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Differentiating Between DKA and HHS
CLINICAL
DIFFERENTIATING BETWEEN DKA
AND
HHS
Authors: Christy McDonald Lenahan, MSN, RN, FNP-BC, and Brenda Holloway, DNSc, MSN, RN, FNP-BC, Lafayette, LA, Mobile, AL
wo of the most common metabolic emergencies associated with diabetes mellitus are diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS). 1 Although each disorder results in severe hyperglycemia, the underlying pathophysiology, clinical presentation, and treatment are vastly different. 2 It is imperative that clinicians be keenly aware of these differences, considering the variation in clinical pathways associated with each hyperglycemic emergency. 3 This article will compare and contrast the epidemiology, associated risk factors, differential diagnoses, clinical presentation, diagnosis, and medical management of DKA and HHS.
T
HHS
Persons of African American ethnicity and older persons are at an increased risk for the development of HHS. 8 Rates of hospital admissions associated with HHS are significantly lower than those associated with DKA and account for less than 1% of all diabetic-related admissions. 3 It should be noted, however, that between the years of 1997 and 2009 there was a 52.4% increase in the HHS hospitalization rate among children and adolescents. 9 Moreover, it is predicted that as the occurrence of type 2 diabetes mellitus (T2DM) continues to rise, so will the occurrence of HHS. 1 Mortality rates associated with HHS are significantly higher than those associated with DKA and range from 10% to 20%. 1
Epidemiology Risk Factors DKA
DKA
Although gender appears to have no effect on the incidence of DKA, being a member of an ethnic minority, including African and Hispanic, places one at an increased risk for the development of DKA. 4 Data suggest that the incidence of DKA has steadily risen, from 80,000 hospital discharges in 1988 to 140,000 hospital discharges in 2009 for cases in which DKA was listed as the primary diagnosis. 5 However, the average length of hospital stay for persons with a primary diagnosis of DKA trended favorably with a declining pattern, from an average of 5.7 days in 1988 to 3.4 days in 2009. 5 Overall, DKA-related mortality ranges from 1% in adults to 5% in elderly patients or patients with additional comorbidities. 6 In children, mortality rates range from 2% to 5%. 7 From an economic perspective, direct and indirect costs associated with DKA average $2.4 billion annually. 6
Multiple risk factors such as younger age, lower body mass index, and new-onset type 1 diabetes mellitus (T1DM) are associated with the development of DKA. 10 Diabetic children younger than 3 years were reported to have a 54% risk for DKA, whereas those aged 3 years or older exhibited a 33% risk of the development of DKA. 11 This trend of decreasing risk for DKA with increasing age appears to remain constant because risk for DKA in adolescents older than 14 years is 16% or less. 12 Although DKA is significantly more common in persons with T1DM, it can also be seen as a complication in persons with T2DM. 13 According to Raghaven, 14 other risk factors for DKA include “underlying infection, disruption of insulin treatment, and new onset of diabetes.” HHS
Christy McDonald Lenahan is Instructor, College of Nursing and Allied Health Professions, University of Louisiana at Lafayette, Lafayette, LA. Brenda Holloway is Professor, College of Nursing, University of South Alabama, Mobile, AL. For correspondence, write: Christy McDonald Lenahan, MSN, RN, FNPBC, 411 East Saint Mary Blvd, Lafayette, LA 70503; E-mail: [email protected]. J Emerg Nurs ■. 0099-1767 Copyright © 2014 Published by Elsevier Inc. on behalf of Emergency Nurses Association. http://dx.doi.org/10.1016/j.jen.2014.08.015
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Several risk factors are associated with the development of HHS; however, infection, and more specifically pneumonia and urinary tract infection, appear to be the leading risk factors for the development of HHS. 15 Often HHS is a result of decreased fluid intake precipitated by an underlying infection. 1 Poor compliance or noncompliance with diabetes treatment regimens is another common risk factor for the development of HHS. 16 Unlike DKA, which is usually associated with T1DM, HHS is more common in persons with T2DM, but it can be seen in persons with T1DM and is seen more commonly in older persons. 1,17
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Typically, the onset of HHS is seen during or after the sixth decade of life. 1
Differential Diagnosis DKA
Ketoacidosis alone does not indicate an exclusive diagnosis of DKA. Differential diagnoses that should be explored via clinical history and plasma glucose levels in patients presenting with ketoacidosis include starvation ketosis and alcoholic ketoacidosis. 18 Alternative causes of high anion gap metabolic acidosis also should be excluded prior to the diagnosis of DKA. These causes include lactic acidosis caused by strenuous exercise, cancer, sepsis, or respiratory failure; excessive ingestion of salicylate or alcohol derivative; and acute or chronic renal failure. 18 Additionally, HHS should be considered a differential diagnosis when assessing for DKA because approximately 50% of patients presenting with HHS may also present with ketoacidosis. 19 HHS
Differential and/or concomitant diagnoses to be considered when evaluating a patient for HHS include diabetes insipidus, DKA, myocardial infarction, and pulmonary embolism. 1 Patients presenting with diabetes insipidus and DKA will exhibit signs and symptoms such as polydipsia and polyuria, similar to signs and symptoms of HHS. Myocardial infarction and pulmonary embolism are precipitating factors for HHS. 15,20 Laboratory values should be assessed as indicated per patient presentation and history of present illness for accurate diagnosis. 20 Additional differential diagnoses associated with HHS include infection, pregnancy, lack of insulin, and ingestion of drugs such as cocaine. 21
Clinical Presentation DKA
Numerous similarities exist between clinical presentations of DKA and HHS and may include malaise, fatigue, anorexia, and existence of a preceding illness or infection. 22 The onset of DKA is generally more rapid than that of HHS, with DKA developing over the course of a few days. 1 Differences that distinguish DKA from HHS are commonly the result of the compensatory mechanisms that are activated as a result of the metabolic acidosis associated with DKA. 23 These differences include the existence of Kussmaul respirations, presenting as a rapid and labor
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intensive breathing pattern, and abdominal pain. 22 Kussmaul respirations occur as the body attempts to compensate for existing metabolic acidosis, and often a fruity odor resulting from exhaled acetone can be detected on the breath of patients with DKA. 24 Abdominal pain may be present in persons with DKA with no underlying disease; however, the pain can be the result of an underlying disorder such as acute pancreatitis and warrants an abdominal workup including but not limited to a physical examination, complete blood cell count, complete metabolic profile, serum lactic acid, glycosylated hemoglobin, serum amylase, serum lipase, anion gap, arterial blood gases, and necessary abdominal imaging as indicated by examination. 25 HHS
As with DKA, the clinical presentation of HHS may include malaise, fatigue, anorexia, and the existence of a preceding illness or infection. 22 Development of HHS is more gradual than is DKA and may take days to weeks to develop. 1 Neurologic disturbances are commonly seen in early HHS as opposed to DKA, in which neurologic disturbances are seen later in the disease process 22 and are a result of abnormal osmolality and electrolyte imbalances. 26 According to Hemphill, 1 neurologic disturbances seen in HHS can include but are not limited to “drowsiness and lethargy, delirium, coma, focal or generalized seizures, visual changes or disturbances, hemiparesis, and sensory deficits.” Diagnosis DKA
Diagnostic criteria for both DKA and HHS are based on several laboratory values (Table 1) including plasma glucose, arterial pH, serum bicarbonate, urine and serum ketones, effective serum osmolality and anion gap (see Appendix), and mental status. 27 Plasma glucose levels in persons with DKA are typically lower than in persons with HHS, but they are generally greater than 250 mg/dL. 18 Arterial pH can range from 7.25 in persons with mild DKA to less than 7.00 in persons with severe DKA. 18 Urine and serum ketones are present in persons with DKA and serum osmolality is variable but usually less than 320 mOsm/kg. 18 Serum bicarbonate can range from 15 to 18 mEq/L in persons with mild DKA, 10 to 15 mEq/L in persons with moderate DKA, and less than 10 mEq/L in persons with severe DKA. 18 In persons with DKA, the anion gap—a difference of the serum cations sodium and potassium and the serum anions chloride and
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TABLE 1
Diagnostic criteria of diabetic ketoacidosis and hyperglycemic hyperosmolar state Plasma glucose Arterial pH Serum bicarbonate
Urine ketones Serum ketones Effective serum osmolality Anion gap Mental status
DKA
HHS
N 250 mg/dL Mild to moderate 7.00-7.25 Severe b 7.00 Mild 15-18 mEq/L Moderate 10-15 mEq/L Severe b 10 mEq/L Present Present Variable Mild N 10 Moderate to severe N 12 Mild—alert Moderate—alert to drowsy Severe—stupor/coma
N 600 mg/dL N 7.30 N 18 mEq/L
Absent to small Absent to small N 320 mOsm/kg b 12 Commonly seen in later stages
DKA, Diabetic ketoacidosis; HHS, hyperglycemic hyperosmolar state.
