Author: Kenny Banh, MD & Jose Acosta, University of California
Editor: David A. Wald, Temple University School of Medicine
Last Updated: November, 2019
A 19-year-male with unknown medical history is found down on subway platform and is brought to the hospital by EMS. He smells of alcohol and experiences two episodes of emesis en-route to the emergency department. In the emergency department, he appears confused and is complaining of abdominal pain.
T: 37.0° C (98.6°F), P: 102/min, BP: 110/80mmHg, RR: 24/min, O2 Sat: 99% on RA
Physical exam is remarkable for: Dry mucus membranes, slurred speech, diffuse abdominal tenderness, and Kussmaul respirations
The objectives of this module will be to:
- Review the classic presentation of a patient with hyperglycemia, including DKA and HHS.
- Review the diagnostic work up of the hyperglycemic patient.
- Review the principles of managing a patient with hyperglycemia.
Hyperglycemia is a very common presentation in the emergency department. The presentation of hyperglycemia ranges from asymptomatic and benign in patients with mild to moderate uncomplicated hyperglycemia to life-threatening, i.e. diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS). DKA and HHS represent a spectrum of complications from diabetes and differ mainly in the level of hyperglycemia, extent of dehydration and presence and degree of ketoacidosis. Each condition revolves around insulin deficiency, either absolute or relative. The complaints associated with these presentations include: polyuria, polydipsia, polyphagia, nausea/vomiting, abdominal pain, and neurological symptoms.
Initial Actions and Primary Survey
In these patients, a thorough history and physical examination should be performed with a focus on trying to identify a precipitating cause of the hyperglycemia. In patients with an incidental finding of mild to moderate hyperglycemia or those with minor symptoms, little else may be necessary beyond anticipatory guidance and proper follow up. In those with blood glucose levels greater than 300 – 350 mg/dL, a urinalysis may help identify the presence of ketones. If present, a basic metabolic profile should be obtained to exclude an increased gap metabolic acidosis. Many of these patients will need intravenous administration of saline.
In a patient who is more ill appearing, hemodynamically unstable and those suspected of having DKA or HHS the following should be instituted:
Close attention should be paid to the ABC’s
2 large bore intravenous lines should be placed
Normal saline 1-2 liters (adult) or bolus of 20 cc/kg (children). Attention should be paid to the volume status of the patient. Be cautious of high volume crystalloid infusion in patients with congestive heart failure or chronic renal failure.
Place the patient on a cardiac monitoring
Patients with mild hyperglycemia may in fact be asymptomatic. Once the blood glucose level rises above approximately 180 mg/dL (renal threshold), patients will start to develop an osmotic diuresis. At this time, patients may present with a variety of complaints including;
- Weight loss
These symptoms will be highly variable from patient to patient. Some will also develop tachycardia, dizziness, lightheadedness and weakness as a result of dehydration and electrolyte imbalance. As the degree of hyperglycemia progresses leading to marked volume depletion, electrolyte disturbance, acidosis, ketosis, etc. additional symptoms may be seen including:
- Abdominal pain
- Hyperpneic respirations (fast and deep Kussmaul respirations)
- Ketotic breath (fruity odor in DKA)
- Marked tachycardia
- Neurologic symptoms (seizures, focal weakness, lethargy, coma, death) – more prevalent in HHS
DKA and HHS are the most serious, acute metabolic complications of diabetes, but other differentials include dietary indiscretion and new onset or uncontrolled diabetes. Generally DKA occurs in younger patients (<65 y/o) with Type 1 diabetes and usually evolves rapidly over 24 hours. HHS usually occurs in older patients (>65 y/o) with poorly controlled Type 2 diabetes and evolves over several days. Both disease entities originate from a reduction in insulin and an increase in counter-regulatory stress hormones.
In the emergency department, hyperglycemia is most often seen as a complication of diabetes (both types 1 and 2). Hyperglycemia is defined as:
- Fasting Blood Glucose (for 8 hrs) > 90 – 130 mg/dL
- Postprandial Blood Glucose > 180 mg/dL
Is a state of absolute insulin deficiency, hyperglycemia, anion gap acidosis, and dehydration. It is classically seen in Type 1 diabetics and typically occurs in younger people. The most common causes are infections, disruption of insulin therapy, or as the presentation of new onset diabetes.
Is a state of hyperglycemia, hyperosmolarity, and dehydration without significant ketoacidosis. It is typically seen in Type 2 diabetics, has a higher mortality rate compared to DKA, and occurs in older patients. It most commonly occurs in poorly controlled Type 2 diabetics with an underlying infection.
