Hyperglycemia in the ED
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In 2016, a total of 16 million ED visits were reported with diabetes listed as a diagnosis, with 224,000 of these being for hyperglycemic crisis (1). In this post, we will explore the evaluation and treatment of various hyperglycemic etiologies in the ED through a series of clinical scenarios.
Case 1 / 2 – Absolute vs. Relative Insulin Deficiency
Case 1
A 43 year-old woman presents to the ED with nausea, and vomiting. According to EMS, she has a past medical history of HTN, HLD, and T1DM. A finger stick glucose in triage reveals an elevated glucose of 389. Vitals are BP: 73/42, HR 132, O2 97% on RA, and a Temp of 97.3. Physical exam reveals an ill, but non-toxic appearing female. Abdominal exam is soft with diffuse tenderness with palpation, but no rebound tenderness or guarding.
Case 2
A 71 year-old male presents to the ED via EMS from a long term care facility with altered mental status. According to EMS the patient has a history of COPD, HTN, HLD, and T2DM. Vitals are BP 87/58, HR 147, O2 91% on 4L NC, and core temp of 102.7. Physical exam reveals an individual that responds to tactile stimulation only, is unable to answer orientation questions, has extremely dry mucous membranes, and is tachycardic with regular rhythm.
One of most important parts of evaluating any patient presenting to the ED with suspected hyperglycemic emergency is looking for a precipitating cause. Death directly from DKA and HHS is relatively uncommon; instead, patients are much more likely to die from a precipitating event. In DKA, the mortality rate is >1% which is significantly lower than the mortality rate in HHS which is reported to be 10-20%.
In patients presenting in DKA or HHS, the 5 main precipitating causes can be identified as
Two of the most common hyperglycemic emergencies associated with diabetes mellitus are diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS). Although both result in severe hyperglycemia, the underlying pathophysiology and clinical presentation can be vastly different.
DKA is a state of near absolute insulin deficiency. It typically occurs in Type 1 diabetics, but also occurs in type 2 diabetes under conditions of extreme stress such as serious infection, trauma, cardiovascular or other emergencies. DKA is more common in those <65 years old whereas HHS most commonly develops in individuals older than 65 years of age.
Additional Laboratory Studies
Ketones*
Effective serum osmolality
Situation Dependent Studies
EKG
Blood & Urine cultures
Pregnancy test
Lactic acid
Troponin
Urine vs. Serum Ketones
The major ketone present in the body in DKA is beta-hydroxybutyrate, but the traditional nitroprusside reaction test used in many laboratories does not detect it. Acetone and acetoacetate are typically detected with high sensitivity, but these are present in much lower levels than beta-hydroxybutyrate. In DKA, the ratio of beta-hydroxybutyrate to acetoacetate changes in response to the increased ketones from a ratio of 1:1 to as much as 5:1. Therefore, urine ketones can underestimate the severity of ketoacidosis. If available, serum ketones detecting beta-hydroxybutyrate should be used to detect ketones in patients with possible DKA.
Differentiating between DKA and HHS is important for many reasons. However, the foundation of treatment for both hyperglycemic emergencies is similar and include:
Fluid replacement
Electrolyte replacement
Insulin therapy
Fluid Replacement
Initial fluid therapy is aimed at expansion of intravascular, interstitial, and intracellular volume, all of which are decreased in DKA and HHS. In the absence of cardiac dysfunction, the ADA recommends infusion of isotonic saline at a rate of 15-20ml/kg/hr during the first hour. Subsequent choice of fluid replacement depends on patient hemodynamics, volume status, and electrolytes. The caveat to the use of isotonic saline is that since these ADA recommendations, several studies have found benefit in using a balanced crystalloid like LR or Plasmalyte instead of NS to avoid hyperchloremic metabolic acidosis. (2)
Electrolyte Replacement
Hyperglycemic emergencies cause total-body potassium depletion. However, hyperkalemia on laboratory studies is not uncommon. To prevent hypokalemia, potassium replacement should be initiated after serum levels fall below the upper level of normal. Rarely, DKA patients may present with hypokalemia. In these cases, potassium replacement should be initiated immediately, and the infusion of insulin should be delayed until serum potassium is >3.3 mEq/L
To bolus or not?
How much insulin is to be given and by which route has been the subject of much debate.
