Diabetic Ketoacidosis in the Adult Patient - CECity

This program can also be completed on-line atwww.novonordisk-us.com. Click on continuing education.

This continuing education activity for pharmacists andnurses is supported by an unrestricted educational grantfrom Novo Nordisk Pharmaceuticals, Inc.

A Continuing Education Activity

for Pharmacists and Nurses

Diabetic Ketoacidosis

in the Adult Patient

Editorial Review Board John B. Buse, MD, PhD, CDEChief, Division of General Internal MedicineDirector, Diabetes Care CenterUniversity of North Carolina School of MedicineChapel Hill, North Carolina

Thomas S. Sisca, PharmD, FCCP, BCPSClinical Manager, PharmacyMemorial HospitalEaston, Maryland

Marsha Menke, RN, BSN, MS, CDE, CPTDirectorDiabetes Care CenterGenesis Medical CenterDavenport, Iowa

Copyright©2002, Novo Nordisk Pharmaceuticals, Inc. All rights reserved. No part of this program may bereproduced, stored in a retrieval system, or transmitted in any form or by any means (electronic, electrostatic,magnetic tape, mechanical, photocopying, recording, or otherwise) without permission from Novo NordiskPharmaceuticals, Inc. Published by HealthAnswers, Inc., 1140 Welsh Road, North Wales, PA 19454.

ii iii

Continuing Nursing EducationThis educational activity for 2.8 contact hoursis provided by the Postgraduate Institute forMedicine. The Postgraduate Institute forMedicine is approved as a provider ofcontinuing education in nursing by theColorado Nurses Association, which isaccredited as an approver of continuingeducation in nursing by the American NursesCredentialing Center’s Commission onAccreditation.

Participants will be required to score at least70% on the self-assessment test and completeand submit an evaluation form to receivecontinuing education credit. A certificate ofcredit will be mailed within 4 weeks ofreceipt of the evaluation form.

Release Date and Time for CompletionThis activity was originally released on July 1, 2002. This activity will expire onJuly 1, 2005, for pharmacists and July 1, 2004,for nurses.

Disclosure DeclarationIt is the policy of Novo NordiskPharmaceuticals, Inc. and PostgraduateInstitute for Medicine to ensureindependence, balance, objectivity, scientificrigor, and integrity in all of their continuingeducation activities. The faculty must discloseto the participants any significantrelationships with the commercial companieswhose products or devices may be mentionedin the monograph or with the commercialsupporter of this continuing educationactivity. The information is for participantinformation only; it is not assumed that theserelationships will have a negative impact onthe content of the activity.

Dr. Buse has disclosed the following financialrelationships: research grants from Eli Lillyand Company.

Dr. Sisca has disclosed that he has no financialrelationships to report.

Ms. Menke has disclosed that she has nofinancial relationships to report.

Unlabeled Use DisclosureThis activity may include discussions ofproducts or devices that are not currentlyapproved for use by the Food and DrugAdministration (FDA).

Novo Nordisk Pharmaceuticals, Inc.,Postgraduate Institute for Medicine, and theeditorial review board do not endorse the useof any product in a manner that is notapproved by the FDA. Healthcare providersshould not use procedures, products, ordiagnostic techniques discussed during thisactivity without evaluation of their patientsfor contraindications or dangers of use.

The opinions and recommendations presentedin this monograph are those of the individualmembers of the editorial review board and donot necessarily reflect the views of NovoNordisk Pharmaceuticals, Inc. Healthcareprofessionals should consult the fullprescribing information before prescribing anydrug mentioned in this monograph.

Program GoalThis monograph is a review of thepathophysiology, diagnosis, treatment, andcomplications of diabetic ketoacidosis (DKA)in adults.

Program OverviewDKA is a life-threatening complication ofdiabetes that is caused by relative or absoluteinsulin deficiency, which results inhyperglycemia, ketonemia, dehydration,electrolyte imbalances, and acidosis.Treatment protocols for adults generallyadvocate a more rapid and aggressive reversalof DKA than is advised for children.1 DKAconsumes a significant proportion of all directmedical costs for adults and children withtype 1 diabetes. The management of DKArequires a full complement of hospital,emergency, and intensive care services. In theUnited States, more than 100,000 individualsare hospitalized each year for DKA and themortality rate is 2% to 5%.

Most cases of DKA can be prevented by usingan effective diabetes management plan thatincludes patient self-care. Early identificationof precipitating signs and symptoms andprompt, appropriate intervention can reducethe frequency of DKA episodes that result ina medical emergency.

The healthcare team must stay informedabout the recent developments in diabetescare and have the necessary clinical skills toprevent and manage DKA episodes. Throughgood self-management and intensiveglycemic control, the incidence, morbidity,and mortality of DKA can be reduced.

Target AudienceThis educational activity is designed forregistered nurses and pharmacists who treatpatients with diabetes.

Educational ObjectivesAfter completing this educational activity,participants should be able to:

■ Define DKA

■ Describe the epidemiology of DKA

■ Outline the pathogenesis and diagnosis ofDKA

■ Identify the signs, symptoms, andcomplications of DKA

■ Discuss methods of treatment and recoverycare for DKA

■ Provide strategies for the prevention of DKA

■ Discuss the economic impact of DKA intoday’s environment

Commercial SupportThis continuing education activity issupported by an unrestricted educational grant from Novo NordiskPharmaceuticals, Inc.

AccreditationContinuing Pharmaceutical Education

Novo Nordisk Pharmaceuticals, Inc.is approved by the AmericanCouncil on Pharmaceutical

Education (ACPE) as a provider of continuingpharmaceutical education.

This program has been assigned the UniversalProgram Number 360-999-01-002-H01 and isacceptable for 1.8 contact hours (.18 CEUs) instates that recognize ACPE-approved providers.

In order to receive credit, participants mustread the entire monograph, complete andreturn an evaluation form, and score at least70% on the self-assessment test. A statementof credit will be mailed within 4 weeks ofreceipt of the evaluation form.

ii iii

Continuing Nursing EducationThis educational activity for 2.8 contact hoursis provided by the Postgraduate Institute forMedicine. The Postgraduate Institute forMedicine is approved as a provider ofcontinuing education in nursing by theColorado Nurses Association, which isaccredited as an approver of continuingeducation in nursing by the American NursesCredentialing Center’s Commission onAccreditation.

Participants will be required to score at least70% on the self-assessment test and completeand submit an evaluation form to receivecontinuing education credit. A certificate ofcredit will be mailed within 4 weeks ofreceipt of the evaluation form.

Release Date and Time for CompletionThis activity was originally released on July 1, 2002. This activity will expire onJuly 1, 2005, for pharmacists and July 1, 2004,for nurses.

Disclosure DeclarationIt is the policy of Novo NordiskPharmaceuticals, Inc. and PostgraduateInstitute for Medicine to ensureindependence, balance, objectivity, scientificrigor, and integrity in all of their continuingeducation activities. The faculty must discloseto the participants any significantrelationships with the commercial companieswhose products or devices may be mentionedin the monograph or with the commercialsupporter of this continuing educationactivity. The information is for participantinformation only; it is not assumed that theserelationships will have a negative impact onthe content of the activity.

Dr. Buse has disclosed the following financialrelationships: research grants from Eli Lillyand Company.

Dr. Sisca has disclosed that he has no financialrelationships to report.

Ms. Menke has disclosed that she has nofinancial relationships to report.

Unlabeled Use DisclosureThis activity may include discussions ofproducts or devices that are not currentlyapproved for use by the Food and DrugAdministration (FDA).

Novo Nordisk Pharmaceuticals, Inc.,Postgraduate Institute for Medicine, and theeditorial review board do not endorse the useof any product in a manner that is notapproved by the FDA. Healthcare providersshould not use procedures, products, ordiagnostic techniques discussed during thisactivity without evaluation of their patientsfor contraindications or dangers of use.

The opinions and recommendations presentedin this monograph are those of the individualmembers of the editorial review board and donot necessarily reflect the views of NovoNordisk Pharmaceuticals, Inc. Healthcareprofessionals should consult the fullprescribing information before prescribing anydrug mentioned in this monograph.

Program GoalThis monograph is a review of thepathophysiology, diagnosis, treatment, andcomplications of diabetic ketoacidosis (DKA)in adults.

Program OverviewDKA is a life-threatening complication ofdiabetes that is caused by relative or absoluteinsulin deficiency, which results inhyperglycemia, ketonemia, dehydration,electrolyte imbalances, and acidosis.Treatment protocols for adults generallyadvocate a more rapid and aggressive reversalof DKA than is advised for children.1 DKAconsumes a significant proportion of all directmedical costs for adults and children withtype 1 diabetes. The management of DKArequires a full complement of hospital,emergency, and intensive care services. In theUnited States, more than 100,000 individualsare hospitalized each year for DKA and themortality rate is 2% to 5%.

Most cases of DKA can be prevented by usingan effective diabetes management plan thatincludes patient self-care. Early identificationof precipitating signs and symptoms andprompt, appropriate intervention can reducethe frequency of DKA episodes that result ina medical emergency.

The healthcare team must stay informedabout the recent developments in diabetescare and have the necessary clinical skills toprevent and manage DKA episodes. Throughgood self-management and intensiveglycemic control, the incidence, morbidity,and mortality of DKA can be reduced.

Target AudienceThis educational activity is designed forregistered nurses and pharmacists who treatpatients with diabetes.

Educational ObjectivesAfter completing this educational activity,participants should be able to:

■ Define DKA

■ Describe the epidemiology of DKA

■ Outline the pathogenesis and diagnosis ofDKA

■ Identify the signs, symptoms, andcomplications of DKA

■ Discuss methods of treatment and recoverycare for DKA

■ Provide strategies for the prevention of DKA

■ Discuss the economic impact of DKA intoday’s environment

Commercial SupportThis continuing education activity issupported by an unrestricted educational grant from Novo NordiskPharmaceuticals, Inc.

AccreditationContinuing Pharmaceutical Education

Novo Nordisk Pharmaceuticals, Inc.is approved by the AmericanCouncil on Pharmaceutical

Education (ACPE) as a provider of continuingpharmaceutical education.

This program has been assigned the UniversalProgram Number 360-999-01-002-H01 and isacceptable for 1.8 contact hours (.18 CEUs) instates that recognize ACPE-approved providers.

In order to receive credit, participants mustread the entire monograph, complete andreturn an evaluation form, and score at least70% on the self-assessment test. A statementof credit will be mailed within 4 weeks ofreceipt of the evaluation form.

iv 1

IntroductionEach year more than 100,000 people arehospitalized for diabetic ketoacidosis (DKA) inthe United States, which representsapproximately 500,000 hospitalization days.2

DKA is a life-threatening illness. The highmortality rate of DKA, estimated at 2% to5%, has remained the same since the 1970s.3,4

In 2001, the American Diabetes Association(ADA) published revised guidelines forglycemic control.5 Treatment aimed atlowering blood glucose levels to normal ornear-normal levels is necessary in all patientsunless contraindicated. Among the benefitsof glycemic control is reduced incidence ofDKA or hyperosmolar hyperglycemic state(HHS) and associated morbidity and mortality.The ADA recommends patients with diabetesmaintain preprandial whole blood glucosevalues between 80 and 120 mg/dL and an A1c

less than 7%. Comprehensive education inself-management is a critical element forachieving and maintaining optimal glycemiccontrol. The physician and patient must settreatment goals with the diabetesmanagement team and family members. Aneffective program requires ongoing supportfrom the clinical care team.

Healthcare professionals who treat patientswith diabetes must know how to prevent andmanage DKA. This monograph defines DKAand describes symptoms and warning signs,diagnosis, current practices, complications,prevention methods, special circumstances,and economic issues.

DefinitionDKA is a reversible but life-threateningcomplication that results from relative orabsolute insulin deficiency.6 In the absence ofinsulin, most cells cannot use glucose. Fatbreakdown provides an alternative source ofenergy. These metabolic abnormalities will, ifnot reversed, culminate in DKA, which ischaracterized by the presence of

hyperglycemia, ketosis, and acidosis (Fig. 1).The common signs and symptoms of DKAinclude “fruity” (acetone) breath secondary toketosis, nausea, vomiting, polydipsia, andpolyuria. Breathing becomes deep and rapid asthe body attempts to correct the acidosis(Kussmaul’s respiration).

Figure 1. Diagnostic triad of diabeticketoacidosis. From Kitabchi AE. Diabetes mellitus. In: Glew RH, PetersSP, eds. Clinical Studies in Medical Biochemistry. New York, NY: Oxford University Press; 1987:102–117.

Although DKA can occur in patients with type1 or type 2 diabetes, HHS is generally acomplication of type 2 diabetes and is mostcommon in older patients.7 In HHS, insulinresistance and relative insulin deficiency canresult in high levels of blood glucose, which is usually a result of a precipitating factor (eg,stroke, infection, myocardial infarction).Because HHS generally occurs in patients withtype 2 diabetes who are capable of someinsulin production, marked ketosis andattendant acidosis are not usually presentingclinical features. HHS and DKA can co-exist,which can make differential diagnosisdifficult.8 The severe hyperglycemic andhyperosmolar (concentrated serum) stateassociated with HHS typically leads toprofound dehydration and confusion orcoma. The excessive water loss throughosmotic diuresis can be a vicious cycle, whichcan only be compensated by adequate fluid

HYPER-GLYCEMIA

ACIDOSIS

KETOSIS

DKA

HYPERGLYCEMIC STATES• Diabetes Mellitus• Hyperosmolar Hyperglycemic State• Impaired Glucose Tolerance• Stress Hyperglycemia

KETOTIC STATES• Ketotic Hypoglycemia• Alcoholic Ketosis• Starvation Ketosis

METABOLIC ACIDOTIC STATES• Lactic Acidosis• Hyperchloremic Acidosis• Uremic Acidosis• Drug-Induced Acidosis (eg, salicylates, methanol, ethylene glycol)

Table of Contents

Introduction ..........................................................................................................................................1

Definition ............................................................................................................................................1

Epidemiology ........................................................................................................................................2

Pathophysiology....................................................................................................................................2

Triggers of Diabetic Ketoacidosis ........................................................................................................4

Warning Signs and Symptoms ............................................................................................................6

Diagnosis ..............................................................................................................................................6

Treatment Guidelines ..........................................................................................................................8

Recovery Care......................................................................................................................................11

Electrolyte Management During Recovery ......................................................................................11

Complications......................................................................................................................................11

Prevention ..........................................................................................................................................12

Special Circumstances ........................................................................................................................14

Economic Issues ..................................................................................................................................14

Summary..............................................................................................................................................15

Appendix A..........................................................................................................................................16

Appendix B ..........................................................................................................................................17

References ..........................................................................................................................................18

Self-Assessment Test ..........................................................................................................................21

Evaluation Form..................................................................................................................................23

iv 1

IntroductionEach year more than 100,000 people arehospitalized for diabetic ketoacidosis (DKA) inthe United States, which representsapproximately 500,000 hospitalization days.2

DKA is a life-threatening illness. The highmortality rate of DKA, estimated at 2% to5%, has remained the same since the 1970s.3,4

In 2001, the American Diabetes Association(ADA) published revised guidelines forglycemic control.5 Treatment aimed atlowering blood glucose levels to normal ornear-normal levels is necessary in all patientsunless contraindicated. Among the benefitsof glycemic control is reduced incidence ofDKA or hyperosmolar hyperglycemic state(HHS) and associated morbidity and mortality.The ADA recommends patients with diabetesmaintain preprandial whole blood glucosevalues between 80 and 120 mg/dL and an A1c

less than 7%. Comprehensive education inself-management is a critical element forachieving and maintaining optimal glycemiccontrol. The physician and patient must settreatment goals with the diabetesmanagement team and family members. Aneffective program requires ongoing supportfrom the clinical care team.

Healthcare professionals who treat patientswith diabetes must know how to prevent andmanage DKA. This monograph defines DKAand describes symptoms and warning signs,diagnosis, current practices, complications,prevention methods, special circumstances,and economic issues.

DefinitionDKA is a reversible but life-threateningcomplication that results from relative orabsolute insulin deficiency.6 In the absence ofinsulin, most cells cannot use glucose. Fatbreakdown provides an alternative source ofenergy. These metabolic abnormalities will, ifnot reversed, culminate in DKA, which ischaracterized by the presence of

hyperglycemia, ketosis, and acidosis (Fig. 1).The common signs and symptoms of DKAinclude “fruity” (acetone) breath secondary toketosis, nausea, vomiting, polydipsia, andpolyuria. Breathing becomes deep and rapid asthe body attempts to correct the acidosis(Kussmaul’s respiration).

Figure 1. Diagnostic triad of diabeticketoacidosis. From Kitabchi AE. Diabetes mellitus. In: Glew RH, PetersSP, eds. Clinical Studies in Medical Biochemistry. New York, NY: Oxford University Press; 1987:102–117.

