Clinical Features and Diagnosis of Diabetic Ketoacidosis in Children

Clinical features and diagnosis of diabetic ketoacidosis in children
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Clinical features and diagnosis of diabetic ketoacidosis in children Authors George S Jeha, MD Morey W Haymond, MD Disclosures All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Sep 2013. | This topic last updated: feb 13, 2013. INTRODUCTION Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes mellitus. DKA can less commonly occur in children with type 2 diabetes mellitus [1,2]. (See "Classification of diabetes mellitus and genetic diabetic syndromes".) In recent years, the incidence and prevalence of type 2 diabetes mellitus have increased across all ethnic groups. This has been coupled with an increasing awareness that children with type 2 diabetes mellitus can present with ketosis or DKA, particularly in obese African American adolescents [1-6]. (See "Classification of diabetes mellitus and genetic diabetic syndromes", section on 'DKA in type 2 diabetes'.) The clinical features and diagnosis of DKA in children will be reviewed here. This discussion is primarily based upon the large collective experience of children with type 1 diabetes mellitus. There is limited experience in the assessment and diagnosis of DKA in children with type 2 diabetes mellitus, although the same principles should apply. The management of diabetes in children, treatment of DKA in children and the epidemiology and pathogenesis of DKA are discussed separately. (See "Management of type 1 diabetes mellitus in children and adolescents" and "Treatment and complications of diabetic ketoacidosis in children" and "Epidemiology and pathogenesis of diabetic ketoacidosis and hyperosmolar hyperglycemic state".) DEFINITION Consensus statements from the European Society for Paediatric Endocrinology/Lawson Wilkins Pediatric Endocrine Society (ESPE/LWPES) in 2004, the American Diabetes Association (ADA) in 2006, and the International Society for Pediatric and Adolescent Diabetes (ISPAD) in 2007 defined the following biochemical criteria for the diagnosis of DKA [7-10]: Hyperglycemia, blood glucose of >200 mg/dL (11 mmol/L) AND Metabolic acidosis, defined as a venous pH <7.3 and/or plasma bicarbonate <15 mEq/L (15 mmol/L). The severity of DKA can be categorized according to the degree of acidosis as mild, moderate, or severe, (pH 7.2-7.3, pH 7.1-7.2, or pH <7.1, respectively) (table 1). These abnormalities are accompanied by hyperketosis (concentration of total ketone bodies >5 mmol/L) and hyperosmolality. The clinical manifestations of DKA are related to the degree of hyperosmolality, volume depletion, and acidosis. Hyperosmolar hyperglycemic state (HHS) is a hyperglycemia emergency which is distinguished from classic DKA by marked hyperglycemia (plasma glucose >600 mg/dL), serum CO2 >15 mmol/L, absent to mild ketonemia and ketonuria, and effective serum osmolality >320 mOsm/L. HHS occurs most commonly in adults with poorly controlled Section Editor Joseph I Wolfsdorf, MB, BCh Deputy Editor Alison G Hoppin, MD
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type 2 diabetes, but has also been reported in African-American adolescents with type 2 diabetes [11-13]. Recognition of HHS is important because it is reported to be associated with more severe dehydration and difficult to manage hypotension than typically occurs in DKA. As in DKA, management of HHS requires carefully monitored fluid and electrolyte management, and it has been suggested that patients may require higher rates of fluid administration than are typically used in DKA. Management of HHS is discussed in a separate topic review. (See "Treatment of diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults", section on 'Fluid replacement'.) EPIDEMIOLOGY DKA is frequently the initial presentation of children with new onset type 1 diabetes mellitus. In a surveillance study of almost 3000 episodes of DKA in the United Kingdom, 38 percent occurred in patients at the time of initial diagnosis of diabetes mellitus [14]. In other studies from Europe and North America, the frequency of DKA as the initial presentation for type 1 diabetes mellitus is approximately 25 percent (range from 15 to 67 percent) [9,15]. Although population-based studies are lacking, the incidence of DKA as the initial presentation in type 2 diabetes mellitus varies considerably. In a systematic review, factors associated with increased risk for having DKA at presentation are younger age (<5 years), ethnic minority status, diagnostic error, lack of health insurance (in the United States), lower body mass index, and delayed treatment [16]. In different studies, 4 percent of Canadian aboriginal children, 25 percent of Irish children, 30 percent of Mexican-American children and more than 40 percent of obese African-American adolescents with type 2 diabetes mellitus initially present in DKA [1-6]. In addition, DKA and its complications are the