For patients presenting with suspected diabetic ketoacidosis (DKA) and the hyperosmolar hyperglycemic state (HHS) understanding of the etiology and pathophysiology will ensure optimal emergency management. Morbidity and mortality is most often due to the underlying precipitating cause, which may include infection, infarction/ischemia, noncompliance with insulin therapy, pregnancy, and dietary indiscretion. Current guidelines are based primarily on expert opinion and consensus statements, but more recent evidence suggests that recommendations related to arterial blood gas, insulin bolus, and IV fluid replacement should be re-evaluated. This issue presents an approach to DKA and HHS management based on current evidence, with a simplified pathway for emergency department management.
Midway through your shift, a 23-year-old woman arrives by EMS. She is ill-appearing, tachypneic, and has a distinct odor you recognize as ketones. Her bedside glucose is 680 mg/dL. You suspect DKA, but wonder what led to it. You know that starting insulin and fluids is indicated, but you wonder whether insulin should be administered as an IV bolus, whether insulin should be given before or after IV fluids, what fluids are most appropriate, or whether you should just proceed with subcutaneous insulin. As if these questions were not enough, your first-year resident tells you the patient has a pH of 7.1 and asks if she needs sodium bicarbonate. He also asks if she should be intubated, since she is breathing so hard…
A 76-year-old man arrives with his wife via EMS. He is slow to respond to you, and his wife says that over the past 10 days he has become increasingly weak, stopped walking, and this morning would not talk to her. His vital signs are: blood pressure, 90/60 mm Hg; pulse, 110 beats/min; and respiratory rate, 16 breaths/min. He is afebrile and has an oxygen saturation of 96% on room air. A fingerstick glucose reads high, and a venous pH is 7.38. You wonder whether his initial therapy should be similar to that for DKA, even with his normal pH, and whether 0.45% saline is the ideal fluid in his hyperosmolar state…
A 30-year-old man presents in DKA. He is a known type 1 diabetic and has an insulin pump that he says has been alarming. He is awake, alert, and his triage vital signs are: blood pressure, 110/60 mm Hg; pulse, 121 beats/min; respiratory rate, 26 breaths/min, temperature, 35.6°C (96°F); and oxygen saturation, 100% on room air. His fingerstick glucose reads high, and his venous pH is 7.12. You turn off his insulin pump and begin him on “standard therapy” of an IV fluid bolus of 20 mL/kg of normal saline followed by 500 mL/hr, 6 units of regular insulin IV, and put him on an insulin drip of 6 units/hr. The patient’s vital signs begin to stabilize, with his blood pressure rising and pulse and respirations slowing towards normal. Three hours after ED entry, the patient has a cardiac arrest and is defibrillated out of torsades de pointes. You wonder what went wrong …
As the incidence of diabetes has risen over the past several decades, so too have the number of patients who present to the emergency department (ED) with diabetes-related emergencies, including diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS).1 DKA alone is responsible for more than 140,000 hospital admissions per year in the United States, with an average length of stay of 3.4 days. This number has increased by 30% over the past decade.2,3 In 2014, charges for DKA hospitalization amounted to $5.1 billion.4 The emergency clinician must be prepared to identify and promptly treat these conditions because, without intervention, morbidity and mortality are high. Being knowledgeable about common precipitants and rapidly identifying their presence is essential, as morbidity is primarily related to the triggering event. The metabolic derangements that occur in these conditions require careful treatment, but the treatment algorithms can seem overly complex. Having a simplified, systematic approach to patients with these conditions will improve efficiency in managing these emergencies.
Unfortunately, consensus statements and guidelines often lag behind recent data. Indeed, the most recent American Diabetes Association (ADA) consensus statement is over 10 years old and thus does not incorporate newer literature that supports changes in practice. This issue of Emergency Medicine Practice focuses on the management of the common diabetic hyperglycemic emergencies, DKA and HHS, and provides treatment strategies that are based on the best available evidence.