Although DKA can occur in patients with type1 or type 2 diabetes, HHS is generally acomplication of type 2 diabetes and is mostcommon in older patients.7 In HHS, insulinresistance and relative insulin deficiency canresult in high levels of blood glucose, which is usually a result of a precipitating factor (eg,stroke, infection, myocardial infarction).Because HHS generally occurs in patients withtype 2 diabetes who are capable of someinsulin production, marked ketosis andattendant acidosis are not usually presentingclinical features. HHS and DKA can co-exist,which can make differential diagnosisdifficult.8 The severe hyperglycemic andhyperosmolar (concentrated serum) stateassociated with HHS typically leads toprofound dehydration and confusion orcoma. The excessive water loss throughosmotic diuresis can be a vicious cycle, whichcan only be compensated by adequate fluid

HYPER-GLYCEMIA

ACIDOSIS

KETOSIS

DKA

HYPERGLYCEMIC STATES• Diabetes Mellitus• Hyperosmolar Hyperglycemic State• Impaired Glucose Tolerance• Stress Hyperglycemia

KETOTIC STATES• Ketotic Hypoglycemia• Alcoholic Ketosis• Starvation Ketosis

METABOLIC ACIDOTIC STATES• Lactic Acidosis• Hyperchloremic Acidosis• Uremic Acidosis• Drug-Induced Acidosis (eg, salicylates, methanol, ethylene glycol)

Table of Contents

Introduction ..........................................................................................................................................1

Definition ............................................................................................................................................1

Epidemiology ........................................................................................................................................2

Pathophysiology....................................................................................................................................2

Triggers of Diabetic Ketoacidosis ........................................................................................................4

Warning Signs and Symptoms ............................................................................................................6

Diagnosis ..............................................................................................................................................6

Treatment Guidelines ..........................................................................................................................8

Recovery Care......................................................................................................................................11

Electrolyte Management During Recovery ......................................................................................11

Complications......................................................................................................................................11

Prevention ..........................................................................................................................................12

Special Circumstances ........................................................................................................................14

Economic Issues ..................................................................................................................................14

Summary..............................................................................................................................................15

Appendix A..........................................................................................................................................16

Appendix B ..........................................................................................................................................17

References ..........................................................................................................................................18

Self-Assessment Test ..........................................................................................................................21

Evaluation Form..................................................................................................................................23

3

EventsHyperglycemia. Hyperglycemia occurssecondary to insulin deficiency,gluconeogenesis, and underutilization ofglucose by the peripheral tissue. Insulindeficiency stimulates glucagon release, whichcontributes to the development of DKA bystimulating gluconeogenesis and ketogenesis.In times of stress, epinephrine stimulatesglucagon release. The presence of increasedconcentrations of epinephrine, cortisol, andgrowth hormone accentuates the impairmentof peripheral glucose utilization.17

Dehydration. Patients with severe DKA mayhave fluid deficits of 6 liters or more with anaverage weight loss of 5% to 10% of theirtotal body weight.18 This may develop over a12- to 24-hour period.6 Dehydration occurssecondary to osmotic diuresis, which resultsfrom glucosuria. Glucosuria develops when

the blood glucose concentration exceeds therenal threshold (160–180 mg/dL) for glucose.The loss of water and dehydration aresecondary to polyuria. Hyperventilation andvomiting may also contribute to fluid loss.The degree of dehydration can be assessed bydetermining the patient’s weight loss andbaseline weight. Otherwise, dehydration mustbe assessed by clinical signs. A dehydratedpatient may present with physical findings,including orthostatic hypotension and drymucous membranes.

Ketone production. Ketogenesis occurs in a state of insulin deficiency and counter-regulatory hormone excess, which results inketonemia and ketonuria. Insulin deficiencyleads to the breakdown of fat in adipose tissue(lipolysis) with the release of free fatty acids.Ketones are formed from free fatty acids inthe liver. The pathophysiologic basis of DKA isshown in Figure 3. Insulin is required for thesuppression of ketone production and thecorrection of acidosis. Insulin inhibitsglycogenolysis and gluconeogenesis,suppresses lipolysis, and facilitates theconservation of sodium and other electrolytesby the kidney.6

Glucagon plays an important role in the development of DKA because it influences

gluconeogenesis and ketogenesis.17

2

replacement.8 Common signs of HHS includestupor, dehydration, and hypotension. Theneurologic signs can range from aphasia toseizures or coma.

EpidemiologyThe incidence of DKA is estimated at 2episodes per 100 patient years. This may varybecause of diverse factors. Omission ofinsulin is a leading precipitating cause ofDKA. Some patients reported that they didnot have the money to buy insulin or fortransportation to a hospital or clinic; otherreasons given were lack of information onsick day protocol and low food intakebecause of lack of appetite.9 Drug and alcoholabuse are commonly associated with DKA.10

DKA episodes can often be attributed to thelack of early recognition and timely treatmentof diabetes.10,11 A diagnosis of diabetes isoften made following a severe DKAepisode.12,13 Approximately 20% to 30% ofDKA cases occur in patients with newlydiagnosed diabetes.12

The precipitating cause of DKA can beidentified in 80% of adult patients.6 AlthoughDKA occurs most often in type 1 diabetes,patients with type 2 diabetes may developDKA after many weeks of symptomatichyperglycemia. In a retrospective medicalrecord review, 39% of patients who presentedwith DKA had type 2 diabetes.14 Many patientshad no obvious precipitating causes other thanprolonged omission of oral hypoglycemictherapy.14 In another retrospective medicalrecord review, 55% of patients who presentedwith DKA had type 2 diabetes and infectionwas the most common cause of DKA.15 Incontrast, poor compliance with insulin therapywas the most frequent cause of DKA inpatients with type 1 diabetes.15

PathophysiologyInsulin deficiency triggers a complex metabolicprocess. This process may begin insidiously anddevelop during a period of hours to days. Type1 diabetes is characterized by a severe insulindeficiency, which results from autoimmunedestruction of pancreatic ß-cells. Type 1diabetes is usually diagnosed in individualsyounger than 30 years of age. Insulin deficiencyand hyperglycemia are usually not present untilapproximately 90% of insulin secretory capacityis lost.6

DKA occurs because of relative or absoluteinsulin deficiency coupled with a concomitantelevation of counter-regulatory hormones.Fleckman’s seesaw analogy describes thehormonal interplay that characterizes DKA(Fig. 2).16 Insulin, on one side of the seesaw,normally counterbalances the effect of thecounter-regulatory hormones (glucagon,catecholamines, cortisol, and growthhormone) on the opposite side.

Figure 2. Fleckman’s seesaw analogy fordiabetic ketoacidosis. Insulin is outweighedby the counter-regulatory hormones. From Fleckman AM. Diabetic ketoacidosis. EndocrinMetab Clin North Am. 1993;22:181-207.

Table 1 summarizes the effect of insulin andthe counter-regulatory hormones.17 A relativeor absolute deficiency of insulin and an excessof counter-regulatory hormones result in: (1) gluconeogenesis, (2) glycogenolysis, (3) inhibition of peripheral glucose utilization,(4) lipolysis, and (5) stimulation of ketogenesis.

Growth hormone

Cortisol

CatecholaminesInsulin

Liver Fat cell

Glucagon

Most patients with severe DKA have somealteration in their level of consciousness.

Table 1. Effects of Insulin and Counter-Regulatory Hormones

Gluconeogenesis Ketogenesis Glucose LipolysisUtilization

Liver Liver Muscle Adipose Tissue

Insulin ! ! " !

Glucagon " " # #

Epinephrine " " ! "

Cortisol " " ! "

Growth Hormone # " ! "

" Increased; ! Decreased; # Minimal or no effect.

From Ennis ED, Stahl E, Kreisberg RA. Diabetic ketoacidosis. In: Porte D Jr, Sherwin RS, eds. Ellenberg & Rifkin’s

Diabetes Mellitus. 5th ed. Stamford, Conn: Appleton & Lange; 1997:829.

3

EventsHyperglycemia. Hyperglycemia occurssecondary to insulin deficiency,gluconeogenesis, and underutilization ofglucose by the peripheral tissue. Insulindeficiency stimulates glucagon release, whichcontributes to the development of DKA bystimulating gluconeogenesis and ketogenesis.In times of stress, epinephrine stimulatesglucagon release. The presence of increasedconcentrations of epinephrine, cortisol, andgrowth hormone accentuates the impairmentof peripheral glucose utilization.17

Dehydration. Patients with severe DKA mayhave fluid deficits of 6 liters or more with anaverage weight loss of 5% to 10% of theirtotal body weight.18 This may develop over a12- to 24-hour period.6 Dehydration occurssecondary to osmotic diuresis, which resultsfrom glucosuria. Glucosuria develops when

the blood glucose concentration exceeds therenal threshold (160–180 mg/dL) for glucose.The loss of water and dehydration aresecondary to polyuria. Hyperventilation andvomiting may also contribute to fluid loss.The degree of dehydration can be assessed bydetermining the patient’s weight loss andbaseline weight. Otherwise, dehydration mustbe assessed by clinical signs. A dehydratedpatient may present with physical findings,including orthostatic hypotension and drymucous membranes.

Ketone production. Ketogenesis occurs in a state of insulin deficiency and counter-regulatory hormone excess, which results inketonemia and ketonuria. Insulin deficiencyleads to the breakdown of fat in adipose tissue(lipolysis) with the release of free fatty acids.Ketones are formed from free fatty acids inthe liver. The pathophysiologic basis of DKA isshown in Figure 3. Insulin is required for thesuppression of ketone production and thecorrection of acidosis. Insulin inhibitsglycogenolysis and gluconeogenesis,suppresses lipolysis, and facilitates theconservation of sodium and other electrolytesby the kidney.6

Glucagon plays an important role in the development of DKA because it influences

gluconeogenesis and ketogenesis.17

2

replacement.8 Common signs of HHS includestupor, dehydration, and hypotension. Theneurologic signs can range from aphasia toseizures or coma.

EpidemiologyThe incidence of DKA is estimated at 2episodes per 100 patient years. This may varybecause of diverse factors. Omission ofinsulin is a leading precipitating cause ofDKA. Some patients reported that they didnot have the money to buy insulin or fortransportation to a hospital or clinic; otherreasons given were lack of information onsick day protocol and low food intakebecause of lack of appetite.9 Drug and alcoholabuse are commonly associated with DKA.10

DKA episodes can often be attributed to thelack of early recognition and timely treatmentof diabetes.10,11 A diagnosis of diabetes isoften made following a severe DKAepisode.12,13 Approximately 20% to 30% ofDKA cases occur in patients with newlydiagnosed diabetes.12

The precipitating cause of DKA can beidentified in 80% of adult patients.6 AlthoughDKA occurs most often in type 1 diabetes,patients with type 2 diabetes may developDKA after many weeks of symptomatichyperglycemia. In a retrospective medicalrecord review, 39% of patients who presentedwith DKA had type 2 diabetes.14 Many patientshad no obvious precipitating causes other thanprolonged omission of oral hypoglycemictherapy.14 In another retrospective medicalrecord review, 55% of patients who presentedwith DKA had type 2 diabetes and infectionwas the most common cause of DKA.15 Incontrast, poor compliance with insulin therapywas the most frequent cause of DKA inpatients with type 1 diabetes.15

PathophysiologyInsulin deficiency triggers a complex metabolicprocess. This process may begin insidiously anddevelop during a period of hours to days. Type1 diabetes is characterized by a severe insulindeficiency, which results from autoimmunedestruction of pancreatic ß-cells. Type 1diabetes is usually diagnosed in individualsyounger than 30 years of age. Insulin deficiencyand hyperglycemia are usually not present untilapproximately 90% of insulin secretory capacityis lost.6

DKA occurs because of relative or absoluteinsulin deficiency coupled with a concomitantelevation of counter-regulatory hormones.Fleckman’s seesaw analogy describes thehormonal interplay that characterizes DKA(Fig. 2).16 Insulin, on one side of the seesaw,normally counterbalances the effect of thecounter-regulatory hormones (glucagon,catecholamines, cortisol, and growthhormone) on the opposite side.

Figure 2. Fleckman’s seesaw analogy fordiabetic ketoacidosis. Insulin is outweighedby the counter-regulatory hormones. From Fleckman AM. Diabetic ketoacidosis. EndocrinMetab Clin North Am. 1993;22:181-207.

Table 1 summarizes the effect of insulin andthe counter-regulatory hormones.17 A relativeor absolute deficiency of insulin and an excessof counter-regulatory hormones result in: (1) gluconeogenesis, (2) glycogenolysis, (3) inhibition of peripheral glucose utilization,(4) lipolysis, and (5) stimulation of ketogenesis.

Growth hormone

Cortisol

CatecholaminesInsulin

Liver Fat cell

Glucagon

Most patients with severe DKA have somealteration in their level of consciousness.

Table 1. Effects of Insulin and Counter-Regulatory Hormones

Gluconeogenesis Ketogenesis Glucose LipolysisUtilization

Liver Liver Muscle Adipose Tissue

Insulin ! ! " !

Glucagon " " # #

Epinephrine " " ! "

Cortisol " " ! "

Growth Hormone # " ! "

" Increased; ! Decreased; # Minimal or no effect.

From Ennis ED, Stahl E, Kreisberg RA. Diabetic ketoacidosis. In: Porte D Jr, Sherwin RS, eds. Ellenberg & Rifkin’s

Diabetes Mellitus. 5th ed. Stamford, Conn: Appleton & Lange; 1997:829.

5

discontinuation of insulin.17 A precipitatingfactor may not be identified in approximately20% to 30% of DKA cases.17 To prevent DKA,it is important for the healthcare team tounderstand factors that may precipitate anevent. These factors include the following:

■ Infection is the most common precipitatingfactor in the development of DKA.7 Itstimulates the release of counter-regulatoryhormones, which promote gluconeogenesisand glycogenolysis. Cytokines (eg,interleukin-1) are increased and may alsobe implicated.19

■ Cardiovascular events can occur as acomplication of DKA or trigger DKAbecause of acutely increased insulinrequirements. Cardiovascular events are a major cause of DKA-associated death.Myocardial infarction should always beconsidered as a possibility in an elderlypatient with DKA.20 In some patients,warning signs or symptoms of acutemyocardial infarction may be absent. Thiscould result in a treatment delay becausethe patient may not seek medical attentionat the critical time.

■ Substance abuse causes about 10% of theDKA cases. Patients with diabetes who areunder the influence of alcohol or illicitdrugs may not be able to administer insulinappropriately, which can result in insulindeficiency and DKA.21

■ Pregnancy may cause DKA secondary to anincrease in counter-regulatory hormones.The second and third trimesters ofpregnancy are associated with increasedinsulin requirements and insulin resistance.22

■ Psychiatric problems or any dramaticemotional responses to stress cancontribute to the development of DKA secondary to increased levels ofcounter-regulatory hormones.

■ Fasting and dehydration can contribute to DKA.

■ Errors in insulin/medication administrationmay precipitate DKA. These includedeliberate or inadvertent omission ofinsulin and inappropriate dosing of insulinduring sick days. DKA may also result frominappropriately withholding or reducingthe dose of insulin in a patient who isvomiting and unable to eat.

■ Insulin infusion pump malfunction can leadto an interruption in insulin delivery andresult in DKA.23 In the Diabetes Control andComplications Trial, DKA events werehigher in the insulin pump group (1.8 events/100 patient years) whencompared with the multiple-dose insulingroup (0.8 events/100 patient years).Complete insulin deficiency occurs inpatients with type 1 diabetes within a fewhours after a pump malfunction. Pumppatients must understand the importanceof maintaining appropriate insulin deliveryto minimize the risk of DKA. Good self-carecan prevent pump malfunction in themajority of cases. Routine monitoring ofblood glucose and attentiveness tosymptoms of hyperglycemia should helppump users promptly identify insulininfusion problems (eg, empty insulinreservoir, displaced needle, improperplacement of the pump reservoir, andinfusion line blockage). Inflammation orinfection at the injection site can beminimized by adhering to good hygieneand appropriate changes of the catheterinsertion site.

■ Other precipitating factors of DKA includepancreatitis, cerebrovascular accident,trauma, and drugs that affect carbohydratemetabolism (thiazide diuretics,corticosteroids, and others).7

4

Ionic changes. Ketoacids are excreted assodium and potassium salts, which contributeto the electrolyte disturbances seen in DKA. Inan attempt to correct or buffer the acidosis,potassium ions move from the intracellularspace to the extracellular space as hydrogenions move to the intracellular space. As aresult of the potassium shift to extracellularfluid and urinary potassium loss, patients withDKA have a deficit of total body potassium.However, initial lab values may show low,normal, or high values of potassium.

Figure 3. Pathophysiologic changes due toinsulin deficiency.

Compensatory AttemptsExcessive ketone production causes metabolicacidosis. DKA occurs when the increasedproduction of ketoacids overwhelms attemptsat compensation. The rapid overproduction ofketoacids depletes the buffering effect ofbicarbonate and results in acidosis. The bodyuses three defense mechanisms in an attemptto counter impending acidosis: (1) respiratorycompensation, (2) intracellular buffering, and(3) renal correction.12,19 Excess carbon dioxide isexhaled to correct the metabolic acidosis. Thisresults in tachypnea or Kussmaul’s respiration.In addition, buffering occurs when excesshydrogen ions move intracellularly inexchange for potassium ions to maintain aneutral intracellular charge. The kidneysattempt to correct ketoacidosis by increasingthe excretion of ketoacids. Acidosis willcontinue to worsen if not corrected by theadministration of insulin.

