Hyperglycemic Emergencies in Adults

Diabetes Canada Clinical Practice Guidelines Expert Committee

Jeannette Goguen MD, MEd, FRCPC, Jeremy Gilbert MD, FRCPC

  • Key Messages
  • Recommendations
  • Figures
  • Full Text
  • References

Key Messages

  • Diabetic ketoacidosis and hyperosmolar hyperglycemic state should be suspected in people who have diabetes and are ill. If either diabetic ketoacidosis or hyperosmolar hyperglycemic state is diagnosed, precipitating factors must be sought and treated.
  • Diabetic ketoacidosis and hyperosmolar hyperglycemic state are medical emergencies that require treatment and monitoring for multiple metabolic abnormalities and vigilance for complications.
  • A normal or mildly elevated blood glucose level does not rule out diabetic ketoacidosis in certain conditions, such as pregnancy or with SGLT2 inhibitor use.
  • Diabetic ketoacidosis requires intravenous insulin administration (0.1 units/kg/h) for resolution. Bicarbonate therapy may be considered only for extreme acidosis (pH ≤7.0).

Key Messages for People with Diabetes

When you are sick, your blood glucose levels may fluctuate and be unpredictable:

  • During these times, it is a good idea to check your blood glucose levels more often than usual (for example, every 2 to 4 hours).
  • Drink plenty of sugar-free fluids or water.
  • If you have type 1 diabetes with blood glucose levels remaining over 14 mmol/L before meals, or if you have symptoms of diabetic ketoacidosis (see Table 1), check for ketones by performing a urine ketone test or blood ketone test. Blood ketone testing is preferred over urine testing.
  • Develop a sick-day plan with your diabetes health-care team. This should include information on:
    • Which diabetes medications you should continue and which ones you should temporarily stop

    • Guidelines for insulin adjustment if you are on insulin

    • Advice on when to contact your health-care provider or go to the emergency room.

Note: Although the diagnosis and treatment of diabetic ketoacidosis (DKA) in adults and in children share general principles, there are significant differences in their application, largely related to the increased risk of life-threatening cerebral 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. S234.


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). In DKA, ketoacidosis is prominent while, in HHS, the main features are ECFV depletion and hyperosmolarity. HHS is the preferred term to describe this condition as opposed to hyperosmolar nonketotic coma (HONKC) since less than one-third of people with HHS actually present with a coma (1).

Risk factors for DKA include new diagnosis of diabetes mellitus, insulin omission, infection, myocardial infarction (MI), abdominal crisis, trauma and, possibly, continuous subcutaneous insulin infusion (CSII) therapy, thyrotoxicosis, cocaine, atypical antipsychotics and, possibly, interferon. HHS is much less common than DKA (2,3). In addition to the precipitating factors noted above for DKA, HHS also has been reported following cardiac surgery and with the use of certain drugs, including diuretics, glucocorticoids, lithium and atypical antipsychotics. Infections are present in 40% to 60% of people with HHS (4). In up to 20% of cases of HHS, individuals had no prior history of diabetes (4).

The clinical presentation of DKA includes symptoms and signs of hyperglycemia, acidosis and the precipitating illness (Table 1). In HHS, there is often more profound ECFV contraction and decreased level of consciousness (proportional to the elevation in plasma osmolality). In addition, in HHS, there can be a variety of neurological presentations, including seizures and a stroke-like state that can resolve once osmolality returns to normal (3,5,6). In HHS, there also may be evidence of a precipitating condition similar to DKA.

In individuals with type 2 diabetes, the incidence of DKA is estimated to be in the range of 0.32 to 2.0 per 1,000 patient-years (7) while, in people with type 1 diabetes, the incidence is higher at 4.6 to 8.0 per 1000 patient-years (8). There is a group of individuals with diabetes that present with DKA but do not have the typical features of type 1 diabetes. There are various terms given to characterize this condition, such as flatbush diabetes, type 1.5 diabetes, atypical diabetes or type 1B diabetes, but it may be most useful to label this state as ketosis-prone diabetes (KPD). There are several classification systems used to describe KPD that take into account pathophysiology and prognosis. Individuals with KPD have very little beta cell function, may or may not have beta cell antibodies, and some may require temporary or lifelong insulin therapy (9).

Table 1
Clinical presentation of DKA
  Symptoms Signs
Hyperglycemia Polyuria, polydipsia, weakness ECFV contraction
Acidosis Air hunger, nausea, vomiting and abdominal pain
Altered sensorium
Precipitating condition
Precipitating condition See list of conditions in Table 2  


Sick-day management that includes capillary beta-hydroxybutyrate monitoring reduces emergency room visits and hospitalizations in young people (10).

