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Hyperglycemic crisis and electrolyte imbalances

Hyperglycemic crisis and electrolyte imbalances

Electrolytte replacement should correct estimated deficits within the first 24 Lean Body Transformations. Body composition tracker could be due Electtolyte the lack ekectrolyte cerebral autoregulation, presentation with more severe acidosis and dehydration among children and adolescents Intensive Care Med. Metabolic findings in hyperosmolar non-ketotic diabetic stupor. Joint British Diabetes Societies Guideline for the Management of Diabetic Ketoacidosis: Diabetic Ketoacidosis Guidelines.

Rlectrolyte E. KitabchiGuillermo E. UmpierrezJohn Rlectrolyte. MilesJoseph N. Fisher; Hyperglycwmic Crises crizis Adult Hyperglycemoc With Diabetes. Diabetes Care 1 July ; 32 7 : — Diabetic ketoacidosis DKA and Hyperylycemic hyperosmolar hyperglycemic state HHS are the two Hypergoycemic serious acute metabolic crieis of Dairy-free meal prep. DKA is imbalancew for crksis thanhospital days aand year 12 at an estimated annual direct medical expense and elcetrolyte cost of 2.

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HHS is characterized by severe hyperglycemia, hyperosmolality, and electrolyt in the absence of significant immbalances. These metabolic derangements result from the Hypergycemic of absolute or relative insulin eletcrolyte and Anx increase in counterregulatory hormones glucagon, catecholamines, crisls, and growth hormone.

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In DKA, reduced effective insulin concentrations and increased concentrations of counterregulatory hormones catecholamines, cortisol, glucagon, and growth hormone Hypertlycemic to hyperglycemia imbalancds ketosis. Hyperglycemia develops as a result of three processes: increased gluconeogenesis, accelerated glycogenolysis, and impaired Hyperglycemi utilization by peripheral tissues 12Beta-alanine and anaerobic performance, Hyperglycemjc,— Alternative herbal treatments is magnified by Beta-alanine and anaerobic performance insulin Hyperglyfemic due to the anc imbalance itself as electroolyte as the eleectrolyte free imbalaances acid concentrations 4 The combination of insulin deficiency and Raw Coconut Oil counterregulatory hormones in DKA cirsis leads Pomegranate BBQ sauce recipes the release of free fatty acids into the circulation from adipose tissue lipolysis and to unrestrained hepatic fatty electrolgte oxidation in the electrolye to ketone bodies β-hydroxybutyrate and imbqlances 19with resulting ketonemia and Antivenom manufacturing Beta-alanine and anaerobic performance.

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The procoagulant and inflammatory states may be due crisiss nonspecific phenomena of stress and may partially explain the association of hyperglycemic crises with a hypercoagulable state Hyperglycemif pathogenesis of HHS is not e,ectrolyte well understood as that of DKA, but a greater elcetrolyte of dehydration due to Almond-based skincare diuresis and differences in insulin availability distinguish it from DKA 4 elecrrolyte, Although ikbalances insulin imbalznces is clearly present in HHS, endogenous eelctrolyte secretion reflected by C-peptide levels appears imbalsnces be greater than electrolyts DKA, where it is jmbalances Table Huperglycemic.

Insulin levels in HHS are inadequate to facilitate glucose utilization by insulin-sensitive tissues but adequate to prevent Hyperglycemoc and subsequent ketogenesis criisis IRI, immunoreactive insulin. Adapted from ref. The most common precipitating factor in imbalahces development of Imbalqnces and HHS is infection 14 Other precipitating factors include discontinuation Body composition tracker or inadequate insulin therapy, pancreatitis, myocardial infarction, cerebrovascular accident, and drugs 10elecrolyte In addition, new-onset type 1 diabetes or discontinuation of insulin in established type Innovative culinary techniques diabetes commonly leads to the development of DKA.

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Beforethe use of continuous subcutaneous insulin infusion devices had also been associated with an increased frequency of DKA 23 ; however, with improvement in technology and better education of patients, the incidence of DKA appears to have reduced in pump users. However, additional prospective studies are needed to document reduction of DKA incidence with the use of continuous subcutaneous insulin infusion devices Underlying medical illness that provokes the release of counterregulatory hormones or compromises the access to water is likely to result in severe dehydration and HHS.

In most patients with HHS, restricted water intake is due to the patient being bedridden and is exacerbated by the altered thirst response of the elderly. Elderly individuals with new-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 10 Drugs that affect carbohydrate metabolism, such as corticosteroids, thiazides, sympathomimetic agents, and pentamidine, may precipitate the development of HHS or DKA 4.

Recently, a number of case reports indicate that the conventional antipsychotic as well as atypical antipsychotic drugs may cause hyperglycemia and even DKA or HHS 26 An increasing number of DKA cases without precipitating cause have been reported in children, adolescents, and adult subjects with type 2 diabetes.

Observational and prospective studies indicate that over half of newly diagnosed adult African American and Hispanic subjects with unprovoked DKA have type 2 diabetes 28,— The clinical presentation in such cases is acute as in classical type 1 diabetes ; however, after a short period of insulin therapy, prolonged remission is often possible, with eventual cessation of insulin treatment and maintenance of glycemic control with diet or oral antihyperglycemic agents.

In such patients, clinical and metabolic features of type 2 diabetes include a high rate of obesity, a strong family history of diabetes, a measurable pancreatic insulin reserve, a low prevalence of autoimmune markers of β-cell destruction, and the ability to discontinue insulin therapy during follow-up 2831 This unique, transient insulin-requiring profile after DKA has been recognized mainly in blacks and Hispanics but has also been reported in Native American, Asian, and white populations Some experimental work has shed a mechanistic light on the pathogenesis of ketosis-prone type 2 diabetes.

At presentation, they have markedly impaired insulin secretion and insulin action, but aggressive management with insulin improves insulin secretion and action to levels similar to those of patients with type 2 diabetes without DKA 2831 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.

Occasionally, the entire symptomatic presentation may evolve or develop more acutely, and the patient may present with DKA with no prior clues or symptoms. For both DKA and HHS, the classical clinical picture includes a history of polyuria, polydipsia, weight loss, vomiting, dehydration, weakness, and mental status change.

Physical findings may include poor skin turgor, Kussmaul respirations in DKAtachycardia, and hypotension. Mental status can vary from full alertness to profound lethargy or coma, with the latter more frequent in HHS.

Focal neurologic signs hemianopia and hemiparesis and seizures focal or generalized may also be features of HHS 4 Although infection is a common precipitating factor for both DKA and HHS, patients can be normothermic or even hypothermic primarily because of peripheral vasodilation.

Severe hypothermia, if present, is a poor prognostic sign Caution needs to be taken with patients who complain of abdominal pain on presentation because the symptoms could be either a result of the DKA or an indication of a precipitating cause of DKA, particularly in younger patients or in the absence of severe metabolic acidosis 34 Further evaluation is necessary if this complaint does not resolve with resolution of dehydration and metabolic acidosis.

The diagnostic criteria for DKA and HHS are shown in Table 1. The initial laboratory evaluation of patients include determination of plasma glucose, blood urea nitrogen, creatinine, electrolytes with calculated anion gaposmolality, serum and urinary ketones, and urinalysis, as well as initial arterial blood gases and a complete blood count with a differential.

An electrocardiogram, chest X-ray, and urine, sputum, or blood cultures should also be obtained. The severity of DKA is classified as mild, moderate, or severe based on the severity of metabolic acidosis blood pH, bicarbonate, and ketones and the presence of altered mental status 4.

Significant overlap between DKA and HHS has been reported in more than one-third of patients Severe hyperglycemia and dehydration with altered mental status in the absence of significant acidosis characterize HHS, which clinically presents with less ketosis and greater hyperglycemia than DKA.

This may result from a plasma insulin concentration as determined by baseline and stimulated C-peptide [ Table 2 ] adequate to prevent excessive lipolysis and subsequent ketogenesis but not hyperglycemia 4.

The key diagnostic feature in DKA is the elevation in circulating total blood ketone concentration. Assessment of augmented ketonemia is usually performed by the nitroprusside reaction, which provides a semiquantitative estimation of acetoacetate and acetone levels.

Although the nitroprusside test both in urine and in serum is highly sensitive, it can underestimate the severity of ketoacidosis because this assay does not recognize the presence of β-hydroxybutyrate, the main metabolic product in ketoacidosis 4 If available, measurement of serum β-hydroxybutyrate may be useful for diagnosis Accumulation of ketoacids results in an increased anion gap metabolic acidosis.

Hyperglycemia is a key diagnostic criterion of DKA; however, a wide range of plasma glucose can be present on admission. Elegant studies on hepatic glucose production rates have reported rates ranging from normal or near normal 38 to elevated 1215possibly contributing to the wide range of plasma glucose levels in DKA that are independent of the severity of ketoacidosis This could be due to a combination of factors, including exogenous insulin injection en route to the hospital, antecedent food restriction 3940and inhibition of gluconeogenesis.

On admission, leukocytosis with cell counts in the 10,—15, mm 3 range is the rule in DKA and may not be indicative of an infectious process. In ketoacidosis, leukocytosis is attributed to stress and maybe correlated to elevated levels of cortisol and norepinephrine The admission serum sodium is usually low because of the osmotic flux of water from the intracellular to the extracellular space in the presence of hyperglycemia.

An increased or even normal serum sodium concentration in the presence of hyperglycemia indicates a rather profound degree of free water loss. To assess the severity of sodium and water deficit, serum sodium may be corrected by adding 1.

Studies on serum osmolality and mental alteration have established a positive linear relationship between osmolality and mental obtundation 9 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 careful cardiac monitoring and more vigorous potassium replacement because treatment lowers potassium further and can provoke cardiac dysrhythmia.

Pseudonormoglycemia 44 and pseudohyponatremia 45 may occur in DKA in the presence of severe chylomicronemia. The admission serum phosphate level in patients with DKA, like serum potassium, is usually elevated and does not reflect an actual body deficit that uniformly exists due to shifts of intracellular phosphate to the extracellular space 1246 Insulin deficiency, hypertonicity, and increased catabolism all contribute to the movement of phosphate out of cells.

A serum lipase determination may be beneficial in the differential diagnosis of pancreatitis; however, lipase could also be elevated in DKA in the absence of pancreatitis Not all patients with ketoacidosis have DKA.

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 acute chronic renal failure 4.

Because lactic acidosis is more common in patients with diabetes than in nondiabetic persons and because elevated lactic acid levels may occur in severely volume-contracted patients, plasma lactate should be measured on admission.