Triggers of Diabetic KetoacidosisDKA can be precipitated by many conditionsthat result in insufficient circulating levels ofinsulin or lead to the development of insulinresistance (Fig. 4). Some of these conditionsmay promote transient hyperglycemia inpatients without established diabetes. DKAmay occur in new onset patients with diabetesor in previously diagnosed patients who donot exercise proper self-care (eg, omission ofor inadequate doses of insulin) or are notbeing properly managed.

Figure 4. Precipitating diabetic ketoacidosisfactors in 202 patients admitted to theUniversity of Tennessee – Memphis, ClinicalResearch Center. From Kitabchi AE, Fisher JN, Murphy MB, Rumbak MJ.Diabetic ketoacidosis and hyperglycemic, hyperosmolarnonketotic state. In: Kahn CR, Weir GC, eds. Joslin’sDiabetes Mellitus. 13th ed. Baltimore, Md: LippincottWilliams & Wilkins, 1994:738–770.

Intercurrent medical illness is the triggeringevent in 50% to 60% of adult cases of DKA.17

Unfortunately, intercurrent illness is oftenerroneously accompanied by the

Infections38%

Omission of orInadequate Insulin

28%

Unknown2%

Other10%

NewlyDiagnosed DM

22%

Ketogenesis may rapidly overwhelm allattempts at compensation.

INSULIN DEFICIENCY

LIVERIncreased

Gluconeogenesis

PERIPHERYDecreased Glucose

Utilization

ADIPOSE TISSUEIncreasedLipolysis

LIVERIncreased

Ketogenesis

HYPERGLYCEMIA KETOACIDOSIS

5

discontinuation of insulin.17 A precipitatingfactor may not be identified in approximately20% to 30% of DKA cases.17 To prevent DKA,it is important for the healthcare team tounderstand factors that may precipitate anevent. These factors include the following:

■ Infection is the most common precipitatingfactor in the development of DKA.7 Itstimulates the release of counter-regulatoryhormones, which promote gluconeogenesisand glycogenolysis. Cytokines (eg,interleukin-1) are increased and may alsobe implicated.19

■ Cardiovascular events can occur as acomplication of DKA or trigger DKAbecause of acutely increased insulinrequirements. Cardiovascular events are a major cause of DKA-associated death.Myocardial infarction should always beconsidered as a possibility in an elderlypatient with DKA.20 In some patients,warning signs or symptoms of acutemyocardial infarction may be absent. Thiscould result in a treatment delay becausethe patient may not seek medical attentionat the critical time.

■ Substance abuse causes about 10% of theDKA cases. Patients with diabetes who areunder the influence of alcohol or illicitdrugs may not be able to administer insulinappropriately, which can result in insulindeficiency and DKA.21

■ Pregnancy may cause DKA secondary to anincrease in counter-regulatory hormones.The second and third trimesters ofpregnancy are associated with increasedinsulin requirements and insulin resistance.22

■ Psychiatric problems or any dramaticemotional responses to stress cancontribute to the development of DKA secondary to increased levels ofcounter-regulatory hormones.

■ Fasting and dehydration can contribute to DKA.

■ Errors in insulin/medication administrationmay precipitate DKA. These includedeliberate or inadvertent omission ofinsulin and inappropriate dosing of insulinduring sick days. DKA may also result frominappropriately withholding or reducingthe dose of insulin in a patient who isvomiting and unable to eat.

■ Insulin infusion pump malfunction can leadto an interruption in insulin delivery andresult in DKA.23 In the Diabetes Control andComplications Trial, DKA events werehigher in the insulin pump group (1.8 events/100 patient years) whencompared with the multiple-dose insulingroup (0.8 events/100 patient years).Complete insulin deficiency occurs inpatients with type 1 diabetes within a fewhours after a pump malfunction. Pumppatients must understand the importanceof maintaining appropriate insulin deliveryto minimize the risk of DKA. Good self-carecan prevent pump malfunction in themajority of cases. Routine monitoring ofblood glucose and attentiveness tosymptoms of hyperglycemia should helppump users promptly identify insulininfusion problems (eg, empty insulinreservoir, displaced needle, improperplacement of the pump reservoir, andinfusion line blockage). Inflammation orinfection at the injection site can beminimized by adhering to good hygieneand appropriate changes of the catheterinsertion site.

■ Other precipitating factors of DKA includepancreatitis, cerebrovascular accident,trauma, and drugs that affect carbohydratemetabolism (thiazide diuretics,corticosteroids, and others).7

4

Ionic changes. Ketoacids are excreted assodium and potassium salts, which contributeto the electrolyte disturbances seen in DKA. Inan attempt to correct or buffer the acidosis,potassium ions move from the intracellularspace to the extracellular space as hydrogenions move to the intracellular space. As aresult of the potassium shift to extracellularfluid and urinary potassium loss, patients withDKA have a deficit of total body potassium.However, initial lab values may show low,normal, or high values of potassium.

Figure 3. Pathophysiologic changes due toinsulin deficiency.

Compensatory AttemptsExcessive ketone production causes metabolicacidosis. DKA occurs when the increasedproduction of ketoacids overwhelms attemptsat compensation. The rapid overproduction ofketoacids depletes the buffering effect ofbicarbonate and results in acidosis. The bodyuses three defense mechanisms in an attemptto counter impending acidosis: (1) respiratorycompensation, (2) intracellular buffering, and(3) renal correction.12,19 Excess carbon dioxide isexhaled to correct the metabolic acidosis. Thisresults in tachypnea or Kussmaul’s respiration.In addition, buffering occurs when excesshydrogen ions move intracellularly inexchange for potassium ions to maintain aneutral intracellular charge. The kidneysattempt to correct ketoacidosis by increasingthe excretion of ketoacids. Acidosis willcontinue to worsen if not corrected by theadministration of insulin.

Triggers of Diabetic KetoacidosisDKA can be precipitated by many conditionsthat result in insufficient circulating levels ofinsulin or lead to the development of insulinresistance (Fig. 4). Some of these conditionsmay promote transient hyperglycemia inpatients without established diabetes. DKAmay occur in new onset patients with diabetesor in previously diagnosed patients who donot exercise proper self-care (eg, omission ofor inadequate doses of insulin) or are notbeing properly managed.

Figure 4. Precipitating diabetic ketoacidosisfactors in 202 patients admitted to theUniversity of Tennessee – Memphis, ClinicalResearch Center. From Kitabchi AE, Fisher JN, Murphy MB, Rumbak MJ.Diabetic ketoacidosis and hyperglycemic, hyperosmolarnonketotic state. In: Kahn CR, Weir GC, eds. Joslin’sDiabetes Mellitus. 13th ed. Baltimore, Md: LippincottWilliams & Wilkins, 1994:738–770.

Intercurrent medical illness is the triggeringevent in 50% to 60% of adult cases of DKA.17

Unfortunately, intercurrent illness is oftenerroneously accompanied by the

Infections38%

Omission of orInadequate Insulin

28%

Unknown2%

Other10%

NewlyDiagnosed DM

22%

Ketogenesis may rapidly overwhelm allattempts at compensation.

INSULIN DEFICIENCY

LIVERIncreased

Gluconeogenesis

PERIPHERYDecreased Glucose

Utilization

ADIPOSE TISSUEIncreasedLipolysis

LIVERIncreased

Ketogenesis

HYPERGLYCEMIA KETOACIDOSIS

7

membranes, tachycardia, and orthostatichypotension. A change in systolic pressure ofmore than 10 mmHg represents a fluidvolume deficit and may be indicative ofsystemic dehydration. Urinary output maydecrease to less than 30 mL/hr and the patientmay develop anuria.24

DKA must be differentiated from other causesof acidosis. The diagnosis of DKA may beconfused with alcoholic ketoacidosis orstarvation ketosis because both conditionscause ketonemia and acidosis. Isolatedalcoholic ketoacidosis is usually characterizedby mild to moderate metabolic acidosis, anincreased anion gap, and normoglycemia orhypoglycemia. Starvation ketosis is usuallycharacterized by a normal arterial pH, amildly increased anion gap, and the absenceof significant ketonemia.8 The diagnosticcriteria and typical total body deficits in DKAare listed in Table 3.

Table 3. Diagnostic Criteria and Typical TotalBody Deficits in Diabetic Ketoacidosis

Diagnostic Criteria*

Blood glucose > 250 mg/dL (13.9 mmol/L)

Arterial pH < 7.3

Serum bicarbonate < 15 mEq/L

Urinary ketone† Positive

Serum ketone Positive at 1:2 dilutions

Serum osmolality Variable

Typical Deficits

Water 6 L or 100 mL/kbw

Sodium 7–10 mEq/kbw

Potassium 3–5 mEq/kbw

Phosphate ~1 mmol/kbw

From Kitabchi AE, Wall BM. Management of diabeticketoacidosis. Am Fam Physician. 1999;60:456.

kbw, kg body weight.

*Not all patients will meet all diagnostic criteria, depending onhydration status, previous administration of diabetestreatment, and other factors.

†Nitroprusside reaction method.

Anion GapArterial pH is a measure of the acidity oralkalinity of the blood. The arterial pH in apatient with DKA reflects the degree ofrespiratory compensation and severity of acid-base disturbance. In DKA, ketoacidsionize at physiologic pH and the hydrogenion of the ketoacids is buffered essentiallymole for mole by bicarbonate, which resultsin the consumption and decrease in theserum bicarbonate. Since bicarbonate isoverwhelmed by ketogenesis, metabolicacidosis occurs, bicarbonate depletes, and theanion gap increases. In DKA, the increase inthe anion gap is usually equivalent to thedecrease in the bicarbonate concentration.Table 4 lists average laboratory findings inDKA and compares them with averagenormal laboratory values.17

The anion gap is calculated bysubtracting the sum of the chloride and bicarbonate concentrations fromthe “uncorrected” serum sodiumconcentration:

[Na+ – (Cl– + HCO3

–)]

The normal range is from 8 to 16 mEq/Lbecause of the unmeasured anions thatare present in the plasma, primarilyalbumin and phosphate. The change ingap is equal to the patient’s calculatedanion gap minus 12 mEq/L.17

Normal IndividualNa 140, Cl 101, HCO3 27Anion gap: [140 - (101 + 27)] = 12An anion gap of 12 is normal (range 8–16)

Patient With DKANa 130, Cl 98, HCO3 10Anion gap: [130 - (98 + 10)] = 22This anion gap is elevated; therefore,calculate the change in anion gap, whichis 22 - 12 (normal) = 10

6

Warning Signs andSymptomsClinical signs and symptoms of DKA mayinclude polyuria, polydipsia, vomiting,“fruity”(acetone) breath, dehydration,abdominal pain, and hyperventilation (Table 2). Symptoms of DKA may mimic otherdisease states or medical conditions. Non-specific symptoms include lethargy, malaise,headache, and weakness. DKA should beconsidered in any ill person with diabetes,especially if nausea and vomiting are present.Although the clinical diagnosis of DKA isusually clear in a patient with type 1 diabetes,DKA should not be ruled out in an ill, elderlypatient with type 2 diabetes.

Table 2. Common Symptoms and Signs ofDiabetic Ketoacidosis

Symptoms

■ Nausea and vomiting ■ Abdominal pain

■ Thirst and polyuria ■ Visual disturbances

■ Weakness and/or ■ Somnolenceanorexia

Signs

■ Tachycardia ■ Weight loss

■ Hypotension ■ Warm, dry skin

■ Hyperpnea or ■ Impaired

Kussmaul’s respiration consciousness

■ “Fruity” breath and/or coma

(odor of ketones) ■ Dehydration

Adapted from American Diabetes Association. Diabeticketoacidosis. In: American Diabetes Association. MedicalManagement of Type 1 Diabetes. 3rd ed. Alexandria, Va:American Diabetes Association; 1998:123.

Vomiting may signal an advanced stage ofDKA. Polydipsia cannot compensate fordehydration. Urinary output continues because

of persistent osmotic diuresis. Alterations inmental status, ranging from drowsiness tocoma, may be seen in 10% to 20% of allpatients with DKA.24 Electrolyte and metabolicabnormalities seen in DKA include:

■ pH < 7.3

■ Hypokalemia (usually after therapy hasbeen initiated)

■ Hypernatremia or hyponatremia

■ Hyperosmolality

■ Hyperglycemia

■ Hypertriglyceridemia

DiagnosisThe diagnosis of DKA must be made rapidlyto prevent morbidity and mortality. Thediagnosis of DKA can be difficult to make ininfants, young children, and the elderly. Thepatient may present with some or all of thesymptoms previously discussed. The diagnosiscan be made after obtaining a medical historyand physical examination. The patient’smedical history should be taken with specialattention paid to recent infections,compliance with insulin or oral antidiabetictherapy, concomitant medication use, andconcurrent medical illnesses. It is importantfor the physician to obtain thoroughinformation about the patient’s diabetichistory. If the patient is comatose, familymembers should be carefully questioned.

Hypotension, tachycardia, and tachypnea maybe present. A rectal temperature may berequired if tachypnea precludes oralmeasurement. An elevated body temperaturewarrants a careful examination andevaluation for possible infection. However,patients may not be febrile, even in thepresence of an underlying infection.24 Asubnormal temperature may result fromvasodilation. Hypothermia is an alarming signand may be associated with increasedmortality.24 Dehydration may result in poorskin turgor, warm dry skin, dry mucous

7

membranes, tachycardia, and orthostatichypotension. A change in systolic pressure ofmore than 10 mmHg represents a fluidvolume deficit and may be indicative ofsystemic dehydration. Urinary output maydecrease to less than 30 mL/hr and the patientmay develop anuria.24

DKA must be differentiated from other causesof acidosis. The diagnosis of DKA may beconfused with alcoholic ketoacidosis orstarvation ketosis because both conditionscause ketonemia and acidosis. Isolatedalcoholic ketoacidosis is usually characterizedby mild to moderate metabolic acidosis, anincreased anion gap, and normoglycemia orhypoglycemia. Starvation ketosis is usuallycharacterized by a normal arterial pH, amildly increased anion gap, and the absenceof significant ketonemia.8 The diagnosticcriteria and typical total body deficits in DKAare listed in Table 3.

Table 3. Diagnostic Criteria and Typical TotalBody Deficits in Diabetic Ketoacidosis

Diagnostic Criteria*

Blood glucose > 250 mg/dL (13.9 mmol/L)

Arterial pH < 7.3

Serum bicarbonate < 15 mEq/L

Urinary ketone† Positive

Serum ketone Positive at 1:2 dilutions

Serum osmolality Variable

Typical Deficits

Water 6 L or 100 mL/kbw

Sodium 7–10 mEq/kbw

Potassium 3–5 mEq/kbw

Phosphate ~1 mmol/kbw

From Kitabchi AE, Wall BM. Management of diabeticketoacidosis. Am Fam Physician. 1999;60:456.

kbw, kg body weight.

*Not all patients will meet all diagnostic criteria, depending onhydration status, previous administration of diabetestreatment, and other factors.

†Nitroprusside reaction method.

Anion GapArterial pH is a measure of the acidity oralkalinity of the blood. The arterial pH in apatient with DKA reflects the degree ofrespiratory compensation and severity of acid-base disturbance. In DKA, ketoacidsionize at physiologic pH and the hydrogenion of the ketoacids is buffered essentiallymole for mole by bicarbonate, which resultsin the consumption and decrease in theserum bicarbonate. Since bicarbonate isoverwhelmed by ketogenesis, metabolicacidosis occurs, bicarbonate depletes, and theanion gap increases. In DKA, the increase inthe anion gap is usually equivalent to thedecrease in the bicarbonate concentration.Table 4 lists average laboratory findings inDKA and compares them with averagenormal laboratory values.17

The anion gap is calculated bysubtracting the sum of the chloride and bicarbonate concentrations fromthe “uncorrected” serum sodiumconcentration:

[Na+ – (Cl– + HCO3

–)]

The normal range is from 8 to 16 mEq/Lbecause of the unmeasured anions thatare present in the plasma, primarilyalbumin and phosphate. The change ingap is equal to the patient’s calculatedanion gap minus 12 mEq/L.17

Normal IndividualNa 140, Cl 101, HCO3 27Anion gap: [140 - (101 + 27)] = 12An anion gap of 12 is normal (range 8–16)

Patient With DKANa 130, Cl 98, HCO3 10Anion gap: [130 - (98 + 10)] = 22This anion gap is elevated; therefore,calculate the change in anion gap, whichis 22 - 12 (normal) = 10

6

Warning Signs andSymptomsClinical signs and symptoms of DKA mayinclude polyuria, polydipsia, vomiting,“fruity”(acetone) breath, dehydration,abdominal pain, and hyperventilation (Table 2). Symptoms of DKA may mimic otherdisease states or medical conditions. Non-specific symptoms include lethargy, malaise,headache, and weakness. DKA should beconsidered in any ill person with diabetes,especially if nausea and vomiting are present.Although the clinical diagnosis of DKA isusually clear in a patient with type 1 diabetes,DKA should not be ruled out in an ill, elderlypatient with type 2 diabetes.

