|
 |
|
|||||||
|
|||||||||
© American Diabetes Association ®, Inc., 2001
Position Statement |
Hyperglycemic Crises in Patients With Diabetes Mellitus
Ketoacidosis and hyperosmolar hyperglycemia are the two most serious acute metabolic complications of diabetes, even if managed properly. These disorders can occur in both type 1 and type 2 diabetes. The mortality rate in patients with diabetic ketoacidosis (DKA) is <5% in experienced centers, whereas the mortality rate of patients with hyperosmolar hyperglycemic state (HHS) still remains high at 
15%. The prognosis of both conditions is substantially worsened at the extremes of age and in the presence of coma and hypotension.1–10
This position statement will outline precipitating factors and recommendations for the diagnosis, treatment, and prevention of DKA and HHS. It is based on the technical review,11 which should be consulted for further information.
PATHOGENESIS
Although the pathogenesis of DKA is better understood than that of HHS, the basic underlying mechanism for both disorders is a reduction in the net effective action of circulating insulin coupled with a concomitant elevation of counterregulatory hormones, such as glucagon, catecholamines, cortisol, and growth hormone. These hormonal alterations in DKA and HHS lead to increased hepatic and renal glucose production and impaired glucose utilization in peripheral tissues, which result in hyperglycemia and parallel changes in osmolality of the extracellular space.12,13 The combination of insulin deficiency and increased counterregulatory hormones in DKA also leads to release of free fatty acids into the circulation from adipose tissue (lipolysis) and to unrestrained hepatic fatty acid oxidation to ketone bodies (ß-hydroxybutyrate [ß-OHB] and acetoacetate), with resulting ketonemia and metabolic acidosis. HHS on the other hand may be due to plasma insulin concentration inadequate to facilitate glucose utilization by insulin-sensitive tissues but adequate (as determined by residual C-peptide) to prevent lipolysis and subsequent ketogenesis, although the evidence for this is weak.14 Both DKA and HHS are associated with glycosuria, leading to osmotic diuresis with loss of water, sodium, potassium, and other electrolytes.3,15–20 The laboratory and clinical characteristics of DKA and HHS are summarized in Tables 1 and 2. As can be seen, DKA and HHS differ in magnitude of dehydration and degree of ketosis (and acidosis).
|
|
PRECIPITATING FACTORS
The most common precipitating factor in the development of DKA or HHS is infection. Other precipitating factors include cerebrovascular accident, alcohol abuse, pancreatitis, myocardial infarction, trauma, and drugs. In addition, newly onset type 1 diabetes or discontinuation of or inadequate insulin in established type 1 diabetes commonly leads to the development of DKA. Elderly individuals with newly onset diabetes (particularly residents of chronic care facilities) or individuals with known diabetes who become hyperglycemic and are unaware of it or are unable to take fluids when necessary are at risk for HHS.6
Drugs that affect carbohydrate metabolism, such as corticosteroids, thiazides, and sympathomimetic agents (e.g., dobutamine and terbutaline), may precipitate the development of HHS or DKA. In young patients with type 1 diabetes, psychological problems complicated by eating disorders may be a contributing factor in 20% of recurrent ketoacidosis. Factors that may lead to insulin omission in younger patients include fear of weight gain with improved metabolic control, fear of hypoglycemia, rebellion from authority, and stress of chronic disease.13
DIAGNOSIS
History and physical examination
The process of HHS usually evolves over several days to weeks, whereas the evolution of the acute DKA episode in type 1 diabetes or even in type 2 diabetes tends to be much shorter. Although the symptoms of poorly controlled diabetes may be present for several days, the metabolic alterations typical of ketoacidosis usually evolve within a short time frame (typically <24 h). Occasionally, the entire symptomatic presentation may evolve or develop more acutely, and the patient may present in DKA with no prior clues or symptoms. For both DKA and HHS, the classical clinical picture includes a history of polyuria, polydipsia, polyphagia, weight loss, vomiting, abdominal pain (only in DKA), dehydration, weakness, clouding of sensorium, and finally coma. Physical findings may include poor skin turgor, Kussmaul respirations (in DKA), tachycardia, hypotension, alteration in mental status, shock, and ultimately coma (more frequent in HHS). Up to 25% of DKA patients have emesis, which may be coffee-ground in appearance and guaiac positive. Endoscopy has related this finding to the presence of hemorrhagic gastritis. Mental status can vary from full alertness to profound lethargy or coma, with the latter more frequent in HHS. Although infection is a common precipitating factor for both DKA and HHS, patients can be normothermic or even hypothermic primarily because of peripheral vasodilation. Hypothermia, if present, is a poor prognostic sign.21 Caution needs to be taken with patients who complain of abdominal pain on presentation, because the symptoms could be either a result or a cause (particularly in younger patients) of DKA. Further evaluation is necessary if this complaint does not resolve with resolution of dehydration and metabolic acidosis.