SGLT2 Inhibitors and DKA

SGLT2 inhibitors may lower the threshold for developing DKA through a variety of different mechanisms (11–13). The presentation of the DKA is similar to those who develop DKA without SGLT2 inhibitor exposure, except that the blood glucose (BG) levels on presentation may not be as elevated as expected. In randomized controlled trials, the incidence of DKA associated with SGLT2 inhibitors is low (≤0.1% of treated people) (14,15). In most cases, there is usually a known precipitant as a contributing factor, such as insulin dose reduction or omission, bariatric surgery or other surgery, alcohol, exercise, or low carbohydrate or reduced food intake (16–20).


DKA or HHS should be suspected whenever people have significant hyperglycemia, especially if they are ill or highly symptomatic (see above). As outlined in Figure 1, to make the diagnosis and determine the severity of DKA or HHS, the following should be assessed: plasma levels of electrolytes (and anion gap), plasma glucose (PG), creatinine, osmolality and beta-hydroxybutyric acid (beta-OHB) (if available), blood gases, serum and urine ketones, fluid balance, level of consciousness, precipitating factors and complications (1). Arterial blood gases may be required for more ill individuals, when knowing the adequacy of respiratory compensation and the A-a gradient is necessary. Otherwise, venous blood gases are usually adequate—the pH is typically 0.015 to 0.03 lower than arterial pH (21-23). Point-of-care capillary blood beta-OHB measurement in emergency is sensitive and specific for DKA and, as a screening tool, may allow more rapid identification of hyperglycemic persons at risk for DKA (24–29). This test is less accurate with hemoconcentration and/or when the beta-OHB level is >3 mmol/L (30).

There are no definitive criteria for the diagnosis of DKA. Typically, the arterial pH is ≤7.3, serum bicarbonate is ≤15 mmol/L and the anion gap is >12 mmol/L with positive serum and/or urine ketones (1,31–33). PG is usually ≥14.0 mmol/L but can be lower, especially with the use of SGLT2 inhibitors (34). DKA is more challenging to diagnose in the presence of the following conditions: 1) mixed acid-base disorders (e.g. associated vomiting, which will raise the bicarbonate level); 2) if there has been a shift in the redox potential, favouring the presence of beta-OHB (rendering serum ketone testing negative); or 3) if the loss of keto anions with sodium or potassium in osmotic diuresis has occurred, leading to a return of the plasma anion gap toward normal. It is, therefore, important to measure ketones in both the serum and urine. If there is an elevated anion gap and serum ketones are negative, beta-OHB levels should be measured. Negative urine ketones should not be used to rule out DKA (35).

Measurement of serum lactate should be considered in hypoxic states. In HHS, a more prolonged duration of relative insulin insufficiency and inadequate fluid intake (or high glucose intake) results in higher PG levels (typically ≥34.0 mmol/L), plasma osmolality >320 mOsm/kg and greater ECFV contraction, but minimal acid-base disturbance (1,31).

Pregnant women in DKA typically present with lower PG levels than nonpregnant women (36), and there are case reports of euglycemic DKA in pregnancy (37,38).

Table 2
Priorities* to be addressed in the management of adults presenting with hyperglycemic emergencies
DKA, diabetic ketoacidosis; ECFV, extracellular fluid volume; HHS, hyperosmolar hyperglycemic state.
Severity of issue will dictate priority of action.
Metabolic Precipitating cause of DKA/HHS Other complications of DKA/HHS
  • ECFV contraction
  • Potassium deficit and abnormal concentration
  • Metabolic acidosis
  • Hyperosmolality (water deficit leading to increased corrected sodium concentration plus hyperglycemia)
  • New diagnosis of diabetes
  • Insulin omission
  • Infection
  • Myocardial infarction
  • Stroke
  • ECG changes may reflect hyperkalemia (78,79)
  • A small increase in troponin may occur without overt ischemia (80)
  • Thyrotoxicosis (81)
  • Trauma
  • Drugs
  • Hyper/hypokalemia
  • ECFV overexpansion
  • Cerebral edema
  • Hypoglycemia
  • Pulmonary emboli
  • Aspiration
  • Hypocalcemia (if phosphate used)
  • Stroke
  • Acute renal failure
  • Deep vein thrombosis


Objectives of management include restoration of normal ECFV and tissue perfusion; resolution of ketoacidosis; correction of electrolyte imbalances and hyperglycemia; and the diagnosis and treatment of coexistent illness. The issues that must be addressed in the individual presenting with DKA or HHS are outlined in Table 2. A summary of fluid therapy is outlined in Table 3, and a management algorithm and formulas for calculating key measurements are provided in Figure 1.