bicarbonate—can range from greater than 10 mEq/L in mild DKA to greater than 12 mEq/L in moderate to severe DKA. 18 Mental status can range from alert in persons with mild DKA to alert or drowsy in persons with moderate DKA to stupor or coma in persons with severe DKA. 18 Typically, the presence of a plasma glucose level greater than 250 mg/dL and an arterial pH less than 7.3 and the presence of urine and/or serum ketones are considered diagnostic criteria for DKA. 27 HHS
Plasma glucose levels seen in persons with HHS are usually significantly higher than those seen with DKA and are normally greater than 600 mg/dL when HHS is diagnosed. 18 Arterial pH is typically greater than 7.30 and serum bicarbonate is routinely greater than 18 mEq/L in persons with HHS. 18 Urine and serum ketones may be present, but often they are present only in small amounts. 18 Although effective serum osmolality may vary in DKA, it is consistently greater than 320 mOsm/kg in HHS. 18 Anion gaps associated with HHS are frequently reported as less than 12 mEq/dL. 18 In persons with severe HHS, stupor and coma are often present. 18 Diagnosis of HHS is ordinarily based on plasma glucose levels greater than 600 mg/dL, an effective serum osmolality of greater than 330 mOsm/kg, and the absence of severe ketoacidosis. 27
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Medical Management in the Adult Patient DKA
Management of DKA requires fluid and electrolyte replacement, administration of insulin, and treatment of any underlying cause if one is present or suspected (Table 2). 22 Fluid deficits in patients presenting with DKA range from 3 to 5 L and should be replenished by a rapid normal saline solution bolus of 1 L with an additional infusion of normal saline solution at 250 to 500 mL/h for several hours thereafter in patients with low serum sodium levels or an additional infusion of half normal saline solution in patients with high to normal serum sodium levels. 18,22 Fluid replacement may vary depending on patient hemodynamics, electrolyte levels, and urinary output. 18 Of special concern is the pediatric population in which rapid fluid correction to correct hyperosmolality can result in cerebral edema and potential death, with mortality rates as high as 24%. 28 Electrolyte imbalances of serum potassium, phosphate, magnesium, and bicarbonate may be present in both DKA and HHS. 29 Rapid shifts in serum potassium are present as a result of extracellular shifts related to insulin deficiency and acidosis. 22 In persons with DKA specifically, death in the initial phases of resuscitation is usually related to hyperkalemia, whereas the most common cause of death in later phases of resuscitation is related to hypokalemia; thus,
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TABLE 2
Management of diabetic ketoacidosis and hyperglycemic hyperosmolar state in the adult patient Fluid replacement
DKA
HHS
Expected deficit: 3-5 L Initial bolus: 1 L Continuous: 500 mL/h for several hours
Expected deficit: N 10 L Initial bolus: 500 mL Continuous: 1-2 L over first 2 h; replace ½ estimated fluid loss over first 12 h
Add dextrose once blood glucose falls below 250 mg/dL Electrolyte replacement Potassium
Phosphate Magnesium
Bicarbonate Insulin therapy
Resolution
Treat after patient has voided N 5.3 mEq/L: no treatment 4.0-5.3 mEq/L: 10 mEq/L/h 3.5 - b 4.0 mEq/L: 20 mEq/L/h b 3.5 mEq/L: Hold insulin 20-60 mEq/L/h b 1.5 mg/dL: dipotassium phosphate at 0.5 mg/dL b 1.8 mg/dL and symptomatic b 50 kg: 1-2 gm N 50 kg: 2-3 gm b 1.2 mg/dL and symptomatic b 50 kg: 2-3 gm N 50 kg: 3-4 gm Only replace if pH b 6.9 Loading dose: 0.1 units/kg of body weight of regular insulin (not to exceed 10 units) Subsequent infusion: 0.1 units/kg of body weight of regular insulin per hour (not to exceed 10 units/h) If blood glucose does not decrease by 10% in the first hour a second loading dose may be given: 0.14 units/kg of body weight of regular insulin/h Blood glucose: b 200 mg/dL Serum bicarbonate: N 18 mEq/L pH: N 7.3 Anion gap: b 12
Treat after patient has voided b 5.2 mEq/L: 20-30 mEq/L/h
Same as DKA Same as DKA
Not recommended Same as DKA
Or
Fluid replacement and if blood glucose does not decrease by 50-70 mg/dL/h give a bolus of 0.1 units/kg of body weight of regular insulin Serum osmolality: b 315 mOsm/kg Normal mental state observed Patient is able to eat
DKA, Diabetic ketoacidosis; HHS, hyperglycemic hyperosmolar state.