most common cause of hospitalization, mortality, and morbidity in children with established type 1 diabetes mellitus [14]. Initial presentation of type 1 diabetes mellitus Children who are young (<6 years of age) or from a low socioeconomic background are at increased risk for DKA at initial presentation [17-22]. The data supporting these conclusions are illustrated by the following observations: A retrospective study from Germany reviewed 2121 newly diagnosed children with type 1 diabetes mellitus, 558 of whom (26 percent) presented in DKA [17]. The incidence of DKA was higher (36 percent) in children less than five years of age. The importance of socioeconomic status was illustrated in a review of 139 patients with newly diagnosed type 1 diabetes mellitus seen at a single center in the United States [18]. The investigators used the lack of private insurance as a proxy for low socioeconomic status. A disproportionate number of children having either Medicaid or no insurance presented in DKA compared to those with private insurance (62 versus 34 percent). Children less than five years of age were also at increased risk for DKA (relative risk 2.7 compared to older children). In established type 1 diabetes mellitus The incidence of DKA in children who are known to have type 1 diabetes mellitus was 8 episodes per 100 person years in the largest reported prospective study in which 1243 American children were followed for five years [23]. Risk factors for recurrent DKA included: Higher A1C values and higher reported insulin requirements Female adolescents, with the highest risk in female adolescents over 13 years of age Children over 13 years of age, regardless of gender, who are underinsured and/or have a history of psychiatric disorders Longer duration of diabetes mellitus Almost 60 percent of DKA episodes occurred in only 5 percent of children. Similar findings were noted in the United Kingdom surveillance study cited above [14]. Patients with known diabetes mellitus who had four or more episodes of DKA (4.8 percent of patients) accounted for 35 percent of all episodes. Thus, a small group of patients consume a disproportionate amount of healthcare resources and costs [23]. The identification of these patients at high risk for recurrence of DKA and the establishment of a comprehensive diabetes treatment program may reduce the rates of DKA and possibly healthcare costs [24]. Such a program should
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emphasize compliance with management recommendations, including adherence to the insulin regimen and the use of home glucose monitoring. Type 2 diabetes mellitus Although less common, ketosis and DKA can occur in children with type 2 diabetes mellitus, particularly in African-American children [1-6]. In a retrospective review of 69 patients (between 9 and 18 years of age) who presented with DKA at a tertiary center, 13 percent had type 2 diabetes mellitus [5]. At presentation, there was no difference in the serum pH level but patients with type 2 diabetes mellitus compared to those with type 1 diabetes mellitus had higher blood glucose levels. (See "Classification of diabetes mellitus and genetic diabetic syndromes", section on 'DKA in type 2 diabetes'.) PRECIPITATING FACTORS Recurrent episodes of DKA with established type 1 diabetes mellitus are primarily the result of underlying poor metabolic control and frequently missed insulin injections [23]. Omission of insulin injections is particularly common among adolescents. Stress is also an important precipitating factor. Stress increases the secretion of catecholamines, cortisol, and glucagon, which promote both glucose and ketoacid production. As an example, infection can precede an episode of DKA [25]. (See "Epidemiology and pathogenesis of diabetic ketoacidosis and hyperosmolar hyperglycemic state".) In addition, medications such as corticosteroids, atypical antipsychotics, diazoxide, and high dose thiazides, have precipitated DKA in individuals not previously diagnosed with type 1 diabetes mellitus. DIAGNOSTIC EVALUATION The clinical diagnosis of diabetes in a previously healthy child requires a high index of suspicion. Signs and symptoms of DKA are related to the degree of hyperosmolality, volume depletion, and acidosis. Signs and symptoms The earliest symptoms are related to hyperglycemia. Older children and adolescents typically present with polyuria (due to the glucose-induced osmotic diuresis), polydipsia (due to the increased urinary losses), and fatigue. Other findings include weight loss, nocturia (with or without secondary enuresis), daytime enuresis, and vaginal or cutaneous moniliasis. Hypovolemia may be severe if the urinary losses are not replaced. In infants, the diagnosis is more difficult because the patients are not toilet trained and they cannot express thirst. As a result, polyuria may not be detected and polydipsia is not apparent. However, decreased energy and activity, irritability, weight loss, and physical signs