People with DKA and HHS are best managed in an intensive care unit or step-down setting (1,31,32) with specialist care (39,40). Protocols and insulin management software systems (41) may be beneficial (42,43), but there can be challenges with achieving adherence (44,45). Volume status (including fluid intake and output), vital signs, neurological status, plasma concentrations of electrolytes, anion gap, osmolality and glucose need to be monitored closely, initially as often as every 2 hours (1,31,32). Capillary blood glucose (CBG) measurements are unreliable in the setting of severe acidosis (46). Precipitating factors must be diagnosed and treated (1,31,32).

Extracellular fluid volume contraction

The sodium deficit is typically 7 to 10 mmol/kg in DKA (47) and 5 to 13 mmol/kg in HHS, which, along with water losses (100 mL/kg and 100 to 200 mL/kg, respectively), results in decreased ECFV, usually with decreased intracellular fluid volume (47). Restoring ECFV improves tissue perfusion and reduces plasma glucose levels both by dilution and by increasing urinary glucose losses. ECFV re-expansion, using a rapid rate of initial fluid administration, was associated with an increased risk of cerebral edema in 1 study (48) but not in another (49). In adults, one should initially administer intravenous normal saline 1 to 2 L/h to correct shock, otherwise 500 mL/h for 4 hours, then 250 mL/h of intravenous fluids (50,51).

Figure 1
Management of diabetic ketoacidosis in adults.

Beta-OHB, beta-hydroxybutyric acid; DKA, diabetic ketoacidosis; ECFV, extracelluar fluid volume; IV, intravenous.
*Plasma glucose may be lower than expected in some settings.
**Anion gap = plasma [Na+] − plasma [Cl] − plasma [HCO3].
†Corrected plasma [Na+] = measured [Na+] + 3/10 × ([plasma glucose (mmol/L)] − 5).
‡Effective plasma osmolality = [Na+] × 2 + [plasma glucose (mmol/L)], reported as mmol/kg.

Potassium deficit

The typical potassium deficit range is 2 to 5 mmol/kg in DKA and 4 to 6 mmol/kg in HHS (48). There have been no randomized trials that have studied strategies for potassium replacement. Typical recommendations suggest that potassium supplementation should be started for plasma potassium <5.0 to 5.5 mmol/L once diuresis has been established, usually with the second litre of saline. If the individual at presentation is normo- or hypokalemic, potassium should be given immediately, at concentrations in the intravenous fluid between 10 to 40 mmol/L, at a maximum rate of 40 mmol/h.

In the case of frank hypokalemia (serum potassium <3.3 mmol/L), insulin should be withheld until potassium replacement at 40 mmol/h has restored plasma potassium to ≥3.3 mmol/L (1,31). It is reasonable to treat the potassium deficit of HHS in the same way.

Table 3
Summary of fluid therapy for DKA and HHS in adults
DKA, diabetic ketoacidosis; HHS, hyperosmolar hyperglycemic state; IV, intravenous.
  1. AdministerIV0.9%sodiumchlorideinitially.Ifthepersonisinshock, give 1 to 2 L/hour initially to correct shock; otherwise, give 500 mL/hour for 4 h, then 250 mL/hour for 4 h, then as required.
  2. Addpotassiumimmediatelyifpersonisnormo-orhypokalemic. Otherwise, if initially hyperkalemic, only add potassium once serum potassium falls to <5 to 5.5 mmol/L and person is diuresing.
  3. Once plasma glucose reaches 14.0 mmol/L, add glucose to maintain plasma glucose at 12.0 to 14.0 mmol/L.
  4. Afterhypotensionhasbeencorrected,switch0.9%sodiumchlorideto 0.45% sodium chloride (with potassium chloride). However, if plasma osmolality is falling more rapidly than 3 mmol/kg/hour and/or the corrected plasma sodium is reduced, maintain intravenous fluids at higher osmolality (i.e. may need to maintain on normal saline).

