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Diabetic Ketoacidosis (DKA)Managing hyperglycemic crisis -
Human insulin NPH and regular are usually given in two or three doses per day. More recently, basal-bolus regimens with basal glargine and detemir and rapid-acting insulin analogs lispro, aspart, or glulisine have been proposed as a more physiologic insulin regimen in patients with type 1 diabetes.
A prospective randomized trial compared treatment with a basal-bolus regimen, including glargine once daily and glulisine before meals, with a split-mixed regimen of NPH plus regular insulin twice daily following the resolution of DKA.
Hypoglycemia and hypokalemia are two common complications with overzealous treatment of DKA with insulin and bicarbonate, respectively, but these complications have occurred less often with the low-dose insulin therapy 4 , 56 , Frequent blood glucose monitoring every 1—2 h is mandatory to recognize hypoglycemia because many patients with DKA who develop hypoglycemia during treatment do not experience adrenergic manifestations of sweating, nervousness, fatigue, hunger, and tachycardia.
Hyperchloremic non—anion gap acidosis, which is seen during the recovery phase of DKA, is self-limited with few clinical consequences This may be caused by loss of ketoanions, which are metabolized to bicarbonate during the evolution of DKA and excess fluid infusion of chloride containing fluids during treatment 4.
Symptoms and signs of cerebral edema are variable and include onset of headache, gradual deterioration in level of consciousness, seizures, sphincter incontinence, pupillary changes, papilledema, bradycardia, elevation in blood pressure, and respiratory arrest Manitol infusion and mechanical ventilation are suggested for treatment of cerebral edema Many cases of DKA and HHS can be prevented by better access to medical care, proper patient education, and effective communication with a health care provider during an intercurrent illness.
Paramount in this effort is improved education regarding sick day management, which includes the following:. Emphasizing the importance of insulin during an illness and the reasons never to discontinue without contacting the health care team.
Similarly, adequate supervision and staff education in long-term facilities may prevent many of the admissions for HHS due to dehydration among elderly individuals who are unable to recognize or treat this evolving condition.
The use of home glucose-ketone meters may allow early recognition of impending ketoacidosis, which may help to guide insulin therapy at home and, possibly, may prevent hospitalization for DKA.
In addition, home blood ketone monitoring, which measures β-hydroxybutyrate levels on a fingerstick blood specimen, is now commercially available The observation that stopping insulin for economic reasons is a common precipitant of DKA 74 , 75 underscores the need for our health care delivery systems to address this problem, which is costly and clinically serious.
The rate of insulin discontinuation and a history of poor compliance accounts for more than half of DKA admissions in inner-city and minority populations 9 , 74 , Several cultural and socioeconomic barriers, such as low literacy rate, limited financial resources, and limited access to health care, in medically indigent patients may explain the lack of compliance and why DKA continues to occur in such high rates in inner-city patients.
These findings suggest that the current mode of providing patient education and health care has significant limitations. Addressing health problems in the African American and other minority communities requires explicit recognition of the fact that these populations are probably quite diverse in their behavioral responses to diabetes Significant resources are spent on the cost of hospitalization.
Based on an annual average of , hospitalizations for DKA in the U. A recent study 2 reported that the cost burden resulting from avoidable hospitalizations due to short-term uncontrolled diabetes including DKA is substantial 2. However, the long-term impact of uncontrolled diabetes and its economic burden could be more significant because it can contribute to various complications.
Because most cases occur in patients with known diabetes and with previous DKA, 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 so that new-onset diabetes can be diagnosed at an earlier time.
Recent studies suggest that any type of education for nutrition has resulted in reduced hospitalization In fact, the guidelines for diabetes self-management education were developed by a recent task force to identify ten detailed standards for diabetes self-management education An American Diabetes Association consensus statement represents the authors' collective analysis, evaluation, and opinion at the time of publication and does not represent official association opinion.
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Advanced Search. User Tools Dropdown. Sign In. Skip Nav Destination Close navigation menu Article navigation. Volume 32, Issue 7. Previous Article Next Article. Article Navigation. Consensus Statements July 01 Hyperglycemic Crises in Adult Patients With Diabetes Abbas E.
Kitabchi, PHD, MD ; Abbas E. Kitabchi, PHD, MD. Corresponding author: Abbas E. Kitabchi, akitabchi utmem. This Site. Google Scholar. Guillermo E. Umpierrez, MD ; Guillermo E. Umpierrez, MD. John M. Miles, MD ; John M. Miles, MD.
Joseph N. Fisher, MD Joseph N. Fisher, MD. Diabetes Care ;32 7 — Get Permissions. toolbar search Search Dropdown Menu. toolbar search search input Search input auto suggest. Table 1 Diagnostic criteria for DKA and HHS. Arterial pH 7. View Large.