A clinical history of previous drug abuse should be sought. Measurement of serum salicylate and blood methanol level may be helpful. 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 A recent report states that active cocaine use is an independent risk factor for recurrent DKA Recently, one case report has shown that a patient with diagnosed acromegaly may present with DKA as the primary manifestation of the disease

: Hyperglycemic crisis and electrolyte imbalances

Beware: Diabetes Results in Significant Electrolyte Disturbances

These metabolic derangements result from the combination of absolute or relative insulin deficiency and an increase in counterregulatory hormones glucagon, catecholamines, cortisol, and growth hormone.

Most patients with DKA have autoimmune type 1 diabetes; however, patients with type 2 diabetes are also at risk during the catabolic stress of acute illness such as trauma, surgery, or infections.

This consensus statement will outline precipitating factors and recommendations for the diagnosis, treatment, and prevention of DKA and HHS in adult subjects. It is based on a previous technical review 4 and more recently published peer-reviewed articles since , which should be consulted for further information.

Data adapted from ref. Recent epidemiological studies indicate that hospitalizations for DKA in the U. are increasing. DKA is the most common cause of death in children and adolescents with type 1 diabetes and accounts for half of all deaths in diabetic patients younger than 24 years of age 5 , 6.

Death in these conditions is rarely due to the metabolic complications of hyperglycemia or ketoacidosis but relates to the underlying precipitating illness 4 , 9.

The prognosis of both conditions is substantially worsened at the extremes of age in the presence of coma, hypotension, and severe comorbidities 1 , 4 , 8 , 12 , The events leading to hyperglycemia and ketoacidosis are depicted in Fig.

In DKA, reduced effective insulin concentrations and increased concentrations of counterregulatory hormones catecholamines, cortisol, glucagon, and growth hormone lead to hyperglycemia and ketosis.

Hyperglycemia develops as a result of three processes: increased gluconeogenesis, accelerated glycogenolysis, and impaired glucose utilization by peripheral tissues 12 , , , , — This is magnified by transient insulin resistance due to the hormone imbalance itself as well as the elevated free fatty acid concentrations 4 , The combination of insulin deficiency and increased counterregulatory hormones in DKA also leads to the release of free fatty acids into the circulation from adipose tissue lipolysis and to unrestrained hepatic fatty acid oxidation in the liver to ketone bodies β-hydroxybutyrate and acetoacetate 19 , with resulting ketonemia and metabolic acidosis.

Increasing evidence indicates that the hyperglycemia in patients with hyperglycemic crises is associated with a severe inflammatory state characterized by an elevation of proinflammatory cytokines tumor necrosis factor-α and interleukin-β, -6, and -8 , C-reactive protein, reactive oxygen species, and lipid peroxidation, as well as cardiovascular risk factors, plasminogen activator inhibitor-1 and free fatty acids in the absence of obvious infection or cardiovascular pathology All of these parameters return to near-normal values with insulin therapy and hydration within 24 h.

The procoagulant and inflammatory states may be due to nonspecific phenomena of stress and may partially explain the association of hyperglycemic crises with a hypercoagulable state The pathogenesis of HHS is not as well understood as that of DKA, but a greater degree of dehydration due to osmotic diuresis and differences in insulin availability distinguish it from DKA 4 , Although relative insulin deficiency is clearly present in HHS, endogenous insulin secretion reflected by C-peptide levels appears to be greater than in DKA, where it is negligible Table 2.

Insulin levels in HHS are inadequate to facilitate glucose utilization by insulin-sensitive tissues but adequate to prevent lipolysis and subsequent ketogenesis IRI, immunoreactive insulin. Adapted from ref.

The most common precipitating factor in the development of DKA and HHS is infection 1 , 4 , Other precipitating factors include discontinuation of or inadequate insulin therapy, pancreatitis, myocardial infarction, cerebrovascular accident, and drugs 10 , 13 , In addition, new-onset type 1 diabetes or discontinuation of insulin in established type 1 diabetes commonly leads to the development of DKA.

Factors that may lead to insulin omission in younger patients include fear of weight gain with improved metabolic control, fear of hypoglycemia, rebellion against authority, and stress of chronic disease.

Before , the use of continuous subcutaneous insulin infusion devices had also been associated with an increased frequency of DKA 23 ; however, with improvement in technology and better education of patients, the incidence of DKA appears to have reduced in pump users.

However, additional prospective studies are needed to document reduction of DKA incidence with the use of continuous subcutaneous insulin infusion devices Underlying medical illness that provokes the release of counterregulatory hormones or compromises the access to water is likely to result in severe dehydration and HHS.

In most patients with HHS, restricted water intake is due to the patient being bedridden and is exacerbated by the altered thirst response of the elderly. Elderly individuals with new-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 10 , Drugs that affect carbohydrate metabolism, such as corticosteroids, thiazides, sympathomimetic agents, and pentamidine, may precipitate the development of HHS or DKA 4.

Recently, a number of case reports indicate that the conventional antipsychotic as well as atypical antipsychotic drugs may cause hyperglycemia and even DKA or HHS 26 , An increasing number of DKA cases without precipitating cause have been reported in children, adolescents, and adult subjects with type 2 diabetes.

Observational and prospective studies indicate that over half of newly diagnosed adult African American and Hispanic subjects with unprovoked DKA have type 2 diabetes 28 , , , — The clinical presentation in such cases is acute as in classical type 1 diabetes ; however, after a short period of insulin therapy, prolonged remission is often possible, with eventual cessation of insulin treatment and maintenance of glycemic control with diet or oral antihyperglycemic agents.

In such patients, clinical and metabolic features of type 2 diabetes include a high rate of obesity, a strong family history of diabetes, a measurable pancreatic insulin reserve, a low prevalence of autoimmune markers of β-cell destruction, and the ability to discontinue insulin therapy during follow-up 28 , 31 , This unique, transient insulin-requiring profile after DKA has been recognized mainly in blacks and Hispanics but has also been reported in Native American, Asian, and white populations Some experimental work has shed a mechanistic light on the pathogenesis of ketosis-prone type 2 diabetes.

At presentation, they have markedly impaired insulin secretion and insulin action, but aggressive management with insulin improves insulin secretion and action to levels similar to those of patients with type 2 diabetes without DKA 28 , 31 , 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.

Occasionally, the entire symptomatic presentation may evolve or develop more acutely, and the patient may present with DKA with no prior clues or symptoms.

For both DKA and HHS, the classical clinical picture includes a history of polyuria, polydipsia, weight loss, vomiting, dehydration, weakness, and mental status change. Physical findings may include poor skin turgor, Kussmaul respirations in DKA , tachycardia, and hypotension.

Mental status can vary from full alertness to profound lethargy or coma, with the latter more frequent in HHS. Focal neurologic signs hemianopia and hemiparesis and seizures focal or generalized may also be features of HHS 4 , Although infection is a common precipitating factor for both DKA and HHS, patients can be normothermic or even hypothermic primarily because of peripheral vasodilation.

Severe hypothermia, if present, is a poor prognostic sign Caution needs to be taken with patients who complain of abdominal pain on presentation because the symptoms could be either a result of the DKA or an indication of a precipitating cause of DKA, particularly in younger patients or in the absence of severe metabolic acidosis 34 , Further evaluation is necessary if this complaint does not resolve with resolution of dehydration and metabolic acidosis.

The diagnostic criteria for DKA and HHS are shown in Table 1. The initial laboratory evaluation of patients include determination of plasma glucose, blood urea nitrogen, creatinine, electrolytes with calculated anion gap , osmolality, serum and urinary ketones, and urinalysis, as well as initial arterial blood gases and a complete blood count with a differential.

An electrocardiogram, chest X-ray, and urine, sputum, or blood cultures should also be obtained. The severity of DKA is classified as mild, moderate, or severe based on the severity of metabolic acidosis blood pH, bicarbonate, and ketones and the presence of altered mental status 4.

Significant overlap between DKA and HHS has been reported in more than one-third of patients Severe hyperglycemia and dehydration with altered mental status in the absence of significant acidosis characterize HHS, which clinically presents with less ketosis and greater hyperglycemia than DKA.

This may result from a plasma insulin concentration as determined by baseline and stimulated C-peptide [ Table 2 ] adequate to prevent excessive lipolysis and subsequent ketogenesis but not hyperglycemia 4. The key diagnostic feature in DKA is the elevation in circulating total blood ketone concentration.

Assessment of augmented ketonemia is usually performed by the nitroprusside reaction, which provides a semiquantitative estimation of acetoacetate and acetone levels. Although the nitroprusside test both in urine and in serum is highly sensitive, it can underestimate the severity of ketoacidosis because this assay does not recognize the presence of β-hydroxybutyrate, the main metabolic product in ketoacidosis 4 , If available, measurement of serum β-hydroxybutyrate may be useful for diagnosis Accumulation of ketoacids results in an increased anion gap metabolic acidosis.

Hyperglycemia is a key diagnostic criterion of DKA; however, a wide range of plasma glucose can be present on admission. Elegant studies on hepatic glucose production rates have reported rates ranging from normal or near normal 38 to elevated 12 , 15 , possibly contributing to the wide range of plasma glucose levels in DKA that are independent of the severity of ketoacidosis This could be due to a combination of factors, including exogenous insulin injection en route to the hospital, antecedent food restriction 39 , 40 , and inhibition of gluconeogenesis.

On admission, leukocytosis with cell counts in the 10,—15, mm 3 range is the rule in DKA and may not be indicative of an infectious process. In ketoacidosis, leukocytosis is attributed to stress and maybe correlated to elevated levels of cortisol and norepinephrine The admission serum sodium is usually low because of the osmotic flux of water from the intracellular to the extracellular space in the presence of hyperglycemia.

An increased or even normal serum sodium concentration in the presence of hyperglycemia indicates a rather profound degree of free water loss. To assess the severity of sodium and water deficit, serum sodium may be corrected by adding 1.

Studies on serum osmolality and mental alteration have established a positive linear relationship between osmolality and mental obtundation 9 , 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 careful cardiac monitoring and more vigorous potassium replacement because treatment lowers potassium further and can provoke cardiac dysrhythmia.

Pseudonormoglycemia 44 and pseudohyponatremia 45 may occur in DKA in the presence of severe chylomicronemia. The admission serum phosphate level in patients with DKA, like serum potassium, is usually elevated and does not reflect an actual body deficit that uniformly exists due to shifts of intracellular phosphate to the extracellular space 12 , 46 , Insulin deficiency, hypertonicity, and increased catabolism all contribute to the movement of phosphate out of cells.

