Diabetic Ketoacidosis Diabetic Ketoacidosis

Diabetic KetoacidosisDiabetic Ketoacidosis

An anion gap acidosis due to severe insulin An anion gap acidosis due to severe insulin deficiency and excess of counterregulatory deficiency and excess of counterregulatory hormoneshormones

Insulin DeficiencyInsulin Deficiency

Insulin is required for efficient transport of glucose into muscle, Insulin is required for efficient transport of glucose into muscle, adipose, and liver cellsadipose, and liver cells

Proper utilization of glucose within liver cells is also dependent Proper utilization of glucose within liver cells is also dependent on insulinon insulin

In the absence of insulin glucose cannot be effectively In the absence of insulin glucose cannot be effectively transported into cells and it accumulates in the bloodtransported into cells and it accumulates in the blood

The liver begins to manufacture glucose from amino acids The liver begins to manufacture glucose from amino acids (gluconeogenesis)(gluconeogenesis)

Additional glucose is thus secreted into the bloodstreamAdditional glucose is thus secreted into the bloodstream

Insulin Deficiency: Effects on the Insulin Deficiency: Effects on the KidneyKidney

When the degree of hyperglycemia exceeds the When the degree of hyperglycemia exceeds the kidney’s capacity for tubular reabsorption glucose kidney’s capacity for tubular reabsorption glucose appears in the urineappears in the urine

Osmotic diuresis ensues and the patient develops Osmotic diuresis ensues and the patient develops polyuriapolyuria

Severe dehydration may resultSevere dehydration may result

Insulin Deficiency: Effects on Insulin Deficiency: Effects on LipolysisLipolysis

Under normal circumstances insulin inhibits lipolysisUnder normal circumstances insulin inhibits lipolysis In the absense of insulin adipose cells degrade their In the absense of insulin adipose cells degrade their

stores of triglycerides into fatty acidsstores of triglycerides into fatty acids Fatty acids are converted by the liver into ketone Fatty acids are converted by the liver into ketone

bodies (acetoacetate and b-hydroxybutyrate)bodies (acetoacetate and b-hydroxybutyrate) A metabolic acidosis developsA metabolic acidosis develops

Actions of GlucagonActions of Glucagon

Glucagon when unopposed by normal insulin is Glucagon when unopposed by normal insulin is responsible for the hepatic components of diabetic responsible for the hepatic components of diabetic decompensationdecompensation

Increased glycogenolysisIncreased glycogenolysis Increased gluconeogenesisIncreased gluconeogenesis Increased ketogenesisIncreased ketogenesis

Insulin deficiency causes augmented delivery to the Insulin deficiency causes augmented delivery to the liver of substrates for glucose and ketone liver of substrates for glucose and ketone productionproduction

Glucagon is the switch that activates the hepatic Glucagon is the switch that activates the hepatic production machinery for glucose and ketonesproduction machinery for glucose and ketones

Precipitating Factors in DKAPrecipitating Factors in DKA

Failure to take insulin Failure to take insulin Failure to increase insulin during acute illness, infectionFailure to increase insulin during acute illness, infection Other intercurrent illness such as myocardial infarction, Other intercurrent illness such as myocardial infarction,

pancreatitis, stroke, trauma or severe emotional stresspancreatitis, stroke, trauma or severe emotional stress

The counterregulatory hormones released during medical The counterregulatory hormones released during medical stress oppose insulin and stimulate glucagon releasestress oppose insulin and stimulate glucagon release

Hypovolemia increases the secretion of glucagon, Hypovolemia increases the secretion of glucagon, catecholamines by decreasing renal blood flow and this further catecholamines by decreasing renal blood flow and this further reduces glucagon degradation by the kidneyreduces glucagon degradation by the kidney

Signs and Symptoms of DKASigns and Symptoms of DKA

Polyuria and polydipsiaPolyuria and polydipsia Kussmaul hyperventiationKussmaul hyperventiation Vomiting and abdominal painVomiting and abdominal pain An acetone odor to breathAn acetone odor to breath DehydrationDehydration Stupor and comaStupor and coma

Initial Lab FindingsInitial Lab Findings

HyperglycemiaHyperglycemia Anion gap acidosisAnion gap acidosis Positive urine and serum ketonesPositive urine and serum ketones HyperosmolarityHyperosmolarity