Table 2. Common Symptoms and Signs ofDiabetic Ketoacidosis

Symptoms

■ Nausea and vomiting ■ Abdominal pain

■ Thirst and polyuria ■ Visual disturbances

■ Weakness and/or ■ Somnolenceanorexia

Signs

■ Tachycardia ■ Weight loss

■ Hypotension ■ Warm, dry skin

■ Hyperpnea or ■ Impaired

Kussmaul’s respiration consciousness

■ “Fruity” breath and/or coma

(odor of ketones) ■ Dehydration

Adapted from American Diabetes Association. Diabeticketoacidosis. In: American Diabetes Association. MedicalManagement of Type 1 Diabetes. 3rd ed. Alexandria, Va:American Diabetes Association; 1998:123.

Vomiting may signal an advanced stage ofDKA. Polydipsia cannot compensate fordehydration. Urinary output continues because

of persistent osmotic diuresis. Alterations inmental status, ranging from drowsiness tocoma, may be seen in 10% to 20% of allpatients with DKA.24 Electrolyte and metabolicabnormalities seen in DKA include:

■ pH < 7.3

■ Hypokalemia (usually after therapy hasbeen initiated)

■ Hypernatremia or hyponatremia

■ Hyperosmolality

■ Hyperglycemia

■ Hypertriglyceridemia

DiagnosisThe diagnosis of DKA must be made rapidlyto prevent morbidity and mortality. Thediagnosis of DKA can be difficult to make ininfants, young children, and the elderly. Thepatient may present with some or all of thesymptoms previously discussed. The diagnosiscan be made after obtaining a medical historyand physical examination. The patient’smedical history should be taken with specialattention paid to recent infections,compliance with insulin or oral antidiabetictherapy, concomitant medication use, andconcurrent medical illnesses. It is importantfor the physician to obtain thoroughinformation about the patient’s diabetichistory. If the patient is comatose, familymembers should be carefully questioned.

Hypotension, tachycardia, and tachypnea maybe present. A rectal temperature may berequired if tachypnea precludes oralmeasurement. An elevated body temperaturewarrants a careful examination andevaluation for possible infection. However,patients may not be febrile, even in thepresence of an underlying infection.24 Asubnormal temperature may result fromvasodilation. Hypothermia is an alarming signand may be associated with increasedmortality.24 Dehydration may result in poorskin turgor, warm dry skin, dry mucous

9

the re-evaluation is hourly for the first 4 hoursand continues every 2 to 4 hours, dependingon the patient’s condition.

The healthcare team may follow a “criticalpathway,” a comprehensive guide fortreatment that includes anticipatedinterventions and expected outcomes.Appendix B is an example of a criticalpathway used to guide a multidisciplinaryteam through the management of DKA.These protocols improve the quality of carereceived by patients and are cost-effective.24

The ADA guidelines for fluid replacement,insulin administration, and potassiumreplacement in adult patients with DKA aredepicted in Figure 5. Adequate rehydrationrestores and maintains intravascular volumeand preserves adequate renal blood flow.

Regular insulin by continuous intravenousinfusion is the treatment of choice for DKA unless the DKA episode is mild. Anintravenous bolus of regular insulin at 0.15 units/kg body weight, followed bycontinuous infusion of regular insulin at adose of 0.1 units/kg/hr should beadministered.7 This low dose of insulin usuallydecreases plasma glucose concentration at arate of 50–70 mg/dL/hr, which is similar to ahigher dose insulin regimen (Fig. 5). If theplasma glucose levels do not decrease by atleast 50 mg/dL from the original value in thefirst hour, the hydration status should bechecked. If the hydration status is acceptable,then the insulin infusion may be doubledevery hour until a steady decline in glucosebetween 50–70 mg/hr is achieved.7 Once theplasma glucose reaches 250 mg/dL, the insulininfusion rate can be decreased to 0.05–0.1 units/kg/hr, and 5% to 10% dextrosecan be added to the intravenous fluids.

Insulin enhances the intracellular movementof potassium during the treatment of DKA.Timely potassium replacement during therapyfor DKA is essential to avoid potentially life-threatening hypokalemia. Appropriatecaution is necessary in patients with severehypokalemia associated with dehydration andhyperglycemia to avoid potentially fatalcardiac arrhythmias.

Potassium is generally initiated after serumlevels decrease below 5.0 mEq/L (see Fig. 5).Potassium replacement is started earlier inpatients with serum potassium levels below 3.3 mEq/L, exhibiting electrocardiogram (ECG)signs of flat or inverted T waves, depressed STsegments, and emergence of U waves. Somephysicians may recommend temporarilywithholding insulin and bicarbonateadministration until sufficient intravenouspotassium is administered.7

The risks and benefits of sodium bicarbonatereplacement are listed in Table 5. Bicarbonatelevels increase during insulin therapy. The use of bicarbonate in DKA is controversial. IfpH is less than 7.0, bicarbonate may beadministered (see Fig. 5). Some physiciansrecommend administering bicarbonate whenpatients are severely acidotic, especially ifhypotension, shock, or arrhythmias arepresent.6 However, no prospective,randomized studies have shown benefitsassociated with bicarbonate administration.7

Patients with DKA are usually phosphate-depleted, secondary to decreased food intake,excessive catabolism, and increased urinaryexcretion. However, serum phosphate is oftennormal or increased at presentation.7 Theadministration of insulin enhances theintracellular movement of phosphate, whichreduces the plasma phosphate concentration.Potassium phosphate can be administeredcautiously during treatment to preventhypophosphatemia, although there are nocontrolled trials demonstrating a definitebenefit. For patients with serum phosphate

Modern management of DKAemphasizes the use of lower doses of

insulin to avoid hypoglycemia and othercomplications of treatment.

8

Treatment GuidelinesThe goal of treatment is to reverse theunderlying metabolic abnormalities andnormalize the serum glucose. Emergencytreatment of DKA involves correctingdehydration, hyperglycemia, and electrolyteimbalances. The degree of hyperglycemia,acidosis, dehydration, and impairment ofconsciousness may vary depending on theseverity of metabolic derangement,nutritional status, duration of DKA,

concomitant medications and illnesses, andthe degree of insulin deficiency.

The reversal of these abnormalities should beundertaken with meticulous care and frequentmonitoring to correct and avoid seriouselectrolyte imbalances and fluid overload.Appendix A provides an example of a DKAflow sheet used by healthcare professionals torecord treatment and successive changes in thepatient’s status. During the first 12 hours oftherapy, the frequency of re-evaluationdepends on the patient’s condition. Typically,

Table 4. Average Laboratory Findings in Diabetic Ketoacidosis Versus Average Normal Laboratory Values

Parameter Diabetic NormalKetoacidosis* Values†

Plasma glucose (mg/dL) 475 60–110

Serum osmolality (mosm/kg) 309 275–293

Sodium (mEq/L) 131 135–145

Potassium (mEq/L) 4.8 3.5–5.0

HCO3- (mEq/L) 9 23–29

BUN (mg/dL) 21 8–20

Anion gap (mEq/L) 29 8–16

∆ Gap (anion gap – 12) (mEq/L) 17 N/A

Arterial pH < 7.3 7.35–7.45

Ketonuria ≥ 3+ N/A

Growth hormone (ng/mL) 7.9 0–5

Cortisol, 8 AM (µg/dL) 49 5–20

Free fatty acids (mmol/L) 2.26 0.19–0.9

Glucagon (pg/mL) 400–500 50–200

Lactate, plasma (mmol/L) 4.6 Venous 0.5–2.02Arterial 0.5–1.6

ß-hydroxybutyrate (mmol/L) 13.7 N/A

Catecholamines, total free (µg/mL) 1.78 ± 4 4–126 µg/24 hr

*All average laboratory values for diabetic ketoacidosis were taken from Ennis ED, Stahl E, Kreisberg RA. Diabetic ketoacidosis. In: Porte D Jr, Sherwin RS, eds. Ellenberg & Rifkin’s Diabetes Mellitus. 5th ed. Stamford, Conn: Appleton & Lange; 1997:831.

†All normal laboratory values were taken from Spraycar M, ed. Stedman’s Medical Dictionary. 26th ed. Philadelphia, Pa: Williams &Wilkins; 1995:1992–2010; Beers MH, Berkow R, eds. The Merck Manual of Diagnosis and Therapy. 17th ed. Centennial Edition. 1999.Available at http://www.merck.com/pubs/mmanual/. Accessed on May 6, 2002; and Tierney LM Jr, McPhee SJ, Papadakis MA, eds.Current Medical Diagnosis & Treatment. 41st ed. New York, NY: The McGraw-Hill Companies; 2002:1711–1719.

9

the re-evaluation is hourly for the first 4 hoursand continues every 2 to 4 hours, dependingon the patient’s condition.

The healthcare team may follow a “criticalpathway,” a comprehensive guide fortreatment that includes anticipatedinterventions and expected outcomes.Appendix B is an example of a criticalpathway used to guide a multidisciplinaryteam through the management of DKA.These protocols improve the quality of carereceived by patients and are cost-effective.24

The ADA guidelines for fluid replacement,insulin administration, and potassiumreplacement in adult patients with DKA aredepicted in Figure 5. Adequate rehydrationrestores and maintains intravascular volumeand preserves adequate renal blood flow.

Regular insulin by continuous intravenousinfusion is the treatment of choice for DKA unless the DKA episode is mild. Anintravenous bolus of regular insulin at 0.15 units/kg body weight, followed bycontinuous infusion of regular insulin at adose of 0.1 units/kg/hr should beadministered.7 This low dose of insulin usuallydecreases plasma glucose concentration at arate of 50–70 mg/dL/hr, which is similar to ahigher dose insulin regimen (Fig. 5). If theplasma glucose levels do not decrease by atleast 50 mg/dL from the original value in thefirst hour, the hydration status should bechecked. If the hydration status is acceptable,then the insulin infusion may be doubledevery hour until a steady decline in glucosebetween 50–70 mg/hr is achieved.7 Once theplasma glucose reaches 250 mg/dL, the insulininfusion rate can be decreased to 0.05–0.1 units/kg/hr, and 5% to 10% dextrosecan be added to the intravenous fluids.

Insulin enhances the intracellular movementof potassium during the treatment of DKA.Timely potassium replacement during therapyfor DKA is essential to avoid potentially life-threatening hypokalemia. Appropriatecaution is necessary in patients with severehypokalemia associated with dehydration andhyperglycemia to avoid potentially fatalcardiac arrhythmias.

Potassium is generally initiated after serumlevels decrease below 5.0 mEq/L (see Fig. 5).Potassium replacement is started earlier inpatients with serum potassium levels below 3.3 mEq/L, exhibiting electrocardiogram (ECG)signs of flat or inverted T waves, depressed STsegments, and emergence of U waves. Somephysicians may recommend temporarilywithholding insulin and bicarbonateadministration until sufficient intravenouspotassium is administered.7

The risks and benefits of sodium bicarbonatereplacement are listed in Table 5. Bicarbonatelevels increase during insulin therapy. The use of bicarbonate in DKA is controversial. IfpH is less than 7.0, bicarbonate may beadministered (see Fig. 5). Some physiciansrecommend administering bicarbonate whenpatients are severely acidotic, especially ifhypotension, shock, or arrhythmias arepresent.6 However, no prospective,randomized studies have shown benefitsassociated with bicarbonate administration.7

Patients with DKA are usually phosphate-depleted, secondary to decreased food intake,excessive catabolism, and increased urinaryexcretion. However, serum phosphate is oftennormal or increased at presentation.7 Theadministration of insulin enhances theintracellular movement of phosphate, whichreduces the plasma phosphate concentration.Potassium phosphate can be administeredcautiously during treatment to preventhypophosphatemia, although there are nocontrolled trials demonstrating a definitebenefit. For patients with serum phosphate

Modern management of DKAemphasizes the use of lower doses of

insulin to avoid hypoglycemia and othercomplications of treatment.

8

Treatment GuidelinesThe goal of treatment is to reverse theunderlying metabolic abnormalities andnormalize the serum glucose. Emergencytreatment of DKA involves correctingdehydration, hyperglycemia, and electrolyteimbalances. The degree of hyperglycemia,acidosis, dehydration, and impairment ofconsciousness may vary depending on theseverity of metabolic derangement,nutritional status, duration of DKA,

concomitant medications and illnesses, andthe degree of insulin deficiency.

The reversal of these abnormalities should beundertaken with meticulous care and frequentmonitoring to correct and avoid seriouselectrolyte imbalances and fluid overload.Appendix A provides an example of a DKAflow sheet used by healthcare professionals torecord treatment and successive changes in thepatient’s status. During the first 12 hours oftherapy, the frequency of re-evaluationdepends on the patient’s condition. Typically,

Table 4. Average Laboratory Findings in Diabetic Ketoacidosis Versus Average Normal Laboratory Values

Parameter Diabetic NormalKetoacidosis* Values†

Plasma glucose (mg/dL) 475 60–110

Serum osmolality (mosm/kg) 309 275–293

Sodium (mEq/L) 131 135–145

Potassium (mEq/L) 4.8 3.5–5.0

HCO3- (mEq/L) 9 23–29

BUN (mg/dL) 21 8–20

Anion gap (mEq/L) 29 8–16

∆ Gap (anion gap – 12) (mEq/L) 17 N/A

Arterial pH < 7.3 7.35–7.45

Ketonuria ≥ 3+ N/A

Growth hormone (ng/mL) 7.9 0–5

Cortisol, 8 AM (µg/dL) 49 5–20

Free fatty acids (mmol/L) 2.26 0.19–0.9

Glucagon (pg/mL) 400–500 50–200

Lactate, plasma (mmol/L) 4.6 Venous 0.5–2.02Arterial 0.5–1.6

ß-hydroxybutyrate (mmol/L) 13.7 N/A

Catecholamines, total free (µg/mL) 1.78 ± 4 4–126 µg/24 hr

*All average laboratory values for diabetic ketoacidosis were taken from Ennis ED, Stahl E, Kreisberg RA. Diabetic ketoacidosis. In: Porte D Jr, Sherwin RS, eds. Ellenberg & Rifkin’s Diabetes Mellitus. 5th ed. Stamford, Conn: Appleton & Lange; 1997:831.

†All normal laboratory values were taken from Spraycar M, ed. Stedman’s Medical Dictionary. 26th ed. Philadelphia, Pa: Williams &Wilkins; 1995:1992–2010; Beers MH, Berkow R, eds. The Merck Manual of Diagnosis and Therapy. 17th ed. Centennial Edition. 1999.Available at http://www.merck.com/pubs/mmanual/. Accessed on May 6, 2002; and Tierney LM Jr, McPhee SJ, Papadakis MA, eds.Current Medical Diagnosis & Treatment. 41st ed. New York, NY: The McGraw-Hill Companies; 2002:1711–1719.

11

Table 5. Risks and Benefits of SodiumBicarbonate Replacement

Benefits

■ Corrects extracellular acidosis■ Reduces excessive chloride administration■ Reduces respiratory rate and increasescomfort

■ Reduces cardiac irritability■ Increases responsiveness of vascular system to pressor agents

Risks

■ Accelerated reduction in plasma potassiumconcentration

■ Sodium overload in elderly patients■ Exacerbation of intracellular acidosis

From American Diabetes Association. Diabetic ketoacidosis. In:American Diabetes Association. Medical Management of Type 1Diabetes. 3rd ed. Clinical Education Series. Alexandria, Va:American Diabetes Association; 1998:128–129.

Recovery CarePatients with DKA require intensive medicalcare, monitoring, follow-up, and education.Two important management principles arefollowed during the recovery period: (1) continue administering insulin; and (2) allow patients to eat. Intravenous fluidsand short-acting insulin are continued untilacidosis is corrected and the patient can ingestfood without vomiting. Early feeding isconsidered because the added carbohydrate inthe presence of insulin assists in the clearanceof ketones. It may take 1 week in the adultpatient to correct all biochemical abnormalitiesassociated with an episode of DKA.6

When the decision is made to begin feeding,the patient is switched from intravenous tosubcutaneous insulin. Since subcutaneousinsulin acts more slowly than intravenousinsulin, the transition to subcutaneous insulinis initiated with caution to avoid recurrence

of acidosis during the transition phase. Theinsulin drip is discontinued subsequently.Glucose levels are monitored 2 hours laterand at least every 4 hours subsequently untila relatively stable subcutaneous insulinregimen is established.

Electrolyte ManagementDuring RecoveryHyperchloremic acidosis with a normal aniongap is a common occurrence during recovery.During an episode of DKA, sodium is excretedas the sodium salt of ketoacids. Relativehyperchloremia can occur when treatmentwith intravenous solutions containing equalparts of sodium and chloride is used.16 Becausechloride losses are smaller than sodium losses,relative hyperchloremia occurs with therapy.The correction of DKA causes sodiumbicarbonate to shift into the intracellularspace leaving chloride over-represented in theextracellular space.16 If the anion gapgradually normalizes during therapy, asubsequent period of hyperchloremia-relatednonanion gap acidosis is of no clinical concern.