Metabolic acidosis

Metabolic acidosis is a prominent component of DKA. People with HHS have minimal or no acidosis. Insulin is used to stop ketoacid production; intravenous fluid alone has no impact on parameters of ketoacidosis (52). Short-acting insulin (0.1 units/kg/h) is recommended (53–55). There is no conclusive evidence supporting the use of an initial insulin bolus in adults and it is not recommended in children. Although the use of an initial bolus of intravenous insulin is recommended in some reviews (1), there has been only 1 randomized controlled trial in adults examining the effectiveness of this step (56). In this study, there were 3 arms: a bolus arm (0.07 units/kg, then 0.07 units/kg/h), a low-dose infusion group (no bolus, 0.07 units/kg/h) and a double-dose infusion group (no bolus, 0.14 units/kg/h). Outcomes were identical in the 3 groups, except 5 of 12 participants needed extra insulin in the no-bolus/low-dose infusion group, and the double-dose group had the lowest potassium (nadir of 3.7 mmol/L on average). Unfortunately, this study did not examine the standard dose of insulin in DKA (0.1 units/kg/h). In children, using an initial bolus of intravenous insulin does not result in faster resolution of ketoacidosis (57,58) and increases the risk of cerebral edema (see Type 1 Diabetes in Children and Adolescents chapter, p. S234).

A systematic review based on low- to very-low-quality evidence, showed that subcutaneous hourly analogues provide neither advantages nor disadvantages compared to intravenous regular insulin when treating mild to moderate DKA (59). The dose of insulin should subsequently be adjusted based on ongoing acidosis (60), using the plasma anion gap or beta-OHB measurements.

Use of intravenous sodium bicarbonate to treat acidosis did not affect outcome in randomized controlled trials (61–63). Sodium bicarbonate therapy may be considered in adult individuals in shock or with arterial pH ≤7.0. For example, one can administer 1 ampoule (50 mmol) sodium bicarbonate added to 200 mL D5W (or sterile water, if available) over 1 hour, repeated every 1 to 2 hours, until pH is ≥7.0 (1,31). Potential risks associated with the use of sodium bicarbonate include hypokalemia (64) and delayed occurrence of metabolic alkalosis.


Hyperosmolality is due to hyperglycemia and a water deficit. However, serum sodium concentration may be reduced due to shift of water out of cells. The concentration of sodium needs to be corrected for the level of glycemia to determine if there is also a water deficit (Figure 1). In people with DKA, plasma osmolality is usually ≤320 mmol/kg. In HHS, plasma osmolality is typically >320 mmol/kg. Because of the risk of cerebral edema with rapid reductions in osmolality (65), it has been recommended that the plasma osmolality be lowered no faster than 3 mmol/kg/h (1,31). This can be achieved by monitoring plasma osmolality, by adding glucose to the infusions when PG reaches 14.0 mmol/L to maintain it at that level and by selecting the correct concentration of intravenous saline. Typically, after volume re-expansion, intravenous fluid may be switched to half-normal saline because urinary losses of electrolytes in the setting of osmotic diuresis are usually hypotonic. The potassium in the infusion will also add to the osmolality. If osmolality falls too rapidly despite the administration of glucose, consideration should be given to increasing the sodium concentration of the infusing solution (1,31). Water imbalances can also be monitored using the corrected plasma sodium. Central pontine myelinolysis has been reported in association with overly rapid correction of hyponatremia in HHS (66).

PG levels will fall due to multiple mechanisms, including ECFV re-expansion (67), glucose losses via osmotic diuresis (52), insulin-mediated reduced glucose production and increased cellular uptake of glucose. Once PG reaches 14.0 mmol/L, intravenous glucose should be started to prevent hypoglycemia, targeting a plasma glucose of 12.0 to 14.0 mmol/L. Similar doses of intravenous insulin can be used to treat HHS, although these individuals are not acidemic, and the fall in PG concentration is predominantly due to re-expansion of ECFV and osmotic diuresis (67). Insulin has been withheld successfully in HHS (68), but generally its use is recommended to reduce PG levels (1,31).

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 (72). However, because hypophosphatemia has been associated with rhabdomyolysis in other states, administration of potassium phosphate in cases of severe hypophosphatemia may be considered for the purpose of trying to prevent rhabdomyolysis.


In Ontario, in-hospital mortality in people hospitalized for acute hyperglycemia ranged from <1% at ages 20 to 49 years to 16% in those over 75 years (73). Reported mortality in DKA ranges from 0.65% to 3.3% (3,39,74–76). In HHS, recent studies found mortality rates to be 12% to 17%, but included individuals with mixed DKA and hyperosmolality (2,5,77). About 50% of deaths occur in the first 48 to 72 hours. Mortality is usually due to the precipitating cause, electrolyte imbalances (especially hypo- and hyperkalemia) and cerebral edema.