Differential DiagnosisDifferential Diagnosis

Anion gap acidosis: (Na + K) - (Cl +Bicarb) >16Anion gap acidosis: (Na + K) - (Cl +Bicarb) >16 Alcoholic ketoacidosisAlcoholic ketoacidosis Lactic acidosisLactic acidosis Renal failureRenal failure Ethylene glycol or methyl alcohol poisoningEthylene glycol or methyl alcohol poisoning Starvation in late pregnancy or lactation (rare)Starvation in late pregnancy or lactation (rare)

Initial Lab Findings in DKAInitial Lab Findings in DKA

GlucoseGlucose 475475

SodiumSodium 132132

PotassiumPotassium 4.84.8

BicarbonateBicarbonate <10<10

BUNBUN 2525

AcetoacetateAcetoacetate 4.84.8

B-hydroxybutyrateB-hydroxybutyrate 13.713.7

Free Fatty acidsFree Fatty acids 2.12.1

LactateLactate 4.64.6

OsmolarityOsmolarity 310310

Treatment of DKATreatment of DKA

Replacement of fluid and electrolytesReplacement of fluid and electrolytes Insulin therapyInsulin therapy Glucose administrationGlucose administration

Replacement of Fluid and ElectrolytesReplacement of Fluid and Electrolytes

Restores perfusion of tissues to normal and lowers levels of Restores perfusion of tissues to normal and lowers levels of counterregulatory hormonescounterregulatory hormones

Average fluid deficit is 3-5 litersAverage fluid deficit is 3-5 liters 1-2 liters of normal saline administered rapidly in the first 2 1-2 liters of normal saline administered rapidly in the first 2

hourshours If hypernatremia develops 1/2 NS can be substitutedIf hypernatremia develops 1/2 NS can be substituted Hyperkalemia usually present on admission recedes when Hyperkalemia usually present on admission recedes when

insulin action begins; potassium replacement is then requiredinsulin action begins; potassium replacement is then required Phosphate deficit becomes apparent after insulin administration Phosphate deficit becomes apparent after insulin administration

but is usually clinically silentbut is usually clinically silent Bicarbonate is usually not given unless pH is below 7 or bicarb Bicarbonate is usually not given unless pH is below 7 or bicarb

less than 5 mmol/lless than 5 mmol/l

Insulin TherapyInsulin Therapy

IV bolus of 10-20 units regular insulinIV bolus of 10-20 units regular insulin Follow by hourly insulin infusionFollow by hourly insulin infusion Insulin should be given intravenously until the urine Insulin should be given intravenously until the urine

is free of ketonesis free of ketones

Glucose AdministrationGlucose Administration

Once insulin has restored glucose uptake and Once insulin has restored glucose uptake and suppressed hyperglucagonemia, hypoglycemia will suppressed hyperglucagonemia, hypoglycemia will occur unless exogenous glucose is providedoccur unless exogenous glucose is provided

Glucose levels always fall before ketone levels Glucose levels always fall before ketone levels decrease therefore exogenous glucose must be decrease therefore exogenous glucose must be provided to cover the insulin needed to reverse provided to cover the insulin needed to reverse ketosisketosis

Glucose is usually started when plasma glucose Glucose is usually started when plasma glucose reaches 250-300 mg/dlreaches 250-300 mg/dl

Insulin-Glucose Infusion for DKAInsulin-Glucose Infusion for DKA

Blood glucoseBlood glucose Insulin infusionInsulin infusion D5W infusionD5W infusion

<70<70 0.5 units per hour0.5 units per hour 150 cc/hour150 cc/hour

70-10070-100 1.01.0 125125

101-150101-150 2.02.0 100100

151-200151-200 3.03.0 100100

201-250201-250 4.04.0 7575

251-300251-300 6.06.0 5050

301-350301-350 8.08.0 00

351-400351-400 10.010.0 00

401-450401-450 12.012.0 00

451-500451-500 15.015.0 00

>500>500 20.020.0 00

Following Resolution of DKAFollowing Resolution of DKA

Most patients require 0.5-0.6 units of insulin per kg body Most patients require 0.5-0.6 units of insulin per kg body weightweight

1/2 - 2/3 requirement is given as long-acting insulin - NPH, 1/2 - 2/3 requirement is given as long-acting insulin - NPH, Lente, Ultralente or LantusLente, Ultralente or Lantus

1/3-1/2 is given as short-acting meal time insulin - regular, 1/3-1/2 is given as short-acting meal time insulin - regular, Humalog or NovologHumalog or Novolog

Give both long and short acting insulin subcutaneously about Give both long and short acting insulin subcutaneously about 2 hours prior to tapering insulin infusion2 hours prior to tapering insulin infusion

