CME INDIA Case Presentation by Dr. A. K. Singh, MD, DM (Endo), Endocrinologist – G D Hospital & Diabetes Institute, Kolkata. Ad Editor – William Textbook of Endocrinology 14th Ed’2020. Asso. Editor – UDDC, World J Diabetes.

CME INDIA Case Study

It is undisputed fact that top priority is to reverse Hypoglycemia as fast as possible. But in the midst of stabilizing the patient, do we consider the potential aftermath of concentrated glucose?

Dr. A.K Singh, DM (Endo), Kolkata asks:

• 57-year lady known T2DM and CKD (on Glimepiride 4 mg and Vildagliptin 50mg BD) admitted with hypoglycaemia on 19th Jan 2022 and given 25% dextrose several times but didn’t get rid of hypos. Referred to me, I saw patient at 5:30 pm yesterday. And since then no hypoglycaemia! What do I do?

CME INDIA Case Discussion:

Dr. Venkatesh Molio, Internist, Maregoan, Goa:

• Stop OHA.
• Switch over to repaglinide or insulin.
• CKD stage?
• Inj glucagon possibly.

Dr. Mayura Kale, Diabetologist, Aurangabad:

• Extended action of glimepiride due to reduced clearance.
• Only monitoring of blood glucose at present.
• Linagliptin if rising blood glucose.
• SOS work up for hypoglycaemia, in case it’s persistent.

Dr. Ranjeet, Internist, Ramgarh:

• Serum cortisol and Thyroid profile?

Dr. Awadhesh K. Singh, DM (Endo.), Kolkata:

• Not required.
• Cortisol 8 am: 34.
• TFT: normal.

Dr. Supriyo Mukherjee, Physician, Samstipur (Bihar):

• Dexamethasone inj 😊

Dr. Awadhesh K. Singh, DM (Endo.), Kolkata:

• No steroids given

Dr. Rajiv Awasthi, Internist, Lucknow:

• Perhaps the effects of OAD waned off and controlled on simple DNS. 3 days already passed.

Dr. Supriyo Mukherjee, Samstipur:

• Octreotide?

Dr. D. Ramesh, Professor in Dept. of General Medicine, Coimbatore:

• Stop OHA.
• Dextrose.
• Glucagon.
• Octreotide.

Dr. Pankaj Singhal Kota:

• Prolonged half-life of OHA.
• Slow infusion of 10 percent dextrose with constant monitoring of blood sugar.

Dr. Rajiv Kovil, Diabetologist, Mumbai:

• Stopped the dextrose.
• Dextrose was stimulating more insulin release.

Dr. Awadhesh K. Singh, DM (Endo.), Kolkata:

• 25% dextrose precisely 👏🏻👏🏻👏🏻😊😜
• Received 10 ampules in less than 24 hours.
• Put on Ryle’s tube and given complex carbohydrate and job was done!
• Morale: Don’t use 25% dextrose too aggressively.

Dr. Satish Kumar, Cardiologist, Wellmark Hospital, Bokaro:

• A good lesson learnt.

Dr. Mayura Kale, Aurangabad:

• True.
• Were plasma SU levels done at the time of hypo?

Dr. Raka Sheohare, Diabetologist, Raipur:

• Great. Potentiating consensus again to gut axis.
• Incretin effect.
• Intravenous sugar dextrose was more stimulating to raw insulin peaks.
• But when gut started absorbing sugar from complex carbs slowly.
• It doesn’t switche on abrupt insulin release wow🙏🙏
• Good learning for all.

Dr. Meenakshi Sahapathi, DNB, Family Med., Faridabad:

• If 25 percent dextrose aggressive use was causing Hypoglycemia then how to correct Hypoglycemia if levels 35-45.
•  Patient should be put be put on continuous 10 percent dextrose ,will it cause same effect as 25 percent and cause insulin stimulation.
• OHA are known to cause Hypoglycemia for 48 to 72 hrs. Should we check serum cortisol in all patients of Hypoglycemia thyroid related to Hypoglycemia?

Dr. Santosh Singh, DM (Endo.), Patna:

• The main issue is a continuous supply of glucose. The fault is not in 25% dextrose. I somehow don’t agree with the complex carbohydrate concept. I reiterate the significance of continuous supply of glucose.