  • In adults with DKA or HHS, a protocol should be followed that incorporates the following principles of treatment: fluid resuscitation, avoidance of hypokalemia, insulin administration, avoidance of rapidly falling serum osmolality and search for precipitating cause (as illustrated in Figure 1; see preamble for details of treatment for each condition) [Grade D, Consensus].

  • Point-of-care capillary beta-hydroxybutyrate may be measured in the hospital or outpatient setting [Grade D, Level 4 (33)] in adults with type 1 diabetes with CBG >14.0 mmol/L to screen for DKA, and a beta-hydroxybutyrate >1.5 mmol/L warrants further testing for DKA [Grade B, Level 2 (24–29)]. Negative urine ketones should not be used to rule out DKA [Grade D, Level 4 (35)].

  • In adults with DKA, intravenous 0.9% sodium chloride should be administered initially at 500 mL/h for 4 hours, then 250 mL/h for 4 hours [Grade B, Level 2 (50)] with consideration of a higher initial rate (1–2 L/h) in the presence of shock [Grade D, Consensus]. For adults with HHS, intravenous fluid administration should be individualized [Grade D, Consensus].

  • In adults with DKA, an infusion of short-acting intravenous insulin of 0.10 units/kg/h should be used [Grade B, Level 2 (54,55)]. The insulin infusion rate should be maintained until the resolution of ketosis [Grade B, Level 2 (60)] as measured by the normalization of the plasma anion gap [Grade D, Consensus]. Once the PG concentration falls to 14.0 mmol/L, intravenous dextrose should be started to avoid hypoglycemia [Grade D, Consensus].

  • Individuals treated with SGLT2 inhibitors with symptoms of DKA should be assessed for this condition even if BG is not elevated [Grade D, Consensus].


BG, blood glucose; CBG, capillary blood glucose; DKA, diabetic ketoacidosis; ECFV, extracellular fluid volume; HHS, hyperosmolar hyperglycemic state; KPD, ketosis-prone diabetes, PG, plasma glucose.

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. S234

Relevant Appendix

  • Appendix 8: Sick-Day Medication List

Literature Review Flow Diagram for Chapter 15: Hyperglycemic Emergencies in Adults

*Excluded based on: population, intervention/exposure, comparator/control or study design.

From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6(6): e1000097. doi:10.1371/journal.pmed1000097 (82).

For more information, visit www.prisma-statement.org.

Author Disclosures

Dr. Gilbert reports personal fees from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, and Sanofi, outside the submitted work. Dr. Goguen does not have anything to disclose.