of dehydration are common findings. In addition, severe Candida diaper rash or otherwise unexplained metabolic acidosis or hypovolemia should heighten the suspicion for diabetes. (See "Overview of diaper dermatitis in infants and children".) A number of other clinical findings may be seen: Polyphagia usually occurs early in the course of the illness. However, once insulin deficiency becomes more severe and ketoacidosis develops, appetite is suppressed. Some patients present with anorexia, nausea, vomiting, and abdominal pain, which at times can mimic appendicitis or gastroenteritis. (See "Acute appendicitis in children: Clinical manifestations and diagnosis".) Hyperventilation and deep (Kussmaul) respirations represent the respiratory compensation for metabolic acidosis. Hyperpnea results from an increase in minute volume (rate x tidal volume) and can be increased by tidal volume alone without an increase in respiratory rate. As a result, the patient's chest excursion as well as respiratory rate should be carefully observed. In infants, the hyperpnea may be manifested only by tachypnea. Patients may also have a fruity breath secondary to exhaled acetone. Although children with DKA are volume depleted, they are less likely to show the classic signs of hypovolemia such as dry oral mucous membranes and decreased skin turgor than patients with the same degree of weight loss from vomiting or diarrhea due to gastroenteritis. This important distinction is a reflection of water loss in excess of sodium with a glucosuria-induced osmotic diuresis and water loss from hyperventilation. Water is freely distributed between the extracellular and intracellular fluids. As a result, water loss produces less extracellular fluid volume depletion than salt and water loss. Water loss also is largely responsible for the
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marked rise in plasma osmolality. Neurologic findings, ranging from drowsiness, lethargy, and obtundation to coma, are related to the severity of hyperosmolality and/or to the degree of acidosis [26]. Cerebral edema occurs in 0.5 to 1 percent of cases of DKA in children, and is the leading cause of mortality. The clinician should be vigilant for early signs of cerebral edema and should treat promptly if cerebral edema is suspected (table 2). (See "Cerebral edema in children with diabetic ketoacidosis".) Fluid and electrolyte deficits Studies estimating water and electrolyte losses in DKA were conducted in the 1940s and 1950s. Most included adults, but one was a detailed study of a 10-year-old female [27-29]. The data from the available studies are consistent with the following average losses in severe DKA: Water 70 (range 30 to 100) mL/kg Sodium 5 to 13 mEq/kg Potassium 6 to 7 mEq/kg It is difficult to assess clinically the degree of dehydration in children presenting with DKA as these children are less likely to show the classic signs of hypovolemia because of chronic and acute losses of intracellular and extracellular water as compared with children with more acute causes of dehydration [30]. Children with DKA generally present with a 5 to 10 percent fluid deficit [4,7]. Initial fluid management is based on the assumption of a 5 to 7 percent deficit for moderate DKA, and 10 percent dehydration for severe DKA [9]. This recommendation is consistent with the above studies that assessed fluid and electrolyte losses. However, to minimize risks for cerebral edema and electrolyte imbalances, hypovolemia should be corrected gradually. The maximal volume of isotonic solution used for initial treatment is 10 mL/kg, unless the patient is objectively hypotensive. (See 'Signs and symptoms' above.) Laboratory findings Initial laboratory testing should include serum testing for glucose, electrolytes, creatinine and urea nitrogen, blood gases, and hematocrit [7,8]. Direct measurement of beta-hydroxybutyrate in the blood should also be performed if possible; accurate bedside meters for this measurement are available [31]. The diagnosis of DKA is confirmed by the findings of hyperglycemia, a high anion gap acidosis, ketonuria, and ketonemia. Treatment of these abnormalities is discussed elsewhere. (See "Treatment and complications of diabetic ketoacidosis in children".) Serum glucose The serum glucose is, by definition, greater than 200 mg/dL (11 mmol/L) [7,8]. This degree of hyperglycemia exceeds the renal tubular threshold for glucose reabsorption, resulting in an osmotic diuresis with polyuria and subsequent volume depletion. Glucosuria also predisposes to candidal infections in diapered children and adolescent girls. Acid-base status The second criterion for the diagnosis of DKA is a serum bicarbonate <15 mEq/L or a venous pH <7.3. Insulin deficiency and increased plasma concentrations of glucagon, cortisol and epinephrine increase glucose production, lipolysis and ketogenesis which collectively contribute to the development of both the hyperglycemia and the ketoacidosis. Acetoacetic acid is the