The presence of hypophosphatemia at theoutset of treatment suggests the possibility ofprofound total body phosphate depletion.6

Potassium phosphate administration may beneeded to prevent severe hypophosphatemiaduring treatment.

ComplicationsThe majority of cases of DKA are treatedsuccessfully without complications. However,potentially life-threatening complications are possible and include: hypoglycemia,hypokalemia, hyperchloremia,thromboembolic events, congestive heartfailure, cerebral edema, and acute respiratorydistress syndrome.

Hypoglycemia can occur if an excess of insulinis administered relative to glucose supply.Severe hypoglycemia can be a life-

10

Management of Adult Patients with DKA*

Complete initial evaluation.† Start IV fluids: 1.0 L of 0.9% NaCl per hour initially (15–20 mL • kg-1 • h-1).

IV Fluids

Determine hydration status IV Route pH < 6.9 pH 6.9–7.0 pH > 7.0SC/IM Route

If serum K+ is < 3.3 mEq/L, hold

insulin and give 40 mEq K+ per h

(2/3 KCL and 1/3 KPO4) until K ≥ 3.3 mEq/L

Insulin Potassium

Dilute NaHCO3

(100 mmol) in400 mL H2O. Infuse

at 200 mL/h.

Repeat HCO3 administration every2 h until pH > 7.0. Monitor serum K+.

Dilute NaHCO3


at 200 mL/h.

NoHCO3

If serum K+ ≥ 3.3 but < 5.0 mEq/L,

give 20–30 mEq K+ in each liter

of IV fluid (2/3 as KCL and 1/3 as KPO4) to keep serum K

+

at 4–5 mEq/L

If serum K+ ≥ 5.0 mEq/L, do not

give K+ but check K

+ every 2 h

Insulin: Regular0.15 units/kg as

IV bolus

Hypovolemicshock

Mildhypotension

Cardiogenicshock

Serum Nahigh

Serum Nanormal

Serum Nalow

0.9% NaCl(4–14 mL • kg-1 • h-1)

depending onhydration state

0.45% NaCl(4–14 mL • kg-1 • h-1)


Administer0.9% NaCl

(1.0 L/h) and/orplasma expander

Hemodynamicmonitoring

Insulin: Regular0.4 units/kg 1/2 IV bolus, 1/2 IM or SC

0.1 units • kg-1 • h-1 IVinsulin infusion

0.1 units • kg-1 • h-1

Regular insulinSC or IM

Double insulin infusion hourly until

glucose falls by 50–70 mg/dL

Give hourly IV insulinbolus (10 units) until

glucose falls by50–70 mg/dL

If serum glucose does not fall by50–70 mg/dL in first hour.

Assess Need for Bicarbonate

Evaluate corrected serum Na+++

When serum glucose reaches 250 mg/dL

Change to 5% dextrose with 0.45% NaCl at 150–250 mL/h with adequate insulin (0.05–0.1 units • kg-1 • h-1 IV infusion or 5–10 units SC every 2 h) to keep the serum glucose between 150 and 200 mg/dL until metabolic control is achieved.

Check electrolytes, BUN, creatinine and glucose every 2–4 h until stable. After resolution of DKA, if the patient is NPO, continue IV insulin and supplement with SC regular insulin as needed. When the patient can eat, initiate a multidose insulin regimen and adjust as needed. Continue IV insulin infusion for 1–2 h after SC insulin is begun to ensure adequate plasma insulin levels. Continue to look for precipitating cause(s).

Figure 5. A flow diagram for the management of adult patients with diabetic ketoacidosis. Copyright ©2002 American Diabetes Association. From Diabetes Care, Vol. 25, Supplement 1, 2002; S100–S108. Reprinted withpermission from the American Diabetes Association. *Diagnostic criteria for DKA include: blood glucose >250 mg/dL, arterial pH <7.3,bicarbonate <15 mEq/L, with moderate ketonuria or ketonemia. †After patient history and physical examination, obtain arterialblood gases, urinalysis, complete blood count with differential, blood glucose, blood urea nitrogen (BUN), chemistry profile,electrolytes, and creatinine levels, as well as an electrocardiogram. Chest x-ray and cultures should be obtained as needed. ‡Serumsodium should be corrected for hyperglycemia (for each 100 mg/dL glucose >100 mg/dL, add 1.6 mEq to sodium value for correctedserum sodium value). IM, intramuscular; IV, intravenous; SC, subcutaneous.

concentration less than 0.1 mg/dL, 20–30 mEq/Lof potassium phosphate can be added toreplacement fluids.7 The administration of toomuch phosphate can induce hypocalcemia.6

Calcium levels should be checked beforephosphate is administered and duringphosphate replacement.6

11

Table 5. Risks and Benefits of SodiumBicarbonate Replacement

Benefits

■ Corrects extracellular acidosis■ Reduces excessive chloride administration■ Reduces respiratory rate and increasescomfort

■ Reduces cardiac irritability■ Increases responsiveness of vascular system to pressor agents

Risks

■ Accelerated reduction in plasma potassiumconcentration

■ Sodium overload in elderly patients■ Exacerbation of intracellular acidosis

From American Diabetes Association. Diabetic ketoacidosis. In:American Diabetes Association. Medical Management of Type 1Diabetes. 3rd ed. Clinical Education Series. Alexandria, Va:American Diabetes Association; 1998:128–129.

Recovery CarePatients with DKA require intensive medicalcare, monitoring, follow-up, and education.Two important management principles arefollowed during the recovery period: (1) continue administering insulin; and (2) allow patients to eat. Intravenous fluidsand short-acting insulin are continued untilacidosis is corrected and the patient can ingestfood without vomiting. Early feeding isconsidered because the added carbohydrate inthe presence of insulin assists in the clearanceof ketones. It may take 1 week in the adultpatient to correct all biochemical abnormalitiesassociated with an episode of DKA.6

When the decision is made to begin feeding,the patient is switched from intravenous tosubcutaneous insulin. Since subcutaneousinsulin acts more slowly than intravenousinsulin, the transition to subcutaneous insulinis initiated with caution to avoid recurrence

of acidosis during the transition phase. Theinsulin drip is discontinued subsequently.Glucose levels are monitored 2 hours laterand at least every 4 hours subsequently untila relatively stable subcutaneous insulinregimen is established.

Electrolyte ManagementDuring RecoveryHyperchloremic acidosis with a normal aniongap is a common occurrence during recovery.During an episode of DKA, sodium is excretedas the sodium salt of ketoacids. Relativehyperchloremia can occur when treatmentwith intravenous solutions containing equalparts of sodium and chloride is used.16 Becausechloride losses are smaller than sodium losses,relative hyperchloremia occurs with therapy.The correction of DKA causes sodiumbicarbonate to shift into the intracellularspace leaving chloride over-represented in theextracellular space.16 If the anion gapgradually normalizes during therapy, asubsequent period of hyperchloremia-relatednonanion gap acidosis is of no clinical concern.

The presence of hypophosphatemia at theoutset of treatment suggests the possibility ofprofound total body phosphate depletion.6

Potassium phosphate administration may beneeded to prevent severe hypophosphatemiaduring treatment.

ComplicationsThe majority of cases of DKA are treatedsuccessfully without complications. However,potentially life-threatening complications are possible and include: hypoglycemia,hypokalemia, hyperchloremia,thromboembolic events, congestive heartfailure, cerebral edema, and acute respiratorydistress syndrome.

Hypoglycemia can occur if an excess of insulinis administered relative to glucose supply.Severe hypoglycemia can be a life-

10

Management of Adult Patients with DKA*

Complete initial evaluation.† Start IV fluids: 1.0 L of 0.9% NaCl per hour initially (15–20 mL • kg-1 • h-1).

IV Fluids

Determine hydration status IV Route pH < 6.9 pH 6.9–7.0 pH > 7.0SC/IM Route

If serum K+ is < 3.3 mEq/L, hold

insulin and give 40 mEq K+ per h

(2/3 KCL and 1/3 KPO4) until K ≥ 3.3 mEq/L

Insulin Potassium

Dilute NaHCO3


at 200 mL/h.

Repeat HCO3 administration every2 h until pH > 7.0. Monitor serum K+.

Dilute NaHCO3


at 200 mL/h.

NoHCO3

If serum K+ ≥ 3.3 but < 5.0 mEq/L,

give 20–30 mEq K+ in each liter

of IV fluid (2/3 as KCL and 1/3 as KPO4) to keep serum K

+

at 4–5 mEq/L

If serum K+ ≥ 5.0 mEq/L, do not

give K+ but check K

+ every 2 h

Insulin: Regular0.15 units/kg as

IV bolus

Hypovolemicshock

Mildhypotension

Cardiogenicshock

Serum Nahigh

Serum Nanormal

Serum Nalow

0.9% NaCl(4–14 mL • kg-1 • h-1)


0.45% NaCl(4–14 mL • kg-1 • h-1)


Administer0.9% NaCl

(1.0 L/h) and/orplasma expander

Hemodynamicmonitoring

Insulin: Regular0.4 units/kg 1/2 IV bolus, 1/2 IM or SC

0.1 units • kg-1 • h-1 IVinsulin infusion

0.1 units • kg-1 • h-1

Regular insulinSC or IM

Double insulin infusion hourly until

glucose falls by 50–70 mg/dL

Give hourly IV insulinbolus (10 units) until

glucose falls by50–70 mg/dL

If serum glucose does not fall by50–70 mg/dL in first hour.

Assess Need for Bicarbonate

Evaluate corrected serum Na+++

When serum glucose reaches 250 mg/dL

Change to 5% dextrose with 0.45% NaCl at 150–250 mL/h with adequate insulin (0.05–0.1 units • kg-1 • h-1 IV infusion or 5–10 units SC every 2 h) to keep the serum glucose between 150 and 200 mg/dL until metabolic control is achieved.

Check electrolytes, BUN, creatinine and glucose every 2–4 h until stable. After resolution of DKA, if the patient is NPO, continue IV insulin and supplement with SC regular insulin as needed. When the patient can eat, initiate a multidose insulin regimen and adjust as needed. Continue IV insulin infusion for 1–2 h after SC insulin is begun to ensure adequate plasma insulin levels. Continue to look for precipitating cause(s).

Figure 5. A flow diagram for the management of adult patients with diabetic ketoacidosis. Copyright ©2002 American Diabetes Association. From Diabetes Care, Vol. 25, Supplement 1, 2002; S100–S108. Reprinted withpermission from the American Diabetes Association. *Diagnostic criteria for DKA include: blood glucose >250 mg/dL, arterial pH <7.3,bicarbonate <15 mEq/L, with moderate ketonuria or ketonemia. †After patient history and physical examination, obtain arterialblood gases, urinalysis, complete blood count with differential, blood glucose, blood urea nitrogen (BUN), chemistry profile,electrolytes, and creatinine levels, as well as an electrocardiogram. Chest x-ray and cultures should be obtained as needed. ‡Serumsodium should be corrected for hyperglycemia (for each 100 mg/dL glucose >100 mg/dL, add 1.6 mEq to sodium value for correctedserum sodium value). IM, intramuscular; IV, intravenous; SC, subcutaneous.

concentration less than 0.1 mg/dL, 20–30 mEq/Lof potassium phosphate can be added toreplacement fluids.7 The administration of toomuch phosphate can induce hypocalcemia.6

Calcium levels should be checked beforephosphate is administered and duringphosphate replacement.6

13

The following types of intervention havereduced the number of episodes of DKA andthe amount of healthcare resources used totreat DKA28:

■ Patient education

■ Comprehensive management programs

■ Psychotherapy

■ Treatment protocols

■ Stepwise intervention programs

■ Decentralized nurse-managed, pharmacist-managed, and physician-backed programs

It may be possible to identify risk factors byevaluating the patient’s social environment.Patients with limited financial resourcesshould be referred to a social worker forassistance. A referral to appropriatecommunity resources and associations forsupport and education may help patients andtheir families.

The risk of DKA in patients who usecontinuous subcutaneous insulin infusionpumps can be reduced by limiting the use ofthese devices to patients who are highlymotivated and properly trained in its usage.The patient must have a clear understandingof the pump function, exercise good hygiene,plan for sick days, adjust insulin appropriately,and recognize the signs and symptoms ofDKA. Patients are instructed to performfrequent SMBG tests (at least 4 times a day),perform urine or blood ketone tests whenappropriate, and respond appropriately tosigns and symptoms of hyperglycemia andhypoglycemia. Healthcare professionals whoare experienced in pump use should educateand guide these patients. Improved pumptechnology reduces the equipmentmalfunctions that can lead to DKA.

Table 6. Patient Self-Care for Sick Days

■ Prepare a personal sick day plan with yourphysician before you become ill

■ When you are sick, always take yourdiabetes medicine

■ Test your blood glucose level every 4 hoursor more frequently if needed

■ Test your urine or blood for ketones

■ Call the doctor if

– Your blood glucose is consistently > 250 mg/dL

– Your ketone test is moderate or high

– You feel sick or vomit

– You think you might have an infection

■ Keep well hydrated

■ Replace solid foods that contain starch and sugar (bread, fruit) with liquids thatcontain sugar (fruit juices, soft drinks)through the guidance of your diabetes care team

Outpatient prevention measures. Interventionwith supplemental injections of short-actinginsulin or insulin analogs and oraladministration of fluids are often initiated inpatients with mild ketosis. In the absence ofnausea and vomiting, patients with mild tomoderate ketosis (a glucose level > 250 mg/dL,with moderate to large amounts of urinaryketones detected by urine ketone dipstick)may respond to supplemental doses of short-acting insulin or analogs, which can berepeated in 4 hours or less if the problem hasnot resolved. The development of nausea andvomiting or failure to clear ketonesnecessitates further evaluation in a hospitalemergency room.

Preventing recurrent diabetic ketoacidosis.Frequent, recurrent DKA indicates the needfor a detailed assessment by the diabetes careteam. The team must determine whether the

12

threatening complication. Sweating, tremors,and palpitations may occur with mildhypoglycemia; loss of consciousness andconvulsions can occur with severehypoglycemia. Patients should receive hourlymonitoring of plasma glucose to detect arapidly decreasing blood glucose level and toprevent the development of hypoglycemia.

Hypokalemia is potentially life-threatening ifpotassium replacement is delayed orinadequate. Hypokalemia usually occurs afterthe initiation of insulin therapy, secondary tothe intracellular movement of potassium.Increased potassium supplementation may beneeded if bicarbonate therapy is required tocorrect ketoacidosis. Bicarbonate promotesthe intracellular movement of potassium andincreases the risk of hypokalemia.

Hyperchloremia, or hyperchloremic normalanion gap metabolic acidosis, is present inapproximately 10% of patients admitted withDKA and is common in most patientsrecovering from DKA.25 It is usually caused byan excessive use of saline for fluid andelectrolyte replacement during treatment.However, other causes of hyperchloremiainclude loss of potential bicarbonate due toexcretion of ketoanions as potassium andsodium salts, decrease in availability ofbicarbonate in proximal tubule which leads toan increase in chloride reabsorption, andreduction of bicarbonate and other bufferingcapacities in other body compartments.25

Thromboembolic events may cause death inadults with DKA.12 Prolonged stasis,immobility, and hemoconcentration are majorprecipitating factors of a thromboembolicevent.12

Congestive heart failure can develop withfluid replacement therapy, especially if anacute myocardial infarction or an underlyingdiabetic cardiomyopathy is missed.

Cerebral edema is a rare, often fatalcomplication that usually occurs within thefirst 4 to 24 hours after the initiation oftherapy. It is more common in children,

especially those younger than 4 to 5 years ofage with DKA and new onset diabetes. Thereare no established warning signs or clinicalpredictors.24 Frequent ongoing neurologicassessments of the patient are critical duringfluid replacement and insulin therapy.24 Signsand symptoms may include headache,lethargy, abnormal pupil response, behavioralchanges, seizures, bradycardia, papilledema,or unconsciousness.

Acute respiratory distress syndrome is a formof acute lung injury that may occur as a resultof various insults. This may lead to decreasedintravascular osmotic pressure and fluid shiftsresulting in pulmonary edema. Sepsis is thepredominant risk factor.26,27 Other predisposingconditions include multiple transfusions, severenonthoracic trauma, pulmonary contusion,aspiration of gastric contents, multiplefractures, drug overdose, and pneumonia.26,27

PreventionPreventing DKA is one of the primary goals indiabetes management. The diabetes careteam, including physicians, nurses, pharmacists,and diabetes educators, should train patientswith diabetes to recognize the early signs andsymptoms of DKA and to take immediate andappropriate action (see Table 2). When signsand symptoms suggestive of DKA occur,patients must contact a diabetes care teammember promptly. Patients should performand interpret self-monitoring blood glucose(SMBG) results and urine or blood ketone tests.Patients should minimize the risk of DKA bymaintaining blood glucose levels as close aspossible to their target range, followingappropriate sick day management strategies(including notifying their diabetes care team inthe event of a vomiting episode), and ensuringthat insulin therapy is never omitted (Table 6).