serum potassium levels should be measured every 2 hours until the patient is deemed stable, and all patients should be monitored continuously with a cardiac monitor. 21 Potassium should be administered only after serum potassium
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levels are known and after the patient has voided. Urinary potassium loss is a common occurrence in persons with DKA and is caused by extracellular potassium egression seen in acidosis. 30 Hypophosphatemia is another common
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manifestation of DKA, and any serum phosphate less than 1.5 mg/dL should be treated with intravenous dipotassium phosphate at a rate of 0.5 mL/h. 21 A serum phosphate deficit of 0.5 to 1 mmol/L is normally present in patients presenting with DKA. 31 Symptoms of hypomagnesaemia such as paresthesias, tremor, carpopedal spasm, seizures, and cardiac disturbances usually occur at levels below 1.2 mg/dL; thus, treatment should begin if levels fall below 1.8 mg/dL and symptoms of hypomagnesaemia are present. 31 Although bicarbonate imbalances can be present in persons with DKA or HHS, many studies indicate minimal efficacy of bicarbonate replacement when used in patients with a pH of greater than 6.9. 21 In patients with severe DKA, current recommendations for insulin therapy include an intravenous loading dose of regular insulin at 0.1 units/kg of body weight, not to exceed a total loading dose of 10 units. 18,21 If a patient’s initial blood glucose does not decrease by 10% within the first hour, an additional intravenous loading dose of 0.14 units/kg of body weight should be administered. 18,21 Subsequent to the initial loading dose, an intravenous infusion of regular insulin should begin at a rate of 0.1 units/kg of body weight per hour, not to exceed 10 units per hour. 18 In patients with DKA who have an arterial pH between 7.00 and 7.25, an intravenous infusion of regular insulin at a rate of 0.1 units/kg of body weight per hour may be started without a loading dose. 21 Careful monitoring of blood glucose level should be conducted hourly in patients with DKA or HHS. 21 In persons with DKA, once the blood glucose level falls below 250 mg/dL, 5% dextrose should be added to intravenous fluids. 21 Resolution of DKA is acknowledged when blood glucose levels are less than 200 mg/dL, serum bicarbonate is greater than or equal to 18 mEq/L, pH is greater than 7.3, and the anion gap is less than or equal to 12 mEq/L. 32 HHS
Management of HHS requires fluid and electrolyte replacement and treatment of any underlying cause if one is present or suspected. 22 Variable guidelines for the use of insulin therapy in the management of HHS are discussed later. Severe dehydration is often associated with HHS, and deficits of 10 L or more can exist in patients presenting with this condition. 21 Considering the vast amount of fluid deficit associated with HHS, clinicians should consider replacement of one half of the estimated fluid loss during the first 12 hours of treatment, with the remainder of the deficit being replaced in the following 12 hours. 1 An initial bolus of 500 mL of
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normal saline solution is considered appropriate, and 1 to 2 L of normal saline solution should be delivered within the first 2 hours of therapy. 1 Advanced age and comorbidities associated with HHS should cause the clinician to be conscientious of potential complications associated with rapid fluid replacement and may require slower initial rates. 1 As with DKA, cerebral edema is a concern in the pediatric population when rapid fluid resuscitation is performed in patients with HHS. 32 Early signs of cerebral edema are headache and lethargy culminating to neurologic deterioration (seizures and coma) and respiratory arrest in later stages. 33 Symptoms typically occur 4 to 12 hours into treatment. 34 Hyperkalemia is often more severe in HHS than in DKA and results from an extracellular shift and osmotic diuresis. 29 HHS-related hyperkalemia often will correct itself with the administration of fluids and insulin treatment, which encourage a shift of potassium back into the cell. 22 To prevent hypokalemia, it is suggested that potassium replacement be initiated via the addition of 20 to 30 mEq of potassium in each liter of infused fluid once serum potassium levels fall below 5.2 mEq/L. 18 No studies were found to support waiting until the patient voids prior to administering intravenous potassium in persons with HHS. As with DKA, the potential for cardiac disturbances remain secondary to hyperkalemia and hypokalemia affiliated with HHS; potassium levels should be checked every 2 hours, and patients should be monitored continuously with a cardiac monitor. 21 Phosphate and magnesium imbalances are less common in persons with HHS, but levels should be monitored and replacement begun when levels fall below normal limits. 35 Bicarbonate is not recommended in the treatment of HHS. 21 Clinical guidelines for insulin therapy in the treatment of HHS are variable and are related to the potential for euglycemia obtained with fluid therapy alone. 1 Some authors suggest using the same insulin guidelines for HHS and DKA, 1 whereas more conservative authors suggest not giving any insulin as part of the initial therapy in persons with HHS; instead, they suggest that glucose levels be monitored hourly and that insulin therapy be initiated as a bolus of 0.1 units/kg of body weight only if serum glucose levels do not decrease by 50 to 70 mg/dL per hour with appropriate fluid management. 21 As with DKA, blood glucose levels should be monitored hourly in the patient with HHS. 21 The addition of dextrose in intravenous fluids is not suggested for persons with HHS unless blood glucose levels fall below 300 mg/dL and unless signs of oliguric renal failure and/or cardiovascular collapse are present. 21 Resolution of HHS is acknowledged when serum osmolality levels fall below 315 mOsm/kg, the patient returns to a normal mental state, and the patient is able to eat. 36
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Prevention
Clinicians should be mindful of preventive measures when treating patients with diabetes. Diabetic ketoacidosis alone is responsible for 500,000 US hospital days per year and a total economic cost of $2.4 billion annually. 18 Moreover, mortality rates can exceed 15% in patients with HHS compared with mortality rates of less than 5% in patients with DKA. 37 Multiple preventive measures such as increased access to medical care, education, and communication can decrease the occurrence of DKA and HHS. 18 Considering the high incidence of DKA and HHS precipitated by illness or infection, education of patients with T1DM and T2DM regarding sick day management is of particular importance. 3 Appropriate educational interventions for sick day management include (1) initiation of contact with the health care provider early in the illness, (2) maintaining an insulin regimen during the illness, (3) treatment of the underlying illness, (4) maintaining ingestion of carbohydrates and sodium despite nausea, and (5) recruitment of family members or caregivers to assist with sick day management, especially in elderly persons. 18
4. Usher-Smith J, Thompson MJ, Sharp S, Walter FM. Factors associated with the presence of diabetic ketoacidosis at diagnosis of diabetes in children and young adults: a systematic review. BMJ. 2011;343:d4092. 5. Centers for Disease Control and Prevention. Diabetes public health resource. http://www.cdc.gov/diabetes/statistics/dkafirst/fig1.htm. Updated May 17, 2012. Reviewed November 19, 2013. Accessed September 15, 2014. 6. Clinical Key Staff. Diabetic ketoacidosis. https://www.clinicalkey.com/ topics/endocrinology/diabetic-ketoacidosis.html. Published 2012. Accessed September 15, 2014. 7. Lamb WH. Pediatric diabetic ketoacidosis. http://emedicine.medscape. com/article/907111-overview. Updated April 25, 2014. Accessed September 15, 2014. 8. Epocrates Staff. Hyperosmolar hyperglycemic state. https://online. epocrates.com/u/29231011/Hyperosmolar+hyperglycemic+state/Basics/ Epidemiology. Published 2014. Accessed September 15, 2014. 9. Bagdure D, Rewers A, Campagna E, Sills MR. Epidemiology of hyperglycemic hyperosmolar syndrome in children hospitalized in USA. Pediatr Diabetes. 2013;14(1):18-24. 10. Butalia S, Johonson JA, Ghali WA, Rabi DM. Clinical and sociodemographic factors associated with diabetic ketoacidosis hospitalization in adults with type 1 diabetes. Diabet Med. 2013;30(5):567-573. 11. Klingensmith GJ, Tamborlane WV, Wood J, et al. Diabetic ketoacidosis at diabetes onset: still an all too common threat in youth. J Pediatr. 2013;162(2):330-334. 12. Wolfsdorf J, Glaser N, Sperling MA. Diabetic ketoacidosis in infants, children, and adolescents: a consensus statement from the American Diabetes Association. Diabetes Care. 2006;29(5):1150-1159.
