EM Pharm Pearls: Estimated rise in blood glucose concentration with dextrose administration

A common question is how much should we expect the blood glucose concentration to increase after dextrose 50% (D50) administration. Fortunately, there is an answer from 3 studies.

  1. Balentine JR, Gaeta TJ, Kessler D, Bagiella E, Lee T. Effect of 50 milliliters of 50% dextrose in water administration on the blood sugar of euglycemic volunteers. Acad Emerg Med. 1998;5(7):691-694. doi:10.1111/j.1553-2712.1998.tb02487.x PMID 9678393
    • Population: Healthy volunteers in the ED
    • Intervention: 25 gm (1 ampule of D50)
    • Result: Mean increase of 162 mg/dL at 5 min. Glucose concentrations returned to baseline by 30 minutes.
  1. Murthy MS, Duby JJ, Parker PL, Durbin-Johnson BP, Roach DM, Louie EL. Blood glucose response to rescue dextrose in hypoglycemic, critically ill patients receiving an insulin infusion. Ann Pharmacother. 2015;49(8):892-896. doi:10.1177/1060028015585574. PMID 25986006
    • Population: Critically ill patients experiencing hypoglycemia while on insulin infusions
    • Intervention: D50
    • Result: Median increase of 4 mg/dL per gm of D50 administered
  1. Adler PM. Serum glucose changes after administration of 50% dextrose solution: pre- and in-hospital calculationsAm J Emerg Med. 1986;4(6):504-506. doi:10.1016/S0735-6757(86)80004-3. PMID 3778594
    • Population: ED patients with altered mental status (23 with diabetes, 28 without diabetes)
    • Intervention: 25 gm (50 mL of D50)
    • Result: Mean increase of 166 mg/dL

Take Home Points

  • Glucose concentrations increase 4-6 mg/dL per gm of dextrose administered
    • 50 mL of D50 = 25 gm = expected 100-150 mg/dL glucose rise
  • D50 rescue glucose is short-lived (30 minutes)
  • If the blood glucose does not respond as anticipated, investigate further (e.g., IV decannulation)


Want to learn more about EM Pharmacology?

Read other articles in the EM Pharm Pearls Series and find previous pearls on the PharmERToxguy site.

Balanced Fluids in Diabetic Ketoacidosis


Many guidelines and treatment algorithms for diabetic ketoacidosis (DKA) recommend sodium chloride 0.9% as the replacement fluid of choice, though alternative fluids may be a better option [1-4]. Randomized trials, in adult and pediatric patients, demonstrate faster resolution of DKA when using balanced solutions (e.g.PlasmaLyte-A, lactated Ringer’s) compared to sodium chloride [5-7]. Dr. Josh Farkas provides further review of this topic in 3 excellent and detailed EMCrit posts [8-10].


A phase-2 study published in 2021, SCOPE-DKA, randomized 93 patients with severe DKA (median venous pH 7.0) to receive PlasmaLyte-148 (PlasmaLyte-A) or sodium chloride 0.9% [11]. During the first 48 hours of treatment, patients received a average of ~6.5 L of fluid. At 24-hours, more patients in the PlasmaLyte group had resolution of DKA (defined as base excess ≥ -3 mEq/L) as compared to the sodium chloride group (69% vs 36%, p=0.002). However, by 48-hours, both groups had similar rates of DKA resolution (96% vs 86%, p=0.111). The study authors concluded that PlasmaLyte-148 may lead to faster resolution of metabolic acidosis in patients with DKA without an increase in ketosis, in line with findings from previous studies, but these results need to be confirmed in a larger, Phase 3 trial.

To further explore the nuances, strengths, and weaknesses of this study, please read the REBEL EM review by Dr. Mark Ramzy [13].

Bottom Line

  • The available data suggests that balanced fluids are beneficial in mild, moderate, and severe DKA.
  • PlasmaLyte-148 (PlasemaLyte A) may lead to faster resolution of metabolic acidosis than sodium chloride 0.9%. Though these findings need confirmation in a large, Phase 3 trial.
  • Generally, the composition of the initial liter is less important than prompt administration. However, for subsequent liters, a balance crystalloid (e.g., PlasmaLyte-148, or lactated Ringer’s) should be used instead of sodium chloride 0.9%.

Want to learn more about EM Pharmacology?

Read other articles in the EM Pharm Pearls Series and find previous pearls on the PharmERToxguy site.