Figure 1. View large Download slide. Pathogenesis of DKA and HHS: stress, infection, or insufficient insulin. FFA, free fatty acid. Table 2 Admission biochemical data in patients with HHS or DKA.
Figure 2. Early contact with the health care provider. Review of blood glucose goals and the use of supplemental short- or rapid-acting insulin.
Having medications available to suppress a fever and treat an infection. Initiation of an easily digestible liquid diet containing carbohydrates and salt when nauseated. No potential conflicts of interest relevant to this article were reported.
National Center for Health Statistics. Burden of hospitalizations primarily due to uncontrolled diabetes: implications of inadequate primary health care in the United States. Search ADS. Agency for Healthcare Research and Quality. Databases and related tools from the healthcare cost and utilization project HCUP [article online].
National Center for Health Statistics, Centers for Disease Control. Available from www. Diabetic ketoacidosis in infants, children, and adolescents: a consensus statement from the American Diabetes Association.
Detailed diagnoses and procedures: National Hospital Discharge Survey, Diabetic ketoacidosis and the hyperglycemic hyperosmolar nonketotic state. Diabetic ketoacidosis: a combined metabolic-nephrologic approach to therapy. Metabolic effects of low-dose insulin therapy on glucose metabolism in diabetic ketoacidosis.
van de Werve. Effects of free fatty acid availability, glucagon excess and insulin deficiency on ketone body production in postabsorptive man. Proinflammatory cytokines, markers of cardiovascular risks, oxidative stress, and lipid peroxidation in patients with hyperglycemic crises.
Diabetic ketoacidosis during long-term treatment with continuous subcutaneous insulin infusion. Sever hyperglycemic hyperosmolar nonketotic coma in a nondiabetic patient receiving aripiprazole.
Immunogenetic analysis suggest different pathogenesis between obese and lean African-Americans with diabetic ketoacidosis. As outlined in Figure 1 , to make the diagnosis and determine the severity of DKA or HHS, the following should be assessed: plasma levels of electrolytes and anion gap , plasma glucose PG , creatinine, osmolality and beta-hydroxybutyric acid beta-OHB if available , blood gases, serum and urine ketones, fluid balance, level of consciousness, precipitating factors and complications 1.
Arterial blood gases may be required for more ill individuals, when knowing the adequacy of respiratory compensation and the A-a gradient is necessary. Otherwise, venous blood gases are usually adequate—the pH is typically 0. Point-of-care capillary blood beta-OHB measurement in emergency is sensitive and specific for DKA and, as a screening tool, may allow more rapid identification of hyperglycemic persons at risk for DKA 24— There are no definitive criteria for the diagnosis of DKA.
DKA is more challenging to diagnose in the presence of the following conditions: 1 mixed acid-base disorders e. associated vomiting, which will raise the bicarbonate level ; 2 if there has been a shift in the redox potential, favouring the presence of beta-OHB rendering serum ketone testing negative ; or 3 if the loss of keto anions with sodium or potassium in osmotic diuresis has occurred, leading to a return of the plasma anion gap toward normal.
It is, therefore, important to measure ketones in both the serum and urine. If there is an elevated anion gap and serum ketones are negative, beta-OHB levels should be measured.
Negative urine ketones should not be used to rule out DKA Measurement of serum lactate should be considered in hypoxic states.
Pregnant women in DKA typically present with lower PG levels than nonpregnant women 36 , and there are case reports of euglycemic DKA in pregnancy 37, Objectives of management include restoration of normal ECFV and tissue perfusion; resolution of ketoacidosis; correction of electrolyte imbalances and hyperglycemia; and the diagnosis and treatment of coexistent illness.
The issues that must be addressed in the individual presenting with DKA or HHS are outlined in Table 2. A summary of fluid therapy is outlined in Table 3 , and a management algorithm and formulas for calculating key measurements are provided in Figure 1.
People with DKA and HHS are best managed in an intensive care unit or step-down setting 1,31,32 with specialist care 39, Protocols and insulin management software systems 41 may be beneficial 42,43 , but there can be challenges with achieving adherence 44, Volume status including fluid intake and output , vital signs, neurological status, plasma concentrations of electrolytes, anion gap, osmolality and glucose need to be monitored closely, initially as often as every 2 hours 1,31, Capillary blood glucose CBG measurements are unreliable in the setting of severe acidosis Precipitating factors must be diagnosed and treated 1,31, Restoring ECFV improves tissue perfusion and reduces plasma glucose levels both by dilution and by increasing urinary glucose losses.