Conclusion
Clinicians must be vigilant in differentiating between hyperglycemic emergencies such as DKA and HHS. A thorough history, physical examination, and evaluation of available laboratory data can assist the clinician in differentiating DKA from HHS and quickly lead to the appropriate clinical pathway. Although DKA and HHS have many similarities, significant differences exist in pathology, diagnostic criteria, management, and resolution of each disorder, and thus accurate diagnosis is critical.
13. Lin MV, Bishop G, Benito-Herrero M. Diabetic ketoacidosis in type 2 diabetics: a novel presentation of pancreatic adenocarcinoma. J Geriatr Intern Med. 2010;25(4):369-373.
REFERENCES
17. American Diabetes Association. Hyperosmolar hyperglycemic nonketotic syndrome (HHNS). http://www.diabetes.org/living-with-diabetes/ complications/hyperosmolar-hyperglycemic.html. Updated December 6, 2013. Accessed September 15, 2014.
1. Hemphill RR. Hyperosmolar hyperglycemic state. http://emedicine. medscape.com/article/1914705-overview. Updated April 30, 2014. Accessed September 15, 2014. 2. Kitabchi AE. Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: treatment. http://www.uptodate.com/contents/ treatment-of-diabetic-ketoacidosis-and-hyperosmolar-hyperglycemicstate-in-adults. Published June 26, 2012. Updated July 3, 2014. Accessed September 15, 2014. 3. Chaitnogi N, Subauste JS, Koch CA, Geraci SA. Diagnosis and management of hyperglycemic emergencies. Hormones. 2011;10(4):250-260. http://www. hormones.gr/738/article/article.html. Accessed September 15, 2014.
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14. Raghaven VA. Diabetic ketoacidosis. http://emedicine.medscape.com/ article/118361-overview. Updated April 10, 2014. Accessed September 15, 2014. 15. Stoner GD. Hyperosmolar hyperglycemic state. Am Fam Physician. 2005;71(9):1723-1730. http://www.aafp.org/afp/2005/0501/p1723.html. Published May 1, 2005. Accessed September 15, 2014. 16. Pietrangelo A. Diabetic hyperglycemic hyperosmolar syndrome. http:// www.healthline.com/health/type-2-diabetes/hyperglycemichyperosmolar-syndrome#Overview1. Published September 16, 2012. Accessed September 15, 2014.
18. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7): 1335-1343. 19. Lang A, Satterfield K. When there are acute changes in mental status in patients with diabetes. Podiatry Today. 2010;23(3):16-25. http://www. podiatrytoday.com/when-there-are-acute-changes-in-mental-statusin-patients-with-diabetes?page=2. Published March 2010. Accessed September 15, 2014.
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20. Stunkard ME, Pikul VT, Foley K. Hyperosmolar hyperglycemic syndrome with rhabdomyolysis. Clin Lab Sci. 2011;24(1):8-13.
Clinical/Resources/Documents/BDCDKATreatmentProtocol2012.pdf. Published 2012. Accessed September 15, 2014.
21. McNaughton CD, Self WH, Slovis C. Diabetes in the emergency department: acute care of diabetes patients. Clin Diabetes. 2011;29(2):51-59.
31. Trachtenbarg DE. Diabetic ketoacidosis. Am Fam Physician. 2005;71(9):1705-14. http://www.aafp.org/afp/2005/0501/p1705. html#afp20050501p1705-b42. Published May 1, 2005. Accessed September 15, 2014.
22. Maletkovic J, Drexler A. Diabetic ketoacidosis and hyperglycemic hyperosmolar state. Endocrinol Metab Clin. 2013;42(4):677-695. 23. Thomas C. Metabolic acidosis clinical presentation. http://emedicine. medscape.com/article/242975-clinical. Updated March 27, 2013. Accessed September 15, 2014. 24. Kishore P. Diabetic ketoacidosis. http://www.merckmanuals.com/professional/ endocrine_and_metabolic_disorders/diabetes_mellitus_and_disorders_ of_carbohydrate_metabolism/diabetic_ketoacidosis_dka.html. Revised June 2014. Accessed September 15, 2014. 25. Kadaria D, Murillo LC, Yataco JC, et al. Abdominal pathology in patients with diabetic ketoacidosis. Am J Med Sci. 2012;344(5):341-344. 26. Chalela JA, Kasner SE. Acute toxic-metabolic encephalopathy in adults. http:// www.uptodate.com/contents/acute-toxic-metabolic-encephalopathy-inadults. Updated August 9, 2013. Accessed September 15, 2014. 27. Epocrates Staff. Diabetic ketoacidosis: diagnostic criteria. http://online. epocrates.com/u/2936162/Diabetic+ketoacidosis/Diagnosis/Criteria. Published 2014. Accessed September 15, 2014. 28. Orlowski JP, Cramer CL, Fiallos MR. Diabetic ketoacidosis in the pediatric ICU. Pediatr Clin North Am. 2008;55(3):577-587. 29. DeBeer K, Michael S, Thacker M, et al. Diabetic ketoacidosis and hyperglycaemic hyperosmolar syndrome—clinical guidelines. Nurs Crit Care. 2008;13(1):5-11. 30. Barbara Davis Center for Diabetes. DKA treatment protocol. http://www. ucdenver.edu/academics/colleges/medicalschool/centers/BarbaraDavis/
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32. Maciel AT, Park M. A physiochemical acid-base approach for managing diabetic ketoacidosis. Clinics. 2009;64(7):714-718. 33. Kershaw MJR, Newton T, Barrett TG, Berry K, Kirk J. Childhood diabetes presenting with hyperosmolar dehydration but without ketoacidosis: a report of three cases. Diabet Med. 2005;22(5):645-647. 34. Banh K, Tsukamaki J. Hyperglycemia. CDEM Self Study Modules. http :/ /www.cde mc ur riculum.org /ssm/end o/hy perg lyc emia/ hyperglycemia.php. Published 2010. Accessed September 15, 2014. 35. Venkatraman R, Signhi SC. Hyperglycemic hyperosmolar nonketotic syndrome. Indian J Pediatr. 2006;73(1):55-60. 36. Makrilakis K, Katsilambros N. Diabetic emergencies, diagnosis and clinical management: hyperosmolar non-ketotic hyperglycemia, part 4. www.diabetesincontrol.com/articles/85-/14686-diabeticemergencies-diagnosis-and-clinical-management-hyperosmolar-nonketotic-hyperglycemia-part4. Published May 27, 2013. Accessed September 15, 2014. 37. Kitabchi AE, Razavi L. Hyperglycemic crises: diabetic ketoacidosis (DKA), and hyperglycemic hyperosmolar state (HHS). http://diabetesmanager. pbworks.com/w/page/17680206/Hyperglycemic%20Crises% 3A%20Diabetic%20Ketoacidosis%20%28DKA%29%2C%20And% 20Hyperglycemic%20Hyperosmolar%20State%20%28HHS%29. Revised 2009. Accessed September 15, 2014.
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Appendix. Calculations
Effective Serum Osmolality
2(Na + + K +) + glucose Anion Gap a Na + – (Cl – + HCO3 –) or (Na + + K +) – (Cl – + HCO3 –) a It is a common practice to omit potassium from the formula when calculating anion gap and is considered clinically acceptable.