Cerebral edema is an extremely serious,although rare, complication of DKA and

occurs more often in children than adults.

13

The following types of intervention havereduced the number of episodes of DKA andthe amount of healthcare resources used totreat DKA28:

■ Patient education

■ Comprehensive management programs

■ Psychotherapy

■ Treatment protocols

■ Stepwise intervention programs

■ Decentralized nurse-managed, pharmacist-managed, and physician-backed programs

It may be possible to identify risk factors byevaluating the patient’s social environment.Patients with limited financial resourcesshould be referred to a social worker forassistance. A referral to appropriatecommunity resources and associations forsupport and education may help patients andtheir families.

The risk of DKA in patients who usecontinuous subcutaneous insulin infusionpumps can be reduced by limiting the use ofthese devices to patients who are highlymotivated and properly trained in its usage.The patient must have a clear understandingof the pump function, exercise good hygiene,plan for sick days, adjust insulin appropriately,and recognize the signs and symptoms ofDKA. Patients are instructed to performfrequent SMBG tests (at least 4 times a day),perform urine or blood ketone tests whenappropriate, and respond appropriately tosigns and symptoms of hyperglycemia andhypoglycemia. Healthcare professionals whoare experienced in pump use should educateand guide these patients. Improved pumptechnology reduces the equipmentmalfunctions that can lead to DKA.

Table 6. Patient Self-Care for Sick Days

■ Prepare a personal sick day plan with yourphysician before you become ill

■ When you are sick, always take yourdiabetes medicine

■ Test your blood glucose level every 4 hoursor more frequently if needed

■ Test your urine or blood for ketones

■ Call the doctor if

– Your blood glucose is consistently > 250 mg/dL

– Your ketone test is moderate or high

– You feel sick or vomit

– You think you might have an infection

■ Keep well hydrated

■ Replace solid foods that contain starch and sugar (bread, fruit) with liquids thatcontain sugar (fruit juices, soft drinks)through the guidance of your diabetes care team

Outpatient prevention measures. Interventionwith supplemental injections of short-actinginsulin or insulin analogs and oraladministration of fluids are often initiated inpatients with mild ketosis. In the absence ofnausea and vomiting, patients with mild tomoderate ketosis (a glucose level > 250 mg/dL,with moderate to large amounts of urinaryketones detected by urine ketone dipstick)may respond to supplemental doses of short-acting insulin or analogs, which can berepeated in 4 hours or less if the problem hasnot resolved. The development of nausea andvomiting or failure to clear ketonesnecessitates further evaluation in a hospitalemergency room.

Preventing recurrent diabetic ketoacidosis.Frequent, recurrent DKA indicates the needfor a detailed assessment by the diabetes careteam. The team must determine whether the

12

threatening complication. Sweating, tremors,and palpitations may occur with mildhypoglycemia; loss of consciousness andconvulsions can occur with severehypoglycemia. Patients should receive hourlymonitoring of plasma glucose to detect arapidly decreasing blood glucose level and toprevent the development of hypoglycemia.

Hypokalemia is potentially life-threatening ifpotassium replacement is delayed orinadequate. Hypokalemia usually occurs afterthe initiation of insulin therapy, secondary tothe intracellular movement of potassium.Increased potassium supplementation may beneeded if bicarbonate therapy is required tocorrect ketoacidosis. Bicarbonate promotesthe intracellular movement of potassium andincreases the risk of hypokalemia.

Hyperchloremia, or hyperchloremic normalanion gap metabolic acidosis, is present inapproximately 10% of patients admitted withDKA and is common in most patientsrecovering from DKA.25 It is usually caused byan excessive use of saline for fluid andelectrolyte replacement during treatment.However, other causes of hyperchloremiainclude loss of potential bicarbonate due toexcretion of ketoanions as potassium andsodium salts, decrease in availability ofbicarbonate in proximal tubule which leads toan increase in chloride reabsorption, andreduction of bicarbonate and other bufferingcapacities in other body compartments.25

Thromboembolic events may cause death inadults with DKA.12 Prolonged stasis,immobility, and hemoconcentration are majorprecipitating factors of a thromboembolicevent.12

Congestive heart failure can develop withfluid replacement therapy, especially if anacute myocardial infarction or an underlyingdiabetic cardiomyopathy is missed.

Cerebral edema is a rare, often fatalcomplication that usually occurs within thefirst 4 to 24 hours after the initiation oftherapy. It is more common in children,

especially those younger than 4 to 5 years ofage with DKA and new onset diabetes. Thereare no established warning signs or clinicalpredictors.24 Frequent ongoing neurologicassessments of the patient are critical duringfluid replacement and insulin therapy.24 Signsand symptoms may include headache,lethargy, abnormal pupil response, behavioralchanges, seizures, bradycardia, papilledema,or unconsciousness.

Acute respiratory distress syndrome is a formof acute lung injury that may occur as a resultof various insults. This may lead to decreasedintravascular osmotic pressure and fluid shiftsresulting in pulmonary edema. Sepsis is thepredominant risk factor.26,27 Other predisposingconditions include multiple transfusions, severenonthoracic trauma, pulmonary contusion,aspiration of gastric contents, multiplefractures, drug overdose, and pneumonia.26,27

PreventionPreventing DKA is one of the primary goals indiabetes management. The diabetes careteam, including physicians, nurses, pharmacists,and diabetes educators, should train patientswith diabetes to recognize the early signs andsymptoms of DKA and to take immediate andappropriate action (see Table 2). When signsand symptoms suggestive of DKA occur,patients must contact a diabetes care teammember promptly. Patients should performand interpret self-monitoring blood glucose(SMBG) results and urine or blood ketone tests.Patients should minimize the risk of DKA bymaintaining blood glucose levels as close aspossible to their target range, followingappropriate sick day management strategies(including notifying their diabetes care team inthe event of a vomiting episode), and ensuringthat insulin therapy is never omitted (Table 6).

Cerebral edema is an extremely serious,although rare, complication of DKA and

occurs more often in children than adults.

15

patient with DKA estimated at $13,000 perepisode, the overall annual hospital cost forpatients with DKA is more than $1 billion peryear.25 A substantial proportion of the cost fordirect medical care for adults with type 1diabetes is attributable to DKA. It is estimatedthat about one-half of the DKA cost derivesfrom patients who experience multipleepisodes.28

The average length of stay for DKA is 3 to 10 days. Two studies show that specialistsprovide more cost-effective care compared with non-specialists. Patients under the care ofspecialists have a shorter hospital stay, fewermedical procedures, lower medical costs($10,109 for non-specialists care versus $5463for specialist care), and a lower rate ofrecurrent DKA.2,31 Early conversion to oralfeeding and subcutaneous insulin therapy arealso associated with a shorter hospital stay.

SummaryDKA is a reversible but potentially life-threatening illness that results from relativeor absolute insulin deficiency. Without insulin,the body cannot utilize glucose as a fuelsource and must obtain an alternative sourceof energy. This triggers a complex metabolicprocess that causes the breakdown of fat inadipose tissue and electrolyte disturbancesthat ultimately produces ketones and makesthe blood acidic. The characteristics of DKAare hyperglycemia, ketosis, and acidosis. Theclinical signs and symptoms include polyuria,polydipsia, progressive dehydration, andKussmaul’s respiration.

DKA usually can be prevented in theoutpatient setting through effective patienteducation and timely intervention by thediabetes care team. Prompt and appropriatetreatment of DKA most often results insatisfactory outcomes. Critical care personnelmust know how to stabilize the patient’scondition rapidly, administer appropriatemedical treatment, and initiate a thoroughevaluation to identify possible precipitating

factors. Insulin administration, rehydration,and electrolyte replacement are thecornerstones of treatment. Early conversionto oral feeding and subcutaneous insulintherapy after the metabolic derangement iscorrected is associated with a shorter lengthof hospital stay. Healthcare professionals whotreat patients with diabetes should heedthese important observations andrecommendations:

■ Treatment should be initiated immediatelywhen DKA is diagnosed or suspected.

■ An excellent clinical outcome is usuallypossible with meticulous care of patientswith DKA.

■ Successful treatment of patients with DKAis based on understanding that theetiology of DKA is severe insulin deficiency.

■ Management of DKA includesadministering insulin, correcting metabolicabnormalities by replacing fluids andelectrolytes, identifying and treatingprecipitating causes, and monitoring forcomplications.

■ Prevention and timely reversal of DKA canreduce morbidity and mortality and thecost of treatment.

14

diabetes management plan is appropriateand identify any factors that promote non-compliance. Typical factors include:

■ Inadequate patient education

■ Cognitive impairment

■ Substance abuse

■ Lack of motivation

■ Financial issues

■ Emotional or psychiatric disorders

■ Sensory impairment

■ Problem with insulin/insulin deliverysystem

If patients or their families cannot achieveeffective self-management, the team shouldfocus on teaching them to identify thesymptoms that require prompt medicalattention. Patients who have repeatedepisodes of DKA may need psychologicalconsultation.

Special CircumstancesPregnancy. DKA is present in 1% to 3% ofpregnancies complicated by diabetes.29 It is anacute medical emergency.29 An episode of DKAlasting 2 to 5 hours or longer can result in thedeath of the fetus. DKA most commonly occursin the second and third trimesters whenincreased insulin resistance is present. Prenataland perinatal counseling is imperative inpregnant patients with diabetes. DKAfrequently occurs when pregnancy appears inthe presence of undiagnosed diabetes. Factorsthat predispose pregnant women to DKA are30:

■ Accelerated starvation (eg, eating disorder)

■ Dehydration secondary to vomiting

■ Lowered buffering capacity

■ Increased production of insulin antagonists

■ Stress

Other precipitating factors of DKA werereviewed earlier (see “Triggers of DiabeticKetoacidosis”). Fetal loss, the most seriousconsequence, occurs in about 9% of pregnantwomen presenting with DKA, even with useof insulin and fluid therapy.29 The mechanismof fetal mortality is unclear and could berelated to fetal distress and hypoxia. Maternalketoacids cross the placenta and cause fetalacidosis. Management of this condition is thesame as for a nonparous individual.

Elderly. There are special considerationsinvolved in caring for the elderly with DKA because of the high mortality rate inthis population. Elderly patients have anincreased risk for fluid overload, decreasedpulmonary capacity, silent cardiac events, and thromboembolic events.24 It is criticalthat cardiopulmonary function be monitored,good pulmonary hygiene be practiced, andabdominal complaints be evaluated in theelderly. Initial therapy is usually conducted in an intensive care unit. Once patients arestabilized, they are transferred to a general unit.

Economic IssuesThe costs of DKA prevention with medication,monitoring SMBG, urine, and ketones, andpatient education are a fraction of the cost ofan emergency hospitalization. The treatmentof DKA requires a full complement of hospital,emergency, and intensive services, whichconsumes significant healthcare resources. Thisis especially true for patients hospitalized formultiple episodes. Treating a patient with DKArequires a full-time team of specialists toadminister intravenous medications and fluids,perform careful hourly monitoring, frequentlaboratory tests requiring rapid turnaroundtime and interpretation, and reliable bedsideblood glucose monitoring.

From population-based studies, the annualincidence rate for DKA is estimated to rangefrom 4.6 to 8 episodes per 1000 patients withdiabetes.7 With the mean medical care for a

15

patient with DKA estimated at $13,000 perepisode, the overall annual hospital cost forpatients with DKA is more than $1 billion peryear.25 A substantial proportion of the cost fordirect medical care for adults with type 1diabetes is attributable to DKA. It is estimatedthat about one-half of the DKA cost derivesfrom patients who experience multipleepisodes.28

The average length of stay for DKA is 3 to 10 days. Two studies show that specialistsprovide more cost-effective care compared with non-specialists. Patients under the care ofspecialists have a shorter hospital stay, fewermedical procedures, lower medical costs($10,109 for non-specialists care versus $5463for specialist care), and a lower rate ofrecurrent DKA.2,31 Early conversion to oralfeeding and subcutaneous insulin therapy arealso associated with a shorter hospital stay.

SummaryDKA is a reversible but potentially life-threatening illness that results from relativeor absolute insulin deficiency. Without insulin,the body cannot utilize glucose as a fuelsource and must obtain an alternative sourceof energy. This triggers a complex metabolicprocess that causes the breakdown of fat inadipose tissue and electrolyte disturbancesthat ultimately produces ketones and makesthe blood acidic. The characteristics of DKAare hyperglycemia, ketosis, and acidosis. Theclinical signs and symptoms include polyuria,polydipsia, progressive dehydration, andKussmaul’s respiration.

DKA usually can be prevented in theoutpatient setting through effective patienteducation and timely intervention by thediabetes care team. Prompt and appropriatetreatment of DKA most often results insatisfactory outcomes. Critical care personnelmust know how to stabilize the patient’scondition rapidly, administer appropriatemedical treatment, and initiate a thoroughevaluation to identify possible precipitating

factors. Insulin administration, rehydration,and electrolyte replacement are thecornerstones of treatment. Early conversionto oral feeding and subcutaneous insulintherapy after the metabolic derangement iscorrected is associated with a shorter lengthof hospital stay. Healthcare professionals whotreat patients with diabetes should heedthese important observations andrecommendations:

■ Treatment should be initiated immediatelywhen DKA is diagnosed or suspected.

■ An excellent clinical outcome is usuallypossible with meticulous care of patientswith DKA.

■ Successful treatment of patients with DKAis based on understanding that theetiology of DKA is severe insulin deficiency.

■ Management of DKA includesadministering insulin, correcting metabolicabnormalities by replacing fluids andelectrolytes, identifying and treatingprecipitating causes, and monitoring forcomplications.

■ Prevention and timely reversal of DKA canreduce morbidity and mortality and thecost of treatment.

14

diabetes management plan is appropriateand identify any factors that promote non-compliance. Typical factors include:

■ Inadequate patient education

■ Cognitive impairment

■ Substance abuse

■ Lack of motivation

■ Financial issues

■ Emotional or psychiatric disorders

■ Sensory impairment

■ Problem with insulin/insulin deliverysystem

If patients or their families cannot achieveeffective self-management, the team shouldfocus on teaching them to identify thesymptoms that require prompt medicalattention. Patients who have repeatedepisodes of DKA may need psychologicalconsultation.

Special CircumstancesPregnancy. DKA is present in 1% to 3% ofpregnancies complicated by diabetes.29 It is anacute medical emergency.29 An episode of DKAlasting 2 to 5 hours or longer can result in thedeath of the fetus. DKA most commonly occursin the second and third trimesters whenincreased insulin resistance is present. Prenataland perinatal counseling is imperative inpregnant patients with diabetes. DKAfrequently occurs when pregnancy appears inthe presence of undiagnosed diabetes. Factorsthat predispose pregnant women to DKA are30:

■ Accelerated starvation (eg, eating disorder)

■ Dehydration secondary to vomiting

■ Lowered buffering capacity

■ Increased production of insulin antagonists

■ Stress

Other precipitating factors of DKA werereviewed earlier (see “Triggers of DiabeticKetoacidosis”). Fetal loss, the most seriousconsequence, occurs in about 9% of pregnantwomen presenting with DKA, even with useof insulin and fluid therapy.29 The mechanismof fetal mortality is unclear and could berelated to fetal distress and hypoxia. Maternalketoacids cross the placenta and cause fetalacidosis. Management of this condition is thesame as for a nonparous individual.

Elderly. There are special considerationsinvolved in caring for the elderly with DKA because of the high mortality rate inthis population. Elderly patients have anincreased risk for fluid overload, decreasedpulmonary capacity, silent cardiac events, and thromboembolic events.24 It is criticalthat cardiopulmonary function be monitored,good pulmonary hygiene be practiced, andabdominal complaints be evaluated in theelderly. Initial therapy is usually conducted in an intensive care unit. Once patients arestabilized, they are transferred to a general unit.

Economic IssuesThe costs of DKA prevention with medication,monitoring SMBG, urine, and ketones, andpatient education are a fraction of the cost ofan emergency hospitalization. The treatmentof DKA requires a full complement of hospital,emergency, and intensive services, whichconsumes significant healthcare resources. Thisis especially true for patients hospitalized formultiple episodes. Treating a patient with DKArequires a full-time team of specialists toadminister intravenous medications and fluids,perform careful hourly monitoring, frequentlaboratory tests requiring rapid turnaroundtime and interpretation, and reliable bedsideblood glucose monitoring.