A number of other conditions can affect diabetic patients resulting in an increase in counter regulatory hormones and hyperglycemia, some of which can precipitate DKA or HHS.
The I’s of DKA and HHS
- Insulin deficiency (New onset T1DM, failure to take enough insulin)
- Infection is the most common precipitating factor (Pneumonia, UTI)
- Ischemia or Infarction (MI, CVA, Acute Mesenteric Ischemia)
- Inflammation (Pancreatitis, Cholecystitis)
- Intoxication (Alcohol, Drugs)
- Iatrogenesis (Glucocorticoids, Thiazides)
The extent of diagnostic testing will depend on the patients presenting complaints and suspicion for complications related to their diabetes / hyperglycemia. Some patients may need no more than bedside glucose testing +/- urinalysis.
In patients suspected of having DKA or HHS, additional tests should be obtained:
- Basic metabolic profile
- Complete blood count (often obtained when suspicious for an infectious etiology, sensitive, not specific)
- Blood gas determination (venous blood gas sample provides accurate information regarding blood pH and closely approximates that of arterial pH)
- Additional electrolytes (phosphorus, magnesium) may be important in patients profoundly dehydrated
- Electrocardiogram (ECG) (In patients with marked acidemia or severe hyperglycemia, extracellular potassium shifts may result in ECG manifestations of hyperkalemia despite total body losses)
- Additional testing based on patient presentation (lipase, hepatic functions, chest radiograph, blood cultures, etc.)
- ETCO2 can be used for bedside assessment of DKA
- ETCO2 of ≥35 is 100% sensitive to rule out DKA
- ETCO2 of ≤21 is 100% specific to diagnose DKA
- Additional testing based on patient presentation (lipase, hepatic functions, chest radiograph, blood cultures, etc.)
Diagnosing DKA or HHS is done at the bedside with a high clinical suspicion based on the patient history, physical exam, and initial laboratory findings. The following table presents the diagnostic criteria for DKA and HHS. It should be remembered that HHS can present with both an anion gap and ketosis (approximately 50% of patients) but usually will not have a significant acidosis.
Table 1. Diagnostic Criteria for Diabetic Ketoacidosis (DKA) and Hyperosmolar Hyperglycemic State
In patients with an uncomplicated presentation associated with mild – moderate hyperglycemia, often no urgent treatment is required, however in some cases, patients may requires intravenous fluids.
Treatment for DKA and HHS is centered around correcting the intravascular volume depletion, management of electrolyte abnormalities, insulin replacement therapy and identification of and treatment of any underlying precipitants.
Average fluid loss in DKA 3-6 liters and HHS 8-12 liters
Historically, isotonic saline (0.9%) at 15-20 ml/kg per hour for the first few hours has been the fluid of choice (in the average adult this will be approximately 1 liter/hr). Lactated Ringers may be a better option to avoid hyperchloremic non-anion gap metabolic acidosis. Neither has proven superior to each other in time to pH normalization.
Switch to one-half isotonic saline (0.45%) when the serum sodium normalizes
Add dextrose to the intravenous fluids when serum glucose reaches 250 mg/dL
- Check potassium prior to starting insulin treatment (3.5 – 5.5 rule).
- Potassium is above 5.5, start insulin infusion
- Potassium is between 3.5-5.5, add potassium to the fluids
- Potassium is less than 3.5, hold insulin, supplement K and restart insulin later
- Insulin therapy involves the administration of regular insulin via IV infusion or subcutaneous injections.
- IV infusion of regular insulin is preferred route because of short half-life and easy titration.
- Insulin therapy should only be started after adequate fluid resuscitation
- Start with an infusion of regular insulin at 0.1 U/kg/hr. A bolus dose of insulin is not necessary if the patient receives an hourly insulin infusion of 0.14units/kg (10units/h in a 70-kg patient). If administering a loading dose use 0.1 U/kg of regular insulin.
- If serum glucose does not fall by at least 10% in the first hour, give 0.14 U/kg as IV bolus, then continue previous.
- Do not stop insulin infusion until anion gap normalizes and bicarbonate normalizes, despite resolution of blood sugar.
- Persistent anion gap: Continue drip
- Resolution of anion gap: Change to subcutaneous insulin (overlap IV with SC by 1-2 hours)
- When glucose ≤200mg/dL in DKA & ≤300 mg/dL in HHS, reduce insulin infusion to 0.02-0.05 U/kg/h IV or change to subcutaneous insulin 0.1 U/kg q2hr.