A serum lipase determination may be beneficial in the differential diagnosis of pancreatitis; however, lipase could also be elevated in DKA in the absence of pancreatitis Not all patients with ketoacidosis have DKA.

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 acute chronic renal failure 4.

Because lactic acidosis is more common in patients with diabetes than in nondiabetic persons and because elevated lactic acid levels may occur in severely volume-contracted patients, plasma lactate should be measured on admission.

A clinical history of previous drug abuse should be sought. Measurement of serum salicylate and blood methanol level may be helpful. 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 A recent report states that active cocaine use is an independent risk factor for recurrent DKA Recently, one case report has shown that a patient with diagnosed acromegaly may present with DKA as the primary manifestation of the disease In addition, an earlier report of pituitary gigantism was presented with two episodes of DKA with complete resolution of diabetes after pituitary apoplexy 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.

Protocols for the management of patients with DKA and HHS are summarized in Fig. Protocol for management of adult patients with DKA or HHS.

Bwt, body weight; IV, intravenous; SC, subcutaneous. Has insulin been started and at what rate? Have they given any supplemental potassium yet? Regarding where to admit the patient, they will need a step-down bed ie, a location with closer monitoring including the ability to monitor arterial lines due to a lower nurse-to-patient ratio than a standard ward bed at minimum because of the frequency of bloodwork required.

However, we often monitor their initial response to fluids and insulin therapy in the emergency department ED to see if they are making improvements. If they are, this means they would be appropriate for a step-down bed. In order of most urgent to least urgent, the issues you will have to manage are hemodynamic instability, electrolyte abnormalities, anion gap metabolic acidosis, hyperglycemia, and identification and treatment of the precipitating cause.

Hemodynamic instability: When a patient presents with DKA, they already have a volume deficit of several liters.

First they need IV fluid normal saline [NS] or Ringer lactate boluses to correct this volume depletion. Be more cautious in patients with underlying congestive heart failure or renal failure.

Watch fluid balance and urine output carefully. Electrolyte abnormalities: The primary issue here is total body potassium deficit see Hypokalemia. At first, the potassium may appear elevated due to the shift out of cells in metabolic acidosis.

However, once the acidosis improves, the potassium levels will swiftly drop. This will be exacerbated by insulin therapy.

Therefore, it is important to be proactive to ensure that the potassium levels stay in the normal range. For example, even with potassium up to 5. You may also need to supplement potassium orally every 1 to 2 hours.

Anion gap metabolic acidosis AGMA : This will be corrected with IV insulin and fluids. Start at approximately 0.

The goal of the insulin infusion is not to correct the hyperglycemia—the goal is to correct the elevated anion gap metabolic acidosis. One reason to hold the insulin infusion briefly would be if the potassium levels fall below 3.

Hyperglycemia: This will be corrected primarily by IV fluid administration, IV insulin therapy, and treating the precipitating cause. Balanced Crystalloid Solutions.

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Eur J Heart Fail 20 9 —5. Vanden Hoek TL, Morrison LJ, Shuster M, Donnino M, Sinz E, Lavonas EJ, et al. Part Cardiac Arrest in Special Situations- American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation suppl 3 :S— Masharani U. McGraw Hill.

Keenan CR, Murin S, White RH. High Risk for Venous Thromboembolism in Diabetics With Hyperosmolar State: Comparison With Other Acute Medical Illnesses.

J Thromb Haemostasis 5 6 — Glaser N, Barnett P, McCaslin I, Nelson D, Trainor J, Louie J, et al. Risk Factors for Cerebral Edema in Children With Diabetic Ketoacidosis. New Engl J Med —9. Goguen J, Gilbert J. Hyperglycemic Emergencies in Adults. Can J Diabetes S72—6.

Kuppermann N, Ghetti S, Schunk JE, Stoner MJ, Rewers A, McManemy JK, et al. Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis. N Engl J Med 24 — Keywords: diabetic ketoacidosis, hyperosmolar hyperglycemic syndrome, hyperglycemia crisis, hyperglycemic emergencies, diabetes mellitus.

Citation: Aldhaeefi M, Aldardeer NF, Alkhani N, Alqarni SM, Alhammad AM and Alshaya AI Updates in the Management of Hyperglycemic Crisis. Diabetes Healthc. Received: 23 November ; Accepted: 24 December ; Published: 09 February Copyright © Aldhaeefi, Aldardeer, Alkhani, Alqarni, Alhammad and Alshaya.

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Check for updates. REVIEW article. Aldardeer 4 Nada Alkhani 5 Shatha Mohammed Alqarni 6 Abdullah M. Alhammad 7,8 Abdulrahman I. Alshaya 1,2,3. Introduction Diabetes mellitus DM is a chronic metabolic disorder that disrupts the metabolism of primary macronutrients such as proteins, fats, and carbohydrates 1 , 2.

Pathophysiology DKA and HHS have similar pathophysiology with some differences. Diagnosis Signs and Symptoms DKA develops more rapidly in comparison to HHS.

PRECIPITATING FACTORS

This could be due to the lack of cerebral autoregulation, presentation with more severe acidosis and dehydration among children and adolescents The exact mechanism of cerebral edema development is unknown. Some reports suggest that the risk of cerebral edema during hyperglycemic crisis management might be induced by rapid hydration, especially in the pediatric population.

However, a recent multicenter study for children with DKA who were randomized to receive isotonic versus hypotonic sodium IV fluid with different infusions rates did not show a difference in neurological outcomes Early identification and prompt therapy with mannitol or hypertonic saline can prevent neurological deterioration from DKA management 7 , Furthermore, higher blood urea nitrogen BUN and sodium concentrations have been identified as cerebral edema risk factors Thus, careful hydration with close electrolytes and BUN is recommended Other serious complications of hyperglycemic crisis may include transient AKI, pulmonary edema in patients with congestive heart failure, myocardial infarction, a rise in pancreatic enzymes with or without acute pancreatitis, cardiomyopathy, rhabdomyolysis in patients presented with severe dehydration 7 , All authors have contributed equally in writing, organizing, and reviewing this publication.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic Crises in Adult Patients With Diabetes.

Diabetes Care 32 7 — doi: PubMed Abstract CrossRef Full Text Google Scholar. Goyal A, Mathew UE, Golla KK, Mannar V, Kubihal S, Gupta Y, et al. A Practical Guidance on the Use of Intravenous Insulin Infusion for Management of Inpatient Hyperglycemia.

Diabetes Metab Syndrome: Clin Res Rev 15 5 CrossRef Full Text Google Scholar. Saeedi P. Global and Regional Diabetes Prevalence Estimates for and Projections for and Results From the International Diabetes Federation Diabetes Atlas, 9th Edition.

Diabetes Res Clin Pract Pasquel FJ, Umpierrez GE. Hyperosmolar Hyperglycemic State: A Historic Review of the Clinical Presentation, Diagnosis, and Treatment. Dia Care 37 11 — Kitabchi AE, Umpierrez GE, Murphy MB, Barrett EJ, Kreisberg RA, Malone JI, et al.

Management of Hyperglycemic Crises in Patients With Diabetes. Diabetes Care 24 1 — Kitabchi AE, Umpierrez GE, Murphy MB, Kreisberg RA. Hyperglycemic Crises in Adult Patients With Diabetes: A Consensus Statement From the American Diabetes Association.

Diabetes Care 29 12 — Karslioglu French E, Donihi AC, Korytkowski MT. Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic Syndrome: Review of Acute Decompensated Diabetes in Adult Patients. BMJ I Fayfman M, Pasquel FJ, Umpierrez GE. Management of Hyperglycemic Crises.

Med Clinics North Am 3 — Rains JL, Jain SK. Oxidative Stress, Insulin Signaling, and Diabetes. Free Radical Biol Med 50 5 — Hoffman WH, Burek CL, Waller JL, Fisher LE, Khichi M, Mellick LB. Cytokine Response to Diabetic Ketoacidosis and Its Treatment.

Clin Immunol 3 — Hayami T, Kato Y, Kamiya H, Kondo M, Naito E, Sugiura Y, et al. Case of Ketoacidosis by a Sodium-Glucose Cotransporter 2 Inhibitor in a Diabetic Patient With a Low-Carbohydrate Diet. J Diabetes Investig , 6 5 — Umpierrez GE, Murphy MB, Kitabchi AE. Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar Syndrome.

Diabetes Spectr 15 1 Kraut JA, Madias NE. Serum Anion Gap: Its Uses and Limitations in Clinical Medicine. Clin J Am Soc Nephrol 2 1 — Dhatariya K, Savage M, Claydon A, et al. Joint British Diabetes Societies for Inpatient Care JBDS-IP Revised Guidelines.

The Management of Diabetic Ketoacidosis in Adults Revised Google Scholar. Kitabchi AE, Umpierrez GE, Murphy MB. Diabetic Ketoacidosis and Hyperosmolar State. In: DeFronzo RA, Ferrannini E, Zimmet P, Alberti KGMM, editors.

International Textbook of Diabetes Mellitus. Trachtenbarg DE. Diabetic Ketoacidosis. Am Fam Phys 71 9 — Katz MA. Hyperglycemia-Induced Hyponatremia-Calculation of Expected Serum Sodium Depression. N Engl J Med 16 —4. Rudloff E, Hopper K. Crystalloid and Colloid Compositions and Their Impact. Front Vet Sci Semler MW, Kellum JA.

Balanced Crystalloid Solutions. Am J Respir Crit Care Med 8 — Van Zyl DG, Rheeder P, Delport E. QJM 4 — Mahler SA, Conrad SA, Wang H, Arnold TC. Resuscitation With Balanced Electrolyte Solution Prevents Hyperchloremic Metabolic Acidosis in Patients With Diabetic Ketoacidosis.

Am J Emerg Med 29 6 —4. Self WH, Evans CS, Jenkins CA, Brown RM, Casey JD, Collins SP, et al. Clinical Effects of Balanced Crystalloids vs Saline in Adults With Diabetic Ketoacidosis: A Subgroup Analysis of Cluster Randomized Clinical Trials. JAMA Netw. Open 3 11 :e Ramanan M, Attokaran A, Murray L, Bhadange N, Stewart D, Rajendran G, et al.