From population-based studies, the annualincidence rate for DKA is estimated to rangefrom 4.6 to 8 episodes per 1000 patients withdiabetes.7 With the mean medical care for a

1716

Health History• Medication history, immediate past

illnesses or life events, time andamount of last insulin dose, nutritionalpatterns

Physical Assessment• Neuro checks to assess for cerebral

edema • Cardiovascular assessment: BP, HR, skin

turgor• Respiratory assessment: tachypnea,

Kussmaul respirations• Musculoskeletal assessment: muscle

weakness, fatigue• GI assessment: nausea, vomiting,

abdominal pain, bowel sounds• Temperature

Physical Assessment• Continue neuro checks to assess for

cerebral edema • Respiratory, cardiovascular, GI, and skin

integrity assessments• Vital signs every 2 hours• Monitor for signs of hypoglycemia

Physical Assessment• Respiratory, cardiovascular, GI, and skin

integrity assessments• Vital signs every 4 hours • Monitor for signs of hypoglycemia

Physical Assessment• Routine assessment and vital signs• Monitor for signs of hypoglycemia

Lab and Other Data• Initial serum glucose• Bedside glucose monitoring every

1– 2 hours; awareness of potential forhypoglycemia

• Serum ketones • Urine ketones• Potassium every 1– 2 hours• Phosphorus• BUN/creatinine • Bicarb• ABGs• CBC with differential• Other electrolytes• Blood cultures if indicated• Intake and output

Lab and Other Data• Continue bedside glucose monitoring

every 2 hours• Urine ketones• Monitor electrolytes, especially

potassium • Intake and output


every 2 hours• Urine ketones• Monitor electrolytes• Intake and output


q.i.d.• Monitor electrolytes• Intake and output

Other Diagnostics• 12-lead ECG• Continuous ECG monitoring

Other Diagnostics• Continuous ECG monitoring if

indicated; otherwise d/c

Treatment• IV access• NS @ 1 L/hr for 2– 3 hours• Replace potassium 10– 30 mEq/hr• Replace other electrolytes as indicated

by lab data• Regular insulin 0.1– 0.2 U/kg/hr• NG intubation• Foley catheter • Initiate appropriate antibiotic therapy

as needed• Anti-embolic therapy

Treatment• Change fluids to D5W or D51/2NS

when serum glucose = 250– 300 mg/dL• Regular insulin 0.1 U/kg/hr• Replace electrolytes as indicated by lab

data • NG tube to low intermittent suction• Foley catheter• Pulmonary hygiene• Continue anti-embolic therapy• Begin education with family to prevent

reoccurrence

Treatment• Begin SC insulin injections 1– 2 hours

before discontinuing IV insulin. Includesliding scale

• Discontinue NG if bowel soundspresent and patient is alert

• Begin oral feeding and advance diet astolerated

• Dietary consultation, if indicated • Discontinue the Foley catheter• Up in chair and advance activity

as tolerated • Continue anti-embolic therapy• Review patient knowledge concerning

sick day management, blood glucoseand urine monitoring, signs andsymptoms of hypoglycemia, and DKA

• Educate patient and family to preventreoccurrence

Treatment• Adjust SC insulin dosage as indicated

as lab data. Include sliding scale • ADA diet as prescribed • Continue patient and family education

to prevent reoccurrence • Provide written instructions • Consider home care referral

as indicated

ON ADMISSION DAY 2 DAY 3 DAY 4

Appendix BCritical Pathway

Appendix ADiabetic Ketoacidosis Flow Sheet

HOUR 0 1 2 3 4 5 6 7 8 9 10 11 12Weight (daily)Mental Status*TemperaturePulse

Respiration/Depth†

Blood PressureSerum Glucose (mg/dL)/LSerum KetonesUrine Ketones

ElectrolytesSerum Na (mEq/L)Serum K (mEq/L)Serum Cl (mEq/L)Serum HCO3 (mEq/L)

Serum BUN (mg/dL)

Effective Osmolality‡

Anion Gap

Blood AciditypH Venous pH Arterial

Blood GasesPO2

PCO2

O2 Saturation

InsulinUnits (past hour) Route

Intake (past hour)0.45% Saline (mL)0.9% Saline (mL)5% Dextrose (mL)KCl (mEq)PO4 (mg/dL)

Other

OutputUrine (mL)

Other

*A, Alert; D, Drowsy; S, Stupor; C, Comatose.†D, Deep; S, Shallow; N, Normal.‡2 x measured serum Na (mEq/L) + glucose (mg/dL)/18.

From Kitabchi AE, Fisher JN, Murphy MB, Rumbak MJ. Diabetic ketoacidosis and the hyperglycemic, hyperosmolar nonketotic state.In: Kahn CR, Weir GC, eds. Joslin’s Diabetes Mellitus. 13th ed. Baltimore, Md: Lippincott Williams & Wilkins, 1994:738–770.

Expected Outcomes• Hemodynamic stability• Begin lowering of the blood glucose

level • Preventing complications of treatment

and immobility

Expected Outcomes• Blood glucose decreased to

250 mg/dL• Alert and oriented x 3• Preventing complications of treatment

and immobility

Expected Outcomes• Blood glucose below 200 mg/dL• Tolerating oral fluids and foods• Tolerating activity• Preventing complications of treatment

and immobility

Expected Outcomes• Demonstrates satisfactory knowledge

of treatment, sick day management,DKA prevention, signs and symptomsof hypoglycemia and blood glucosemonitoring

• Discharge without complications

From Grinslade S, Buck EA. Diabetic ketoacidosis: implications for the medical-surgical nurse. Medsurg Nurs. 1999;8:40–41.

1716

Health History• Medication history, immediate past

illnesses or life events, time andamount of last insulin dose, nutritionalpatterns

Physical Assessment• Neuro checks to assess for cerebral

edema • Cardiovascular assessment: BP, HR, skin

turgor• Respiratory assessment: tachypnea,

Kussmaul respirations• Musculoskeletal assessment: muscle

weakness, fatigue• GI assessment: nausea, vomiting,

abdominal pain, bowel sounds• Temperature

Physical Assessment• Continue neuro checks to assess for

cerebral edema • Respiratory, cardiovascular, GI, and skin

integrity assessments• Vital signs every 2 hours• Monitor for signs of hypoglycemia

Physical Assessment• Respiratory, cardiovascular, GI, and skin

integrity assessments• Vital signs every 4 hours • Monitor for signs of hypoglycemia

Physical Assessment• Routine assessment and vital signs• Monitor for signs of hypoglycemia

Lab and Other Data• Initial serum glucose• Bedside glucose monitoring every

1– 2 hours; awareness of potential forhypoglycemia

• Serum ketones • Urine ketones• Potassium every 1– 2 hours• Phosphorus• BUN/creatinine • Bicarb• ABGs• CBC with differential• Other electrolytes• Blood cultures if indicated• Intake and output


every 2 hours• Urine ketones• Monitor electrolytes, especially

potassium • Intake and output


every 2 hours• Urine ketones• Monitor electrolytes• Intake and output


q.i.d.• Monitor electrolytes• Intake and output

Other Diagnostics• 12-lead ECG• Continuous ECG monitoring

Other Diagnostics• Continuous ECG monitoring if

indicated; otherwise d/c

Treatment• IV access• NS @ 1 L/hr for 2– 3 hours• Replace potassium 10– 30 mEq/hr• Replace other electrolytes as indicated

by lab data• Regular insulin 0.1– 0.2 U/kg/hr• NG intubation• Foley catheter • Initiate appropriate antibiotic therapy

as needed• Anti-embolic therapy

Treatment• Change fluids to D5W or D51/2NS

when serum glucose = 250– 300 mg/dL• Regular insulin 0.1 U/kg/hr• Replace electrolytes as indicated by lab

data • NG tube to low intermittent suction• Foley catheter• Pulmonary hygiene• Continue anti-embolic therapy• Begin education with family to prevent

reoccurrence

Treatment• Begin SC insulin injections 1– 2 hours

before discontinuing IV insulin. Includesliding scale

• Discontinue NG if bowel soundspresent and patient is alert

• Begin oral feeding and advance diet astolerated

• Dietary consultation, if indicated • Discontinue the Foley catheter• Up in chair and advance activity

as tolerated • Continue anti-embolic therapy• Review patient knowledge concerning

sick day management, blood glucoseand urine monitoring, signs andsymptoms of hypoglycemia, and DKA

• Educate patient and family to preventreoccurrence

Treatment• Adjust SC insulin dosage as indicated

as lab data. Include sliding scale • ADA diet as prescribed • Continue patient and family education

to prevent reoccurrence • Provide written instructions • Consider home care referral

as indicated

ON ADMISSION DAY 2 DAY 3 DAY 4

Appendix BCritical Pathway

Appendix ADiabetic Ketoacidosis Flow Sheet

HOUR 0 1 2 3 4 5 6 7 8 9 10 11 12Weight (daily)Mental Status*TemperaturePulse

Respiration/Depth†

Blood PressureSerum Glucose (mg/dL)/LSerum KetonesUrine Ketones

ElectrolytesSerum Na (mEq/L)Serum K (mEq/L)Serum Cl (mEq/L)Serum HCO3 (mEq/L)

Serum BUN (mg/dL)

Effective Osmolality‡

Anion Gap

Blood AciditypH Venous pH Arterial

Blood GasesPO2

PCO2

O2 Saturation

InsulinUnits (past hour) Route

Intake (past hour)0.45% Saline (mL)0.9% Saline (mL)5% Dextrose (mL)KCl (mEq)PO4 (mg/dL)

Other

OutputUrine (mL)

Other

*A, Alert; D, Drowsy; S, Stupor; C, Comatose.†D, Deep; S, Shallow; N, Normal.‡2 x measured serum Na (mEq/L) + glucose (mg/dL)/18.

From Kitabchi AE, Fisher JN, Murphy MB, Rumbak MJ. Diabetic ketoacidosis and the hyperglycemic, hyperosmolar nonketotic state.In: Kahn CR, Weir GC, eds. Joslin’s Diabetes Mellitus. 13th ed. Baltimore, Md: Lippincott Williams & Wilkins, 1994:738–770.

Expected Outcomes• Hemodynamic stability• Begin lowering of the blood glucose

level • Preventing complications of treatment

and immobility

Expected Outcomes• Blood glucose decreased to

250 mg/dL• Alert and oriented x 3• Preventing complications of treatment

and immobility

Expected Outcomes• Blood glucose below 200 mg/dL• Tolerating oral fluids and foods• Tolerating activity• Preventing complications of treatment

and immobility

Expected Outcomes• Demonstrates satisfactory knowledge

of treatment, sick day management,DKA prevention, signs and symptomsof hypoglycemia and blood glucosemonitoring

• Discharge without complications

From Grinslade S, Buck EA. Diabetic ketoacidosis: implications for the medical-surgical nurse. Medsurg Nurs. 1999;8:40–41.

1918

23. Castillo MJ, Scheen AJ, Lefebvre PJ. Treatment with insulin infusion pumps and ketoacidotic episodes: fromphysiology to troubleshooting. Diabetes Metab Rev. 1995;11:161–177.

24. Grinslade S, Buck EA. Diabetic ketoacidosis: implications for the medical-surgical nurse. Medsurg Nurs.1999;8:37–45.

25. Kitabchi AE, Umpierrez GE, Murphy MB, et al. Management of hyperglycemic crises in patients with diabetes. Diabetes Care. 2001;24:131–153.

26. Montgomery AB, Stager MA, Carrico CJ, Hudson LD. Causes of mortality in patients with the adult respiratorydistress syndrome. Am Rev Respir Dis. 1985;132:485–489.

27. Eisner MD, Thompson T, Hudson LD, et al. Efficacy of low tidal volume ventilation in patients with different clinicalrisk factors for acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med.2001;164:231–236.

28. Javor KA, Kotsanos JG, McDonald RC, Baron AD, Kesterson JG, Tierney WM. Diabetic ketoacidosis charges relativeto medical charges of adult patients with type I diabetes. Diabetes Care. 1997;20:349–354.

29. Ramin KD. Diabetic ketoacidosis in pregnancy. Obstet Gynecol Clin North Am. 1999;26:481–488.

30. Chauhan SP, Perry KG Jr, McLaughlin BN, Roberts WE, Sullivan CA, Morrison JC. Diabetic ketoacidosis complicatingpregnancy. J Perinatol. 1996;16:173–175.

31. Levetan CS, Salas JR, Wilets IF, Zumoff B. Impact of endocrine and diabetes team consultation on hospital lengthof stay for patients with diabetes. Am J Med. 1995;99:22–28.

References1. Kaufman FR, Halvorson M. The treatment and prevention of diabetic ketoacidosis in children and adolescents

with type I diabetes mellitus. Pediatr Ann. 1999;28:576–582.

2. Levetan CS, Passaro MD, Jablonski KA, Ratner RE. Effect of physician specialty on outcomes in diabeticketoacidosis. Diabetes Care. 1999;22:1790–1795.

3. Wagner A, Risse A, Brill HL, et al. Therapy of severe diabetic ketoacidosis. Zero-mortality under very-low-doseinsulin application. Diabetes Care. 1999;22:674–677.

4. Umpierrez GE, Murphy MB, Kitabchi AE. Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome.Diabetes Spectrum. 2002;15:28–36.

5. American Diabetes Association. Clinical Practice Recommendations. Diabetes Care. 2001;24(suppl 1):S1–S126.

6. American Diabetes Association. Medical management of type 1 diabetes. 3rd ed. Clinical Education Series.Alexandria, Va: American Diabetes Association; 1998:122–133.

7. American Diabetes Association. Hyperglycemic crises in patients with diabetes mellitus. Diabetes Care.2002;25(suppl 1):S100–S108.

8. Buse JB, Polonsky KS. Diabetic ketoacidosis, hyperglycemic hyperosmolar nonketotic coma, and hypoglycemia. In:Hall JB, Schmidt GA, Woods LDH, eds. Principles of Critical Care. 2nd ed. New York, NY: McGraw Hill;1998:1183–1193.

9. Musey VC, Lee JK, Crawford R, Klatka MA, McAdams D, Phillips LS. Diabetes in urban African-Americans. I.Cessation of insulin therapy is the major precipitating cause of diabetic ketoacidosis. Diabetes Care.1995;18:483–489.

10. Brink SJ. Diabetic ketoacidosis: prevention, treatment and complications in children and adolescents. DiabetesNutr Metab. 1999;12:122–135.

11. Yu EH, Wu TJ. Clinical profiles in adult diabetic ketoacidotic patients in a tertiary referral medical center insouthern Taiwan. J Formos Med Assoc. 1998;97:85–89.

12. Bell DS, Alele J. Diabetic ketoacidosis. Why early detection and aggressive treatment are crucial. Postgrad Med.1997;101:193–198, 203–204.

13. Westphal SA. The occurrence of diabetic ketoacidosis in non-insulin-dependent diabetes and newly diagnoseddiabetic adults. Am J Med. 1996;101:19–24.

14. Balasubramanyam A, Zern JW, Hyman DJ, Pavlik V. New profiles of diabetic ketoacidosis: type 1 vs type 2 diabetesand the effect of ethnicity. Arch Intern Med. 1999;159:2317–2322.

15. Yan SH, Sheu WH, Song YM, Tseng LN. The occurrence of diabetic ketoacidosis in adults. Intern Med.2000;39:10–14.

16. Fleckman AM. Diabetic ketoacidosis. Endocrinol Metab Clin North Am. 1993;22:181–207.

17. Ennis ED, Stahl E, Kreisberg RA. Diabetic ketoacidosis. In: Porte D Jr, Sherwin RS, eds. Ellenberg & Rifkin’s DiabetesMellitus. 5th ed. Stamford, Conn: Appleton & Lange; 1997:827–844.

18. Kitabchi AE, Wall BM. Management of diabetic ketoacidosis. Am Fam Physician. 1999;60:455–464.

19. Silink M. Practical management of diabetic ketoacidosis in childhood and adolescence. Acta Paediatr Suppl.1998;425:63–66.

20. Miller J. Management of diabetic ketoacidosis. J Emerg Nurs. 1999;25:514–519.

21. Warner EA, Greene GS, Buchsbaum MS, Cooper DS, Robinson BE. Diabetic ketoacidosis associated with cocaineuse. Arch Intern Med. 1998;158:1799–1802.

22. Bedalov A, Balasubramanyam A. Glucocorticoid-induced ketoacidosis in gestational diabetes: sequela of the acutetreatment of preterm labor. A case report. Diabetes Care. 1997;20:922–924.

1918

23. Castillo MJ, Scheen AJ, Lefebvre PJ. Treatment with insulin infusion pumps and ketoacidotic episodes: fromphysiology to troubleshooting. Diabetes Metab Rev. 1995;11:161–177.

24. Grinslade S, Buck EA. Diabetic ketoacidosis: implications for the medical-surgical nurse. Medsurg Nurs.1999;8:37–45.

25. Kitabchi AE, Umpierrez GE, Murphy MB, et al. Management of hyperglycemic crises in patients with diabetes. Diabetes Care. 2001;24:131–153.

26. Montgomery AB, Stager MA, Carrico CJ, Hudson LD. Causes of mortality in patients with the adult respiratorydistress syndrome. Am Rev Respir Dis. 1985;132:485–489.

27. Eisner MD, Thompson T, Hudson LD, et al. Efficacy of low tidal volume ventilation in patients with different clinicalrisk factors for acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med.2001;164:231–236.

28. Javor KA, Kotsanos JG, McDonald RC, Baron AD, Kesterson JG, Tierney WM. Diabetic ketoacidosis charges relativeto medical charges of adult patients with type I diabetes. Diabetes Care. 1997;20:349–354.