  1. A.E.KitabchiG.E.UmpierrezM.B.MurphyManagement of hyperglycemic crises in patients with diabetesDiabetes Care242001131153
  2. P.S.HamblinD.J.ToplissN.ChosichDeaths associated with diabetic ketoacidosis and hyperosmolar coma. 1973–1988Med J Aust1511989414244
  3. R.C.HolmanC.A.HerronP.SinnockEpidemiologic characteristics of mortality from diabetes with acidosis or coma, United States, 1970–78Am J Public Health73198311691173
  4. F.J.PasquelG.E.UmpierrezHyperosmolar hyperglycemic state: A historic review of the clinical presentation, diagnosis, and treatmentDiabetes Care37201431243131
  5. T.J.WachtelL.M.Tetu-MouradjianD.L.GoldmanHyperosmolarity and acidosis in diabetes mellitus: A three-year experience in Rhode IslandJ Gen Intern Med61991495502
  6. M.L.MaloneV.GennisJ.S.GoodwinCharacteristics of diabetic ketoacidosis in older versus younger adultsJ Am Geriatr Soc40199211001104
  7. WangZ.H.E.Kihl-SelstamJ.W.ErikssonKetoacidosis occurs in both type 1 and type 2 diabetes–a population-based study from Northern SwedenDiabet Med252008867870
  8. A.E.KitabchiG.E.UmpierrezM.B.MurphyHyperglycemic crises in adult patients with diabetes: A consensus statement from the American Diabetes AssociationDiabetes Care29200627392748
  9. A.BalasubramanyamG.GarzaL.RodriguezAccuracy and predictive value of classification schemes for ketosis-prone diabetesDiabetes Care29200625752579
  10. L.M.LaffelK.WentzellC.LoughlinSick day management using blood 3-hydroxybutyrate (3-OHB) compared with urine ketone monitoring reduces hospital visits in young people with T1DM: A randomized clinical trialDiabet Med232006278284
  11. W.OgawaK.SakaguchiEuglycemic diabetic ketoacidosis induced by SGLT2 inhibitors: Possible mechanism and contributing factorsJ Diabetes Investig72016135138
  12. J.RosenstockE.FerranniniEuglycemic diabetic ketoacidosis: A predictable, detectable, and preventable safety concern with SGLT2 inhibitorsDiabetes Care38201516381642
  13. A.K.SinghSodium-glucose co-transporter-2 inhibitors and euglycemic ketoacidosis: Wisdom of hindsightIndian J Endocrinol Metab192015722730
  14. N.EronduM.DesaiK.WaysDiabetic ketoacidosis and related events in the canagliflozin type 2 diabetes clinical programDiabetes Care38201516801686
  15. B.ZinmanC.WannerJ.M.LachinEmpagliflozin, cardiovascular outcomes, and mortality in type 2 diabetesN Engl J Med373201521172128
  16. T.HayamiY.KatoH.KamiyaCase of ketoacidosis by a sodium-glucose cotransporter 2 inhibitor in a diabetic patient with a low-carbohydrate dietJ Diabetes Investig62015587590
  17. A.L.PetersE.O.BuschurJ.B.BuseEuglycemic diabetic ketoacidosis: A potential complication of treatment with sodium-glucose cotransporter 2 inhibitionDiabetes Care38201516871693
  18. C.RedfordL.DohertyJ.SmithSGLT2 inhibitors and the risk of diabetic ketoacidosisPractical Diabetes322015263264
  19. R.St HilaireH.CostelloPrescriber beware: Report of adverse effect of sodium-glucose cotransporter 2 inhibitor use in a patient with contraindicationAm J Emerg Med332015604e3-.4
  20. R.M.GoldenbergL.D.BerardChengA.Y.Y.SGLT2 inhibitor-associated diabetic ketoacidosis: Clinical review and recommendations for prevention and diagnosisClin Ther38201626542664e1
  21. G.MalateshaN.K.SinghA.BharijaComparison of arterial and venous pH, bicarbonate, PCO2 and PO2 in initial emergency department assessmentEmerg Med J242007569571
  22. M.A.BrandenburgD.J.DireComparison of arterial and venous blood gas values in the initial emergency department evaluation of patients with diabetic ketoacidosisAnn Emerg Med311998459465
  23. MaO.J.M.D.RushM.M.GodfreyArterial blood gas results rarely influence emergency physician management of patients with suspected diabetic ketoacidosisAcad Emerg Med102003836841
  24. R.A.CharlesY.M.BeeP.H.EngPoint-of-care blood ketone testing: Screening for diabetic ketoacidosis at the emergency departmentSingapore Med J482007986989
  25. R.NaunheimT.J.JangG.BanetPoint-of-care test identifies diabetic ketoacidosis at triageAcad Emerg Med132006683685
  26. E.SefediniM.PrašekZ.MetelkoUse of capillary beta-hydroxybutyrate for the diagnosis of diabetic ketoacidosis at emergency room: Our one-year experienceDiabetol Croat3720087380
  27. L.MackayM.J.LyallS.DelaneyAre blood ketones a better predictor than urine ketones of acid base balance in diabetic ketoacidosis?Pract Diabetes Int272010396399