Laboratory findings
The initial laboratory evaluation of patients with suspected DKA or HHS should include determination of plasma glucose, blood urea nitrogen/creatinine, serum ketones, electrolytes (with calculated anion gap), osmolality, urinalysis, urine ketones by dipstick, as well as initial arterial blood gases, complete blood count with differential, and electrocardiogram. Bacterial cultures of urine, blood, and throat, etc., should be obtained and appropriate antibiotics given if infection is suspected. HbA1c may be useful in determining whether this acute episode is the culmination of an evolutionary process in previously undiagnosed or poorly controlled diabetes or a truly acute episode in an otherwise well-controlled patient. A chest X ray should also be obtained if indicated. Tables 1 and 2 depict typical laboratory findings in patients with DKA or HHS.
The majority of patients with hyperglycemic emergencies present with leukocytosis proportional to blood ketone body concentration. Serum sodium concentration is usually decreased because of the osmotic flux of water from the intracellular to the extracellular space in the presence of hyperglycemia, and less commonly, serum sodium concentration may be falsely lowered by severe hypertriglyceridemia. Serum potassium concentration may be elevated because of an extracellular shift of potassium caused by insulin deficiency, hypertonicity, and acidemia. Patients with low-normal or low serum potassium concentration on admission have severe total-body potassium deficiency and require very careful cardiac monitoring and more vigorous potassium replacement, because treatment lowers potassium further and can provoke cardiac dysrhythmia. The occurrence of stupor or coma in diabetic patients in the absence of definitive elevation of effective osmolality (
320 mOsm/kg) demands immediate consideration of other causes of mental status change. Effective osmolality may be calculated by the following formula: 2[measured Na (mEq/l)] + glucose (mg/dl)/18. Amylase levels are elevated in the majority of patients with DKA, but this may be due to nonpancreatic sources, such as the parotid gland. A serum lipase determination may be beneficial in the differential diagnosis of pancreatitis. However, lipase could also be elevated in DKA. Abdominal pain and elevation of serum amylase and liver enzymes are noted more commonly in DKA than in HHS.
Differential diagnosis
Not all patients with ketoacidosis have DKA. Starvation ketosis and alcoholic ketoacidosis (AKA) are distinguished by clinical history and by plasma glucose concentrations that range from mildly elevated (rarely >250 mg/dl) to hypoglycemia. In addition, although AKA can result in profound acidosis, the serum bicarbonate concentration in starvation ketosis is usually not lower than 18 mEq/l. DKA must also be distinguished from other causes of high–anion gap metabolic acidosis, including lactic acidosis, ingestion of drugs such as salicylate, methanol, ethylene glycol, and paraldehyde, and chronic renal failure (which is more typically hyperchloremic acidosis rather than high–anion gap acidosis). Clinical history of previous drug intoxications or metformin use should be sought. Measurement of blood lactate, serum salicylate, and blood methanol level can be helpful in these situations. Ethylene glycol (antifreeze) is suggested by the presence of calcium oxalate and hippurate crystals in the urine. Paraldehyde ingestion is indicated by its characteristic strong odor on the breath. Because these intoxicants are low–molecular weight organic compounds, they can produce an osmolar gap in addition to the anion gap acidosis.14–16
TREATMENT
Successful treatment of DKA and HHS requires correction of dehydration, hyperglycemia, and electrolyte imbalances; identification of comorbid precipitating events; and above all, frequent patient monitoring. Guidelines for the management of patients with DKA and HHS follow and are summarized in Figs. 1, 2, and 3. Table 3 includes a summary of major recommendations and evidence gradings.
|
After history and physical examination, obtain arterial blood gases; complete blood count with differential, urinalysis, blood glucose, blood urea nitrogen, electrolytes, chemistry profile, and creatinine levels STAT as well as an electrocardiogram. Obtain chest X ray and cultures as needed. 