Currently ADA guidelines recommend:
Goyal et al prospectively compared the utility of the initial insulin bolus in 157 patients. In this study, both groups were similar at baseline and received the same amount of IV fluids, as well as insulin infusions. There was no significant difference in the incidence of hypoglycemia, rate of serum glucose change, anion gap change, or length of ED or hospital stay. (3)
Most of the current studies have focused specifically on bolus vs. no bolus in the DKA patient population. How does this translate to the treatment of HHS? Review of the literature revealed there isn’t much out there specifically addressing the use or omittance of bolus insulin prior to infusion in HHS. However, understanding the pathophysiology underlying both DKA and HHS leads to plausible conclusions. Unlike DKA, in HHS there is only a relative deficiency of insulin and no ketone production. Endogenous insulin production is adequate to prevent a total catabolic state, however, there is insufficient insulin to permit tissue utilization of glucose and thus hyperglycemia occurs. The foundation of the treatment of HHS centers more around the replacement of fluids given the patients often large fluid deficit (9-12L). In HHS, insulin is administered after initiation of fluid replacement with the goal to slowly lower glucose, not clear ketones. Given this major difference between the two etiologies, and the fact that insulin bolus in DKA has been shown to have no clear benefit, the omittance of the insulin bolus in HHS seems reasonable.
Case 3 – Hyperglycemia without the emergency
58 year-old woman with past medical history (PMH) of hypertension, obesity, and hyperlipidemia presents to the ED with high blood sugar on a routine blood draw today. He reports increased thirst and urinary frequency over the last several weeks, but otherwise feels well. Vitals are within normal limits. Exam shows a well-appearing, overweight female with dry mucous membranes. Blood glucose is 312 mg/dL. Laboratory studies reveal no ketones, no anion gap, and no acidosis.
Can we give a new diagnosis of diabetes from the Emergency Department?
According to ADA guidelines (8), a diagnosis of diabetes can be made from the ED using the following criteria:
Random plasma glucose >200 mg/dL AND classic symptoms of hyperglycemia or hyperglycemic crisis
OR
A1C >6.5%
Fasting plasma glucose > 126 mg/dL
A 2-hour plasma glucose > 200 during an oral glucose tolerance test
Do I need to lower the glucose prior to discharge?
Driver et al. performed a single center, retrospective cohort chart review to determine if there was an association between discharge glucose and 7-day adverse outcomes. Adverse outcomes was defined as:
Diabetic Ketoacidosis (DKA)
Hyperosmolar Hyperglycemic State
Repeat ED visit for Hyperglycemia
Hospitalization for any reason
566 ED encounters with hyperglycemia were included in the study and showed no significant adverse outcomes at 7 days. Therefore, attaining a specific glucose goal before discharge in patients with hyperglycemia may be less important than originally thought. Management should focus on improving long-term glucose management and arranging good follow up. (9)
References
National Diabetes Statistics Report 2020. Estimates of diabetes and its burden in the United States. Published online 2020:32.
Oliver WD, Willis GC, Hines MC, Hayes BD. Comparison of Plasma-Lyte A and Sodium Chloride 0.9% for Fluid Resuscitation of Patients With Diabetic Ketoacidosis. Hosp Pharm. 2018 Oct;53(5):326-330. doi: 10.1177/0018578718757517. Epub 2018 Feb 16. PMID: 30210151; PMCID: PMC6130112.
Goyal, N., Miller, J. B., Sankey, S. S., & Mossallam, U. (2010). Utility of initial bolus insulin in the treatment of diabetic ketoacidosis. The Journal of emergency medicine, 38(4), 422–427. https://doi.org/10.1016/j.jemermed.2007.11.033
Clinical presentation, diagnosis, and initial evaluation of diabetes mellitus in adults – UpToDate. Accessed October 30th, 2021. https://www.uptodate.com/contents/initial-management-of-hyperglycemia-in-adults-with-type-2-diabetes-mellitus
Butler AE, Misselbrook D. Distinguishing between type 1 and type 2 diabetes. BMJ. 2020;370:m2998. doi:10.1136/bmj.m2998
Ginde AA, Delaney KE, Pallin DJ, Camargo CA. Multicenter Survey of Emergency Physician Management and Referral for Hyperglycemia. J Emerg Med. 2010;38(2):264-270. doi:10.1016/j.jemermed.2007.11.088
Charfen MA, Ipp E, Kaji AH, Saleh T, Qazi MF, Lewis RJ. Detection of Undiagnosed Diabetes and Prediabetic States in High-risk Emergency Department Patients. Acad Emerg Med. 2009;16(5):394-402. doi:https://doi.org/10.1111/j.1553-2712.2009.00374.x
American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2021. 2021;44:19.
Driver BE, Olives TD, Bischof JE, Salmen MR, Miner JR. Discharge Glucose Is Not Associated With Short-Term Adverse Outcomes in Emergency Department Patients With Moderate to Severe Hyperglycemia. Ann Emerg Med. 2016;68(6):697-705.e3. doi:10.1016/j.annemergmed.2016.04.057
Authorship
Written by Jazmyn Shaw, MD PGY-1 University of Cincinnati Department of Emergency Medicine
Peer Review, Editing, and Posting - Jeffery Hill, MD MEd, Associate Professor, University of Cincinnati Dept of Emergency Medicine