  28. F.BektasO.ErayR.SariPoint of care blood ketone testing of diabetic patients in the emergency departmentEndocr Res302004395402
  29. S.HarrisR.NgH.SyedNear patient blood ketone measurements and their utility in predicting diabetic ketoacidosisDiabet Med222005221224
  30. S.MisraN.S.OliverUtility of ketone measurement in the prevention, diagnosis and management of diabetic ketoacidosisDiabet Med3220151423
  31. J.L.ChiassonN.Aris-JilwanR.BelangerDiagnosis and treatment of diabetic ketoacidosis and the hyperglycemic hyperosmolar stateCMAJ1682003859866
  32. H.E.LebovitzDiabetic ketoacidosisLancet3451995767772
  33. CaoX.ZhangX.XianY.The diagnosis of diabetic acute complications using the glucose-ketone meter in outpatients at endocrinology departmentInt J Clin Exp Med7201457015705
  34. J.F.MunroI.W.CampbellA.C.McCuishEuglycaemic diabetic ketoacidosisBr Med J21973578580
  35. B.KuruM.SeverE.AksayComparing finger-stick beta-hydroxybutyrate with dipstick urine tests in the detection of ketone bodiesTurk J Emerg Med1420144752
  36. GuoR.X.YangL.Z.LiL.X.Diabetic ketoacidosis in pregnancy tends to occur at lower blood glucose levels: Case-control study and a case report of euglycemic diabetic ketoacidosis in pregnancyJ Obstet Gynaecol Res342008324330
  37. R.OliverP.JagadeesanR.J.HowardEuglycaemic diabetic ketoacidosis in pregnancy: An unusual presentationJ Obstet Gynaecol272007308
  38. A.ChicoI.SaigiA.Garcia-PattersonGlycemic control and perinatal outcomes of pregnancies complicated by type 1 diabetes: Influence of continuous subcutaneous insulin infusion and lispro insulinDiabetes Technol Ther122010937945
  39. M.E.MayC.YoungJ.KingResource utilization in treatment of diabetic ketoacidosis in adultsAm J Med Sci3061993287294
  40. C.S.LevetanM.D.PassaroK.A.JablonskiEffect of physician specialty on outcomes in diabetic ketoacidosisDiabetes Care22199917901795
  41. J.UllalR.McFarlandM.BachandUse of a computer-based insulin infusion algorithm to treat diabetic ketoacidosis in the emergency departmentDiabetes Technol Ther182016100103
  42. S.V.BullI.S.DouglasM.FosterMandatory protocol for treating adult patients with diabetic ketoacidosis decreases intensive care unit and hospital lengths of stay: Results of a nonrandomized trialCrit Care Med3520074146
  43. S.L.WallerS.DelaneyM.W.StrachanDoes an integrated care pathway enhance the management of diabetic ketoacidosis?Diabet Med242007359363
  44. B.DevaliaAdherance to protocol during the acute management of diabetic ketoacidosis: Would specialist involvement lead to better outcomes?Int J Clin Pract64201015801582
  45. M.SalahuddinM.N.AnwarStudy on effectiveness of guidelines and high dependency unit management on diabetic ketoacidosis patientsJ Postgrad Med Inst232009120123
  46. D.E.CorlYinT.S.M.E.MillsEvaluation of point-of-care blood glucose measurements in patients with diabetic ketoacidosis or hyperglycemic hyperosmolar syndrome admitted to a critical care unitJ Diabetes Sci Technol7201312651274
  47. R.A.KreisbergDiabetic ketoacidosis: New concepts and trends in pathogenesis and treatmentAnn Intern Med881978681695
  48. C.P.MahoneyB.W.VlcekM.DelAguilaRisk factors for developing brain herniation during diabetic ketoacidosisPediatr Neurol211999721727
  49. A.L.RosenbloomIntracerebral crises during treatment of diabetic ketoacidosisDiabetes Care1319902233
  50. H.J.AdrogueJ.BarreroG.EknoyanSalutary effects of modest fluid replacement in the treatment of adults with diabetic ketoacidosis. Use in patients without extreme volume deficitJAMA262198921082113
  51. I.A.FeinE.C.RachowC.L.SprungRelation of colloid osmotic pressure to arterial hypoxemia and cerebral edema during crystalloid volume loading of patients with diabetic ketoacidosisAnn Intern Med961982570575
  52. O.E.OwenJ.H.LichtD.G.SapirRenal function and effects of partial rehydration during diabetic ketoacidosisDiabetes301981510518
  53. A.E.KitabchiV.AyyagariS.M.GuerraThe efficacy of low-dose versus conventional therapy of insulin for treatment of diabetic ketoacidosisAnn Intern Med841976633638
  54. D.HeberM.E.MolitchM.A.SperlingLow-dose continuous insulin therapy for diabetic ketoacidosis. Prospective comparison with “conventional” insulin therapyArch Intern Med137197713771380
  55. E.K.ButkiewiczC.L.LeibsonP.C.O'BrienInsulin therapy for diabetic ketoacidosis. Bolus insulin injection versus continuous insulin infusionDiabetes Care18199511871190