Sodium Chloride or Plasmalyte Evaluation in Severe Diabetic Ketoacidosis Scope-Dka - a Cluster, Crossover, Randomized, Controlled Trial. Intensive Care Med 47 11 — Savage MW, Dhatariya KK, Kilvert A, Rayman G, Rees JAE, Courtney CH, et al.

Joint British Diabetes Societies Guideline for the Management of Diabetic Ketoacidosis: Diabetic Ketoacidosis Guidelines. Diabetic Med 28 5 — Umpierrez GE, Jones S, Smiley D, Mulligan P, Keyler T, Temponi A, et al. Insulin Analogs Versus Human Insulin in the Treatment of Patients With Diabetic Ketoacidosis: A Randomized Controlled Trial.

Diabetes Care 32 7 —9. Laskey D, Vadlapatla R, Hart K. Stability of High-Dose Insulin in Normal Saline Bags for Treatment of Calcium Channel Blocker and Beta Blocker Overdose.

Clin Toxicol 54 9 — Lindsay R, Bolte RG. The Use of an Insulin Bolus in Low-Dose Insulin Infusion for Pediatric Diabetic Ketoacidosis. Pediatrs Emerg Care 5 2 —9. Kitabchi AE, Murphy MB, Spencer J, Matteri R, Karas J. Is a Priming Dose of Insulin Necessary in a Low-Dose Insulin Protocol for the Treatment of Diabetic Ketoacidosis?

Diabetes Care 31 11 Wolfsdorf JI, Glaser N, Agus M, Fritsch M, Hanas R, Rewers A, et al. ISPAD Clinical Practice Consensus Guidelines Diabetic Ketoacidosis and the Hyperglycemic Hyperosmolar State. Pediatr Diabetes — Umpierrez GE, Latif K, Stoever J, Cuervo R, Park L, Freire AX, et al.

Efficacy of Subcutaneous Insulin Lispro Versus Continuous Intravenous Regular Insulin for the Treatment of Patients With Diabetic Ketoacidosis.

Am J Med 5 —6. Ersöz HÖ, Ukinc K, Köse M, Erem C, Gunduz A, Hacihasanoglu AB, et al. Subcutaneous Lispro and Intravenous Regular Insulin Treatments are Equally Effective and Safe for the Treatment of Mild and Moderate Diabetic Ketoacidosis in Adult Patients: SC Lispro and IV Regular Insulin Treatments in DKA.

Int J Clin Pract 60 4 — Huang SK, Huang CY, Lin CH, Cheng BW, Chiang YT, Lee YC, et al. Acute Kidney Injury is a Common Complication in Children and Adolescents Hospitalized for Diabetic Ketoacidosis.

Shimosawa T, Ed. PloS One 15 10 :e Frankel AH, Kazempour-Ardebili S, Bedi R, Chowdhury TA, De P, El-Sherbini N, et al. Management of Adults With Diabetes on the Haemodialysis Unit: Summary of Guidance From the Joint British Diabetes Societies and the Renal Association.

Diabetes Med 35 8 — Goldberg PA, Kedves A, Walter K, Groszmann A, Belous A, Inzucchi SE. Diabetes Technol Ther 8 5 — Thompson CD, Vital-Carona J, Faustino EVS. The Effect of Tubing Dwell Time on Insulin Adsorption During Intravenous Insulin Infusions.

Diabetes Technol Ther 14 10 —6. Wilson HK, Keuer SP, Lea AS, Iii AEB, Eknoyan G. Phosphate Therapy in Diabetic Ketoacidosis. Arch Intern Med — Patel MP, Ahmed A, Gunapalan T, Hesselbacher SE. Use of Sodium Bicarbonate and Blood Gas Monitoring in Diabetic Ketoacidosis: A Review. WJD 9 11 — Chua HR, Schneider A, Bellomo R.

Bicarbonate in Diabetic Ketoacidosis - a Systematic Review. Ann Intensive Care 1 1 Jaber S, Paugam C, Futier E, Lefrant JY, Lasocki S, Lescot T, et al. Sodium Bicarbonate Therapy for Patients With Severe Metabolic Acidaemia in the Intensive Care Unit BICAR-ICU : A Multicentre, Open-Label, Randomised Controlled, Phase 3 Trial.

Lancet — Adeva-Andany MM, Fernández-Fernández C, Mouriño-Bayolo D, Castro-Quintela E, Domínguez-Montero A. Sodium Bicarbonate Therapy in Patients With Metabolic Acidosis. Sci World J — Butler J, Vijayakumar S, Pitt B.

Revisiting Hyperkalaemia Guidelines: Rebuttal: Revisiting Hyperkalaemia Guidelines: Rebuttal. Eur J Heart Fail 20 9 —5. Vanden Hoek TL, Morrison LJ, Shuster M, Donnino M, Sinz E, Lavonas EJ, et al.

Part Cardiac Arrest in Special Situations- American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation suppl 3 :S— Masharani U. McGraw Hill. Keenan CR, Murin S, White RH. High Risk for Venous Thromboembolism in Diabetics With Hyperosmolar State: Comparison With Other Acute Medical Illnesses.

J Thromb Haemostasis 5 6 — Glaser N, Barnett P, McCaslin I, Nelson D, Trainor J, Louie J, et al. Risk Factors for Cerebral Edema in Children With Diabetic Ketoacidosis.

New Engl J Med —9. Goguen J, Gilbert J. Hyperglycemic Emergencies in Adults. 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. Author Disclosures Dr. References Kitabchi AE, Umpierrez GE, Murphy MB, et al.

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Hyperosmolar hyperglycemic state: A historic review of the clinical presentation, diagnosis, and treatment. Wachtel TJ, Tetu-Mouradjian LM, Goldman DL, et al. Hyperosmolarity and acidosis in diabetes mellitus: A three-year experience in Rhode Island.

J Gen Intern Med ;— Malone ML, Gennis V, Goodwin JS. Characteristics of diabetic ketoacidosis in older versus younger adults.

J Am Geriatr Soc ;—4. Wang ZH, Kihl-Selstam E, Eriksson JW. Ketoacidosis occurs in both type 1 and type 2 diabetes—a population-based study from Northern Sweden.

Diabet Med ;— Kitabchi AE, Umpierrez GE, Murphy MB, et al. Hyperglycemic crises in adult patients with diabetes: A consensus statement from the American Diabetes Association. Balasubramanyam A, Garza G, Rodriguez L, et al. Accuracy and predictive value of classification schemes for ketosis-prone diabetes.

Diabetes Care ;—9. Laffel LM, Wentzell K, Loughlin C, et al. Sick day management using blood 3-hydroxybutyrate 3-OHB compared with urine ketone monitoring reduces hospital visits in young people with T1DM: A randomized clinical trial.

OgawaW, Sakaguchi K. Euglycemic diabetic ketoacidosis induced by SGLT2 inhibitors: Possible mechanism and contributing factors. J Diabetes Investig ;—8. Rosenstock J, Ferrannini E. Euglycemic diabetic ketoacidosis: A predictable, detectable, and preventable safety concern with SGLT2 inhibitors.

Singh AK. Sodium-glucose co-transporter-2 inhibitors and euglycemic ketoacidosis: Wisdom of hindsight. Indian J Endocrinol Metab ;— Erondu N, Desai M, Ways K, et al.

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Case of ketoacidosis by a sodium-glucose cotransporter 2 inhibitor in a diabetic patient with a low-carbohydrate diet. J Diabetes Investig ;— Peters AL, Buschur EO, Buse JB, et al.

Euglycemic diabetic ketoacidosis: A potential complication of treatment with sodium-glucose cotransporter 2 inhibition. Redford C, Doherty L, Smith J.

SGLT2 inhibitors and the risk of diabetic ketoacidosis. Practical Diabetes ;—4. St Hilaire R, Costello H. Prescriber beware: Report of adverse effect of sodiumglucose cotransporter 2 inhibitor use in a patient with contraindication.

Am J Emerg Med ;, e Goldenberg RM, Berard LD, Cheng AYY, et al. SGLT2 inhibitor-associated diabetic ketoacidosis: Clinical reviewand recommendations for prevention and diagnosis.

Clin Ther ;—64, e1. Malatesha G, Singh NK, Bharija A, et al. Comparison of arterial and venous pH, bicarbonate, PCO2 and PO2 in initial emergency department assessment. Emerg Med J ;— Brandenburg MA, Dire DJ. Comparison of arterial and venous blood gas values in the initial emergency department evaluation of patients with diabetic ketoacidosis.

Ann Emerg Med ;— Ma OJ, Rush MD, Godfrey MM, et al. Arterial blood gas results rarely influence emergency physician management of patients with suspected diabetic ketoacidosis. Acad Emerg Med ;— Charles RA, Bee YM, Eng PH, et al. Point-of-care blood ketone testing: Screening for diabetic ketoacidosis at the emergency department.

Singapore Med J ;—9. Naunheim R, Jang TJ, Banet G, et al. Point-of-care test identifies diabetic ketoacidosis at triage. Acad Emerg Med ;—5. Sefedini E, Prašek M, Metelko Z, et al. Use of capillary beta-hydroxybutyrate for the diagnosis of diabetic ketoacidosis at emergency room: Our one-year experience.

Diabetol Croat ;— Mackay L, Lyall MJ, Delaney S, et al. Are blood ketones a better predictor than urine ketones of acid base balance in diabetic ketoacidosis?

Pract Diabetes Int ;—9. Bektas F, Eray O, Sari R, et al. Point of care blood ketone testing of diabetic patients in the emergency department.

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Diabet Med ;—4. Misra S, Oliver NS. Utility of ketone measurement in the prevention, diagnosis and management of diabetic ketoacidosis. Chiasson JL, Aris-Jilwan N, Belanger R, et al. Diagnosis and treatment of diabetic ketoacidosis and the hyperglycemic hyperosmolar state.

CMAJ ;— Lebovitz HE. Diabetic ketoacidosis. Lancet ;— Cao X, Zhang X, Xian Y, et al. The diagnosis of diabetic acute complications using the glucose-ketone meter in outpatients at endocrinology department. Int J Clin Exp Med ;—5.

Munro JF, Campbell IW, McCuish AC, et al. Euglycaemic diabetic ketoacidosis. Br Med J ;— Kuru B, Sever M, Aksay E, et al. Comparing finger-stick beta-hydroxybutyrate with dipstick urine tests in the detection of ketone bodies. Turk J Emerg Med ;— Guo RX, Yang LZ, Li LX, et al.

Diabetic ketoacidosis in pregnancy tends to occur at lower blood glucose levels: Case-control study and a case report of euglycemic diabetic ketoacidosis in pregnancy.