Serum Na should be corrected for hyperglycemia (for each 100 mg/dl glucose >100 mg/dl, add 1.6 mEq to sodium value for corrected serum sodium value).
|
|
Usually 1.5 times the 24-h maintenance requirements (
|
Fluid therapy
Adult patients. Initial fluid therapy is directed toward expansion of the intravascular and extravascular volume and restoration of renal perfusion. In the absence of cardiac compromise, isotonic saline (0.9% NaCl) is infused at a rate of 15–20 ml · kg-1 body wt · h-1 or greater during the 1st hour (
1–1.5 liters in the average adult). Subsequent choice for fluid replacement depends on the state of hydration, serum electrolyte levels, and urinary output. In general, 0.45% NaCl infused at 4–14 ml · kg-1 · h-1 is appropriate if the corrected serum sodium is normal or elevated; 0.9% NaCl at a similar rate is appropriate if corrected serum sodium is low. Once renal function is assured, the infusion should include 20–30 mEq/l potassium (2/3 KCl and 1/3 KPO4) until the patient is stable and can tolerate oral supplementation. Successful progress with fluid replacement is judged by hemodynamic monitoring (improvement in blood pressure), measurement of fluid input/output, and clinical examination. Fluid replacement should correct estimated deficits within the first 24 h. The induced change in serum osmolality should not exceed 3 mOsm · kg-1 H2O · h-1.14–20,22 In patients with renal or cardiac compromise, monitoring of serum osmolality and frequent assessment of cardiac, renal, and mental status must be performed during fluid resuscitation to avoid iatrogenic fluid overload.14–20,22
Pediatric patients (<20 years of age). Initial fluid therapy is directed toward expansion of the intravascular and extravascular volume and restoration of renal profusion. The need for vascular volume expansion must be offset by the risk of cerebral edema associated with rapid fluid administration. The 1st hour of fluids should be isotonic saline (0.9% NaCl) at the rate of 10–20 ml · kg-1 · h-1. In a severely dehydrated patient, this may need to be repeated, but the initial reexpansion should not exceed 50 ml/kg over the first 4 h of therapy. Continued fluid therapy is calculated to replace the fluid deficit evenly over 48 h. In general, 0.9% NaCl infused at a rate of 1.5 times the 24-h maintenance requirements (5 ml · kg-1 · h-1) will accomplish a smooth rehydration, with a decrease in osmolality not exceeding 3 mOsm · kg-1 H2O · h-1. Once renal function is assured and serum potassium is known, the infusion should include 20–40 mEq/l potassium (2/3 KCl or potassium-acetate and 1/3 KPO4). Once serum glucose reaches 250 mg/dl, fluid should be changed to 5% dextrose and 0.45–0.75% NaCl, with potassium as described above. Therapy should include monitoring mental status to rapidly identify changes that might indicate iatrogenic fluid overload, which can lead to symptomatic cerebral edema.23–25
Insulin therapy
Unless the episode of DKA is mild (Table 1), regular insulin by continuous intravenous infusion is the treatment of choice. Once hypokalemia (K+ <3.3 mEq/l) is excluded, an intravenous bolus of regular insulin at 0.15 U/kg body wt, followed by a continuous infusion of regular insulin at a dose of 0.1 U · kg-1 · h-1 (5–7 U/h in adults), should be administered. This low dose of insulin usually decreases plasma glucose concentration at a rate of 50–75 mg · dl-1 · h-1, similar to a higher dose insulin regimen.26 If plasma glucose does not fall by 50 mg/dl from the initial value in the 1st hour, check hydration status; if acceptable, the insulin infusion may be doubled every hour until a steady glucose decline between 50 and 75 mg/h is achieved. When the plasma glucose reaches 250 mg/dl in DKA or 300 mg/dl in HHS, it may be possible to decrease the insulin infusion rate to 0.05–0.1 U · kg-1 · h-1 (3–6 U/h), and dextrose (5–10%) may be added to the intravenous fluids. Thereafter, the rate of insulin administration or the concentration of dextrose may need to be adjusted to maintain the above glucose values until acidosis in DKA or mental obtundation and hyperosmolarity in HHS are resolved.