Dr. Awadhesh K. Singh, DM (Endo.), Kolkata:

• Fault is at 25% w/v not at continuous glucose in low concentration. Complex carb is the key of hypo Rx! 🙏🏽

Dr. S. K. Goenka, Physician, Begusarai, Bihar:

• For long we suggest the diabetic patients to consume sugar/chocolate candy or sugar drinks in case of Hypoglycemia. These are simple carb, and suppose to raise the glucose level instantly, however the effect may not last longer. In that situation what is the best complex carb to suggest?

Dr. Awadhesh K. Singh, DM (Endo.), Kolkata:

• 👍🏼 Biscuit, bread, chapati etc.

Dr. Santosh Malpani, Diabetologist, Nanded:

• 25 present glucose instantly raises glucose levels. It potentiates the action of OHA and thereby increase in indigenous insulin levels further leading to Hypoglycemia. If oral feed or if patient is NBM slow infusion of glucose is given then this recurrent hypo can be avoided. Still will have to be vigilant till OHA is eliminated from blood stream.

Dr. Noni G. Singha, Internist, Dibrugarh, Assam:

• It is wiser to find out whether patient is on Alpha glucosidase inhibitors. If so then all these foods won’t be much help as AGI will slow down its (complex sugars) absorption. One need to give glucose powder or tablet (so one AGI is prescribed it is advisable to keep glucose powder or tab in hand). If glucose is not available then sugar or honey can be tried under tongue (buccal absorption) bypassing GI tract.
• Again same AGI can be useful in treating reactive Hypoglycemia

Dr. S. K. Gupta, Senior Consultant, Physician, Delhi:

• Message is clear in Hypoglycemia.
• Dextrose should be infused as long as patient doesn’t start taking orally.
• Initially 25% Dextrose infused IV works wonders. It should be used immediately but afterwards patient may not be left unattended just seeing that Blood Sugar Level has reached 300mg% as OHA are long-acting drugs and continue to exert their hypoglycaemic effect over long term. We keep patients in indoor care for around 18 to 24 hours when their blood sugars repeatedly maintained over 250 mg.
• Initially Simple sugars like Home based Chini is the best and easily available taken orally.
• Rushing for complex sugars like chocolates and Sweets like Rasgulla may rather delay absorption of Sugar in initial stages.
• Later of course complex sugars may have a role.
• Above discussion portrays 25% in very bad light. The drugs saves lives and many of them.
• It testified the role of oral sugar intake.

Dr. Vinay Dhandhania, Diabetologist, Ranchi:

• OHA specially SU which is known to cause prolonged hypoglycaemia, release insulin independent of glucose level in blood. I don’t think hyperglycaemia will accentuate the effect of SU and hypoglycaemia will not.
• Prolonged hypo is common   in CKD patients where excretion of SU is decreased and renal gluconeogenesis is impaired.

Dr. Awadhesh K. Singh, DM (Endo.), Kolkata:

• What’s new in this? Question was why it did not correct despite 20 ampoules of 25% dextrose intermittently and continuous 5%/10% dextrose drip? But it got corrected when 25% dextrose administration was stopped. Hope you got it now 😊

Dr. Vinay Dhandhania, Diabetologist, Ranchi:

• SU releasing more insulin in response to hyperglycaemia.

Dr. Awadhesh K. Singh, DM (Endo.) Kolkata:

• Not SU but human body will respond to hyperglycaemia by releasing more insulin. Action of SU is glucose independent If you apply SU in people with glucose of 50 mg it will further lower blood glucose thus this theory doesn’t explain 😊

Dr. Vinay Dhandhania, Diabetologist, Ranchi:

• This is true in reactive hypoglycaemia in non-diabetics.

Dr. Prashant Waichal Mahar, Akola:

• Very interesting.
• Similar type of patient female 70 yr.  came to me with drowsiness 7 days back. Comorbidities: hypothyroidism and HT.
• Non-diabetic.
• Had hypoglycaemia (RBS 56 mg) responded to 25%. Recovered. Again developed hypoglycaemia after 4 hrs and put in DNS drip. Well for 24 hrs. Started with oral diet, off IV fluids then well for 24 hrs. Later developed severe hypoglycaemic GTCs —unconscious—took 1 hr for seizures control and 48 hrs for neurological complete recovery.
• Done her endo work up. Insulin levels & Cortisol levels Thyroid profile normal. Covid and fever profile along with metabolic screen normal.
• MRI brain, Triple phase act abdomen and HRCT chest — inconclusive.
• At present Patient is conscious oriented with no focal deficit but required nearly 72 hrs for recovery.