Patient education key to avoiding future episodesPatient education key to avoiding future episodes

Clinical ErrorsClinical Errors

Administration of hypertonic glucose solutions at the outsetAdministration of hypertonic glucose solutions at the outset Giving insulin in patients with severe volume deficit without Giving insulin in patients with severe volume deficit without

sufficient fluids can cause fluid shift into cells can precipitate sufficient fluids can cause fluid shift into cells can precipitate shockshock

Premature administration of potassium before insulin has Premature administration of potassium before insulin has begun to act can cause fatal hyperkalemiabegun to act can cause fatal hyperkalemia

Failure to administer potassium after insulin has begun to act Failure to administer potassium after insulin has begun to act can lead to fatal hypokalemiacan lead to fatal hypokalemia

Recurrent ketoacidosis caused by failure to maintain IV insulin Recurrent ketoacidosis caused by failure to maintain IV insulin and glucose until ketones have cleared or by failure to and glucose until ketones have cleared or by failure to administer subcutaneous insulin before stopping IV infusionadminister subcutaneous insulin before stopping IV infusion

Hypoglycemia caused by insufficient glucose administrationHypoglycemia caused by insufficient glucose administration

DKA and PregnancyDKA and Pregnancy

Pregnancy is a state of relative insulin resistance marked by Pregnancy is a state of relative insulin resistance marked by enhanced lipolysis and ketogenesisenhanced lipolysis and ketogenesis

High serum ketones may be teratogenicHigh serum ketones may be teratogenic DKA represents a substantial risk for the fetal compromiseDKA represents a substantial risk for the fetal compromise

Complications of DKAComplications of DKA

Death is usually due to precipitating or complicating Death is usually due to precipitating or complicating illness such as MI, pancreatitis or sepsisillness such as MI, pancreatitis or sepsis

InfectionInfection Vascular thrombosisVascular thrombosis Cerebral edemaCerebral edema Respiratory distress syndromeRespiratory distress syndrome

Hyperosmolar Nonketotic ComaHyperosmolar Nonketotic Coma

Extreme hyperglycemia and dehydration which results when Extreme hyperglycemia and dehydration which results when the ability to excrete glucose as rapidly as it enters the the ability to excrete glucose as rapidly as it enters the extracellular spaceextracellular space

Maximum hepatic glucose output results in a plateau of plasma Maximum hepatic glucose output results in a plateau of plasma glucose no higher than 300-500 mg/dlglucose no higher than 300-500 mg/dl

When sum of glucose When sum of glucose excretionexcretion plus metabolism is less than plus metabolism is less than the rate at which glucose enters extracellular spacethe rate at which glucose enters extracellular space

Hyperosmolar Nonketotic ComaHyperosmolar Nonketotic Coma

Older patients with intercurrent illness with impaired ability to Older patients with intercurrent illness with impaired ability to ingest fluidsingest fluids

When urine volume falls the ability to excrete glucose fallsWhen urine volume falls the ability to excrete glucose falls As glucose rises CNS dysfunction occurs and water intake is As glucose rises CNS dysfunction occurs and water intake is

additionally impairedadditionally impaired The result is extreme hyperglycemia and hyperosmolarity with The result is extreme hyperglycemia and hyperosmolarity with

high mortalityhigh mortality Either enough insulin is present to prevent ketosis or the Either enough insulin is present to prevent ketosis or the

extreme hyperglycemia inhibits lipolysisextreme hyperglycemia inhibits lipolysis

Admission Findings: Hyperosmolar Admission Findings: Hyperosmolar Nonketotic ComaNonketotic Coma

Extreme dehydrationExtreme dehydration Supine or orthostatic hypotensionSupine or orthostatic hypotension Confusion to comaConfusion to coma Seizures or other neurological findingsSeizures or other neurological findings

Admission Findings: Hyperosmolar Admission Findings: Hyperosmolar Nonketotic ComaNonketotic Coma

Average glucose 1200Average glucose 1200 Na 144Na 144 K 5K 5 Bicarb 17Bicarb 17 Osm 384Osm 384

Treatment of HONKTreatment of HONK

Fluid repletion: give first 2-3 liters rapidlyFluid repletion: give first 2-3 liters rapidly Total deficit may be 10 liters: replete 1/2 the Total deficit may be 10 liters: replete 1/2 the

deficit in the first 6 hoursdeficit in the first 6 hours Insulin 10 unit bolus followed by sliding scale Insulin 10 unit bolus followed by sliding scale

hourlyhourly Treat underlying precipitating illnessTreat underlying precipitating illness