Ketonemia typically takes longer to clear than hyperglycemia. The nitroprusside method only measures acetoacetic acid and acetone. However, ß-OHB, the strongest and most prevalent acid in DKA, is not measured by the nitroprusside method. During therapy, ß-OHB is converted to acetoacetic acid, which may lead the clinician to believe that ketosis has worsened. Therefore, assessments of urinary or serum ketone levels by the nitroprusside method should not be used as an indicator of response to therapy. During therapy for DKA or HHS, blood should be drawn every 2–4 h for determination of serum electrolytes, glucose, blood urea nitrogen, creatinine, osmolality, and venous pH (for DKA). Generally, repeat arterial blood gases are unnecessary; venous pH (which is usually 0.03 U lower than arterial pH) and anion gap can be followed to monitor resolution of acidosis. With mild DKA, regular insulin given either subcutaneously or intramuscularly every hour is as effective as intravenous administration in lowering blood glucose and ketone bodies.27 Patients with mild DKA should first receive a "priming" dose of regular insulin of 0.4–0.6 U/kg body wt, half as an intravenous bolus and half as a subcutaneous or intramuscular injection.22 Thereafter, 0.1 U · kg-1 · h-1 of regular insulin should be given subcutaneously or intramuscularly.
After resolution of DKA (glucose <200 mg/dl, serum bicarbonate 18 mEq/l, venous pH >7.3, anion gap <12 mEq/l) and when patients are able to take fluids orally, a multidose regimen may be initiated based on history of previous treatment. However, for newly diagnosed patients, a total insulin dose of 0.6–0.7 U · kg-1 · day-1 may be initiated as a multidose regimen of short- and intermediate-/long-acting insulin, with subsequent modification based on glucose testing. Finally, some type 2 diabetic patients may be discharged on oral agents and dietary therapy.
Potassium
Despite total-body potassium depletion, mild to moderate hyperkalemia is not uncommon in patients with hyperglycemic crises. Insulin therapy, correction of acidosis, and volume expansion decrease serum potassium concentration. To prevent hypokalemia, potassium replacement is initiated after serum levels fall below 5.5 mEq/l, assuming the presence of adequate urine output. Generally, 20–30 mEq potassium (2/3 KCl and 1/3 KPO4) in each liter of infusion fluid is sufficient to maintain a serum potassium concentration within the normal range of 4–5 mEq/l. Rarely, DKA patients may present with significant hypokalemia. In such cases, potassium replacement should begin with fluid therapy, and insulin treatment should be delayed until potassium concentration is restored to >3.3 mEq/l to avoid arrhythmias or cardiac arrest and respiratory muscle weakness.
Bicarbonate
Bicarbonate use in DKA remains controversial.28 At a pH >7.0, reestablishing insulin activity blocks lipolysis and resolves ketoacidosis without any added bicarbonate. Prospective randomized studies have failed to show either beneficial or deleterious changes in morbidity or mortality with bicarbonate therapy in DKA patients with pH between 6.9 and 7.1.29 No prospective randomized studies concerning the use of bicarbonate in DKA with pH values <6.9 have been reported. Given that severe acidosis may lead to a myriad of adverse vascular effects, it seems prudent that for adult patients with a pH <6.9, 100 mmol sodium bicarbonate be added to 400 ml sterile water and given at a rate of 200 ml/h. In patients with a pH of 6.9–7.0, 50 mmol sodium bicarbonate is diluted in 200 ml sterile water and infused at a rate of 200 ml/h. No bicarbonate is necessary if pH is >7.0.