  1. Wolfsdorf J, Glaser N, Sperling MA, American Diabetes Association. Diabetic ketoacidosis in infants, children, and adolescents: A consensus statement from the American Diabetes Association. Diabetes Care. 2006;29(5):1150-1159. PMID: 16644656. doi: 10.2337/diacare.2951150.
  2. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7):1335-1343. PMID: 19564476. doi: 10.2337/dc09-9032.
  3. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee, Goguen J, Gilbert J. Hyperglycemic emergencies in adults. Can J Diabetes. 2013;37 Suppl 1:S72-76. PMID: 24070967. doi: 10.1016/j.jcjd.2013.01.023.
  4. Joint British Diabetes Societies Inpatient Care Group. The Management of Diabetic Ketoacidosis in Adults. 2021; online publication. Accessed January 3, 2022. https://abcd.care/sites/abcd.care/files/site_uploads/JBDS_02%20_DKA_Guideline_amended_v2_June_2021.pdf.
  5. 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. 2011;29(6):670-674. PMID: 20825879. doi: 10.1016/j.ajem.2010.02.004.
  6. Williams V, Jayashree M, Nallasamy K, Dayal D, Rawat A. 0.9% saline versus Plasma-Lyte as initial fluid in children with diabetic ketoacidosis (SPinK trial): a double-blind randomized controlled trial. Crit Care. 2020;24(1):1. PMID: 31898531. doi: 10.1186/s13054-019-2683-3.
  7. Self WH, Evans CS, Jenkins CA, 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. 2020;3(11):e2024596. PMID: 33196806. doi: 10.1001/jamanetworkopen.2020.24596.
  8. Farkas J. Four DKA Pearls. 2014. Accessed January 3, 2022. https://emcrit.org/pulmcrit/four-dka-pearls.
  9. Farkas J. Dominating the acidosis in DKA. 2016. Accessed January 3, 2022. https://emcrit.org/pulmcrit/bicarbonate-dka.
  10. Farkas J. IBCC – Diabetic Ketoacidosis (DKA). 2021. Accessed January 3, 2022. https://emcrit.org/ibcc/dka.
  11. Ramanan M, Attokaran A, Murray L, et al. Sodium chloride or Plasmalyte-148 evaluation in severe diabetic ketoacidosis (Scope-dka): a cluster, crossover, randomized, controlled trial. Intensive Care Med. 2021;47(11):1248-1257. PMID: 34609547. doi: 10.1007/s00134-021-06480-5.
  12. Ramzy M. SCOPE-DKA: Normal Saline vs Plasmalyte in Severe DKA. 2021. Accessed January 3, 2022. https://rebelem.com/scope-dka-normal-saline-vs-plasmalyte-in-severe-dka.

SAEM Clinical Image Series: Facial Edema

facial edema

A 44-year-old female presents to the emergency department after noticing swelling of her tongue and face, specifically the cheeks and periorbital area. She states the swelling began two weeks ago and has progressively worsened. She also complains of redness.

Vitals: T 38.6°C; BP 135/78; HR 90; RR 18

General: Lying in bed, somewhat anxious appearing


  • Significant edema of bilateral cheeks and periorbital areas
  • Thinning of hair along scalp and lateral aspect of eyebrows
  • Mild macroglossia


  • Yellow tinge to patient’s skin
  • Horizontal scar noted on the anterior aspect of the neck

TSH: 31.27 mU/L

Free T4: 0.20 pmol/L

Myxedema facies

This patient has a history of thyroidectomy, as indicated by her neck scar, and a history of noncompliance with levothyroxine.

Myxedema is a term used to describe the appearance of nonpitting edema in patients with severe hypothyroidism. While the exact mechanism is not completely understood, this edema is thought to be secondary to increased deposition of dermal hyaluronic acid, a glycosaminoglycan that can grow up to 1000x its normal size when hydrated. Carotenemia is another possible manifestation of hypothyroidism and is secondary to impaired conversion of carotenoids to retinol in the setting of low levels of thyroid hormone. Additionally, patients may exhibit patchy alopecia, fatigue, cold intolerance, goiter, coarsening of the skin, and macroglossia.