initial ketone formed and it may be reduced to beta-hydroxybutyric acid (another organic acid) or decarboxylated to acetone, which will be detected as a ketone but does not contribute to the acidosis. (See "Epidemiology and pathogenesis of diabetic ketoacidosis and hyperosmolar hyperglycemic state".) The severity of metabolic acidosis is dependent upon three factors: The rate of ketoacid production The duration of increased ketoacid production; the acidosis will be less severe in patients who present early due, for example, to abdominal pain or an underlying infection that precipitated the DKA The rate of acid excretion in the urine. Patients with relatively normal renal function can markedly increase acid excretion, thereby minimizing the severity of the acidosis [32]. The magnitude of this effect was illustrated
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in a study of patients with DKA: ketone production averaged 51 mEq/h, while net acid excretion with the ketoacid anions averaged 15 mEq/h or 30 percent of the acid load [33]. The conversion of acetoacetic acid to acetone can neutralize another 15 to 25 percent of the acid load [33]. The adequacy of the compensatory respiratory alkalosis Conventional urine screening tests for ketones are performed with nitroprusside impregnated strips or tablets (Acetest). Nitroprusside reacts with acetoacetate and acetone but not beta-hydroxybutyrate. In DKA, beta-hydroxybutyrate makes up 75 percent of the circulating ketones. Thus, clinical testing with nitroprusside may underestimate the severity of ketoacidosis and ketonuria. On the other hand, during recovery beta-hydroxybutyrate is converted to acetoacetate and acetone, which persist for a longer period. As a result, urine testing may give a false impression of persistent ketoacidosis. Therefore, direct measurement of beta-hydroxybutyrate should be used whenever possible. Blood testing for beta-hydroxybutyrate may be available both in the clinical chemistry laboratory, and more importantly, at points of care such as emergency departments and physician's offices, as well as at home (Precision Xtra, Abbott Laboratories). The meter measures a current produced during oxidation of beta-hydroxybutyrate to acetoacetate, and is accurate in children and adults in a variety of clinical settings for plasma beta-hydroxybutyrate concentrations of up to 5 to 7 mMol/L [34,35]. The Anion Gap (AG) is useful in estimating the severity of ketosis, and the normalization of the anion gap is a direct measure of the resolution of ketoacidemia. However, the anion gap may also underestimate the degree of acidosis. The loss of ketoacid anions in the urine (as the sodium and potassium salts of beta-hydroxybutyrate and to a lesser degree acetoacetate) lowers the anion gap without affecting the plasma bicarbonate concentration or therefore the degree of acidosis. When insulin is given to patients with diabetic ketoacidosis, metabolism of the ketoacid anions results in the regeneration of HCO3- and correction of the metabolic acidosis. For this reason, ketoacid anions have been called "potential bicarbonate," and their loss in the urine represents the loss of HCO3-. As a result, a normal AG acidosis is typically seen during the treatment phase of diabetic ketoacidosis due to the urinary loss of these bicarbonate precursors. (See "Approach to the child with metabolic acidosis", section on 'Overlap'.) The serum anion gap is calculated from the following formula in units of mEq/L or mmol/L: Serum anion gap = Serum sodium - (Serum chloride + bicarbonate) The normal value in children is 122 mmol/L Serum sodium The serum sodium concentration is affected by hyperglycemia. The magnitude of this effect is determined by two major factors. Hyperglycemia will increase the plasma osmolality, resulting in osmotic water movement out of the cells which lowers the serum sodium by dilution. Theoretical calculations suggest that the serum sodium should be lowered by 1.6 mEq/L for every 100 mg/dL (5.5 mmol/L) elevation in serum glucose [36]. There is no experimental verification of this estimate in children. Experimental data in adults suggest that a better overall estimate is a reduction in serum sodium of 2.4 mEq/L for every 100 mg/dL (5.5 mmol/L) elevation of plasma glucose [37]. The direct effect of hyperglycemia to lower the serum sodium is counteracted to a variable degree by the glucosuria-induced osmotic diuresis. The diuresis results in water loss in excess of sodium and potassium, which will tend to raise the serum sodium concentration and plasma osmolality. Inadequate water intake, which may be a particular problem in hot weather and in infants and young children who cannot independently access water, prevents partial correction of the hyperosmolality and can even lead to hypernatremia despite the presence of hyperglycemia. On the other hand, consumption of large volumes of dilute fluid, since thirst is stimulated by hyperosmolality, can contribute to hyponatremia.