In the pediatric patient, there are no randomized studies in patients with pH <6.9. If the pH remains below 7.0 after the initial hour of hydration, it seems prudent to administer 1–2 mEq/kg sodium bicarbonate over an hour. This sodium bicarbonate can be added to 0.45 NaCl, with any required potassium, and this solution can be used as the rehydration solution for that hour. No bicarbonate therapy is required if pH is 7.0.30,31
Insulin, as well as bicarbonate therapy, lowers serum potassium; therefore, potassium supplementation should be maintained in intravenous fluid as described above and carefully monitored. (See Fig. 1 for guidelines.) Thereafter, venous pH should be assessed every 2 h until the pH rises to 7.0, and treatment should be repeated every 2 h if necessary. (See Kitabchi et al.11 for a complete description of studies done to date on the use of bicarbonate in DKA.)
Phosphate
Despite whole-body phosphate deficits in DKA that average 1.0 mmol/kg body wt, serum phosphate is often normal or increased at presentation. Phosphate concentration decreases with insulin therapy. Prospective randomized studies have failed to show any beneficial effect of phosphate replacement on the clinical outcome in DKA,32 and overzealous phosphate therapy can cause severe hypocalcemia with no evidence of tetany.17,32 However, to avoid cardiac and skeletal muscle weakness and respiratory depression due to hypophosphatemia, careful phosphate replacement may sometimes be indicated in patients with cardiac dysfunction, anemia, or respiratory depression and in those with serum phosphate concentration <1.0 mg/dl. When needed, 20–30 mEq/l potassium phosphate can be added to replacement fluids. No studies are available on the use of phosphate in the treatment of HHS.
Continuous monitoring using a flowsheet (Fig. 4) aids in the organization of recovery parameters and treatment interventions.
|
COMPLICATIONS
The most common complications of DKA and HHS include hypoglycemia due to overzealous treatment with insulin, hypokalemia due to insulin administration and treatment of acidosis with bicarbonate, and hyperglycemia secondary to interruption/discontinuance of intravenous insulin therapy after recovery without subsequent coverage with subcutaneous insulin. Commonly, patients recovering from DKA develop hyperchloremia caused by the use of excessive saline for fluid and electrolyte replacement and transient non–anion gap metabolic acidosis as chloride from intravenous fluids replaces ketoanions lost as sodium and potassium salts during osmotic diuresis. These biochemical abnormalities are transient and are not clinically significant except in cases of acute renal failure or extreme oliguria.
Cerebral edema is a rare but frequently fatal complication of DKA, occurring in 0.7–1.0% of children with DKA. It is most common in children with newly diagnosed diabetes, but has been reported in children with known diabetes and in young people in their twenties.33,34 Fatal cases of cerebral edema have also been reported with HHS. Clinically, cerebral edema is characterized by a deterioration in the level of consciousness, with lethargy, decrease in arousal, and headache. Neurological deterioration may be rapid, with seizures, incontinence, pupillary changes, bradycardia, and respiratory arrest. These symptoms progress as brain stem herniation occurs. The progression may be so rapid that papilledema is not found. Once the clinical symptoms other than lethargy and behavioral changes occur, mortality is high (>70%), with only 7–14% of patients recovering without permanent morbidity. Although the mechanism of cerebral edema is not known, it likely results from osmotically driven movement of water into the central nervous system when plasma osmolality declines too rapidly with the treatment of DKA or HHS. There is a lack of information on the morbidity associated with cerebral edema in adult patients; therefore, any recommendations for adult patients are clinical judgements, rather than scientific evidence. Prevention measures that might decrease the risk of cerebral edema in high-risk patients are gradual replacement of sodium and water deficits in patients who are hyperosmolar (maximal reduction in osmolality 3 mOsm · kg-1 H2O · h-1) and the addition of dextrose to the hydrating solution once blood glucose reaches 250 mg/dl. In HHS, a glucose level of 250–300 mg/dl should be maintained until hyperosmolarity and mental status improves and the patient becomes clinically stable.35
Hypoxemia and, rarely, noncardiogenic pulmonary edema may complicate the treatment of DKA. Hypoxemia is attributed to a reduction in colloid osmotic pressure that results in increased lung water content and decreased lung compliance. Patients with DKA who have a widened alveolo-arteriolar oxygen gradient noted on initial blood gas measurement or with pulmonary rales on physical examination appear to be at higher risk for the development of pulmonary edema.