Take-Home Points

  • The presentation of hypothyroidism is widely variable and may be subtle or atypical. Classically, hypothyroidism presents with pretibial myxedema, hyporeflexia, and cold intolerance. In some cases, facial edema may be the predominant feature, as seen in this patient.
  • Brittle, thinning hair on the scalp and eyebrows is a common feature. Thinning of the hair along the lateral eyebrows is called madarosis, also known as “Queen Anne’s Sign.”
  • In a patient with Grave’s disease, maintain a high index of suspicion for hypothyroidism, either as part of the natural history of the disease or as a sequela of treatment.
  1. Safer JD. Thyroid hormone action on skin. Dermatoendocrinol. 2011 Jul;3(3):211-5. doi: 10.4161/derm.3.3.17027. Epub 2011 Jul 1. PMID: 22110782; PMCID: PMC3219173.
  2. Wiersinga WM. Adult Hypothyroidism. 2014 Mar 28. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Grossman A, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–. PMID: 25905416.



ALiEM AIR Series: Endocrine Module

Welcome to the Endocrine Module! After carefully reviewing all relevant posts from the top 50 sites of the Social Media Index, the ALiEM AIR Team is proud to present the highest quality online content related to Endocrine emergencies. blog posts within the past 12 months (as of May 2018) met our standard of online excellence and were curated and approved for residency training by the AIR Series Board. We identified 2 AIR and Honorable Mentions. We recommend programs give 3 hours (about 20 minutes per article) of III credit for this module.

PEM Practice Changing Paper: Clinical Trial of Fluid Infusion Rates for Pediatric DKA

Most protocols for managing pediatric patients with diabetic ketoacidosis (DKA) are based on a theoretical association between fluid resuscitation and subsequent neurological decline. Although the evidence for an association between IV fluids and cerebral edema comes from retrospective reviews, for over 20 years, it is an accepted teaching principle of pediatric DKA.

Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis, published just days ago in the New England Journal of Medicine, challenges this teaching with the first randomized controlled trial designed to investigate the relationship between IV fluids and cerebral edema. We review this publication and present a behind-the-scenes podcast interview with lead authors Dr. Nathan Kuppermann and Dr. Nicole Glaser from the Pediatric Emergency Care Applied Research Network (PECARN). (more…)

A Can’t Miss ED Diagnosis: Euglycemic DKA

Euglycemic DKA blood drawA middle-aged man with a history of diabetes and hypertension presents with nausea, vomiting, and shortness of breath. His laboratory testing is remarkable for a leukocytosis, ketonemia, and an anion gap acidosis (pH of 7.13). The EM resident caring for this patient is surprised to find that the blood glucose is 121 mg/dL.

Which home medication is likely responsible for this presentation?

  1. Metformin
  2. Glipizide
  3. Liraglutide
  4. Canagliflozin

Canagliflozin: An SGLT2 Inhibitor

The patient’s presentation is consistent with diabetic ketoacidosis (DKA) in the absence of hyperglycemia. This entity is known at euglycemic DKA and it is increasingly recognized for an association with a newer oral diabetic medication class, SGLT2 inhibitors. Examples include:

  • Canagliflozin
  • Empagliflozin
  • Dapagliflozin

The FDA has approved these three SGLT2 inhibitors for Type 2 diabetics, and at times, they are prescribed off-label for Type 1. The mechanism involves decreasing glucose reabsorption in the nephron’s proximal tubule (via inhibition of the sodium-glucose linked cotransporter-2 protein). This results in increased urinary excretion of glucose that is independent of the body’s insulin secretion.1

Other potential benefits of this class of medications include:1–3

  • Weight loss
  • Blood pressure reduction
  • Few reported hypoglycemic events

In 2015 the FDA issued a warning, however, that SGLT2 inhibitors may cause ketoacidosis, urinary tract infections, and urosepsis.4 Since then, multiple case reports have been published showing an association between SGLT2 inhibitors and the development of euglycemic DKA.

Euglycemic DKA

Euglycemic DKA is an uncommon and likely under-diagnosed phenomenon, best defined as DKA with a lower than expected blood glucose (less than 250 mg/dL according to the American Diabetes Association).4–6

Potential precipitants, in addition to SGLT2 inhibitors, include:7

  • Carbohydrate restriction
  • Fasting
  • Dehydration
  • Alcohol
  • Partial treatment of hyperglycemic DKA

EPs may delay diagnosis, given the modest glucose levels at the time of presentation. This, however, is false reassurance because DKA is not defined by an absolute blood glucose. Interestingly, patients with euglycemic DKA may have a normal mental status despite marked ketoacidosis, and vomiting seems to be a common complaint.5

Euglycemic DKA treatment is the same as traditional DKA, and includes hydration, insulin, and supportive care. Patients with euglycemic DKA may also need a dextrose infusion given the lower glucose levels.