ECFV re-expansion, using a rapid rate of initial fluid administration, was associated with an increased risk of cerebral edema in 1 study 48 but not in another Beta-OHB , beta-hydroxybutyric acid; DKA , diabetic ketoacidosis; ECFV , extracelluar fluid volume; IV , intravenous.
There have been no randomized trials that have studied strategies for potassium replacement. It is reasonable to treat the potassium deficit of HHS in the same way.
Metabolic acidosis is a prominent component of DKA. People with HHS have minimal or no acidosis. Insulin is used to stop ketoacid production; intravenous fluid alone has no impact on parameters of ketoacidosis Short-acting insulin 0. There is no conclusive evidence supporting the use of an initial insulin bolus in adults and it is not recommended in children.
Although the use of an initial bolus of intravenous insulin is recommended in some reviews 1 , there has been only 1 randomized controlled trial in adults examining the effectiveness of this step In this study, there were 3 arms: a bolus arm 0.
Unfortunately, this study did not examine the standard dose of insulin in DKA 0. In children, using an initial bolus of intravenous insulin does not result in faster resolution of ketoacidosis 57,58 and increases the risk of cerebral edema see Type 1 Diabetes in Children and Adolescents chapter, p.
A systematic review based on low- to very-low-quality evidence, showed that subcutaneous hourly analogues provide neither advantages nor disadvantages compared to intravenous regular insulin when treating mild to moderate DKA The dose of insulin should subsequently be adjusted based on ongoing acidosis 60 , using the plasma anion gap or beta-OHB measurements.
Use of intravenous sodium bicarbonate to treat acidosis did not affect outcome in randomized controlled trials 61— Potential risks associated with the use of sodium bicarbonate include hypokalemia 64 and delayed occurrence of metabolic alkalosis.
Hyperosmolality is due to hyperglycemia and a water deficit. However, serum sodium concentration may be reduced due to shift of water out of cells.
The concentration of sodium needs to be corrected for the level of glycemia to determine if there is also a water deficit Figure 1. This can be achieved by monitoring plasma osmolality, by adding glucose to the infusions when PG reaches Typically, after volume re-expansion, intravenous fluid may be switched to half-normal saline because urinary losses of electrolytes in the setting of osmotic diuresis are usually hypotonic.
The potassium in the infusion will also add to the osmolality. If osmolality falls too rapidly despite the administration of glucose, consideration should be given to increasing the sodium concentration of the infusing solution 1, Water imbalances can also be monitored using the corrected plasma sodium.
Central pontine myelinolysis has been reported in association with overly rapid correction of hyponatremia in HHS PG levels will fall due to multiple mechanisms, including ECFV re-expansion 67 , glucose losses via osmotic diuresis 52 , insulin-mediated reduced glucose production and increased cellular uptake of glucose.
Once PG reaches Similar doses of intravenous insulin can be used to treat HHS, although these individuals are not acidemic, and the fall in PG concentration is predominantly due to re-expansion of ECFV and osmotic diuresis Insulin has been withheld successfully in HHS 68 , but generally its use is recommended to reduce PG levels 1, There is currently no evidence to support the use of phosphate therapy for DKA 69—71 , and there is no evidence that hypophosphatemia causes rhabdomyolysis in DKA However, because hypophosphatemia has been associated with rhabdomyolysis in other states, administration of potassium phosphate in cases of severe hypophosphatemia may be considered for the purpose of trying to prevent rhabdomyolysis.
Reported mortality in DKA ranges from 0. Mortality is usually due to the precipitating cause, electrolyte imbalances especially hypo- and hyperkalemia and cerebral edema. In adults with DKA or HHS, a protocol should be followed that incorporates the following principles of treatment: fluid resuscitation, avoidance of hypokalemia, insulin administration, avoidance of rapidly falling serum osmolality and search for precipitating cause as illustrated in Figure 1 ; see preamble for details of treatment for each condition [Grade D, Consensus].
Negative urine ketones should not be used to rule out DKA [Grade D, Level 4 35 ]. In adults with DKA, intravenous 0. For adults with HHS, intravenous fluid administration should be individualized [Grade D, Consensus].
In adults with DKA, an infusion of short-acting intravenous insulin of 0. The insulin infusion rate should be maintained until the resolution of ketosis [Grade B, Level 2 60 ] as measured by the normalization of the plasma anion gap [Grade D, Consensus]. Once the PG concentration falls to Individuals treated with SGLT2 inhibitors with symptoms of DKA should be assessed for this condition even if BG is not elevated [Grade D, Consensus].
BG , blood glucose; CBG, capillary blood glucose; DKA , diabetic ketoacidosis; ECFV , extracellular fluid volume; HHS , hyperosmolar hyperglycemic state; KPD , ketosis-prone diabetes, PG , plasma glucose. Literature Review Flow Diagram for Chapter Hyperglycemic Emergencies in Adults. From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group P referred R eporting I tems for Systematic Reviews and Meta-Analyses : The PRISMA Statement.