PREVENTION
Many cases of DKA and HHS can be prevented by better access to medical care, proper education, and effective communication with a health care provider during an intercurrent illness. The observation that stopping insulin for economic reasons is a common precipitant of DKA in urban African-Americans36,37 is disturbing and underscores the need for our health care delivery systems to address this problem, which is costly and clinically serious.
Sick-day management should be reviewed periodically with all patients. It should include specific information on 1) when to contact the health care provider, 2) blood glucose goals and use of supplemental short-acting insulin during illness, 3) means to suppress fever and treat infection, and 4) initiation of an easily digestible liquid diet containing carbohydrates and salt. Most importantly, the patient should be advised never to discontinue insulin and to seek professional advice early in the course of the illness. Successful sick-day management depends on involvement by the patient and/or a family member. The patient/family member must be able to accurately measure and record blood glucose, urine ketone determination when blood glucose is >300 mg/dl, insulin administered, temperature, respiratory and pulse rate, and body weight and must be able to communicate this to a health care professional. Adequate supervision and help from staff or family may prevent many of the admissions for HHS due to dehydration among elderly individuals who are unable to recognize or treat this evolving condition. Better education of care givers as well as patients regarding signs and symptoms of new-onset diabetes; conditions, procedures, and medications that worsen diabetes control; and the use of glucose monitoring could potentially decrease the incidence and severity of HHS.
The annual incidence rate for DKA from population-based studies ranges from 4.6 to 8 episodes per 1,000 patients with diabetes, with a trend toward an increased hospitalization rate in the past two decades.38 The incidence of HHS accounts for <1% of all primary diabetic admissions. Significant resources are spent on the cost of hospitalization. Based on an annual average of 100,000 hospitalizations for DKA in the U.S., with an average cost of $13,000 per patient, the annual hospital cost for patients with DKA may exceed $1 billion per year. Many of these hospitalizations could be avoided by devoting adequate resources to apply the measures described above.
Because repeated admissions for DKA are estimated to drain approximately one out of every two health care dollars spent on adult patients with type 1 diabetes, resources need to be redirected toward prevention by funding better access to care and educational programs tailored to individual needs, including ethnic and personal health care beliefs. In addition, resources should be directed toward the education of primary care providers and school personnel so that they can identify signs and symptoms of uncontrolled diabetes and newly onset diabetes can be diagnosed at an earlier time. This has been shown to decrease the incidence of DKA at the onset of diabetes.30,39
Footnotes
The recommendations in this paper are based on the evidence reviewed in the following publication: Management of hyperglycemic crises in patients with diabetes (Technical Review). Diabetes Care 24:131–153, 2001. The initial draft of this position statement was prepared by Abbas E. Kitabchi, PhD, MD, Guillermo E. Umpierrez, MD, Mary Beth Murphy, RN, MS, CDE, MBA, Eugene J. Barrett, MD, PhD, Robert A. Kreisberg, MD, John I. Malone, MD, and Barry M. Wall, MD. The paper was peer-reviewed, modified, and approved by the Professional Practice Committee and the Executive Committee, October 2000.
Reprinted with permission from Diabetes Care 24 (Suppl. 1):S83–S90, 2001. Corrections were made in March 2001. Minor typographical errors were corrected, and the treatment protocols ( Figures 1, 2, 3) were amended. Specifically, protocols for insulin therapy after resolution of DKA and HHS were clarified. In Figure 3, the potassium dosage was corrected and a caution was added to withhold insulin until potassium is >2.5.