J Obstet Gynaecol Res ;— Oliver R, Jagadeesan P, Howard RJ, et al. Euglycaemic diabetic ketoacidosis in pregnancy: An unusual presentation. J Obstet Gynaecol ; Chico A, Saigi I, Garcia-Patterson A, et al.

Glycemic control and perinatal outcomes of pregnancies complicated by type 1 diabetes: Influence of continuous subcutaneous insulin infusion and lispro insulin. Diabetes Technol Ther ;— May ME, Young C, King J. Resource utilization in treatment of diabetic ketoacidosis in adults.

Am J Med Sci ;— Levetan CS, Passaro MD, Jablonski KA, et al. Effect of physician specialty on outcomes in diabetic ketoacidosis. Diabetes Care ;—5. Ullal J, McFarland R, Bachand M, et al.

Use of a computer-based insulin infusion algorithm to treat diabetic ketoacidosis in the emergency department. Diabetes Technol Ther ;—3. Bull SV, Douglas IS, Foster M, et al. Mandatory protocol for treating adult patients with diabetic ketoacidosis decreases intensive care unit and hospital lengths of stay: Results of a nonrandomized trial.

Crit Care Med ;—6. Waller SL, Delaney S, Strachan MW. Does an integrated care pathway enhance the management of diabetic ketoacidosis? Devalia B. Adherance to protocol during the acutemanagement of diabetic ketoacidosis: Would specialist involvement lead to better outcomes?

Int J Clin Pract ;—2. Salahuddin M, Anwar MN. Study on effectiveness of guidelines and high dependency unit management on diabetic ketoacidosis patients. J Postgrad Med Inst ;—3. Corl DE, Yin TS, Mills ME, et al.

Evaluation of point-of-care blood glucose measurements in patients with diabetic ketoacidosis or hyperglycemic hyperosmolar syndrome admitted to a critical care unit. J Diabetes Sci Technol ;— Kreisberg RA.

Diabetic ketoacidosis: New concepts and trends in pathogenesis and treatment. Ann Intern Med ;— Mahoney CP, Vlcek BW, DelAguila M. Risk factors for developing brain herniation during diabetic ketoacidosis. Pediatr Neurol ;—7. Rosenbloom AL. Intracerebral crises during treatment of diabetic ketoacidosis.

Adrogue HJ, Barrero J, Eknoyan G. Salutary effects of modest fluid replacement in the treatment of adults with diabetic ketoacidosis. Use in patients without extreme volume deficit. JAMA ;— Fein IA, Rachow EC, Sprung CL, et al. Relation of colloid osmotic pressure to arterial hypoxemia and cerebral edema during crystalloid volume loading of patients with diabetic ketoacidosis.

Ann Intern Med ;—5. Owen OE, Licht JH, Sapir DG. Renal function and effects of partial rehydration during diabetic ketoacidosis. Diabetes ;— Kitabchi AE, Ayyagari V, Guerra SM. The efficacy of low-dose versus conventional therapy of insulin for treatment of diabetic ketoacidosis.

Ann Intern Med ;—8. Heber D, Molitch ME, Sperling MA. Low-dose continuous insulin therapy for diabetic ketoacidosis. Arch Intern Med ;— Insulin therapy for diabetic ketoacidosis.

Bolus insulin injection versus continuous insulin infusion. Kitabchi AE, Murphy MB, Spencer J, et al. Is a priming dose of insulin necessary in a low-dose insulin protocol for the treatment of diabetic ketoacidosis?

Fort P,Waters SM, Lifshitz F. Low-dose insulin infusion in the treatment of diabetic ketoacidosis: Bolus versus no bolus. J Pediatr ;— Lindsay R, Bolte RG. The use of an insulin bolus in low-dose insulin infusion for pediatric diabetic ketoacidosis.

Pediatr Emerg Care ;—9. Andrade-Castellanos CA, Colunga-Lozano LE, Delgado-Figueroa N, et al. Subcutaneous rapid-acting insulin analogues for diabetic ketoacidosis. Cochrane Database Syst Rev ; 1 :CD Treatment of diabetic ketoacidosis using normalization of blood 3-hydroxybutyrate concentration as the endpoint of emergencymanagement.

A randomized controlled study. Morris LR, Murphy MB, Kitabchi AE. Bicarbonate therapy in severe diabetic ketoacidosis. Gamba G, Oseguera J, Castrejón M, et al. A double blind, randomized, placebo controlled trial.

Human Verification

Prompt therapy for patients with hyperglycemic crisis is essential in reducing morbidity and mortality 6 , If not treated or treated ineffectively, the prognosis can include serious complications such as seizures, organ failures, coma, and death 6 , When treatment is delayed, the overall mortality rate of HHS is higher than that of DKA, especially in older patients.

This difference in prognoses was comparable when patients were matched for age In DKA, prolonged hypotension can lead to acute myocardial and bowel infarction 6 , The kidney plays a vital role in normalizing massive pH and electrolyte abnormalities 6 , Patients with prior kidney dysfunction or patients who developed end-stage chronic kidney disease worsen the prognosis considerably 6 , In HHS, severe dehydration may predispose the patient to complications such as myocardial infarction, stroke, pulmonary embolism, mesenteric vein thrombosis, and disseminated intravascular coagulation 6 , The VTE risk was higher than diabetic patients without hyperglycemic crisis or diabetic acidosis patients Management of hyperglycemic crisis may also be associated with significant complications include electrolyte abnormalities, hypoglycemia, and cerebral edema 7.

This is due to the use of insulin and fluid replacement therapy 4 , 5. Therefore, frequent electrolytes and blood glucose concentrations monitoring are essential while insulin infusions and fluid replacements are continued 4 , 5. Cerebral edema is a rare but severe complication in children and adolescents and rarely affects adult patients older than 28 7.

This could be due to the lack of cerebral autoregulation, presentation with more severe acidosis and dehydration among children and adolescents The exact mechanism of cerebral edema development is unknown.

Some reports suggest that the risk of cerebral edema during hyperglycemic crisis management might be induced by rapid hydration, especially in the pediatric population. However, a recent multicenter study for children with DKA who were randomized to receive isotonic versus hypotonic sodium IV fluid with different infusions rates did not show a difference in neurological outcomes Early identification and prompt therapy with mannitol or hypertonic saline can prevent neurological deterioration from DKA management 7 , Furthermore, higher blood urea nitrogen BUN and sodium concentrations have been identified as cerebral edema risk factors Thus, careful hydration with close electrolytes and BUN is recommended Other serious complications of hyperglycemic crisis may include transient AKI, pulmonary edema in patients with congestive heart failure, myocardial infarction, a rise in pancreatic enzymes with or without acute pancreatitis, cardiomyopathy, rhabdomyolysis in patients presented with severe dehydration 7 , All authors have contributed equally in writing, organizing, and reviewing this publication.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic Crises in Adult Patients With Diabetes. Diabetes Care 32 7 — doi: PubMed Abstract CrossRef Full Text Google Scholar. Goyal A, Mathew UE, Golla KK, Mannar V, Kubihal S, Gupta Y, et al. A Practical Guidance on the Use of Intravenous Insulin Infusion for Management of Inpatient Hyperglycemia.

Diabetes Metab Syndrome: Clin Res Rev 15 5 CrossRef Full Text Google Scholar. Saeedi P. Global and Regional Diabetes Prevalence Estimates for and Projections for and Results From the International Diabetes Federation Diabetes Atlas, 9th Edition. Diabetes Res Clin Pract Pasquel FJ, Umpierrez GE.

Hyperosmolar Hyperglycemic State: A Historic Review of the Clinical Presentation, Diagnosis, and Treatment. Dia Care 37 11 — Kitabchi AE, Umpierrez GE, Murphy MB, Barrett EJ, Kreisberg RA, Malone JI, et al.

Management of Hyperglycemic Crises in Patients With Diabetes. Diabetes Care 24 1 — Kitabchi AE, Umpierrez GE, Murphy MB, Kreisberg RA. Hyperglycemic Crises in Adult Patients With Diabetes: A Consensus Statement From the American Diabetes Association.

Diabetes Care 29 12 — Karslioglu French E, Donihi AC, Korytkowski MT. Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic Syndrome: Review of Acute Decompensated Diabetes in Adult Patients.

BMJ I Fayfman M, Pasquel FJ, Umpierrez GE. Management of Hyperglycemic Crises. Med Clinics North Am 3 — Rains JL, Jain SK. Oxidative Stress, Insulin Signaling, and Diabetes. Free Radical Biol Med 50 5 — Hoffman WH, Burek CL, Waller JL, Fisher LE, Khichi M, Mellick LB.

Cytokine Response to Diabetic Ketoacidosis and Its Treatment. Clin Immunol 3 — Hayami T, Kato Y, Kamiya H, Kondo M, Naito E, Sugiura Y, et al.

Case of Ketoacidosis by a Sodium-Glucose Cotransporter 2 Inhibitor in a Diabetic Patient With a Low-Carbohydrate Diet. J Diabetes Investig , 6 5 — Umpierrez GE, Murphy MB, Kitabchi AE. Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar Syndrome. Diabetes Spectr 15 1 Kraut JA, Madias NE.

Serum Anion Gap: Its Uses and Limitations in Clinical Medicine. Clin J Am Soc Nephrol 2 1 — Dhatariya K, Savage M, Claydon A, et al.

Joint British Diabetes Societies for Inpatient Care JBDS-IP Revised Guidelines. The Management of Diabetic Ketoacidosis in Adults Revised Google Scholar.

Kitabchi AE, Umpierrez GE, Murphy MB. Diabetic Ketoacidosis and Hyperosmolar State. In: DeFronzo RA, Ferrannini E, Zimmet P, Alberti KGMM, editors. International Textbook of Diabetes Mellitus. Trachtenbarg DE. Diabetic Ketoacidosis. Am Fam Phys 71 9 — Katz MA. Hyperglycemia-Induced Hyponatremia-Calculation of Expected Serum Sodium Depression.

N Engl J Med 16 —4. Rudloff E, Hopper K. Crystalloid and Colloid Compositions and Their Impact. Front Vet Sci Semler MW, Kellum JA. Balanced Crystalloid Solutions.

Am J Respir Crit Care Med 8 — Van Zyl DG, Rheeder P, Delport E. QJM 4 — Mahler SA, Conrad SA, Wang H, Arnold TC. Resuscitation With Balanced Electrolyte Solution Prevents Hyperchloremic Metabolic Acidosis in Patients With Diabetic Ketoacidosis. Am J Emerg Med 29 6 —4. Self WH, Evans CS, Jenkins CA, Brown RM, Casey JD, Collins SP, et al.

