagent strip and a reflectance meter has been validatedreflectance meter has been validated
Offers the possibility of bedside diagnosis Offers the possibility of bedside diagnosis with better follow-up parameters of with better follow-up parameters of hyperketonemia during treatmenthyperketonemia during treatment
Once the ketoacidosis in DKA has been Once the ketoacidosis in DKA has been corrected corrected (plasma glucose level < 11.0 (plasma glucose level < 11.0 mmol/L, serum bicarbonate level ≥18 mmol/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 consciousness 12 mmol/L), the clouded consciousness and hyperosmolality in HHS have and hyperosmolality in HHS have resolved, and patients are able to take resolved, and patients are able to take fluids orally)fluids orally),, a multidose insulin regimen a multidose insulin regimen may be initiated based on the patient's may be initiated based on the patient's treatment before DKA or HHS developed treatment before DKA or HHS developed
PhosphatePhosphate
Despite whole-body phosphate deficits in Despite whole-body phosphate deficits in DKA , serum phosphate is often normal or DKA , serum phosphate is often normal or increased at presentation. Phosphate increased at presentation. Phosphate concentration decreases with insulin concentration decreases with insulin therapy. therapy.
Prospective randomized studies have Prospective randomized studies have failed to show any beneficial effect of failed to show any beneficial effect of phosphate replacement on the clinical phosphate replacement on the clinical outcome in DKAoutcome in DKA
However, to avoid cardiac and skeletal However, to avoid cardiac and skeletal muscle weakness and respiratory muscle weakness and respiratory depression due to hypophosphatemia, depression due to hypophosphatemia, careful phosphate careful phosphate replacement may replacement may sometimes be indicated in patients with sometimes be indicated in patients with cardiac dysfunction, anemia, or respiratory cardiac dysfunction, anemia, or respiratory depression and in those with serum depression and in those with serum phosphate concentration <1.0 mg/dl.phosphate concentration <1.0 mg/dl.
When needed, 20–30 mEq/l potassium When needed, 20–30 mEq/l potassium phosphate can be added to replacement phosphate can be added to replacement fluids. fluids.
Overzealous phosphate therapy can Overzealous phosphate therapy can cause cause severe hypocalcemiasevere hypocalcemia with no with no evidence of tetany evidence of tetany
BicarbonateBicarbonate Bicarbonate use in DKA remains controversial.Bicarbonate use in DKA remains controversial. At a pH >7.0, reestablishing insulin activity At a pH >7.0, reestablishing insulin activity
blocks lipolysis and resolves ketoacidosis blocks lipolysis and resolves ketoacidosis without any added bicarbonate. without any added bicarbonate. Studies failed to Studies failed to show either beneficial or deleterious changes in show either beneficial or deleterious changes in morbidity or mortality with bicarbonate therapy in morbidity 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 in No 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.
Severe acidosis may lead to adverse Severe acidosis may lead to adverse vascular effects vascular 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
---
Venous pH should be assessed every 2 h Venous pH should be assessed every 2 h until the pH rises to 7.0, & treatment until the pH rises to 7.0, & treatment should be repeated every 2 h if necessary should be repeated every 2 h if necessary
In the paediatric patient, If pH remains In 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/kg seems prudent to administer 1–2 mEq/kg HCO3 over the course of 1 h. This HCO3 HCO3 over the course of 1 h. This HCO3 can be added to NaCl, with any required can be added to NaCl, with any required K, to produce a solution that does not K, to produce a solution that does not exceed 155 mEq/l sodium. exceed 155 mEq/l sodium.
COMPLICATIONS OF THERAPY COMPLICATIONS OF THERAPY
HypoglycemiaHypoglycemia - overzealous Rx with insulin - overzealous Rx with insulin HypokalemiaHypokalemia due to insulin & treatment of due to insulin & treatment of
acidosis with bicarbonateacidosis with bicarbonate HyperglycemiaHyperglycemia secondary to secondary to
interruption/discontinuance of iv insulin therapy interruption/discontinuance of iv insulin therapy after recoveryafter recovery
HyperchloremiaHyperchloremia caused by the use of excessive caused by the use of excessive saline saline
Transient non-anion gap metabolic acidosisTransient non-anion gap metabolic acidosis as as ClCl‾‾ from iv fluids replaces ketoanions lost as Na from iv fluids replaces ketoanions lost as Na & K salts during osmotic diuresis& K salts during osmotic diuresis
HypoxemiaHypoxemia noncardiogenic noncardiogenic pulmonary oedemapulmonary oedema Cerebral OedemaCerebral Oedema Hypoxemia is attributed to a reduction in colloid Hypoxemia is attributed to a reduction in colloid
osmotic pressure that results in increased lung osmotic 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 blood arteriolar oxygen gradient noted on initial blood gas measurement or with pulmonary rales on gas measurement or with pulmonary rales on physical examination appear to be at higher risk physical examination appear to be at higher risk for the development of pulmonary edema for the development of pulmonary edema
COMPLICATIONS OF THERAPYCOMPLICATIONS OF THERAPY
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 and Heralded 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
Once the clinical symptoms other than Once 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 without Only 7–14% of patients recover without permanent morbidity permanent morbidity
Cerebral Oedema in DKACerebral Oedema in DKA
Mechanism of Cerebral OedemaMechanism of Cerebral Oedema
Not knownNot known Likely results from osmotically driven Likely results from osmotically driven
movement of water into the central movement of water into the central nervous system when plasma osmolality nervous system when plasma osmolality declines too rapidly with the treatment of declines too rapidly with the treatment of DKA or HHS. DKA or HHS.
There is a lack of information on the There is a lack of information on the morbidity associated with cerebral edema morbidity associated with cerebral edema in adult patients in adult patients
Prevention and treatment of cerebral Prevention and treatment of cerebral edemaedema
PreventionPreventionGradual replacement of Na & HGradual replacement of Na & H22 O deficitsO deficits
Once plasma glucose of 200-250 mg/dl Once 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, followed IV mannitol 1G/kg over 30 minutes, followed
by infusion to maintain plasma osmolality by infusion to maintain plasma osmolality and sustain osmotic diuresis of waterand sustain osmotic diuresis of water
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
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