REFERENCES
1 McGarry JD, Woeltje KF, Kuwajima M, Foster DW: Regulation of ketogenesis and the renaissance of carnitine palmitoyl transferase. Diabetes Metab Rev 5:271–284, 1989[Medline]
2 DeFronzo RA, Matsuda M, Barrett E: Diabetic ketoacidosis: a combined metabolic-nephrologic approach to therapy. Diabetes Rev 2:209–238, 1994
3 Atchley DW, Loeb RF, Richards DW, Benedict EM, Driscoll ME: A detailed study of electrolyte balances following withdrawal and reestablishment of insulin therapy. J Clin Invest 12:297–326, 1933
4 Halperin ML, Cheema-Dhadli S: Renal and hepatic aspects of ketoacidosis: a quantitative analysis based on energy turnover. Diabetes Metab Rev 5:321–336, 1989
5 Malone ML, Gennis V, Goodwin JS: Characteristics of diabetic ketoacidosis in older versus younger adults. J Am Geriatr Soc 40:1100–1104, 1992[Medline]
6 Matz R: Hyperosmolar nonacidotic diabetes (HNAD). In Diabetes Mellitus: Theory and Practice. 5th ed. Porte D Jr, Sherwin RS, Eds. Amsterdam, Elsevier, 1997, p. 845–860
7 Morris LE, Kitabchi AE: Coma in the diabetic. In Diabetes Mellitus: Problems in Management. Schnatz JD, Ed. Menlo Park, CA, Addison-Wesley, 1982, p. 234–251
8 Kreisberg RA: Diabetic ketoacidosis: new concepts and trends in pathogenesis and treatment. Ann Int Med 88:681–695, 1978
9 Klekamp J, Churchwell KB: Diabetic ketoacidosis in children: initial clinical assessment and treatment. Pediatric Annals 25:387–393, 1996[Medline]
10 Glaser NS, Kupperman N, Yee CK, Schwartz DL, Styne DM: Variation in the management of pediatric diabetic ketoacidosis by specialty training. Arch Pediatr Adolescent Med 151:1125–1132, 1997[Abstract]
11 Kitabchi AE, Umpierrez GE, Murphy MB, Barrett EJ, Kreisberg RA, Malone JI, Wall BM: Management of hyperglycemic crises in patients with diabetes mellitus (Technical Review). Diabetes Care 24:131–153, 2001
12 Beigelman PM: Severe diabetic ketoacidosis (diabetic coma): 482 episodes in 257 patients: experience of three years. Diabetes 20:490–500, 1971[Medline]
13 Polonsky WH, Anderson BJ, Lohrer PA, Aponte JE, Jacobson AM, Cole CF: Insulin omission in women with IDDM. Diabetes Care 17:1178–1185, 1994[Abstract]
14 Kitabchi AE, Fisher JN, Murphy MB, Rumbak MJ: Diabetic ketoacidosis and the hyperglycemic hyperosmolar nonketotic state. In Joslin’s Diabetes Mellitus. 13th ed. Kahn CR, Weir GC, Eds. Philadelphia, Lea & Febiger, 1994, p. 738–770
15 Ennis ED, Stahl EJVB, Kreisberg RA: The hyperosmolar hyperglycemic syndrome. Diabetes Rev 2:115–126, 1994
16 Marshall SM, Walker M, Alberti KGMM: Diabetic ketoacidosis and hyperglycaemic non-ketotic coma. In International Textbook of Diabetes Mellitus. 2nd ed. Alberti KGMM, Zimmet P, DeFronzo RA, Eds. New York, John Wiley, p. 1215–1229, 1997
17 Carroll P, Matz R: Uncontrolled diabetes mellitus in adults: experience in treating diabetic ketoacidosis and hyperosmolar coma with low-dose insulin and uniform treatment regimen. Diabetes Care 6:579–585, 1983[Abstract]
18 Ennis ED, Stahl EJ, Kreisberg RA: Diabetic ketoacidosis. In Diabetes Mellitus: Theory and Practice. 5th ed. Porte D Jr, Sherwin RS, Eds. Amsterdam, Elsevier, 1997, p. 827–844
19 Hillman K: Fluid resuscitation in diabetic emergencies: a reappraisal. Intensive Care Med 13:4–8, 1987[Medline]
20 Fein IA, Rackow EC, Sprung CL, Grodman R: Relation of colloid osmotic pressure to arterial hypoxemia and cerebral edema during crystalloid volume loading of patients with diabetic ketoacidosis. Ann Intern Med 96:570–575, 1982