29. Ramin KD. Diabetic ketoacidosis in pregnancy. Obstet Gynecol Clin North Am. 1999;26:481–488.

30. Chauhan SP, Perry KG Jr, McLaughlin BN, Roberts WE, Sullivan CA, Morrison JC. Diabetic ketoacidosis complicatingpregnancy. J Perinatol. 1996;16:173–175.

31. Levetan CS, Salas JR, Wilets IF, Zumoff B. Impact of endocrine and diabetes team consultation on hospital lengthof stay for patients with diabetes. Am J Med. 1995;99:22–28.

References1. Kaufman FR, Halvorson M. The treatment and prevention of diabetic ketoacidosis in children and adolescents

with type I diabetes mellitus. Pediatr Ann. 1999;28:576–582.

2. Levetan CS, Passaro MD, Jablonski KA, Ratner RE. Effect of physician specialty on outcomes in diabeticketoacidosis. Diabetes Care. 1999;22:1790–1795.

3. Wagner A, Risse A, Brill HL, et al. Therapy of severe diabetic ketoacidosis. Zero-mortality under very-low-doseinsulin application. Diabetes Care. 1999;22:674–677.

4. Umpierrez GE, Murphy MB, Kitabchi AE. Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome.Diabetes Spectrum. 2002;15:28–36.

5. American Diabetes Association. Clinical Practice Recommendations. Diabetes Care. 2001;24(suppl 1):S1–S126.

6. American Diabetes Association. Medical management of type 1 diabetes. 3rd ed. Clinical Education Series.Alexandria, Va: American Diabetes Association; 1998:122–133.

7. American Diabetes Association. Hyperglycemic crises in patients with diabetes mellitus. Diabetes Care.2002;25(suppl 1):S100–S108.

8. Buse JB, Polonsky KS. Diabetic ketoacidosis, hyperglycemic hyperosmolar nonketotic coma, and hypoglycemia. In:Hall JB, Schmidt GA, Woods LDH, eds. Principles of Critical Care. 2nd ed. New York, NY: McGraw Hill;1998:1183–1193.

9. Musey VC, Lee JK, Crawford R, Klatka MA, McAdams D, Phillips LS. Diabetes in urban African-Americans. I.Cessation of insulin therapy is the major precipitating cause of diabetic ketoacidosis. Diabetes Care.1995;18:483–489.

10. Brink SJ. Diabetic ketoacidosis: prevention, treatment and complications in children and adolescents. DiabetesNutr Metab. 1999;12:122–135.

11. Yu EH, Wu TJ. Clinical profiles in adult diabetic ketoacidotic patients in a tertiary referral medical center insouthern Taiwan. J Formos Med Assoc. 1998;97:85–89.

12. Bell DS, Alele J. Diabetic ketoacidosis. Why early detection and aggressive treatment are crucial. Postgrad Med.1997;101:193–198, 203–204.

13. Westphal SA. The occurrence of diabetic ketoacidosis in non-insulin-dependent diabetes and newly diagnoseddiabetic adults. Am J Med. 1996;101:19–24.

14. Balasubramanyam A, Zern JW, Hyman DJ, Pavlik V. New profiles of diabetic ketoacidosis: type 1 vs type 2 diabetesand the effect of ethnicity. Arch Intern Med. 1999;159:2317–2322.

15. Yan SH, Sheu WH, Song YM, Tseng LN. The occurrence of diabetic ketoacidosis in adults. Intern Med.2000;39:10–14.

16. Fleckman AM. Diabetic ketoacidosis. Endocrinol Metab Clin North Am. 1993;22:181–207.

17. Ennis ED, Stahl E, Kreisberg RA. Diabetic ketoacidosis. In: Porte D Jr, Sherwin RS, eds. Ellenberg & Rifkin’s DiabetesMellitus. 5th ed. Stamford, Conn: Appleton & Lange; 1997:827–844.

18. Kitabchi AE, Wall BM. Management of diabetic ketoacidosis. Am Fam Physician. 1999;60:455–464.

19. Silink M. Practical management of diabetic ketoacidosis in childhood and adolescence. Acta Paediatr Suppl.1998;425:63–66.

20. Miller J. Management of diabetic ketoacidosis. J Emerg Nurs. 1999;25:514–519.

21. Warner EA, Greene GS, Buchsbaum MS, Cooper DS, Robinson BE. Diabetic ketoacidosis associated with cocaineuse. Arch Intern Med. 1998;158:1799–1802.

22. Bedalov A, Balasubramanyam A. Glucocorticoid-induced ketoacidosis in gestational diabetes: sequela of the acutetreatment of preterm labor. A case report. Diabetes Care. 1997;20:922–924.

20

Notes

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21

Self-Assessment TestOne answer is required for each question. Markyour answers on the appropriate boxes on theexam answer key of the evaluation form.

1. Diabetic ketoacidosis is characterized by:

a. Hyperglycemia

b. Normal ketone levels

c. Proper hydration

d. Balanced electrolytes

e. All of the above

2. Which of the following generallydifferentiates hyperosmolar hyperglycemicstate from diabetic ketoacidosis:

a. Insulin deficiency is not as profound

b. Minimal or no increase in lipolysis

c. Absence of ketosis

d. pH may be within normal limits

e. All of the above

3. In isolated alcoholic ketoacidosis, the patientmay present with:

a. Mild metabolic acidosis

b. Elevated anion gap

c. Normal or below normal blood glucose level

d. Respiratory alkalosis

e. All of the above

4. Vital signs in diabetic ketoacidosis typicallyreveal:

a. Hypertension, bradycardia, and normalrespiration

b. Orthostatic hypotension, bradycardia, andtachypnea

c. Orthostatic hypotension, tachycardia, andtachypnea

d. Hypertension, palpitation, and tachypnea

5. The anion gap is determined by:

a. Subtracting the sum of the serum chlorideand phosphate from the serum sodiumconcentration

b. Subtracting the sum of the serum chlorideand bicarbonate from the serum potassiumconcentration

c. Subtracting the sum of the chloride andphosphate from the serum sodium andpotassium concentration

d. Subtracting the sum of the chloride andbicarbonate from the serum sodiumconcentration

6. Which of the following is not a characteristicof diabetic ketoacidosis:

a. Increased anion gap

b. Hyperglycemia

c. Respiratory acidosis

d. Metabolic acidosis

7. Which of the following is a false statement?

a. Diabetic ketoacidosis occurs most oftenwith type 1 diabetes.

b. Diabetic ketoacidosis is a metabolicderangement occurring as a result ofsevere insulin deficiency.

c. Hyperosmolar hyperglycemic state isgenerally a complication of type 2 diabetes.

d. Metabolic acidosis leads to an increase inserum bicarbonate.


a. Diabetic ketoacidosis never occurs in type 2diabetes.

b. Hyperventilation is a consequence ofacidosis.

c. Stress associated with intercurrent illnessesmay increase the body’s requirement forinsulin.

d. Diabetic neuropathy can result in theabsence or delay of signs and symptoms ofa myocardial infarction.

20

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21

Self-Assessment TestOne answer is required for each question. Markyour answers on the appropriate boxes on theexam answer key of the evaluation form.

1. Diabetic ketoacidosis is characterized by:

a. Hyperglycemia

b. Normal ketone levels

c. Proper hydration

d. Balanced electrolytes

e. All of the above

2. Which of the following generallydifferentiates hyperosmolar hyperglycemicstate from diabetic ketoacidosis:

a. Insulin deficiency is not as profound

b. Minimal or no increase in lipolysis

c. Absence of ketosis

d. pH may be within normal limits

e. All of the above

3. In isolated alcoholic ketoacidosis, the patientmay present with:

a. Mild metabolic acidosis

b. Elevated anion gap

c. Normal or below normal blood glucose level

d. Respiratory alkalosis

e. All of the above

4. Vital signs in diabetic ketoacidosis typicallyreveal:

a. Hypertension, bradycardia, and normalrespiration

b. Orthostatic hypotension, bradycardia, andtachypnea

c. Orthostatic hypotension, tachycardia, andtachypnea

d. Hypertension, palpitation, and tachypnea

5. The anion gap is determined by:

a. Subtracting the sum of the serum chlorideand phosphate from the serum sodiumconcentration

b. Subtracting the sum of the serum chlorideand bicarbonate from the serum potassiumconcentration

c. Subtracting the sum of the chloride andphosphate from the serum sodium andpotassium concentration

d. Subtracting the sum of the chloride andbicarbonate from the serum sodiumconcentration

6. Which of the following is not a characteristicof diabetic ketoacidosis:

a. Increased anion gap

b. Hyperglycemia

c. Respiratory acidosis

d. Metabolic acidosis


a. Diabetic ketoacidosis occurs most oftenwith type 1 diabetes.

b. Diabetic ketoacidosis is a metabolicderangement occurring as a result ofsevere insulin deficiency.

c. Hyperosmolar hyperglycemic state isgenerally a complication of type 2 diabetes.

d. Metabolic acidosis leads to an increase inserum bicarbonate.


a. Diabetic ketoacidosis never occurs in type 2diabetes.

b. Hyperventilation is a consequence ofacidosis.

c. Stress associated with intercurrent illnessesmay increase the body’s requirement forinsulin.

d. Diabetic neuropathy can result in theabsence or delay of signs and symptoms ofa myocardial infarction.

2322

9. Which action is not recommended for apatient with diabetes during sick days?

a. Stop taking insulin when not eating.

b. Report infections to the physician.

c. Perform frequent tests of ketones.

d. Keep well hydrated.

10. Which of the following events can triggerdiabetic ketoacidosis:

a. Substance abuse

b. Infection

c. Pregnancy

d. Emotional stress

e. All of the above

11. The following signs are commonly associatedwith diabetic ketoacidosis except:

a. Tachycardia

b. Hypotension

c. Deep, rapid breathing

d. Unequal pupils

12. How does the body compensate for acidosis?

a. Renal elimination of ketones

b. Bicarbonate buffering

c. Retention of carbon dioxide

d. a and b

e. All of the above

13. All of the following are objectives of thehealthcare team for patients who havediabetes except:

a. Teach patients to recognize the early signsof diabetic ketoacidosis

b. Teach patients to perform self-monitoringof ketones

c. Teach patients to omit their insulin doseduring sick days

d. Identify risk factors that may requirespecial intervention

14. The presence of headache, altered mentalstatus, and papilledema during rehydrationleads you to suspect:

a. Migraine headache

b. Volume overload

c. Severe hypophosphatemia

d. Cerebral edema

15. Per year, the overall annual hospital cost forpatients with DKA is more than:

a. $1 million

b. $5 million

c. $1 billion

d. $5 billion

Evaluation FormDiabetic Ketoacidosis in the Adult PatientPostgraduate Institute for Medicine and Novo Nordisk Pharmaceuticals, Inc. respect andappreciate your opinion. To assist us in evaluating the effectiveness of this activity and to makerecommendations for future educational programs, please take a few minutes to complete thisevaluation form. A certificate of completion is only issued upon receipt of your completedevaluation form.

Please answer the following questions by circling the appropriate rating:

5 = Outstanding 4 = Good 3 = Satisfactory 2 = Fair 1 = Poor

Extent That Program Activities Met the Identified Objectives

After completing this educational activity, participants should be able to:

• Define DKA 5 4 3 2 1

• Describe the epidemiology of DKA 5 4 3 2 1

• Outline the pathogenesis and diagnosis of DKA 5 4 3 2 1

• Identify the signs, symptoms, and complications of DKA 5 4 3 2 1

• Discuss methods of treatment and recovery care for DKA 5 4 3 2 1

• Provide strategies for the prevention of DKA 5 4 3 2 1

• Discuss the economic impact of DKA in today’s environment 5 4 3 2 1

Overall Effectiveness of the Activity

• Objectives were related to overall purpose/goal(s) of activity 5 4 3 2 1

• Relates to my practice needs 5 4 3 2 1

• Will influence how I practice 5 4 3 2 1

• Will help me improve patient care 5 4 3 2 1

• Stimulated my intellectual curiosity 5 4 3 2 1

• Overall quality of material 5 4 3 2 1

• Activity met my expectations 5 4 3 2 1

• Avoided commercial bias or influence 5 4 3 2 1

Will the information presented change your practice? ____Yes ___No

If yes, please describe any change(s) you plan to make in your practice as a result of thisprogram.

___________________________________________________________________________________

___________________________________________________________________________________

___________________________________________________________________________________

If no, is it because you already practice this way? ____Yes ___No

2322

9. Which action is not recommended for apatient with diabetes during sick days?

a. Stop taking insulin when not eating.

b. Report infections to the physician.

c. Perform frequent tests of ketones.

d. Keep well hydrated.

10. Which of the following events can triggerdiabetic ketoacidosis:

a. Substance abuse

b. Infection

c. Pregnancy

d. Emotional stress

e. All of the above

11. The following signs are commonly associatedwith diabetic ketoacidosis except:

a. Tachycardia

b. Hypotension

c. Deep, rapid breathing

d. Unequal pupils

12. How does the body compensate for acidosis?

a. Renal elimination of ketones

b. Bicarbonate buffering

c. Retention of carbon dioxide

d. a and b

e. All of the above

13. All of the following are objectives of thehealthcare team for patients who havediabetes except:

a. Teach patients to recognize the early signsof diabetic ketoacidosis

b. Teach patients to perform self-monitoringof ketones

c. Teach patients to omit their insulin doseduring sick days

d. Identify risk factors that may requirespecial intervention

14. The presence of headache, altered mentalstatus, and papilledema during rehydrationleads you to suspect:

a. Migraine headache

b. Volume overload

c. Severe hypophosphatemia

d. Cerebral edema

15. Per year, the overall annual hospital cost forpatients with DKA is more than:

a. $1 million

b. $5 million

c. $1 billion

d. $5 billion

Evaluation FormDiabetic Ketoacidosis in the Adult PatientPostgraduate Institute for Medicine and Novo Nordisk Pharmaceuticals, Inc. respect andappreciate your opinion. To assist us in evaluating the effectiveness of this activity and to makerecommendations for future educational programs, please take a few minutes to complete thisevaluation form. A certificate of completion is only issued upon receipt of your completedevaluation form.

Please answer the following questions by circling the appropriate rating:

5 = Outstanding 4 = Good 3 = Satisfactory 2 = Fair 1 = Poor

Extent That Program Activities Met the Identified Objectives

After completing this educational activity, participants should be able to:

• Define DKA 5 4 3 2 1

• Describe the epidemiology of DKA 5 4 3 2 1

• Outline the pathogenesis and diagnosis of DKA 5 4 3 2 1

• Identify the signs, symptoms, and complications of DKA 5 4 3 2 1

• Discuss methods of treatment and recovery care for DKA 5 4 3 2 1

• Provide strategies for the prevention of DKA 5 4 3 2 1

• Discuss the economic impact of DKA in today’s environment 5 4 3 2 1

Overall Effectiveness of the Activity

• Objectives were related to overall purpose/goal(s) of activity 5 4 3 2 1

• Relates to my practice needs 5 4 3 2 1

• Will influence how I practice 5 4 3 2 1

• Will help me improve patient care 5 4 3 2 1

• Stimulated my intellectual curiosity 5 4 3 2 1

• Overall quality of material 5 4 3 2 1

• Activity met my expectations 5 4 3 2 1

• Avoided commercial bias or influence 5 4 3 2 1

Will the information presented change your practice? ____Yes ___No

If yes, please describe any change(s) you plan to make in your practice as a result of thisprogram.

___________________________________________________________________________________

___________________________________________________________________________________

___________________________________________________________________________________

If no, is it because you already practice this way? ____Yes ___No

24

If you wish to receive credit for this activity, please fill inyour name and address and mail or fax this form to:

Program Management Services, Inc.PO Box 490East Islip, NY 11730FAX (631) 563-1907

Type of credit desired: ❑ Pharmacy ❑ Nursing

Signature

Name (Please Print Clearly)

Specialty SS# or License #

Street Address Box/Suite

City State Zip Code

Phone Number Fax Number

Email Address

Very Not at all committed committed

How committed are you to making these changes? 5 4 3 2 1

Additional comments about this educational activity?

___________________________________________________________________________________

___________________________________________________________________________________

Do you feel future activities on this topic are necessary and/or important to your practice?____Yes ____No

Please list any other topics that would be of interest to you for future educational activities:

___________________________________________________________________________________

How long did it take you to complete this activity (read and complete the self-assessment test)?______hours ______minutes

Degree: ❏ MD ❏ DO ❏ PharmD ❏ RPh ❏ RN ❏ PA ❏ BS ❏ Other__________

To receive credit, you must complete the exam* by selecting the best answer to each question,complete the evaluation form, and send it to Program Management Services, Inc.

Exam Answer Key

1 2 3 4 5 6 7 8

9 10 11 12 13 14 15

*A score of at least 70% in the self-assessment test is required.

Co-sponsored by Novo Nordisk Pharmaceuticals, Inc. and Postgraduate Institute for Medicine

Copyright©2002 Novo Nordisk Pharmaceuticals, Inc. 125158 July 2002 Printed in USA

Diabetic Ketoacidosis in the Adult Patient - CECity

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