Clinical Effects of Balanced Crystalloids vs Saline in Adults With Diabetic Ketoacidosis: A Subgroup Analysis of Cluster Randomized Clinical Trials. JAMA Netw. Open 3 11 :e Ramanan M, Attokaran A, Murray L, Bhadange N, Stewart D, Rajendran G, et al.

Sodium Chloride or Plasmalyte Evaluation in Severe Diabetic Ketoacidosis Scope-Dka - a Cluster, Crossover, Randomized, Controlled Trial. Intensive Care Med 47 11 — Savage MW, Dhatariya KK, Kilvert A, Rayman G, Rees JAE, Courtney CH, et al.

Joint British Diabetes Societies Guideline for the Management of Diabetic Ketoacidosis: Diabetic Ketoacidosis Guidelines. Diabetic Med 28 5 — Umpierrez GE, Jones S, Smiley D, Mulligan P, Keyler T, Temponi A, et al.

Insulin Analogs Versus Human Insulin in the Treatment of Patients With Diabetic Ketoacidosis: A Randomized Controlled Trial. Diabetes Care 32 7 —9. Laskey D, Vadlapatla R, Hart K. Stability of High-Dose Insulin in Normal Saline Bags for Treatment of Calcium Channel Blocker and Beta Blocker Overdose.

Clin Toxicol 54 9 — Lindsay R, Bolte RG. The Use of an Insulin Bolus in Low-Dose Insulin Infusion for Pediatric Diabetic Ketoacidosis. Pediatrs Emerg Care 5 2 —9. Kitabchi AE, Murphy MB, Spencer J, Matteri R, Karas J. Is a Priming Dose of Insulin Necessary in a Low-Dose Insulin Protocol for the Treatment of Diabetic Ketoacidosis?

Diabetes Care 31 11 Wolfsdorf JI, Glaser N, Agus M, Fritsch M, Hanas R, Rewers A, et al. ISPAD Clinical Practice Consensus Guidelines Diabetic Ketoacidosis and the Hyperglycemic Hyperosmolar State.

Pediatr Diabetes — Umpierrez GE, Latif K, Stoever J, Cuervo R, Park L, Freire AX, et al. Efficacy of Subcutaneous Insulin Lispro Versus Continuous Intravenous Regular Insulin for the Treatment of Patients With Diabetic Ketoacidosis.

Am J Med 5 —6. Ersöz HÖ, Ukinc K, Köse M, Erem C, Gunduz A, Hacihasanoglu AB, et al. Subcutaneous Lispro and Intravenous Regular Insulin Treatments are Equally Effective and Safe for the Treatment of Mild and Moderate Diabetic Ketoacidosis in Adult Patients: SC Lispro and IV Regular Insulin Treatments in DKA.

Int J Clin Pract 60 4 — Huang SK, Huang CY, Lin CH, Cheng BW, Chiang YT, Lee YC, et al. Acute Kidney Injury is a Common Complication in Children and Adolescents Hospitalized for Diabetic Ketoacidosis.

Shimosawa T, Ed. PloS One 15 10 :e Frankel AH, Kazempour-Ardebili S, Bedi R, Chowdhury TA, De P, El-Sherbini N, et al. Management of Adults With Diabetes on the Haemodialysis Unit: Summary of Guidance From the Joint British Diabetes Societies and the Renal Association.

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Wilson HK, Keuer SP, Lea AS, Iii AEB, Eknoyan G. Phosphate Therapy in Diabetic Ketoacidosis. Arch Intern Med — Patel MP, Ahmed A, Gunapalan T, Hesselbacher SE. Use of Sodium Bicarbonate and Blood Gas Monitoring in Diabetic Ketoacidosis: A Review.

WJD 9 11 — Chua HR, Schneider A, Bellomo R. Bicarbonate in Diabetic Ketoacidosis - a Systematic Review. Ann Intensive Care 1 1 Jaber S, Paugam C, Futier E, Lefrant JY, Lasocki S, Lescot T, et al.

Sodium Bicarbonate Therapy for Patients With Severe Metabolic Acidaemia in the Intensive Care Unit BICAR-ICU : A Multicentre, Open-Label, Randomised Controlled, Phase 3 Trial. Lancet — Adeva-Andany MM, Fernández-Fernández C, Mouriño-Bayolo D, Castro-Quintela E, Domínguez-Montero A.

Sodium Bicarbonate Therapy in Patients With Metabolic Acidosis. Sci World J — Butler J, Vijayakumar S, Pitt B. Revisiting Hyperkalaemia Guidelines: Rebuttal: Revisiting Hyperkalaemia Guidelines: Rebuttal. Eur J Heart Fail 20 9 —5. Rarely, DKA patients may present with significant hypokalemia.

Bicarbonate use in DKA remains controversial 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.

In patients with a pH of 6. 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. Thereafter, venous pH should be assessed every 2 h until the pH rises to 7.

See Kitabchi et al. 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 , No studies are available on the use of phosphate in the treatment of HHS.

Continuous monitoring using a flowsheet Fig. 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. It is most common in children with newly diagnosed diabetes, but it has been reported in children with known diabetes and in young people in their twenties 25 , 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. 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.

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. 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-Americans 35 , 36 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 the 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 to never discontinue insulin and to seek professional advice early in the course of the illness. 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. Significant resources are spent on the cost of hospitalization.

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 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 new-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 , Protocol for the management of adult patients with DKA. Normal ranges vary by lab; check local lab normal ranges for all electrolytes.

Obtain chest X-ray and cultures as needed. IM, intramuscular; IV, intravenous; SC subcutaneous. Protocol for the management of adult patients with HHS. This protocol is for patients admitted with mental status change or severe dehydration who require admission to an intensive care unit.

For less severe cases, see text for management guidelines. IV, intravenous; SC subcutaneous. From Kitabchi et al. See text for details. Data are from Ennis et al.

The highest ranking A is assigned when there is supportive evidence from well-conducted, generalizable, randomized controlled trials that are adequately powered, including evidence from a meta-analysis that incorporated quality ratings in the analysis. An intermediate ranking B is given to supportive evidence from well-conducted cohort studies, registries, or case-control studies.

A lower rank C is assigned to evidence from uncontrolled or poorly controlled studies or when there is conflicting evidence with the weight of the evidence supporting the recommendation.

Expert consensus E is indicated, as appropriate. For a more detailed description of this grading system, refer to Diabetes Care 24 Suppl. 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 —, 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 Revised Sign In or Create an Account.

Search Dropdown Menu. header search search input Search input auto suggest. filter your search All Content All Journals Diabetes Care. Advanced Search. User Tools Dropdown. Sign In. Skip Nav Destination Close navigation menu Article navigation. Previous Article.

Article Navigation. Position Statements January 01 Hyperglycemic Crises in Diabetes American Diabetes Association American Diabetes Association.

This Site. Google Scholar. Get Permissions. toolbar search Search Dropdown Menu. toolbar search search input Search input auto suggest. Figure 1—. View large Download slide. Figure 2—. Figure 3—. Figure 4—. Table 1— Diagnostic criteria for DKA and HHS.

View Large. Table 3— Summary of major recommendations. Therefore, to avoid the occurrence of cerebral edema, follow the recommendations in the position statement regarding a gradual correction of glucose and osmolality as well as the judicious use of isotonic or hypotonic saline, depending on serum sodium and the hemodynamic status of the patient.

McGarry JD, Woeltje KF, Kuwajima M, Foster DW: Regulation of ketogenesis and the renaissance of carnitine palmitoyl transferase. Diabetes Metab Rev. DeFronzo RA, Matsuda M, Barrett E: Diabetic ketoacidosis: a combined metabolic-nephrologic approach to therapy. Diabetes Rev. Atchley DW, Loeb RF, Richards DW, Benedict EM, Driscoll ME: A detailed study of electrolyte balances following withdrawal and reestablishment of insulin therapy.

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Malone ML, Gennis V, Goodwin JS: Characteristics of diabetic ketoacidosis in older versus younger adults. J Am Geriatr Soc. Matz R: Hyperosmolar nonacidotic diabetes HNAD. In Diabetes Mellitus: Theory and Practice.

Morris LE, Kitabchi AE: Coma in the diabetic. In Diabetes Mellitus: Problems in Management. Kreisberg RA: Diabetic ketoacidosis: new concepts and trends in pathogenesis and treatment.

Ann Int Med. Klekamp J, Churchwell KB: Diabetic ketoacidosis in children: initial clinical assessment and treatment. Pediatric Annals. 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. 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.

Beigelman PM: Severe diabetic ketoacidosis diabetic coma : episodes in patients: experience of three years. Polonsky WH, Anderson BJ, Lohrer PA, Aponte JE, Jacobson AM, Cole CF: Insulin omission in women with IDDM.

Kitabchi AE, Fisher JN, Murphy MB, Rumbak MJ: Diabetic ketoacidosis and the hyperglycemic hyperosmolar nonketotic state. Ennis ED, Stahl EJVB, Kreisberg RA: The hyperosmolar hyperglycemic syndrome.

Marshall SM, Walker M, Alberti KGMM: Diabetic ketoacidosis and hyperglycaemic non-ketotic coma. In International Textbook of Diabetes Mellitus. 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.

Ennis ED, Stahl EJ, Kreisberg RA: Diabetic ketoacidosis. Hillman K: Fluid resuscitation in diabetic emergencies: a reappraisal. Intensive Care Med. 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. Matz R: Hypothermia in diabetic acidosis. Kitabchi AE, Sacks HS, Young RT, Morris L: Diabetic ketoacidosis: reappraisal of therapeutic approach.

PATHOGENESIS

They found that balanced crystalloids significantly resulted with a shorter median time for DKA resolution than saline At the same time, it significantly led to a shorter median time for insulin discontinuation than saline 9. They found no significant difference in DKA resolution at 48 hours, ICU, and hospital length of stay.

However, PL group had significantly reached more DKA resolution at 24 hours in comparison to 0. In conclusion, designing an appropriate fluid repletion therapy for DKA and HHS management will need careful planning and monitoring for choosing the appropriate fluid type, volume, and rate for the patient.