  56. A.E.KitabchiM.B.MurphyJ.SpencerIs a priming dose of insulin necessary in a low-dose insulin protocol for the treatment of diabetic ketoacidosis?Diabetes Care31200820812085
  57. P.FortS.M.WatersF.LifshitzLow-dose insulin infusion in the treatment of diabetic ketoacidosis: Bolus versus no bolusJ Pediatr9619803640
  58. R.LindsayR.G.BolteThe use of an insulin bolus in low-dose insulin infusion for pediatric diabetic ketoacidosisPediatr Emerg Care519897779
  59. C.A.Andrade-CastellanosL.E.Colunga-LozanoN.Delgado-FigueroaSubcutaneous rapid-acting insulin analogues for diabetic ketoacidosisCochrane Database Syst Rev12016CD011281
  60. M.I.WiggamM.J.O'KaneR.HarperTreatment of diabetic ketoacidosis using normalization of blood 3-hydroxybutyrate concentration as the endpoint of emergency management. A randomized controlled studyDiabetes Care20199713471352
  61. L.R.MorrisM.B.MurphyA.E.KitabchiBicarbonate therapy in severe diabetic ketoacidosisAnn Intern Med1051986836840
  62. G.GambaJ.OsegueraM.CastrejónBicarbonate therapy in severe diabetic ketoacidosis. A double blind, randomized, placebo controlled trialRev Invest Clin431991234238
  63. P.J.HaleJ.CraseM.NattrassMetabolic effects of bicarbonate in the treatment of diabetic ketoacidosisBr Med J (Clin Res Ed)289198410351038
  64. N.G.SolerM.A.BennettK.DixonPotassium balance during treatment of diabetic ketoacidosis with special reference to the use of bicarbonateLancet21972665667
  65. A.P.CarlottiD.BohnJ.P.MallieTonicity balance, and not electrolyte-free water calculations, more accurately guides therapy for acute changes in natremiaIntensive Care Med272001921924
  66. G.O'MalleyC.MoranM.S.DramanCentral pontine myelinolysis complicating treatment of the hyperglycaemic hyperosmolar stateAnn Clin Biochem452008440443
  67. W.WaldhauslG.KleinbergerA.KornSevere hyperglycemia: Effects of rehydration on endocrine derangements and blood glucose concentrationDiabetes281979577584
  68. J.E.GerichM.M.MartinL.RecantClinical and metabolic characteristics of hyperosmolar nonketotic comaDiabetes201971228238
  69. U.KellerW.BergerPrevention of hypophosphatemia by phosphate infusion during treatment of diabetic ketoacidosis and hyperosmolar comaDiabetes2919808795
  70. H.K.WilsonS.P.KeuerA.S.LeaPhosphate therapy in diabetic ketoacidosisArch Intern Med1421982517520
  71. J.N.FisherA.E.KitabchiA randomized study of phosphate therapy in the treatment of diabetic ketoacidosisJ Clin Endocrinol Metab571983177180
  72. P.C.SinghalM.AbramoviciS.AyerDeterminants of rhabdomyolysis in the diabetic stateAm J Nephrol111991447450
  73. G.L.BoothFangJ.Acute complications of diabetesJ.E.HuxG.L.BoothP.M.SlaughterDiabetes in Ontario: An iCES practice atlas2003Institute for Clinical Evaluative Science (ICES)Toronto
  74. W.BaggA.SathuS.StreatDiabetic ketoacidosis in adults at Auckland hospital, 1988–1996Aust N Z J Med281998604608
  75. G.E.UmpierrezJ.P.KellyJ.E.NavarreteHyperglycemic crises in urban blacksArch Intern Med1571997669675
  76. V.C.MuseyJ.K.LeeR.CrawfordDiabetes in urban African-Americans. I. Cessation of insulin therapy is the major precipitating cause of diabetic ketoacidosisDiabetes Care181995483489
  77. T.J.WachtelR.A.SillimanP.LambertonPredisposing factors for the diabetic hyperosmolar stateArch Intern Med1471987499501
  78. M.A.BellazziniT.MeyerPseudo-myocardial infarction in diabetic ketoacidosis with hyperkalemiaJ Emerg Med392010e139e141
  79. D.PetrovM.PetrovWidening of the QRS complex due to severe hyperkalemia as an acute complication of diabetic ketoacidosisJ Emerg Med342008459461
  80. J.GeddesK.A.DeansA.CormackCardiac troponin I concentrations in people presenting with diabetic ketoacidosisAnn Clin Biochem442007391393
  81. I.TalapatraD.J.TymmsDiabetic ketoacidosis precipitated by subacute (De Quervain's) thyroiditisPract Diabetes Int2320067677
  82. D.MoherA.LiberatiJ.TetzlaffPreferred reporting items for systematic reviews and meta-analyses: The PRISMA statementPLoS Med62009e1000097
Reproduced with permission from Canadian Journal of Diabetes © 2018 Canadian Diabetes Association. To cite this article, please refer to For citation.

*The Canadian Diabetes Association is the registered owner of the name Diabetes Canada. All content on guidelines.diabetes.ca, CPG Apps and in our online store remains exactly the same. For questions, contact communication@diabetes.ca.