Wednesday, November 19, 2014

Brought in by Ambulance, #4: Pour Some Sugar on Me

Case Scenario: 
Your unit is responding on the quiet to a 36 year-old F with chief complaint of “sick.”  You arrive to find a cachectic woman (BMI 16) who suffers from lifelong anorexia. She complains of shortness of breath, abdominal pain and general malaise. She walks herself to the ambulance and after her vitals are taken, a FSBS is 56.  According to your protocol, this should be treated in the following manner: the EMT-B administers 15 gm oral glucose solution and repeat as needed, while the EMT-P administers 25 gm D50W IV/IO or D10W IV/IO, or glucagon 1 mg IM if no IV/IO access available.  The medic asks your opinion and as the patient was symptomatic, you suggested starting with oral glucose solution. However, this made her feel nauseated. Once again, the medic asks you whether to give D10W or D50W. You elected for D10W, but you admittedly have no evidence for doing so. After an uneventful ride to the hospital, the patient’s repeat blood glucose was 254 mg/dL.

Clinical Question:
What is the best way to treat hypoglycemia in the prehospital environment?

Literature Review:  
Most common sources define hypoglycemia as less than 60-70 mg/dL. According to the Endocrine Society’s Clinical Practice Guidelines, hypoglycemia should only be treated and investigated in patients showing signs of "Whipple’s triad" -- signs and symptoms of hypoglycemia, a low plasma glucose reading, and resolution of symptoms with elevation of plasma glucose concentration [1]. The signs and symptoms of hypoglycemia are quite vague and nonspecific; they can include shakiness, anxiety, headaches, and weakness, progressing to seizures and unconsciousness [2]. Severe symptoms typically occur with serum glucose values less than 40 mg/dL [3]. It seems obvious that seizures and unconsciousness attributed to hypoglycemia should be treated, but any of the minor signs and symptoms could easily be appreciated on almost any primary scene response. Therefore the vast majority of hypoglycemic patients encountered by EMS providers are most likely going to be treated.

Once we have decided to treat prehospital hypoglycemia, we must determine the optimum modality for doing so. We could find no published work doing a heads-up comparison of oral versus intravenous carbohydrate administration, but there has been work related to D10W versus D50W. An EMS system in California published data from their experience replacing 50mL D50W with 100mL D10W as the standard treatment for hypoglycemia [7]. In 164 treated patients, the median pretreatment glucose was 38 mg/dL, and at 8 minutes after treatment was 98 mg/dL.Twenty-nine patients required an additional dose, and one patient required a third. There were no adverse events reported. The authors conclude these results demonstrate the feasibility, safety, and efficacy of D10 as an alternative to D50.

One unblinded randomized controlled trial compared D10W to D50W in prehospital hypoglycemic patients with GCS < 15 (approx. 25 pts in each group) with regards to the ability of the solutions to raise glucose to normal values and the time to reach a GCS of 15 [4]. The mean repeat glucose value in these groups was 112 and 169 in the D10W and D50W groups, respectively (p = 0.003). The authors note that the average D10 given was 10g (100 mL) and D50 given was 25g (50 mL) (p < 0.001). There were no significant differences between the groups in median time to recovery, median post-treatment GCS, or number of patients experiencing another hypoglycemic episode within 24 hours. The authors conclude that due to the efficacy of treatment with lower risk of hyperglycemia, D10 should be the preferred agent.
   
Not only is D50 more likely to cause hyperglycemia after administration, but it also carries with it the risk of hypertonicity and tissue necrosis. D50 has an osmolarity of 2,525 mOsm/L and a pH between 3.5 and 6.5. This is in contrast to D10 which has an osmolarity of 506 mOsm/L and is pH neutral. Usual IV therapy recommendations state that solutions with osmolarity greater than 900 mOsm/L should be administered through central access. There have also been several case reports of extremity amputation after dextrose extravasation [5,8].

To illustrate the difficulty in administering D50, one of our toxicology faculty compared the injection of D50 to injecting maple syrup. This is not a facetious analogy, as a simple look at the nutrition label of a bottle of syrup reveals:



Note that D50 = 50g of sugar per 100mL of soluion. Each "amp" of D50 contains 25g of sugar in 50mL. Compare that to Aunt Jemima's, which contains 32g of sugar in 60mL solution.

The primary EMS agency bringing patients to our facility recently updated their protocols to make D10 the preferred agent for treating hypoglycemia prehospital. The Medical Director of this agency reiterated the preferable safety profile of D10 compared with D50, and remarked on another important advantage of D10 -- it does not need to be diluted for use in pediatric patients.

In the absence of IV/IO access, evidence exists for the efficacy of IM glucagon in treating prehospital hypoglycemia [9]. The response to glucagon may take longer than when oral or IV glucose solutions are used [10, 11], though may cause a greater increase in blood glucose levels than 10g of glucose solution [12].
   
Take-home:
- If mental status allows, hypoglycemic patients should first be offered oral glucose -- preferably 15gm of a standard glucose formula, but syrup, juice, or honey can also be used. (Note that honey has a lower glycemic index than most juices or glucose solution and thus theoretically may not be as effective.) 
- The next line of therapy should probably be IV D10, as there is good evidence to suggest efficacy on par with that of D50 but with a more favorable safety profile.
- If no IV/IO access is available and oral glucose is unable to be administered, it is reasonable to administer 1mg IM glucagon.

References:
[1] Evaluation and management of adult hypoglycemic disorders.  J Clin Endocrinol Metab, 2009, 94(3), 709.
[2] American Diabetes Association.  Diabetes.org
[3] National Diabetes Information Clearinghouse.  Diabetes.niddk.nih.gov
[4] Moore and Woolard. Emerg Med J, 2005, 22, 512-515.
[5] Kumar et al. ANZ Journal of Surgery, 2001, 71, 285-289.
[6] Is D50 Too Much of a Good Thing?  Stephen Wood, 2007, m.jems.com/article/patient-care
[7] Kiefer et al. Prehosp Disaster Med2014, 29(2), 190-194.
[8] Lawson et al. Am J Emerg Med, 2013, 31(5), 886:e3-5.
[9] Vukmir et al. Ann Emerg Med, 1991, 20(4), 375-9.
[10] Howell et al. J Accid Emerg Med, 1997, 14(1), 30-2.
[11] Carstens and Sprehn. Prehosp Disaster Med, 1998, 13(2-4), 44-50.
[12] Vermeulen et al. Diabetes Care, 2003, 26(8), 2472-3.

Submitted by Chris Miller, PGY-2.
Edited by C. Sam Smith (@CSamSmithMD), PGY-3.
Faculty reviewed by Hawnwan P. Moy.

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