A literature search of PubMed was performed without any date filters using the search terms diabetic ketoacidosis, DKA, hyperosmolar hyperglycemic state, and HHS. The initial search produced over 2 million results. The majority of the results were review articles, case studies, and expert opinion. Results were narrowed by filtering for clinical trials published in the past 10 years and review articles published in the past 5 years. Consensus statements released by the ADA in 2009 and the International Society for Pediatric and Adolescent Diabetes (ISPAD) in 2018 were also reviewed.1,5 The ADA and ISPAD guidelines are primarily expert opinion and were developed from studies through their publication years. References used by consensus statements were also evaluated. Final selections were made based on clinical relevance. During the literature search, particular attention was given to prospective studies; however, there are only a few randomized trials evaluating the treatment of DKA and HHS in the ED, and those that do exist tend to be quite small (approximately 50 patients or fewer).6-8
DKA and HHS are 2 distinct entities that exist on a spectrum of hyperglycemic emergencies. DKA typically occurs in younger patients, primarily those with type 1 diabetes (though type 2 diabetics can also develop DKA, particularly when concomitant illness is present). HHS is much more likely to occur in elderly patients with type 2 diabetes who have multiple underlying comorbidities, though it is being diagnosed increasingly in younger adults and even in children. In more than one-third of patients, these conditions overlap.1
Although the exact pathophysiologic mechanisms of DKA and HHS are complex, in general, the pathogenesis begins with insufficient insulin and high levels of counterregulatory hormones (glucagon, cortisol, growth hormone, and catecholamines). This results in hyperglycemia, which promotes an osmotic diuresis, leading to dehydration and electrolyte loss. In both conditions, insulin levels are insufficient for peripheral tissue glucose utilization, resulting in hyperglycemia.
In DKA, there is an absolute insulin deficiency, in which glucose cannot be moved into the cell. To meet the body’s energy needs, fats are metabolized into free fatty acids that are then converted in the liver to ketone bodies. The 2 main ketones, beta-hydroxybutyrate and acetoacetate, are both strong acids, and their presence creates a significant metabolic acidosis in DKA.
Whereas there is an absolute insulin deficiency in DKA, in HHS, there is only a relative insulin deficiency. Endogenous insulin production is adequate to prevent a total catabolic state. Therefore, lipolysis, ketone body production, and significant acidosis do not occur; however, there is insufficient insulin to permit tissue utilization of glucose, and thus hyperglycemia still occurs.1
In both states, the resultant hyperglycemia creates an osmotic diuresis in which tremendous amounts of water are lost through diuresis. It is estimated that there is a 3-L to 6-L fluid deficit in most adult cases of DKA and a 9-L to 12-L fluid deficit in HHS. In children, water loss is estimated to average 70 mL/kg in DKA and 12% to 15% of body weight in HHS.5 Fluid losses tend to be greater in HHS for several reasons, including the prolonged course of onset, delay in recognition, and the fact that many of these patients are elderly, bedridden patients with impaired thirst response. At least 20% of patients presenting with HHS have no documented history of diabetes.1 In addition to fluid loss, osmotic diuresis also causes urinary wasting of electrolytes, resulting in large total body deficits of potassium, magnesium, and phosphate.
Counterregulatory hormones also play a key role in the development of the metabolic derangements seen in these conditions. In both states, there is an increase in cortisol, catecholamines, glucagon, and growth hormone. Together, they promote gluconeogenesis, glycogenolysis, and proteolysis, compounding the development of hyperglycemia.
Both DKA and HHS are usually triggered by a precipitating cause. The major causes of DKA and HHS can be remembered as the “Five Is.” (See Table 1.)
1. “He was very hyperglycemic, so I started insulin right away.”
Starting insulin before the potassium level is known can result in dangerous arrhythmias, such as torsades de pointes, as insulin drives potassium into cells, lowering potassium further. A smaller percentage of patients will present with hypokalemia on arrival. Additionally, initiating volume resuscitation before giving insulin has several benefits, including decreasing serum glucose and restoring renal perfusion.
3. “He was complaining of right-sided weakness, but I assumed it was from being so hyperglycemic.”
While hyperosmolarity can cause neurological deficits, including focal deficits, patients with focal deficits from hyperosmolarity should also have changes in mental status. Assume stroke until proven otherwise.
8. “He was breathing fast, so I intubated him to reduce his work of breathing and metabolic demands.”
DKA patients have a respiratory alkalosis to compensate for their metabolic acidosis. Intubating these patients can be dangerous. During periods of apnea, their pCO2 can rise rapidly. Additionally, after intubation it can be difficult to match pre-intubation minute ventilation. Avoid intubation unless it becomes absolutely necessary; for example, for airway protection or in cases where extreme fatigue is interfering with the patient’s minute ventilation and ability to compensate for metabolic acidosis.
Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.
To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study is included in bold type following the references, where available. In addition, the most informative references cited in this paper, as determined by the author, are highlighted.