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A third factor that can affect the measured serum sodium concentration represents a laboratory artifact. Hyperlipidemia can cause pseudohyponatremia by reducing the fraction of plasma that is water. As a result, the amount of sodium in the specimen is reduced and the measured plasma sodium concentration will be lower, even though the physiologically important plasma water sodium concentration and plasma osmolality are not affected [38]. Ion-selective electrodes have been used to measure directly the plasma water sodium concentration in this setting, but they have been shown to have variable accuracy and are not routinely used [38]. (See "Evaluation of the patient with hyponatremia", section on 'Serum osmolality'.) Serum potassium The osmotic diuresis and increased ketoacid excretion promote urinary potassium loss, while vomiting and diarrhea, if present, increase gastrointestinal potassium losses. In adults, average potassium losses during DKA are 3 to 5 mEq/kg; the estimated potassium loss in children has been less well studied but average losses appear to be 6 to 7 mEq/kg [27]. The potassium losses will tend to produce hypokalemia. However, the combination of insulin deficiency, which impairs potassium entry into the cells, and hyperosmolality, which pulls water and potassium out of the cells, tends to raise the serum potassium concentration. Ketoacidosis itself appears to have little effect on transcellular potassium movement. (See "Potassium balance in acid-base disorders".) Because of these counteracting effects, the serum potassium at the time of presentation can be normal, increased, or decreased. Regardless of the initial level, therapy with insulin and fluids will predictably lower the serum potassium concentration, which needs to be monitored carefully. (See "Treatment and complications of diabetic ketoacidosis in children".) Serum phosphate Children with DKA are typically in negative phosphate balance because of decreased phosphate intake and phosphaturia caused by the glucosuria-induced osmotic diuresis. Despite the presence of phosphate depletion, at presentation the serum phosphate concentration is usually normal or even high because both insulin deficiency and metabolic acidosis cause a shift of phosphate out of the cells [39]. This transcellular shift is reversed and the true state of phosphate balance is unmasked after treatment with insulin. (See "Treatment of diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults", section on 'Phosphate depletion'.) Blood urea nitrogen Patients with severe hypovolemia often have elevated blood urea nitrogen concentrations [40]. This finding at presentation may have predictive value since it is a risk factor for cerebral edema during therapy [41]. Assessment of severity At presentation, the following clinical and laboratory findings may be used to estimate the severity of DKA: Acid-base status The venous pH and serum bicarbonate concentration directly reflect the severity of the acidosis (table 1). The respiratory rate also may be helpful, since the magnitude of the respiratory compensation is directly related to the severity of the acidosis. Ketosis The magnitude of the anion gap is another measure of the severity of the ketosis and can be a helpful estimate of acidosis. A very large anion gap may also reflect decreased renal perfusion, which limits ketoacid excretion. Measurement of plasma beta-hydroxybutyrate is now widely available and is a direct method for monitoring the degree of ketoacidemia. (See 'Acid-base status' above.) Neurologic status Severe neurologic compromise at presentation is a poor prognostic indicator, in part because such patients are at increased risk for developing cerebral edema during therapy. This was illustrated in a retrospective multicenter study of 61 children with DKA and cerebral edema; all patients who either died or survived in a persistent vegetative state presented with Glasgow coma score 7 (score of 6 to 7 includes an abnormal or absent purposeful response to pain) (table 3) [42]. Because of the high morbidity and mortality of cerebral edema, it is important to recognize and treat at the earliest signs of neurologic compromise (table 2). The pathophysiology and treatment of cerebral edema in children with DKA is discussed in detail separately. (See "Cerebral edema in children with diabetic ketoacidosis".)