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DIFFERENTIATING BETWEEN DKA
AND
HHS
Authors: Christy McDonald Lenahan, MSN, RN, FNP-BC, and Brenda Holloway, DNSc, MSN, RN, FNP-BC, Lafayette, LA, Mobile, AL
wo of the most common metabolic emergencies associated with diabetes mellitus are diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS). 1 Although each disorder results in severe hyperglycemia, the underlying pathophysiology, clinical presentation, and treatment are vastly different. 2 It is imperative that clinicians be keenly aware of these differences, considering the variation in clinical pathways associated with each hyperglycemic emergency. 3 This article will compare and contrast the epidemiology, associated risk factors, differential diagnoses, clinical presentation, diagnosis, and medical management of DKA and HHS.
T
HHS
Persons of African American ethnicity and older persons are at an increased risk for the development of HHS. 8 Rates of hospital admissions associated with HHS are significantly lower than those associated with DKA and account for less than 1% of all diabetic-related admissions. 3 It should be noted, however, that between the years of 1997 and 2009 there was a 52.4% increase in the HHS hospitalization rate among children and adolescents. 9 Moreover, it is predicted that as the occurrence of type 2 diabetes mellitus (T2DM) continues to rise, so will the occurrence of HHS. 1 Mortality rates associated with HHS are significantly higher than those associated with DKA and range from 10% to 20%. 1
Epidemiology Risk Factors DKA
DKA
Although gender appears to have no effect on the incidence of DKA, being a member of an ethnic minority, including African and Hispanic, places one at an increased risk for the development of DKA. 4 Data suggest that the incidence of DKA has steadily risen, from 80,000 hospital discharges in 1988 to 140,000 hospital discharges in 2009 for cases in which DKA was listed as the primary diagnosis. 5 However, the average length of hospital stay for persons with a primary diagnosis of DKA trended favorably with a declining pattern, from an average of 5.7 days in 1988 to 3.4 days in 2009. 5 Overall, DKA-related mortality ranges from 1% in adults to 5% in elderly patients or patients with additional comorbidities. 6 In children, mortality rates range from 2% to 5%. 7 From an economic perspective, direct and indirect costs associated with DKA average $2.4 billion annually. 6
Multiple risk factors such as younger age, lower body mass index, and new-onset type 1 diabetes mellitus (T1DM) are associated with the development of DKA. 10 Diabetic children younger than 3 years were reported to have a 54% risk for DKA, whereas those aged 3 years or older exhibited a 33% risk of the development of DKA. 11 This trend of decreasing risk for DKA with increasing age appears to remain constant because risk for DKA in adolescents older than 14 years is 16% or less. 12 Although DKA is significantly more common in persons with T1DM, it can also be seen as a complication in persons with T2DM. 13 According to Raghaven, 14 other risk factors for DKA include “underlying infection, disruption of insulin treatment, and new onset of diabetes.” HHS
Christy McDonald Lenahan is Instructor, College of Nursing and Allied Health Professions, University of Louisiana at Lafayette, Lafayette, LA. Brenda Holloway is Professor, College of Nursing, University of South Alabama, Mobile, AL. For correspondence, write: Christy McDonald Lenahan, MSN, RN, FNPBC, 411 East Saint Mary Blvd, Lafayette, LA 70503; E-mail: [email protected]. J Emerg Nurs ■. 0099-1767 Copyright © 2014 Published by Elsevier Inc. on behalf of Emergency Nurses Association. http://dx.doi.org/10.1016/j.jen.2014.08.015
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Several risk factors are associated with the development of HHS; however, infection, and more specifically pneumonia and urinary tract infection, appear to be the leading risk factors for the development of HHS. 15 Often HHS is a result of decreased fluid intake precipitated by an underlying infection. 1 Poor compliance or noncompliance with diabetes treatment regimens is another common risk factor for the development of HHS. 16 Unlike DKA, which is usually associated with T1DM, HHS is more common in persons with T2DM, but it can be seen in persons with T1DM and is seen more commonly in older persons. 1,17
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Typically, the onset of HHS is seen during or after the sixth decade of life. 1
Differential Diagnosis DKA
Ketoacidosis alone does not indicate an exclusive diagnosis of DKA. Differential diagnoses that should be explored via clinical history and plasma glucose levels in patients presenting with ketoacidosis include starvation ketosis and alcoholic ketoacidosis. 18 Alternative causes of high anion gap metabolic acidosis also should be excluded prior to the diagnosis of DKA. These causes include lactic acidosis caused by strenuous exercise, cancer, sepsis, or respiratory failure; excessive ingestion of salicylate or alcohol derivative; and acute or chronic renal failure. 18 Additionally, HHS should be considered a differential diagnosis when assessing for DKA because approximately 50% of patients presenting with HHS may also present with ketoacidosis. 19 HHS
Differential and/or concomitant diagnoses to be considered when evaluating a patient for HHS include diabetes insipidus, DKA, myocardial infarction, and pulmonary embolism. 1 Patients presenting with diabetes insipidus and DKA will exhibit signs and symptoms such as polydipsia and polyuria, similar to signs and symptoms of HHS. Myocardial infarction and pulmonary embolism are precipitating factors for HHS. 15,20 Laboratory values should be assessed as indicated per patient presentation and history of present illness for accurate diagnosis. 20 Additional differential diagnoses associated with HHS include infection, pregnancy, lack of insulin, and ingestion of drugs such as cocaine. 21
Clinical Presentation DKA
Numerous similarities exist between clinical presentations of DKA and HHS and may include malaise, fatigue, anorexia, and existence of a preceding illness or infection. 22 The onset of DKA is generally more rapid than that of HHS, with DKA developing over the course of a few days. 1 Differences that distinguish DKA from HHS are commonly the result of the compensatory mechanisms that are activated as a result of the metabolic acidosis associated with DKA. 23 These differences include the existence of Kussmaul respirations, presenting as a rapid and labor
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intensive breathing pattern, and abdominal pain. 22 Kussmaul respirations occur as the body attempts to compensate for existing metabolic acidosis, and often a fruity odor resulting from exhaled acetone can be detected on the breath of patients with DKA. 24 Abdominal pain may be present in persons with DKA with no underlying disease; however, the pain can be the result of an underlying disorder such as acute pancreatitis and warrants an abdominal workup including but not limited to a physical examination, complete blood cell count, complete metabolic profile, serum lactic acid, glycosylated hemoglobin, serum amylase, serum lipase, anion gap, arterial blood gases, and necessary abdominal imaging as indicated by examination. 25 HHS
As with DKA, the clinical presentation of HHS may include malaise, fatigue, anorexia, and the existence of a preceding illness or infection. 22 Development of HHS is more gradual than is DKA and may take days to weeks to develop. 1 Neurologic disturbances are commonly seen in early HHS as opposed to DKA, in which neurologic disturbances are seen later in the disease process 22 and are a result of abnormal osmolality and electrolyte imbalances. 26 According to Hemphill, 1 neurologic disturbances seen in HHS can include but are not limited to “drowsiness and lethargy, delirium, coma, focal or generalized seizures, visual changes or disturbances, hemiparesis, and sensory deficits.” Diagnosis DKA
Diagnostic criteria for both DKA and HHS are based on several laboratory values (Table 1) including plasma glucose, arterial pH, serum bicarbonate, urine and serum ketones, effective serum osmolality and anion gap (see Appendix), and mental status. 27 Plasma glucose levels in persons with DKA are typically lower than in persons with HHS, but they are generally greater than 250 mg/dL. 18 Arterial pH can range from 7.25 in persons with mild DKA to less than 7.00 in persons with severe DKA. 18 Urine and serum ketones are present in persons with DKA and serum osmolality is variable but usually less than 320 mOsm/kg. 18 Serum bicarbonate can range from 15 to 18 mEq/L in persons with mild DKA, 10 to 15 mEq/L in persons with moderate DKA, and less than 10 mEq/L in persons with severe DKA. 18 In persons with DKA, the anion gap—a difference of the serum cations sodium and potassium and the serum anions chloride and
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TABLE 1
Diagnostic criteria of diabetic ketoacidosis and hyperglycemic hyperosmolar state Plasma glucose Arterial pH Serum bicarbonate
Urine ketones Serum ketones Effective serum osmolality Anion gap Mental status
DKA
HHS
N 250 mg/dL Mild to moderate 7.00-7.25 Severe b 7.00 Mild 15-18 mEq/L Moderate 10-15 mEq/L Severe b 10 mEq/L Present Present Variable Mild N 10 Moderate to severe N 12 Mild—alert Moderate—alert to drowsy Severe—stupor/coma
N 600 mg/dL N 7.30 N 18 mEq/L
Absent to small Absent to small N 320 mOsm/kg b 12 Commonly seen in later stages
DKA, Diabetic ketoacidosis; HHS, hyperglycemic hyperosmolar state.