Diabetic Hyperglycemic Emergencies: A Systematic Approach, by H. Evan Dingle, MD and Corey Slovis, MD, FACP, FACEP, FAAEM, FAEMS
American Diabetes Association (ADA) and International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines are reviewed in addition to the references used by each consensus statement. Also, a primary literature review was conducted with particular attention given to prospective studies.Show More v
Topics reviewed include:
Dr. Ashoo is a practicing emergency physician, board-certified in emergency medicine and clinical informatics. Join him as he takes you through the February 2020 issue of Emergency Medicine Practice: Diabetic Hyperglycemic Emergencies: A Systematic Approach (Pharmacology CME)
H. Evan Dingle, MD; Corey Slovis, MD, FACP, FACEP, FAAEM, FAEMS
Melissa Parsons, MD, FACEP; Camiron Pfennig-Bass, MD, MHPE
February 1, 2020
March 1, 2023
4 AMA PRA Category 1 Credits™, 4 ACEP Category I Credits, 4 AAFP Prescribed Credits, 4 AOA Category 2-A or 2-B Credits. Specialty CME Credits: Included as part of the 4 credits, this CME activity is eligible for 4 Pharmacology CME credits
Date of Original Release: February 1, 2020. Date of most recent review: January 10, 2020. Termination date: February 1, 2023.
Accreditation: EB Medicine is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. This activity has been planned and implemented in accordance with the accreditation requirements and policies of the ACCME.
Credit Designation: EB Medicine designates this enduring material for a maximum of 4 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
ACEP Accreditation: Emergency Medicine Practice is approved by the American College of Emergency Physicians for 48 hours of ACEP Category I credit per annual subscription.
AAFP Accreditation: This Enduring Material activity, Emergency Medicine Practice, has been reviewed and is acceptable for credit by the American Academy of Family Physicians. Term of approval begins 07/01/2019. Term of approval is for one year from this date. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Approved for 4 AAFP Prescribed credits.
AOA Accreditation: Emergency Medicine Practice is eligible for 4 Category 2-A or 2-B credit hours per issue by the American Osteopathic Association.
Specialty CME: Included as part of the 4 credits, this CME activity is eligible for 4 Pharmacology CME credits.
Needs Assessment: The need for this educational activity was determined by a survey of medical staff, including the editorial board of this publication; review of morbidity and mortality data from the CDC, AHA, NCHS, and ACEP; and evaluation of prior activities for emergency physicians.
Target Audience: This enduring material is designed for emergency medicine physicians, physician assistants, nurse practitioners, and residents.
Goals: Upon completion of this activity, you should be able to: (1) demonstrate medical decision-making based on the strongest clinical evidence; (2) cost-effectively diagnose and treat the most critical presentations; and (3) describe the most common medicolegal pitfalls for each topic covered.
Discussion of Investigational Information: As part of the journal, faculty may be presenting investigational information about pharmaceutical products that is outside Food and Drug Administration–approved labeling. Information presented as part of this activity is intended solely as continuing medical education and is not intended to promote off-label use of any pharmaceutical product.
Faculty Disclosures: It is the policy of EB Medicine to ensure objectivity, balance, independence, transparency, and scientific rigor in all CME-sponsored educational activities. All faculty participating in the planning or implementation of a sponsored activity are expected to disclose to the audience any relevant financial relationships and to assist in resolving any conflict of interest that may arise from the relationship. In compliance with all ACCME Essentials, Standards, and Guidelines, all faculty for this CME activity were asked to complete a full disclosure statement. The information received is as follows: Dr. Dingle, Dr. Slovis, Dr. Parsons, Dr. Pfennig-Bass, Dr. Mishler, Dr. Toscano, Dr. Jagoda, and their related parties report no relevant financial interest or other relationship with the manufacturer(s) of any commercial product(s) discussed in this educational presentation.
Commercial Support: This issue of Emergency Medicine Practice did not receive any commercial support.
Earning Credit: Two Convenient Methods: (1) Go online to www.ebmedicine.net/CME and click on the title of the article. (2) Mail or fax the CME Answer And Evaluation Form (included with your June and December issues) to EB Medicine.
Hardware/Software Requirements: You will need a Macintosh or PC to access the online archived articles and CME testing.
Additional Policies: For additional policies, including our statement of conflict of interest, source of funding, statement of informed consent, and statement of human and animal rights, visit www.ebmedicine.net/policies.