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Volume status Estimated fluid deficit, (generally 5-10% fluid deficit). Duration of symptoms A long duration of symptoms, as well as depressed level of consciousness or compromised circulation, is evidence of severe DKA and should prompt close monitoring for potential complications of DKA, such as cerebral edema [7,8]. Symptoms of cerebral edema typically occur several hours after the initiation of treatment for DKA [9]. The presence of such symptoms at presentation indicates a poor neurologic prognosis. Based upon the severity of presentation, the clinician can ascertain the appropriate clinical setting in which to treat the child. As an example, mild DKA without vomiting may be safely managed in an ambulatory setting under close supervision and with appropriate monitoring by an experienced diabetes team. On the other hand, a patient with severe DKA should be managed in a pediatric intensive care unit [7,8]. (See "Treatment and complications of diabetic ketoacidosis in children".) INFORMATION FOR PATIENTS UpToDate offers two types of patient education materials, The Basics and Beyond the Basics. The Basics patient education pieces are written in plain language, at the 5 to 6 grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10 to 12 grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon. Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on patient info and the keyword(s) of interest.) Basics topics (see "Patient information: Diabetic ketoacidosis (The Basics)") SUMMARY AND RECOMMENDATIONS Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes mellitus. DKA also can occur in children with type 2 diabetes mellitus, particularly in obese African-American adolescents. DKA is diagnosed when patients with diabetes mellitus exhibit BOTH hyperglycemia (blood glucose of >200 mg/dL [11 mmol/L]) and metabolic acidosis (venous pH <7.3 and/or plasma bicarbonate <15 mEq/L [15 mmol/L]), caused by severe hyperketonemia (concentration of total ketone bodies >5 mmol/L). (See 'Definition' above.) DKA is the presenting feature of new onset type 1 diabetes mellitus in approximately 30 to 40 percent of cases. Children who are younger (eg, under six years of age) or from a lower socioeconomic status are more likely to have DKA when they present with type 1 diabetes mellitus. (See 'Initial presentation of type 1 diabetes mellitus' above.) Presenting symptoms of DKA in older children and adolescents include polyuria, polydipsia, and fatigue. Other findings include weight loss, nocturia (with or without secondary enuresis), daytime enuresis, and vaginal or cutaneous moniliasis. Infants tend to present with decreased energy and activity, irritability, weight loss, and physical signs of dehydration; a severe Candida diaper rash is common. (See 'Signs and symptoms' above.) Initial laboratory testing should include serum testing for glucose, electrolytes, creatinine and urea nitrogen, blood gases, and hematocrit. Direct measurement of beta-hydroxybutyrate in the blood should also be performed if possible. The diagnosis of DKA is confirmed by the findings of hyperglycemia, a high anion gap
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acidosis, significant ketonemia, and metabolic acidosis. (See 'Laboratory findings' above.) The venous pH and serum bicarbonate concentration directly reflect the severity of the acidosis (table 1). Neurologic status should also be formally assessed at presentation and periodically during treatment (table 2), because cerebral edema is an important cause of morbidity and mortality in patients with DKA. (See 'Assessment of severity' above.) Hyperosmolar hyperglycemic state (HHS) is a hyperglycemia emergency which is distinguished from classic DKA by marked hyperosmolality (effective osmolality of >320 mOsm/L) due to severe hyperglycemia (plasma glucose >600 mg/dL), in the absence of severe metabolic acidosis (serum CO2 >15 mmol/L, absent to small ketonemia and ketonuria). (See 'Definition' above and "Clinical features and diagnosis of diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults".)