bicarbonate—can range from greater than 10 mEq/L in mild DKA to greater than 12 mEq/L in moderate to severe DKA. 18 Mental status can range from alert in persons with mild DKA to alert or drowsy in persons with moderate DKA to stupor or coma in persons with severe DKA. 18 Typically, the presence of a plasma glucose level greater than 250 mg/dL and an arterial pH less than 7.3 and the presence of urine and/or serum ketones are considered diagnostic criteria for DKA. 27 HHS
Plasma glucose levels seen in persons with HHS are usually significantly higher than those seen with DKA and are normally greater than 600 mg/dL when HHS is diagnosed. 18 Arterial pH is typically greater than 7.30 and serum bicarbonate is routinely greater than 18 mEq/L in persons with HHS. 18 Urine and serum ketones may be present, but often they are present only in small amounts. 18 Although effective serum osmolality may vary in DKA, it is consistently greater than 320 mOsm/kg in HHS. 18 Anion gaps associated with HHS are frequently reported as less than 12 mEq/dL. 18 In persons with severe HHS, stupor and coma are often present. 18 Diagnosis of HHS is ordinarily based on plasma glucose levels greater than 600 mg/dL, an effective serum osmolality of greater than 330 mOsm/kg, and the absence of severe ketoacidosis. 27
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Medical Management in the Adult Patient DKA
Management of DKA requires fluid and electrolyte replacement, administration of insulin, and treatment of any underlying cause if one is present or suspected (Table 2). 22 Fluid deficits in patients presenting with DKA range from 3 to 5 L and should be replenished by a rapid normal saline solution bolus of 1 L with an additional infusion of normal saline solution at 250 to 500 mL/h for several hours thereafter in patients with low serum sodium levels or an additional infusion of half normal saline solution in patients with high to normal serum sodium levels. 18,22 Fluid replacement may vary depending on patient hemodynamics, electrolyte levels, and urinary output. 18 Of special concern is the pediatric population in which rapid fluid correction to correct hyperosmolality can result in cerebral edema and potential death, with mortality rates as high as 24%. 28 Electrolyte imbalances of serum potassium, phosphate, magnesium, and bicarbonate may be present in both DKA and HHS. 29 Rapid shifts in serum potassium are present as a result of extracellular shifts related to insulin deficiency and acidosis. 22 In persons with DKA specifically, death in the initial phases of resuscitation is usually related to hyperkalemia, whereas the most common cause of death in later phases of resuscitation is related to hypokalemia; thus,
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TABLE 2
Management of diabetic ketoacidosis and hyperglycemic hyperosmolar state in the adult patient Fluid replacement
DKA
HHS
Expected deficit: 3-5 L Initial bolus: 1 L Continuous: 500 mL/h for several hours
Expected deficit: N 10 L Initial bolus: 500 mL Continuous: 1-2 L over first 2 h; replace ½ estimated fluid loss over first 12 h
Add dextrose once blood glucose falls below 250 mg/dL Electrolyte replacement Potassium
Phosphate Magnesium
Bicarbonate Insulin therapy
Resolution
Treat after patient has voided N 5.3 mEq/L: no treatment 4.0-5.3 mEq/L: 10 mEq/L/h 3.5 - b 4.0 mEq/L: 20 mEq/L/h b 3.5 mEq/L: Hold insulin 20-60 mEq/L/h b 1.5 mg/dL: dipotassium phosphate at 0.5 mg/dL b 1.8 mg/dL and symptomatic b 50 kg: 1-2 gm N 50 kg: 2-3 gm b 1.2 mg/dL and symptomatic b 50 kg: 2-3 gm N 50 kg: 3-4 gm Only replace if pH b 6.9 Loading dose: 0.1 units/kg of body weight of regular insulin (not to exceed 10 units) Subsequent infusion: 0.1 units/kg of body weight of regular insulin per hour (not to exceed 10 units/h) If blood glucose does not decrease by 10% in the first hour a second loading dose may be given: 0.14 units/kg of body weight of regular insulin/h Blood glucose: b 200 mg/dL Serum bicarbonate: N 18 mEq/L pH: N 7.3 Anion gap: b 12
Treat after patient has voided b 5.2 mEq/L: 20-30 mEq/L/h
Same as DKA Same as DKA
Not recommended Same as DKA
Or
Fluid replacement and if blood glucose does not decrease by 50-70 mg/dL/h give a bolus of 0.1 units/kg of body weight of regular insulin Serum osmolality: b 315 mOsm/kg Normal mental state observed Patient is able to eat
DKA, Diabetic ketoacidosis; HHS, hyperglycemic hyperosmolar state.