- In DKA keep serum glucose between 150-200 and in HHS 200-300.
- Potassium repletion is critical to avoid life-threatening arrhythmias and respiratory muscle weakness.
- Treatment goal is to maintain serum potassium between 4-5 mEq/L.
- Follow the 3.5 to 5.5 rule to start insulin therapy and potassium repletion (see above).
- Use of bicarbonate is controversial
- Prospective randomized studies have failed to show improvements or worsening in morbidity and mortality with the use of sodium bicarbonate therapy in DKA with a pH between 6.9 and 7.1.
- No prospective randomized studies have been reported on the use of bicarbonate in DKA with pH <6.9.
- Despite the lack of evidence many intensivists consider the use of bicarbonate therapy in a DKA patient when pH is <7.1
- Treat any other underlying infections or other disease processes.
- Patients with both DKA and HHS will require serial monitoring of:
- Blood glucose every hour until stable, then every 2 – 4 hours
- Basic metabolic profile and blood pH every 2 – 4 hours during therapy until patient stabilizes
One very serious complication of DKA/HHS is cerebral edema. It is mainly seen in children and young adults, occurring 4-12 hours into treatment with a high degree of morbidity and mortality. Clinically it is often preceded by headache, lethargy, and then neurologic deterioration (seizures, coma) with bradycardia and respiratory arrest. Although not completely understood development of cerebral edema is correlated with bicarbonate administration and massive fluid resuscitation.
Patients with uncomplicated hyperglycemia can typically be managed as an outpatient. Some may be discharged after the administration of intravenous fluids and subcutaneous insulin, while others may not require treatment as long as they have proper follow up with a primary care physician. New onset diabetics may at times be discharged on glucophage provided they are adequately hydrated with eGFR>45 mL/min/m2, are not in DKA and have good outpatient follow up.
All patients with DKA and HHS require hospital admission. Depending on disease severity some may require monitoring in the ICU.
Pearls and Pitfalls
- Consider other coexisting illnesses as a precipitant (infection, myocardial infarction) of DKA and HHS.
- Don’t start insulin therapy prior to administering fluids and checking the potassium level.
- Continue to replete potassium when the levels drop to normal or low normal range.
- Start glucose-containing fluids once the blood glucose levels are < 250 mg/dL in DKA / HHS.
- In children, recognize and promptly treat signs/symptoms of cerebral edema.
Case Study Resolution
The patient’s serum lab values were as follows:
Na+: 130 mEq/L
Glucose: 362 mg/dL
Thiamine B1: 192 nmol/L (within normal limits)
Blood alcohol level: 0.26
Urine ketones: +++
The patient was admitted for alcohol intoxication and DKA. He was placed on the CIWA protocol to monitor for alcohol withdrawal and the initial treatment for his DKA was with normal saline, potassium, insulin. As his glucose improved and his anion gap acidosis cleared, he was then transitioned to subcutaneous insulin and dextrose was added to his fluids. Upon discharge, the patient reported that he was a Type 1 diabetic and was educated on alcohol use and the potential to cause DKA.
Chebl BR, Madden B, Belsky J, et al. Diagnostic value of end tidal capnography in patients with hyperglycemia in the emergency department. BCM Emerg Med. 2016; 16 (1).
Chua HR, Schneider A, Bellomo R. Bicarbonate in diabetic ketoacidosis – a systematic review. Ann Intensive Care. 2011 Jul 6;1(1):23. doi: 10.1186/2110-5820-1-23
Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7):1335–1343
Orman, Rob, and George Willis. “Hyperglycemia but Not DKA.” EMRAP, July 2017, www.emrap.org/episode/sugaruppehomeo2/hyperglycemia.
Kitabchi AE, Rose BD. Treatment of diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults. Uptodate.com. Available at: http://www.uptodate.com/patients/content/topic.do?topicKey=~_wwcvV7HkHijO4w. Accessed June 17, 2010.
Rucker DW. DKA. Emedicine.com. Available at: http://emedicine.medscape.com/article/766275-overview. Accessed June 17, 2010.
Sergot PB. HHS. Emedicine.com. Available at: http://emedicine.medscape.com/article/766804-overview. Accessed June 17, 2010.
Van Zyl et al. Fluid Management in diabetic-acidosis--Ringer's lactate versus normal saline: a randomized controlled trial. http://qjmed.oxfordjournals.org/content/qjmed/105/4/337.full.pdf