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17. Neu A, Willasch A, Ehehalt S, et al. Ketoacidosis at onset of type 1 diabetes mellitus in children--frequency and clinical presentation. Pediatr Diabetes 2003; 4:77. 18. Mallare JT, Cordice CC, Ryan BA, et al. Identifying risk factors for the development of diabetic ketoacidosis in new onset type 1 diabetes mellitus. Clin Pediatr (Phila) 2003; 42:591. 19. Rosenbauer J, Icks A, Giani G. Clinical characteristics and predictors of severe ketoacidosis at onset of type 1 diabetes mellitus in children in a North Rhine-Westphalian region, Germany. J Pediatr Endocrinol Metab 2002; 15:1137. 20. Quinn M, Fleischman A, Rosner B, et al. Characteristics at diagnosis of type 1 diabetes in children younger than 6 years. J Pediatr 2006; 148:366. 21. Roche EF, Menon A, Gill D, Hoey H. Clinical presentation of type 1 diabetes. Pediatr Diabetes 2005; 6:75. 22. Rewers A, Klingensmith G, Davis C, et al. Presence of diabetic ketoacidosis at diagnosis of diabetes mellitus in youth: the Search for Diabetes in Youth Study. Pediatrics 2008; 121:e1258. 23. Rewers A, Chase HP, Mackenzie T, et al. Predictors of acute complications in children with type 1 diabetes. JAMA 2002; 287:2511. 24. Hoffman WH, O'Neill P, Khoury C, Bernstein SS. Service and education for the insulin-dependent child. Diabetes Care 1978; 1:285. 25. Flood RG, Chiang VW. Rate and prediction of infection in children with diabetic ketoacidosis. Am J Emerg Med 2001; 19:270. 26. Edge JA, Roy Y, Bergomi A, et al. Conscious level in children with diabetic ketoacidosis is related to severity of acidosis and not to blood glucose concentration. Pediatr Diabetes 2006; 7:11. 27. DARROW DC, PRATT EL. Retention of water and electrolyte during recovery in a patient with diabetic acidosis. J Pediatr 1952; 41:688. 28. Atchley DW, Loeb RF, Richards DW, et al. ON DIABETIC ACIDOSIS: A Detailed Study of Electrolyte Balances Following the Withdrawal and Reestablishment of Insulin Therapy. J Clin Invest 1933; 12:297. 29. BUTLER AM, TALBOT NB. Metabolic studies in diabetic coma. Trans Assoc Am Physicians 1947; 60:102. 30. Koves IH, Neutze J, Donath S, et al. The accuracy of clinical assessment of dehydration during diabetic ketoacidosis in childhood. Diabetes Care 2004; 27:2485. 31. Bashford J, Acerini CL. How to use near-patient capillary ketone meters. Arch Dis Child Educ Pract Ed 2012; 97:217. 32. Adrogu HJ, Eknoyan G, Suki WK. Diabetic ketoacidosis: role of the kidney in the acid-base homeostasis re-evaluated. Kidney Int 1984; 25:591. 33. Owen OE, Licht JH, Sapir DG. Renal function and effects of partial rehydration during diabetic ketoacidosis. Diabetes 1981; 30:510. 34. Ham MR, Okada P, White PC. Bedside ketone determination in diabetic children with hyperglycemia and ketosis in the acute care setting. Pediatr Diabetes 2004; 5:39. 35. Wallace TM, Meston NM, Gardner SG, Matthews DR. The hospital and home use of a 30-second hand-held blood ketone meter: guidelines for clinical practice. Diabet Med 2001; 18:640. 36. Katz MA. Hyperglycemia-induced hyponatremia--calculation of expected serum sodium depression. N Engl J Med 1973; 289:843. 37. Hillier TA, Abbott RD, Barrett EJ. Hyponatremia: evaluating the correction factor for hyperglycemia. Am J Med 1999; 106:399. 38. Weisberg LS. Pseudohyponatremia: a reappraisal. Am J Med 1989; 86:315. 39. Kebler R, McDonald FD, Cadnapaphornchai P. Dynamic changes in serum phosphorus levels in diabetic ketoacidosis. Am J Med 1985; 79:571. 40. Harris GD, Fiordalisi I. Physiologic management of diabetic ketoacidemia. A 5-year prospective pediatric experience in 231 episodes. Arch Pediatr Adolesc Med 1994; 148:1046. 41. Glaser N, Barnett P, McCaslin I, et al. Risk factors for cerebral edema in children with diabetic ketoacidosis. The Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of
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Pediatrics. N Engl J Med 2001; 344:264. 42. Marcin JP, Glaser N, Barnett P, et al. Factors associated with adverse outcomes in children with diabetic ketoacidosis-related cerebral edema. J Pediatr 2002; 141:793. Topic 5809 Version 12.0
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GRAPHICS
Assessment of severity of diabetic ketoacidosis in children
Mild
Defining features Venous pH Serum bicarbonate (mEq/L) 7.2-7.3 10-15 7.1-7.2 5-10 <7.1 <5
Moderate
Severe
Data from: Wolfsdorf J, Glaser N, Sperling MA, American Diabetes Association. Diabetic ketoacidosis in infants, children, and adolescents: A consensus statement from the American Diabetes Association. Diabetes Care 2006; 29:1150.