serum potassium levels should be measured every 2 hours until the patient is deemed stable, and all patients should be monitored continuously with a cardiac monitor. 21 Potassium should be administered only after serum potassium
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levels are known and after the patient has voided. Urinary potassium loss is a common occurrence in persons with DKA and is caused by extracellular potassium egression seen in acidosis. 30 Hypophosphatemia is another common
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manifestation of DKA, and any serum phosphate less than 1.5 mg/dL should be treated with intravenous dipotassium phosphate at a rate of 0.5 mL/h. 21 A serum phosphate deficit of 0.5 to 1 mmol/L is normally present in patients presenting with DKA. 31 Symptoms of hypomagnesaemia such as paresthesias, tremor, carpopedal spasm, seizures, and cardiac disturbances usually occur at levels below 1.2 mg/dL; thus, treatment should begin if levels fall below 1.8 mg/dL and symptoms of hypomagnesaemia are present. 31 Although bicarbonate imbalances can be present in persons with DKA or HHS, many studies indicate minimal efficacy of bicarbonate replacement when used in patients with a pH of greater than 6.9. 21 In patients with severe DKA, current recommendations for insulin therapy include an intravenous loading dose of regular insulin at 0.1 units/kg of body weight, not to exceed a total loading dose of 10 units. 18,21 If a patient’s initial blood glucose does not decrease by 10% within the first hour, an additional intravenous loading dose of 0.14 units/kg of body weight should be administered. 18,21 Subsequent to the initial loading dose, an intravenous infusion of regular insulin should begin at a rate of 0.1 units/kg of body weight per hour, not to exceed 10 units per hour. 18 In patients with DKA who have an arterial pH between 7.00 and 7.25, an intravenous infusion of regular insulin at a rate of 0.1 units/kg of body weight per hour may be started without a loading dose. 21 Careful monitoring of blood glucose level should be conducted hourly in patients with DKA or HHS. 21 In persons with DKA, once the blood glucose level falls below 250 mg/dL, 5% dextrose should be added to intravenous fluids. 21 Resolution of DKA is acknowledged when blood glucose levels are less than 200 mg/dL, serum bicarbonate is greater than or equal to 18 mEq/L, pH is greater than 7.3, and the anion gap is less than or equal to 12 mEq/L. 32 HHS
Management of HHS requires fluid and electrolyte replacement and treatment of any underlying cause if one is present or suspected. 22 Variable guidelines for the use of insulin therapy in the management of HHS are discussed later. Severe dehydration is often associated with HHS, and deficits of 10 L or more can exist in patients presenting with this condition. 21 Considering the vast amount of fluid deficit associated with HHS, clinicians should consider replacement of one half of the estimated fluid loss during the first 12 hours of treatment, with the remainder of the deficit being replaced in the following 12 hours. 1 An initial bolus of 500 mL of
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normal saline solution is considered appropriate, and 1 to 2 L of normal saline solution should be delivered within the first 2 hours of therapy. 1 Advanced age and comorbidities associated with HHS should cause the clinician to be conscientious of potential complications associated with rapid fluid replacement and may require slower initial rates. 1 As with DKA, cerebral edema is a concern in the pediatric population when rapid fluid resuscitation is performed in patients with HHS. 32 Early signs of cerebral edema are headache and lethargy culminating to neurologic deterioration (seizures and coma) and respiratory arrest in later stages. 33 Symptoms typically occur 4 to 12 hours into treatment. 34 Hyperkalemia is often more severe in HHS than in DKA and results from an extracellular shift and osmotic diuresis. 29 HHS-related hyperkalemia often will correct itself with the administration of fluids and insulin treatment, which encourage a shift of potassium back into the cell. 22 To prevent hypokalemia, it is suggested that potassium replacement be initiated via the addition of 20 to 30 mEq of potassium in each liter of infused fluid once serum potassium levels fall below 5.2 mEq/L. 18 No studies were found to support waiting until the patient voids prior to administering intravenous potassium in persons with HHS. As with DKA, the potential for cardiac disturbances remain secondary to hyperkalemia and hypokalemia affiliated with HHS; potassium levels should be checked every 2 hours, and patients should be monitored continuously with a cardiac monitor. 21 Phosphate and magnesium imbalances are less common in persons with HHS, but levels should be monitored and replacement begun when levels fall below normal limits. 35 Bicarbonate is not recommended in the treatment of HHS. 21 Clinical guidelines for insulin therapy in the treatment of HHS are variable and are related to the potential for euglycemia obtained with fluid therapy alone. 1 Some authors suggest using the same insulin guidelines for HHS and DKA, 1 whereas more conservative authors suggest not giving any insulin as part of the initial therapy in persons with HHS; instead, they suggest that glucose levels be monitored hourly and that insulin therapy be initiated as a bolus of 0.1 units/kg of body weight only if serum glucose levels do not decrease by 50 to 70 mg/dL per hour with appropriate fluid management. 21 As with DKA, blood glucose levels should be monitored hourly in the patient with HHS. 21 The addition of dextrose in intravenous fluids is not suggested for persons with HHS unless blood glucose levels fall below 300 mg/dL and unless signs of oliguric renal failure and/or cardiovascular collapse are present. 21 Resolution of HHS is acknowledged when serum osmolality levels fall below 315 mOsm/kg, the patient returns to a normal mental state, and the patient is able to eat. 36
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Prevention
Clinicians should be mindful of preventive measures when treating patients with diabetes. Diabetic ketoacidosis alone is responsible for 500,000 US hospital days per year and a total economic cost of $2.4 billion annually. 18 Moreover, mortality rates can exceed 15% in patients with HHS compared with mortality rates of less than 5% in patients with DKA. 37 Multiple preventive measures such as increased access to medical care, education, and communication can decrease the occurrence of DKA and HHS. 18 Considering the high incidence of DKA and HHS precipitated by illness or infection, education of patients with T1DM and T2DM regarding sick day management is of particular importance. 3 Appropriate educational interventions for sick day management include (1) initiation of contact with the health care provider early in the illness, (2) maintaining an insulin regimen during the illness, (3) treatment of the underlying illness, (4) maintaining ingestion of carbohydrates and sodium despite nausea, and (5) recruitment of family members or caregivers to assist with sick day management, especially in elderly persons. 18
4. Usher-Smith J, Thompson MJ, Sharp S, Walter FM. Factors associated with the presence of diabetic ketoacidosis at diagnosis of diabetes in children and young adults: a systematic review. BMJ. 2011;343:d4092. 5. Centers for Disease Control and Prevention. Diabetes public health resource. http://www.cdc.gov/diabetes/statistics/dkafirst/fig1.htm. Updated May 17, 2012. Reviewed November 19, 2013. Accessed September 15, 2014. 6. Clinical Key Staff. Diabetic ketoacidosis. https://www.clinicalkey.com/ topics/endocrinology/diabetic-ketoacidosis.html. Published 2012. Accessed September 15, 2014. 7. Lamb WH. Pediatric diabetic ketoacidosis. http://emedicine.medscape. com/article/907111-overview. Updated April 25, 2014. Accessed September 15, 2014. 8. Epocrates Staff. Hyperosmolar hyperglycemic state. https://online. epocrates.com/u/29231011/Hyperosmolar+hyperglycemic+state/Basics/ Epidemiology. Published 2014. Accessed September 15, 2014. 9. Bagdure D, Rewers A, Campagna E, Sills MR. Epidemiology of hyperglycemic hyperosmolar syndrome in children hospitalized in USA. Pediatr Diabetes. 2013;14(1):18-24. 10. Butalia S, Johonson JA, Ghali WA, Rabi DM. Clinical and sociodemographic factors associated with diabetic ketoacidosis hospitalization in adults with type 1 diabetes. Diabet Med. 2013;30(5):567-573. 11. Klingensmith GJ, Tamborlane WV, Wood J, et al. Diabetic ketoacidosis at diabetes onset: still an all too common threat in youth. J Pediatr. 2013;162(2):330-334. 12. Wolfsdorf J, Glaser N, Sperling MA. Diabetic ketoacidosis in infants, children, and adolescents: a consensus statement from the American Diabetes Association. Diabetes Care. 2006;29(5):1150-1159.