Insulin is considered to be one of the three fundamental elements of DKA and HHS management 2 , 6 , It reduces hepatic glucose synthesis, enhances peripheral glucose utilization, and inhibits lipolysis, ketogenesis, and glucagon secretion, lowering plasma glucose levels and decreasing ketone bodies production 6 , Insulin should be given immediately after the initial fluid resuscitation 2 , 6 , The aim of using insulin in DKA and HHS is to close the anion gap generated by the production of ketone bodies rather than aiming for euglycemia 6 , Intravenous administration of insulin regular mixed in NaCl 0.

Insulin can also be used as frequent subcutaneous or intramuscular injections for the treatment of DKA in mild-moderate DKA patients 6 , However, a continuous intravenous insulin regimen is preferred over subcutaneous insulin for DKA management overall due to its short half-life, fast onset, and easy titration 6 , The use of basal insulin analogs in conjunction with regular insulin infusions may speed up the resolution of DKA and minimize rebound hyperglycemia events, resulting in less ICU length of stay and less healthcare cost 6 , Insulin is currently recommended as a continuous infusion at 0.

Insulin loading dose has been linked to increasing the risk of cerebral edema and worsening shock Thus, insulin loading dose should be avoided at the beginning of therapy However, an insulin loading dose of 0.

Multiple factors must be considered when titrating intravenous insulin continuous infusion 2. The rate of blood glucose reduction, insulin sensitivity, prandial coverage, and NPO status should all be taken into consideration 2.

A rapid reduction in BG might be harmful and linked to cerebral edema 2. Moreover, the insulin infusion rate can be increased based on BG around major meals time and can be continued at a higher rate for hours following any major meal 2.

Lastly, it is necessary to monitor BG among NPO patients closely. Randomized clinical trials compared the two strategies and found no difference 27 , Intravenous LD insulin administration has been associated with an increased risk of cerebral edema 27 , An acceptable alternative for patients with mild to moderate DKA could be a bolus of 0.

Patients with end-stage renal disease ESRD and acute kidney injury AKI are considered a high-risk category that necessitates extra care 32 , To avoid rapid increases in osmolality and hypoglycemia in these patients; it is recommended that insulin infusions begin at 0.

Subcutaneous insulin should overlap with intravenous insulin for at least minutes before its discontinuation to ensure the optimal transition of care 6 , A transition to subcutaneous long-acting insulin in addition to ultra-short acting insulin such as glargine and glulisine after resolution of DKA may result in reduced hypoglycemic events compared to other basal bolus regimens such as NPH insulin and insulin regular 24 , For newly diagnosed insulin-dependent diabetes patients, subcutaneous insulin may be started at a dose of 0.

The transition process in patients who were previously using insulin or antidiabetic agents before to DKA admission is still unclear 24 , In ICU settings, clinicians tend to hold all oral antidiabetic agents and rely on insulin regimens for in-patient management given the shorter half-life of insulin and its predictability 24 , This could potentially be an area for further investigation on the transition process and its implication on patient outcomes 24 , Insulin sequestering to plastic IV tubing has been described, resulting in insulin wasting and dose inaccuracy 34 , Flushing the IV tube with a priming fluid of 20 mL is adequate to minimize the insulin losses to IV tube 34 , Patients with hyperglycemic crisiss are at a higher risk of developing hypokalemia due to multifactorial process 1 , Insulin therapy, correction of acidosis, and hydration all together lead to the development of hypokalemia 1 , Additionally, volume depletion seen with hyperglycemic crisis leads to secondary hyperaldosteronism, which exacerbates hypokalemia by enhancing urinary potassium excretion 1 , Serum potassium level should be obtained immediately upon presentation and prior to initiating insulin therapy 1 , Potassium replacement is required regardless of the baseline serum potassium level due to hydration and insulin therapy, except among renal failure patients 1 , It is suggested to administer 20 —30 mEq potassium in each liter of intravenous fluid to keep a serum potassium concentration within the normal range 1 , In addition to possible hypokalemia, patients with the hyperglycemic crisis could present with hypophosphatemia 1 , Osmotic diuresis during hyperglycemic crisis increases the urinary phosphate excretion, and insulin therapy enhances intracellular phosphate shift 1 , Phosphate replacement is not a fundamental part of hyperglycemic crisis management, given the lack of evidence of clinical benefit 1 , 29 , A special consideration with phosphate administration is the secondary hypocalcemia 1 , 29 , Acidemia associated with DKA results from the overproduction of ketoacids, generated from the haptic metabolism of free fatty acids.

This hepatic metabolism occurs as a result of insulin resistance and an increase in the counterregulatory hormones contributing to the pathophysiology of DKA 37 , Tissue acidosis could lead to impaired myocardial contractility, systemic vasodilatation, inhibition of glucose utilization by insulin, and lowering the levels of 2,3-diphosphoglycerate 2,3-DPG in erythrocytes 37 — Sodium bicarbonate decreases the hemoglobin-oxygen affinity leading to tissue hypoxia; moreover, it is associated with hypernatremia, hypocalcemia, hypokalemia, hypercapnia, prolonged QTc interval, intracellular acidosis, and metabolic alkalosis 39 , The use of adjuvant sodium bicarbonate in the setting of DKA consistently shows a lack of clinical benefit and should be prescribed on a case-by-case basis.

Although this recommendation was not supported by solid evidence; many clinicians adopt the practice to avoid the unwanted side effect of severe metabolic acidosis. Sodium bicarbonate moves potassium intracellularly, however, clinical benefit is uncertain, and the use is controversial 41 , Prompt therapy for patients with hyperglycemic crisis is essential in reducing morbidity and mortality 6 , If not treated or treated ineffectively, the prognosis can include serious complications such as seizures, organ failures, coma, and death 6 , When treatment is delayed, the overall mortality rate of HHS is higher than that of DKA, especially in older patients.

This difference in prognoses was comparable when patients were matched for age In DKA, prolonged hypotension can lead to acute myocardial and bowel infarction 6 , The kidney plays a vital role in normalizing massive pH and electrolyte abnormalities 6 , Patients with prior kidney dysfunction or patients who developed end-stage chronic kidney disease worsen the prognosis considerably 6 , In HHS, severe dehydration may predispose the patient to complications such as myocardial infarction, stroke, pulmonary embolism, mesenteric vein thrombosis, and disseminated intravascular coagulation 6 , The VTE risk was higher than diabetic patients without hyperglycemic crisis or diabetic acidosis patients Management of hyperglycemic crisis may also be associated with significant complications include electrolyte abnormalities, hypoglycemia, and cerebral edema 7.

This is due to the use of insulin and fluid replacement therapy 4 , 5. Therefore, frequent electrolytes and blood glucose concentrations monitoring are essential while insulin infusions and fluid replacements are continued 4 , 5. Cerebral edema is a rare but severe complication in children and adolescents and rarely affects adult patients older than 28 7.

This could be due to the lack of cerebral autoregulation, presentation with more severe acidosis and dehydration among children and adolescents The exact mechanism of cerebral edema development is unknown.

Some reports suggest that the risk of cerebral edema during hyperglycemic crisis management might be induced by rapid hydration, especially in the pediatric population.

However, a recent multicenter study for children with DKA who were randomized to receive isotonic versus hypotonic sodium IV fluid with different infusions rates did not show a difference in neurological outcomes Early identification and prompt therapy with mannitol or hypertonic saline can prevent neurological deterioration from DKA management 7 , Furthermore, higher blood urea nitrogen BUN and sodium concentrations have been identified as cerebral edema risk factors Thus, careful hydration with close electrolytes and BUN is recommended Other serious complications of hyperglycemic crisis may include transient AKI, pulmonary edema in patients with congestive heart failure, myocardial infarction, a rise in pancreatic enzymes with or without acute pancreatitis, cardiomyopathy, rhabdomyolysis in patients presented with severe dehydration 7 , All authors have contributed equally in writing, organizing, and reviewing this publication.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.

Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN.

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Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic Syndrome: Review of Acute Decompensated Diabetes in Adult Patients. BMJ I Fayfman M, Pasquel FJ, Umpierrez GE. Management of Hyperglycemic Crises. Med Clinics North Am 3 — Rains JL, Jain SK. Oxidative Stress, Insulin Signaling, and Diabetes. Free Radical Biol Med 50 5 — Hoffman WH, Burek CL, Waller JL, Fisher LE, Khichi M, Mellick LB.

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Sodium Chloride or Plasmalyte Evaluation in Severe Diabetic Ketoacidosis Scope-Dka - a Cluster, Crossover, Randomized, Controlled Trial. Intensive Care Med 47 11 — Savage MW, Dhatariya KK, Kilvert A, Rayman G, Rees JAE, Courtney CH, et al.

Joint British Diabetes Societies Guideline for the Management of Diabetic Ketoacidosis: Diabetic Ketoacidosis Guidelines. The clinical presentation in such cases is acute as in classical type 1 diabetes ; however, after a short period of insulin therapy, prolonged remission is often possible, with eventual cessation of insulin treatment and maintenance of glycemic control with diet or oral antihyperglycemic agents.

In such patients, clinical and metabolic features of type 2 diabetes include a high rate of obesity, a strong family history of diabetes, a measurable pancreatic insulin reserve, a low prevalence of autoimmune markers of β-cell destruction, and the ability to discontinue insulin therapy during follow-up 28 , 31 , This unique, transient insulin-requiring profile after DKA has been recognized mainly in blacks and Hispanics but has also been reported in Native American, Asian, and white populations Some experimental work has shed a mechanistic light on the pathogenesis of ketosis-prone type 2 diabetes.

At presentation, they have markedly impaired insulin secretion and insulin action, but aggressive management with insulin improves insulin secretion and action to levels similar to those of patients with type 2 diabetes without DKA 28 , 31 , 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.

Occasionally, the entire symptomatic presentation may evolve or develop more acutely, and the patient may present with DKA with no prior clues or symptoms. For both DKA and HHS, the classical clinical picture includes a history of polyuria, polydipsia, weight loss, vomiting, dehydration, weakness, and mental status change.

Physical findings may include poor skin turgor, Kussmaul respirations in DKA , tachycardia, and hypotension. Mental status can vary from full alertness to profound lethargy or coma, with the latter more frequent in HHS.

Focal neurologic signs hemianopia and hemiparesis and seizures focal or generalized may also be features of HHS 4 , Although infection is a common precipitating factor for both DKA and HHS, patients can be normothermic or even hypothermic primarily because of peripheral vasodilation.