SGLT2 Inhibitors and Euglycemic DKA: Mechanism

The mechanisms by which SGLT2 inhibitors cause or predispose to euglycemic DKA are unclear and likely complex. SGLT2 inhibitors may lead to a decrease in either endogenous or exogenous insulin, and an increase in glucagon production.8 This insulin deficiency or resistance may be mild in Type 2 diabetics, however, preventing the profound spike in blood glucose seen in traditional DKA.7

SGLT2 Inhibitors and Euglycemic DKA: Evidence

The evidence suggesting a link between SGLT2 inhibitors and euglycemic DKA remains limited to case reports. Both the FDA and the European Medicine Agency have reported cases of DKA with unusually low glucose levels.4,9 Peters et al. reported 13 episodes euglycemic DKA in patients taking SGLT2 inhibitors, though most were Type 1 diabetics.10 In Japan, 28 cases of DKA or ketoacidosis in patients taking SGLT2 inhibitors have been reported as of 2015. Of these, the initial blood glucose is known in only 14 cases, but in 9 cases, it was <300 mg/dL.8

Take-Home Points

  1. DKA is not defined by an absolute blood glucose.
  2. Obtaining a urine sample for ketones and a blood gas early in the ED course is extremely important in all diabetics, especially those who are Type 1 and those on SGLT2 inhibitors.
  3. The treatment of euglycemic DKA is essentially the same as traditional DKA: hydration, replace electrolytes, insulin.



  1. Cefalu W, Leiter L, Yoon K, et al. Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet. 2013;382(9896):941-950. [PubMed]
  2. Tikkanen I, Narko K, Zeller C, et al. Empagliflozin reduces blood pressure in patients with type 2 diabetes and hypertension. Diabetes Care. 2015;38(3):420-428. [PubMed]
  4. FDA Drug Safety Communication: FDA revises labels of SGLT2 inhibitors for diabetes to include warnings about too much acid in the blood and serious urinary tract infections. U.S. Food and Drug Administration: Drug and Safety Availability. https://www.fda.gov/Drugs/DrugSafety/ucm475463.htm. Published January 19, 2018. Accessed March 18, 2018.
  5. Munro J, Campbell I, McCuish A, Duncan L. Euglycaemic diabetic ketoacidosis. Br Med J. 1973;2(5866):578-580. [PubMed]
  6. Kitabchi A, Umpierrez G, Miles J, Fisher J. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7):1335-1343. [PubMed]
  7. Rosenstock J, Ferrannini E. Euglycemic Diabetic Ketoacidosis: A Predictable, Detectable, and Preventable Safety Concern With SGLT2 Inhibitors. Diabetes Care. 2015;38(9):1638-1642. [PubMed]
  8. Ogawa W, Sakaguchi K. Euglycemic diabetic ketoacidosis induced by SGLT2 inhibitors: possible mechanism and contributing factors. J Diabetes Investig. 2016;7(2):135-138. [PubMed]
  9. European Medicines Agency. SGLT2 Inhibitors-Scientific Conclusions. European Medicines Agency; 2016:2-4. http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/SGLT2_inhibitors__20/European_Commission_final_decision/WC500206487.pdf. Accessed February 1, 2018.
  10. Peters A, Buschur E, Buse J, Cohan P, Diner J, Hirsch I. Euglycemic Diabetic Ketoacidosis: A Potential Complication of Treatment With Sodium-Glucose Cotransporter 2 Inhibition. Diabetes Care. 2015;38(9):1687-1693. [PubMed]
By |2021-03-01T09:28:53-08:00Mar 19, 2018|Endocrine-Metabolic, Tox & Medications|

PEM Pearls: Treatment of Pediatric Diabetic Ketoacidosis and the Two-Bag Method

diabetic ketoacidosisInsulin does MANY things in the body, but the role we care about in the Emergency Department is glucose regulation. Insulin allows cells to take up glucose from the blood stream, inhibits liver glucose production, increases glycogen storage, and increases lipid production. When insulin is not present, such as in patients with Type 1 diabetes mellitus (DM), all of the opposite effects occur.


By |2018-04-02T02:54:56-07:00Jul 3, 2017|Endocrine-Metabolic, Pediatrics, PEM Pearls|
Go to Top