Conclusion
Clinicians must be vigilant in differentiating between hyperglycemic emergencies such as DKA and HHS. A thorough history, physical examination, and evaluation of available laboratory data can assist the clinician in differentiating DKA from HHS and quickly lead to the appropriate clinical pathway. Although DKA and HHS have many similarities, significant differences exist in pathology, diagnostic criteria, management, and resolution of each disorder, and thus accurate diagnosis is critical.
13. Lin MV, Bishop G, Benito-Herrero M. Diabetic ketoacidosis in type 2 diabetics: a novel presentation of pancreatic adenocarcinoma. J Geriatr Intern Med. 2010;25(4):369-373.
REFERENCES
17. American Diabetes Association. Hyperosmolar hyperglycemic nonketotic syndrome (HHNS). http://www.diabetes.org/living-with-diabetes/ complications/hyperosmolar-hyperglycemic.html. Updated December 6, 2013. Accessed September 15, 2014.
1. Hemphill RR. Hyperosmolar hyperglycemic state. http://emedicine. medscape.com/article/1914705-overview. Updated April 30, 2014. Accessed September 15, 2014. 2. Kitabchi AE. Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: treatment. http://www.uptodate.com/contents/ treatment-of-diabetic-ketoacidosis-and-hyperosmolar-hyperglycemicstate-in-adults. Published June 26, 2012. Updated July 3, 2014. Accessed September 15, 2014. 3. Chaitnogi N, Subauste JS, Koch CA, Geraci SA. Diagnosis and management of hyperglycemic emergencies. Hormones. 2011;10(4):250-260. http://www. hormones.gr/738/article/article.html. Accessed September 15, 2014.
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14. Raghaven VA. Diabetic ketoacidosis. http://emedicine.medscape.com/ article/118361-overview. Updated April 10, 2014. Accessed September 15, 2014. 15. Stoner GD. Hyperosmolar hyperglycemic state. Am Fam Physician. 2005;71(9):1723-1730. http://www.aafp.org/afp/2005/0501/p1723.html. Published May 1, 2005. Accessed September 15, 2014. 16. Pietrangelo A. Diabetic hyperglycemic hyperosmolar syndrome. http:// www.healthline.com/health/type-2-diabetes/hyperglycemichyperosmolar-syndrome#Overview1. Published September 16, 2012. Accessed September 15, 2014.
18. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7): 1335-1343. 19. Lang A, Satterfield K. When there are acute changes in mental status in patients with diabetes. Podiatry Today. 2010;23(3):16-25. http://www. podiatrytoday.com/when-there-are-acute-changes-in-mental-statusin-patients-with-diabetes?page=2. Published March 2010. Accessed September 15, 2014.
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20. Stunkard ME, Pikul VT, Foley K. Hyperosmolar hyperglycemic syndrome with rhabdomyolysis. Clin Lab Sci. 2011;24(1):8-13.
Clinical/Resources/Documents/BDCDKATreatmentProtocol2012.pdf. Published 2012. Accessed September 15, 2014.
21. McNaughton CD, Self WH, Slovis C. Diabetes in the emergency department: acute care of diabetes patients. Clin Diabetes. 2011;29(2):51-59.
31. Trachtenbarg DE. Diabetic ketoacidosis. Am Fam Physician. 2005;71(9):1705-14. http://www.aafp.org/afp/2005/0501/p1705. html#afp20050501p1705-b42. Published May 1, 2005. Accessed September 15, 2014.
22. Maletkovic J, Drexler A. Diabetic ketoacidosis and hyperglycemic hyperosmolar state. Endocrinol Metab Clin. 2013;42(4):677-695. 23. Thomas C. Metabolic acidosis clinical presentation. http://emedicine. medscape.com/article/242975-clinical. Updated March 27, 2013. Accessed September 15, 2014. 24. Kishore P. Diabetic ketoacidosis. http://www.merckmanuals.com/professional/ endocrine_and_metabolic_disorders/diabetes_mellitus_and_disorders_ of_carbohydrate_metabolism/diabetic_ketoacidosis_dka.html. Revised June 2014. Accessed September 15, 2014. 25. Kadaria D, Murillo LC, Yataco JC, et al. Abdominal pathology in patients with diabetic ketoacidosis. Am J Med Sci. 2012;344(5):341-344. 26. Chalela JA, Kasner SE. Acute toxic-metabolic encephalopathy in adults. http:// www.uptodate.com/contents/acute-toxic-metabolic-encephalopathy-inadults. Updated August 9, 2013. Accessed September 15, 2014. 27. Epocrates Staff. Diabetic ketoacidosis: diagnostic criteria. http://online. epocrates.com/u/2936162/Diabetic+ketoacidosis/Diagnosis/Criteria. Published 2014. Accessed September 15, 2014. 28. Orlowski JP, Cramer CL, Fiallos MR. Diabetic ketoacidosis in the pediatric ICU. Pediatr Clin North Am. 2008;55(3):577-587. 29. DeBeer K, Michael S, Thacker M, et al. Diabetic ketoacidosis and hyperglycaemic hyperosmolar syndrome—clinical guidelines. Nurs Crit Care. 2008;13(1):5-11. 30. Barbara Davis Center for Diabetes. DKA treatment protocol. http://www. ucdenver.edu/academics/colleges/medicalschool/centers/BarbaraDavis/
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32. Maciel AT, Park M. A physiochemical acid-base approach for managing diabetic ketoacidosis. Clinics. 2009;64(7):714-718. 33. Kershaw MJR, Newton T, Barrett TG, Berry K, Kirk J. Childhood diabetes presenting with hyperosmolar dehydration but without ketoacidosis: a report of three cases. Diabet Med. 2005;22(5):645-647. 34. Banh K, Tsukamaki J. Hyperglycemia. CDEM Self Study Modules. http :/ /www.cde mc ur riculum.org /ssm/end o/hy perg lyc emia/ hyperglycemia.php. Published 2010. Accessed September 15, 2014. 35. Venkatraman R, Signhi SC. Hyperglycemic hyperosmolar nonketotic syndrome. Indian J Pediatr. 2006;73(1):55-60. 36. Makrilakis K, Katsilambros N. Diabetic emergencies, diagnosis and clinical management: hyperosmolar non-ketotic hyperglycemia, part 4. www.diabetesincontrol.com/articles/85-/14686-diabeticemergencies-diagnosis-and-clinical-management-hyperosmolar-nonketotic-hyperglycemia-part4. Published May 27, 2013. Accessed September 15, 2014. 37. Kitabchi AE, Razavi L. Hyperglycemic crises: diabetic ketoacidosis (DKA), and hyperglycemic hyperosmolar state (HHS). http://diabetesmanager. pbworks.com/w/page/17680206/Hyperglycemic%20Crises% 3A%20Diabetic%20Ketoacidosis%20%28DKA%29%2C%20And% 20Hyperglycemic%20Hyperosmolar%20State%20%28HHS%29. Revised 2009. Accessed September 15, 2014.
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Appendix. Calculations
Effective Serum Osmolality
2(Na + + K +) + glucose Anion Gap a Na + – (Cl – + HCO3 –) or (Na + + K +) – (Cl – + HCO3 –) a It is a common practice to omit potassium from the formula when calculating anion gap and is considered clinically acceptable.
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