Severe hypothermia, if present, is a poor prognostic sign Caution needs to be taken with patients who complain of abdominal pain on presentation because the symptoms could be either a result of the DKA or an indication of a precipitating cause of DKA, particularly in younger patients or in the absence of severe metabolic acidosis 34 , Further evaluation is necessary if this complaint does not resolve with resolution of dehydration and metabolic acidosis.

The diagnostic criteria for DKA and HHS are shown in Table 1. The initial laboratory evaluation of patients include determination of plasma glucose, blood urea nitrogen, creatinine, electrolytes with calculated anion gap , osmolality, serum and urinary ketones, and urinalysis, as well as initial arterial blood gases and a complete blood count with a differential.

An electrocardiogram, chest X-ray, and urine, sputum, or blood cultures should also be obtained. The severity of DKA is classified as mild, moderate, or severe based on the severity of metabolic acidosis blood pH, bicarbonate, and ketones and the presence of altered mental status 4.

Significant overlap between DKA and HHS has been reported in more than one-third of patients Severe hyperglycemia and dehydration with altered mental status in the absence of significant acidosis characterize HHS, which clinically presents with less ketosis and greater hyperglycemia than DKA.

This may result from a plasma insulin concentration as determined by baseline and stimulated C-peptide [ Table 2 ] adequate to prevent excessive lipolysis and subsequent ketogenesis but not hyperglycemia 4. The key diagnostic feature in DKA is the elevation in circulating total blood ketone concentration.

Assessment of augmented ketonemia is usually performed by the nitroprusside reaction, which provides a semiquantitative estimation of acetoacetate and acetone levels. Although the nitroprusside test both in urine and in serum is highly sensitive, it can underestimate the severity of ketoacidosis because this assay does not recognize the presence of β-hydroxybutyrate, the main metabolic product in ketoacidosis 4 , If available, measurement of serum β-hydroxybutyrate may be useful for diagnosis Accumulation of ketoacids results in an increased anion gap metabolic acidosis.

Hyperglycemia is a key diagnostic criterion of DKA; however, a wide range of plasma glucose can be present on admission.

Elegant studies on hepatic glucose production rates have reported rates ranging from normal or near normal 38 to elevated 12 , 15 , possibly contributing to the wide range of plasma glucose levels in DKA that are independent of the severity of ketoacidosis This could be due to a combination of factors, including exogenous insulin injection en route to the hospital, antecedent food restriction 39 , 40 , and inhibition of gluconeogenesis.

On admission, leukocytosis with cell counts in the 10,—15, mm 3 range is the rule in DKA and may not be indicative of an infectious process. In ketoacidosis, leukocytosis is attributed to stress and maybe correlated to elevated levels of cortisol and norepinephrine The admission serum sodium is usually low because of the osmotic flux of water from the intracellular to the extracellular space in the presence of hyperglycemia.

An increased or even normal serum sodium concentration in the presence of hyperglycemia indicates a rather profound degree of free water loss. To assess the severity of sodium and water deficit, serum sodium may be corrected by adding 1. Studies on serum osmolality and mental alteration have established a positive linear relationship between osmolality and mental obtundation 9 , 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 careful cardiac monitoring and more vigorous potassium replacement because treatment lowers potassium further and can provoke cardiac dysrhythmia.

Pseudonormoglycemia 44 and pseudohyponatremia 45 may occur in DKA in the presence of severe chylomicronemia. The admission serum phosphate level in patients with DKA, like serum potassium, is usually elevated and does not reflect an actual body deficit that uniformly exists due to shifts of intracellular phosphate to the extracellular space 12 , 46 , Insulin deficiency, hypertonicity, and increased catabolism all contribute to the movement of phosphate out of cells.

A serum lipase determination may be beneficial in the differential diagnosis of pancreatitis; however, lipase could also be elevated in DKA in the absence of pancreatitis Not all patients with ketoacidosis have DKA.

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 acute chronic renal failure 4.

Because lactic acidosis is more common in patients with diabetes than in nondiabetic persons and because elevated lactic acid levels may occur in severely volume-contracted patients, plasma lactate should be measured on admission.

A clinical history of previous drug abuse should be sought. Measurement of serum salicylate and blood methanol level may be helpful.

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 A recent report states that active cocaine use is an independent risk factor for recurrent DKA Recently, one case report has shown that a patient with diagnosed acromegaly may present with DKA as the primary manifestation of the disease In addition, an earlier report of pituitary gigantism was presented with two episodes of DKA with complete resolution of diabetes after pituitary apoplexy 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.

Protocols for the management of patients with DKA and HHS are summarized in Fig. Protocol for management of adult patients with DKA or HHS. Bwt, body weight; IV, intravenous; SC, subcutaneous. Initial fluid therapy is directed toward expansion of the intravascular, interstitial, and intracellular volume, all of which are reduced in hyperglycemic crises 53 and restoration of renal perfusion.

In the absence of cardiac compromise, isotonic saline 0. Subsequent choice for fluid replacement depends on hemodynamics, the state of hydration, serum electrolyte levels, and urinary output.

In general, 0. Fluid replacement should correct estimated deficits within the first 24 h. 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 4 , 10 , 15 , Aggressive rehydration with subsequent correction of the hyperosmolar state has been shown to result in a more robust response to low-dose insulin therapy During treatment of DKA, hyperglycemia is corrected faster than ketoacidosis.

The mainstay in the treatment of DKA involves the administration of regular insulin via continuous intravenous infusion or by frequent subcutaneous or intramuscular injections 4 , 56 , Randomized controlled studies in patients with DKA have shown that insulin therapy is effective regardless of the route of administration The administration of continuous intravenous infusion of regular insulin is the preferred route because of its short half-life and easy titration and the delayed onset of action and prolonged half-life of subcutaneous regular insulin 36 , 47 , Numerous prospective randomized studies have demonstrated that use of low-dose regular insulin by intravenous infusion is sufficient for successful recovery of patients with DKA.

Until recently, treatment algorithms recommended the administration of an initial intravenous dose of regular insulin 0.

A recent prospective randomized study reported that a bolus dose of insulin is not necessary if patients receive an hourly insulin infusion of 0. If plasma glucose does not decrease by 50—75 mg from the initial value in the first hour, the insulin infusion should be increased every hour until a steady glucose decline is achieved Fig.

Treatment with subcutaneous rapid-acting insulin analogs lispro and aspart has been shown to be an effective alternative to the use of intravenous regular insulin in the treatment of DKA. Treatment of patients with mild and moderate DKA with subcutaneous rapid-acting insulin analogs every 1 or 2 h in non—intensive care unit ICU settings has been shown to be as safe and effective as the treatment with intravenous regular insulin in the ICU 60 , The rate of decline of blood glucose concentration and the mean duration of treatment until correction of ketoacidosis were similar among patients treated with subcutaneous insulin analogs every 1 or 2 h or with intravenous regular insulin.

However, until these studies are confirmed outside the research arena, patients with severe DKA, hypotension, anasarca, or associated severe critical illness should be managed with intravenous regular insulin in the ICU. Despite total-body potassium depletion, mild-to-moderate hyperkalemia is common 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 the upper level of normal for the particular laboratory 5.

Generally, 20—30 mEq potassium in each liter of infusion fluid is sufficient to maintain a serum potassium concentration within the normal range. Rarely, DKA patients may present with significant hypokalemia.

The use of bicarbonate in DKA is controversial 62 because most experts believe that during the treatment, as ketone bodies decrease there will be adequate bicarbonate except in severely acidotic patients.

Severe metabolic acidosis can lead to impaired myocardial contractility, cerebral vasodilatation and coma, and several gastrointestinal complications A prospective randomized study in 21 patients failed to show either beneficial or deleterious changes in morbidity or mortality with bicarbonate therapy in DKA patients with an admission arterial pH between 6.

Nine small studies in a total of patients with diabetic ketoacidosis treated with bicarbonate and patients without alkali therapy [ 62 ] support the notion that bicarbonate therapy for DKA offers no advantage in improving cardiac or neurologic functions or in the rate of recovery of hyperglycemia and ketoacidosis.

Moreover, several deleterious effects of bicarbonate therapy have been reported, such as increased risk of hypokalemia, decreased tissue oxygen uptake 65 , cerebral edema 65 , and development of paradoxical central nervous system acidosis.

Despite whole-body phosphate deficits in DKA that average 1. 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 46 , 67 , and overzealous phosphate therapy can cause severe hypocalcemia 46 , The maximal rate of phosphate replacement generally regarded as safe to treat severe hypophosphatemia is 4.

No studies are available on the use of phosphate in the treatment of HHS. Patients with DKA and HHS should be treated with continuous intravenous insulin until the hyperglycemic crisis is resolved. Resolution of HHS is associated with normal osmolality and regain of normal mental status. When this occurs, subcutaneous insulin therapy can be started.

To prevent recurrence of hyperglycemia or ketoacidosis during the transition period to subcutaneous insulin, it is important to allow an overlap of 1—2 h between discontinuation of intravenous insulin and the administration of subcutaneous insulin.

Patients with known diabetes may be given insulin at the dosage they were receiving before the onset of DKA so long as it was controlling glucose properly. In insulin-naïve patients, a multidose insulin regimen should be started at a dose of 0.

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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Previous Article Next Article. Article Navigation. Consensus Statements July 01 Hyperglycemic Crises in Adult Patients With Diabetes Abbas E. Kitabchi, PHD, MD ; Abbas E.

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Hyperkalemia Explained Clearly - Fluid and Electrolyte Imbalances Which diabetes Body composition tracker you should electrloyte and which Hyperglycemjc you iimbalances temporarily stop. Elecrrolyte : Green building practices the diagnosis and treatment of diabetic ketoacidosis DKA in adults and in children Body composition tracker general Beta-alanine and anaerobic performance, there are Hyperglyceic differences in their application, largely Hyperglycemi to the increased Hypergylcemic of life-threatening electolyte edema with DKA in children and adolescents. The specific issues related to treatment of DKA in children and adolescents are addressed in the Type 1 Diabetes in Children and Adolescents chapter, p. Diabetic ketoacidosis DKA and hyperosmolar hyperglycemic state HHS are diabetes emergencies with overlapping features. With insulin deficiency, hyperglycemia causes urinary losses of water and electrolytes sodium, potassium, chloride and the resultant extracellular fluid volume ECFV depletion. Potassium is shifted out of cells, and ketoacidosis occurs as a result of elevated glucagon levels and insulin deficiency in the case of type 1 diabetes. There may also be high catecholamine levels suppressing insulin release in the case of type 2 diabetes. Hyperglycemic crisis and electrolyte imbalances

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