21 Matz R: Hypothermia in diabetic acidosis. Hormones 3:36–41, 1972[Medline]
22 Kitabchi AE, Sacks HS, Young RT, Morris L: Diabetic ketoacidosis: reappraisal of therapeutic approach. Ann Rev Med 30:339–357, 1979[Medline]
23 Mahoney CP, Vleck BW, DelAguila M: Risk factors for developing brain herniation during diabetic ketoacidosis. Pediatr Neurology 21:721–727, 1999[Medline]
24 Finberg L: Why do patients with diabetic ketoacidosis have cerebral swelling, and why does treatment sometimes make it worse? Pediatr Adolescent Med 150:785–786, 1996
25 Duck SC, Wyatt DT: Factors associated with brain herniation in the treatment of diabetic ketoacidosis. J Pediatr 113:10–14, 1988[Medline]
26 Kitabchi AE, Ayyagari V, Guerra SMO, Medical House Staff: The efficacy of low dose versus conventional therapy of insulin for treatment of diabetic ketoacidosis. Ann Int Med 84:633–638, 1976
27 Fisher JN, Shahshahani MN, Kitabchi AE: Diabetic ketoacidosis: low dose insulin therapy by various routes. N Engl J Med 297:238–247, 1977[Abstract]
28 Barnes HV, Cohen RD, Kitabchi AE, Murphy MB: When is bicarbonate appropriate in treating metabolic acidosis including diabetic ketoacidosis? In Debates in Medicine. Gitnick G, Barnes HV, Duffy TP, et al., Eds. Chicago, Yearbook, 1990, p. 172
29 Morris LR, Murphy MB, Kitabchi AE: Bicarbonate therapy in severe diabetic ketoacidosis. Ann Int Med 105:836–840, 1986
30 Vanelli M, Chiari G, Ghizzoni L, Costi G, Giacalone T, Chiarelli F: Effectiveness of a prevention program for diabetic ketoacidosis in children. Diabetes Care 22:7–9, 1999
31 Viallon A, Zeni F, Lafond P, Venet C, Tardy B, Page Y, Bertrand JC: Does bicarbonate therapy improve the management of severe diabetic ketoacidosis? Critical Care Medicine 27, December 1999
32 Fisher JN, Kitabchi AE: A randomized study of phosphate therapy in the treatment of diabetic ketoacidosis. J Clin Endocrinol Metab 57:177–180, 1983[Abstract]
33 Rosenbloom AL: Intracerebral crises during treatment of diabetic ketoacidosis. Diabetes Care 13:22–33, 1990[Abstract]
34 Duck SC, Wyatt DT: Factors associated with brain herniation in the treatment of diabetic ketoacidosis. J Pediatr 113:10-14, 1988
35 Holsclaw DS Jr, Torcato B: Acute pulmonary edema in juvenile diabetic ketoacidosis. Pediatr Pulmonology 24:438–443, 1997[Medline]
36 Musey VC, Lee JK, Crawford R, Klatka MA, McAdams D, Phillips LS: Diabetes in urban African Americans. I. Cessation of insulin therapy is the major precipitating cause of diabetic ketoacidosis. Diabetes Care 18:483–489, 1995[Abstract]
37 Umpierrez GE, Kelly JP, Navarrete JE, Casals MMC, Kitabchi AE: Hyperglycemic crises in urban blacks. Arch Int Med 157:669–675, 1997[Abstract]
38 Fishbein HA, Palumbo PJ: Acute metabolic complications in diabetes. In Diabetes in America. National Diabetes Data Group, Ed. Bethesda, MD, National Institutes of Health, 1995, p. 283–291 (NIH pub. no. 95-1468)
39 Kaufman FR, Halvorsen M: The treatment and prevention of diabetic ketoacidosis in children and adolescents with type 1 diabetes mellitus. Pediatr Annals 28:576–582, 1999[Medline]
CiteULike 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  A. E. Kitabchi and G. E. Umpierrez Changes in Serum Leptin in Lean and Obese Subjects with Acute Hyperglycemic Crises J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2593 - 2596. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Diabetes | Diabetes Care | Clinical Diabetes | Diabetes Spectrum |