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Bedside evaluation of neurological state of children with diabetic ketoacidosis (DKA)

Major criteria
Altered mentation/fluctuating level of consciousness Sustained heart rate deceleration (decline of more than 20 beats per minute) not attributable to improved intravascular volume or sleep state Age-inappropriate incontinence
Minor criteria
Vomiting Headache Lethargy or being not easily aroused from sleep Diastolic blood pressure >90 mmHg Age <5 years
Diagnostic criteria
Abnormal motor or verbal response to pain Decorticate or decerebrate posture Cranial nerve palsy (especially III, IV, and VI) Abnormal neurogenic respiratory pattern (eg, grunting, tachypnea, Cheyne-Stokes respiration, apneusis)
Signs that occur before treatment should not be considered in the diagnosis of the cerebral edema. Cerebral edema is diagnosed if any of the diagnostic criteria is present. Cerebral edema is also likely if two major criteria OR one major and two minor criteria are present.
mmHg: millimeters of mercury. Modified with permission from: Muir AB, Quisling RG, Yang MC, Rosenbloom AL. Cerebral edema in childhood diabetic ketoacidosis: natural history, radiographic findings, and early identification. Diabetes Care 2004; 27:1541. Copyright 2004 The American Diabetes Association.
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Glasgow coma scale and pediatric Glasgow coma scale

Sign
Eye opening
Glasgow Coma Scale

Spontaneous To command To pain None
[1]
Pediatric Glasgow Coma Scale

Spontaneous To sound To pain None
[2]
Score
4 3 2 1 5
Verbal response
Oriented
Age-appropriate vocalization, smile, or orientation to sound, interacts (coos, babbles), follows objects Cries, irritable Cries to pain Moans to pain None Spontaneous movements (obeys verbal command) Withdraws to touch (localizes pain) Withdraws to pain Abnormal flexion to pain (decorticate posture) Abnormal extension to pain (decerebrate posture) None
Confused, disoriented Inappropriate words Incomprehensible sounds None Motor response Obeys commands Localizes pain Withdraws Abnormal flexion to pain Abnormal extension to pain None Best total score
4 3 2 1 6 5 4 3 2 1 15
The Glasgow coma scale (GCS) is scored between 3 and 15, 3 being the worst, and 15 the best. It is composed of three parameters: best eye response (E), best verbal response (V), and best motor response (M). The components of the GCS should be recorded individually; for example, E2V3M4 results in a GCS of 9. A score of 13 or higher correlates with mild brain injury; a score of 9 to 12 correlates with moderate injury; and a score of 8 or less represents severe brain injury. The pediatric Glasgow coma scale (PGCS) was validated in children 2 years of age or younger.
Data from: 1. Teasdale G and Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet 1974; 2:81. 2. Holmes JF, Palchak MJ, MacFarlane T, Kuppermann N. Performance of the pediatric Glasgow coma scale in children with blunt head trauma. Acad Emerg Med 2005; 12:814.
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Clinical Features and Diagnosis of Diabetic Ketoacidosis in Children

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Clinical Features and Diagnosis of Diabetic Ketoacidosis in Children

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Clinical features and diagnosis of diabetic ketoacidosis in children

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