PLoS Med 6 6 : e pmed For more information, visit www. Gilbert reports personal fees from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, and Sanofi, outside the submitted work.
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For questions, contact communications diabetes. Become a Member Order Resources Home About Contact DONATE. Next Previous. Key Messages Recommendations Figures Full Text References. Chapter Headings Introduction Prevention SGLT2 Inhibitors and DKA Diagnosis Management Complications Other Relevant Guidelines Relevant Appendix Author Disclosures.
Key Messages Diabetic ketoacidosis and hyperosmolar hyperglycemic state should be suspected in people who have diabetes and are ill. If either diabetic ketoacidosis or hyperosmolar hyperglycemic state is diagnosed, precipitating factors must be sought and treated. Diabetic ketoacidosis and hyperosmolar hyperglycemic state are medical emergencies that require treatment and monitoring for multiple metabolic abnormalities and vigilance for complications.
A normal or mildly elevated blood glucose level does not rule out diabetic ketoacidosis in certain conditions, such as pregnancy or with SGLT2 inhibitor use. Diabetic ketoacidosis requires intravenous insulin administration 0. Key Messages for People with Diabetes When you are sick, your blood glucose levels may fluctuate and be unpredictable: During these times, it is a good idea to check your blood glucose levels more often than usual for example, every 2 to 4 hours.
Drink plenty of sugar-free fluids or water. Blood ketone testing is preferred over urine testing. Develop a sick-day plan with your diabetes health-care team. This should include information on: Which diabetes medications you should continue and which ones you should temporarily stop Guidelines for insulin adjustment if you are on insulin Advice on when to contact your health-care provider or go to the emergency room.
Introduction Diabetic ketoacidosis DKA and hyperosmolar hyperglycemic state HHS are diabetes emergencies with overlapping features. Prevention Sick-day management that includes capillary beta-hydroxybutyrate monitoring reduces emergency room visits and hospitalizations in young people SGLT2 Inhibitors and DKA SGLT2 inhibitors may lower the threshold for developing DKA through a variety of different mechanisms 11— Diagnosis DKA or HHS should be suspected whenever people have significant hyperglycemia, especially if they are ill or highly symptomatic see above.
Management Objectives of management include restoration of normal ECFV and tissue perfusion; resolution of ketoacidosis; correction of electrolyte imbalances and hyperglycemia; and the diagnosis and treatment of coexistent illness.
Figure 1 Management of diabetic ketoacidosis in adults. Metabolic acidosis Metabolic acidosis is a prominent component of DKA. Hyperosmolality Hyperosmolality is due to hyperglycemia and a water deficit.
Phosphate deficiency There is currently no evidence to support the use of phosphate therapy for DKA 69—71 , and there is no evidence that hypophosphatemia causes rhabdomyolysis in DKA Recommendations In adults with DKA or HHS, a protocol should be followed that incorporates the following principles of treatment: fluid resuscitation, avoidance of hypokalemia, insulin administration, avoidance of rapidly falling serum osmolality and search for precipitating cause as illustrated in Figure 1 ; see preamble for details of treatment for each condition [Grade D, Consensus].
Abbreviations: BG , blood glucose; CBG, capillary blood glucose; DKA , diabetic ketoacidosis; ECFV , extracellular fluid volume; HHS , hyperosmolar hyperglycemic state; KPD , ketosis-prone diabetes, PG , plasma glucose. Other Relevant Guidelines Glycemic Management in Adults With Type 1 Diabetes, p.
S80 Pharmacologic Glycemic Management of Type 2 Diabetes in Adults, p. S88 Type 1 Diabetes in Children and Adolescents, p. Relevant Appendix Appendix 8: Sick-Day Medication List.
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Diabetic ketoacidosis Managing hyperglycemic crisis and Managing hyperglycemic crisis hyperosmolar state HHS are Recovery Meal Ideas emergencies Maaging cause Manxging morbidity and Managibg. Their treatment differs in the UK and USA. This review delineates the differences in diagnosis and treatment between the two countries. Large-scale studies to determine optimal management of DKA and HHS are lacking. The diagnosis of DKA is based on disease severity in the USA, which differs from the UK.
The Nutrition for ultra-marathons of Managing hyperglycemic crisis and HHS in crisiis will be reviewed here. The Managng, pathogenesis, clinical Managing hyperglycemic crisis, evaluation, and diagnosis of these disorders are discussed separately. DKA in children is also reviewed separately. Why UpToDate? Product Editorial Subscription Options Subscribe Sign in. Learn how UpToDate can help you. Select the option that best describes you.
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