CME INDIA Learning Points

• It is worth to remember that once the patient of severe Hypoglycemia recovers, regardless of the method used to increase serum glucose (oral, IV, or liver glycogenolysis due to glucagon), the patient should continue to receive supplementation. It is to prevent recurrence and re-establish glycogen stores as necessary.
• Thus, if patient is taking nothing by mouth(NPO), parenteral supplementation should continue to prevent Hypoglycemia.
•  If patient conscious and oral intake is possible, the patient should consume foods with longer-acting sources of energy (complex carbohydrates, fats, proteins) in order to prevent recurrence.
• Why there is Rebound Hypoglycemia?
  • After administration of D50 there is an excess amount of glucose available, leading to increased uptake and utilization by the tissues, which suppresses both gluconeogenesis and glycogenolysis.
  • Without continued administration of dextrose-containing fluids, this may result in rebound Hypoglycemia.
  • One study (ref-1) has suggest that higher concentrations of dextrose-containing fluids do not expedite reversal of Hypoglycemia as compared to lower concentrations, and that lower concentration formulations are more likely to achieve normal glycaemic targets. Authors suggested that While this may be true in many cases, it may not be when dealing with vesicant substances, such as dextrose. Although D50 is intended to be given via intravenous push, it still requires slow administration.
  •  Another misconception is that administration via piggyback is “too slow.” While flow rates will vary depending upon the cooperation of the patient and the intravenous access obtained, even small, 22-gauge catheters can achieve flow rates of between 35-40 mL/min.
• California Contra Costa County EMS system (9) revised current protocol suggests the use of a 100-mL bolus of 10% dextrose for treatment of Hypoglycemia in the field.it says. “In addition to practical reasons of cost and availability, theoretical risks of using 50 mL of D50 in the out-of-hospital setting include extravasation injury, direct toxic effects of hypertonic dextrose, and potential neurotoxic effects of hyperglycaemia. Their study demonstrates the feasibility, safety, and efficacy of using 100 mL of D10 as an alternative. 
• Although hypoglycemia can be quickly restored by carbohydrate supplementation in most cases, determining the underlying etiology is a crucial issue especially in patients without diabetes mellitus. This is because adrenal insufficiency, a possibly life-threatening condition, can be latent. So Serum cortisol estimation is not needed is usual cases.
• Hypothyroidism is linked with various hormonal biochemical and nervous system abnormalities, which may contribute to hypoglycemia. The condition is linked with low growth hormone and cortisol responses to insulin induced hypoglycemia, and this prevents adequate counter regulatory protection.
• Hypothyroid patients have relative adrenal insufficiency, even if they are not associated with primary adrenal failure. In the present case scenario, routine thyroid testing is not mandatory neither was needed.

CME INDIA Tail Piece

Rule of 15 vs Rule of 3

Dextrose Blues

• Dextrose is a monosaccharide absorbed from intestine and distributed, stored, and used by tissues. Parenterally injected, dextrose is used in patients unable to obtain adequate oral (PO) intake. Direct oral absorption results in rapid increase of blood glucose concentrations.
• Dextrose is effective in small doses, and there is no evidence that it may cause toxicity. Concentrated dextrose infusions provide higher amounts of glucose and increased caloric intake with minimum fluid volume.
• IV dextrose is the best treatment for inpatients and for patients found by emergency medical services personnel. IV dextrose is available in different concentrations.
• Concentrated IV dextrose 50% (D50W) is most appropriate for severe Hypoglycemia, providing 25 g of dextrose in a standard 50-mL bag. It is recommended to administer 10 to 25 g (20-50 mL) over 1 to 3 minutes.
• D50W should be administered slowly via peripheral or central sites, and dilution is required when given centrally. Rapid or excessive administration can induce hyperosmolar syndrome, and prolonged use (especially when insulin levels are high) can lead to hypokalemia. After D50W treatment, IV dextrose 5% or 10% in water is used to maintain BG levels >100 mg/dL.

Suggested Reading:

1. Moore C, Woollard M. Dextrose 10% or 50% in the treatment of hypoglycaemia out of hospital? A randomised controlled trial. Emerg Med J. 2005;22(7):512-515. 
2. https://www.aliem.com/d50-vs-d10-severe-hypoglycemia-emergency-department/
3. Balentine J, Gaeta T, 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. 
4. Krinsley J. Glycemic variability: a strong independent predictor of mortality in critically ill patients. Crit Care Med. 2008;36(11):3008-3013. 
5.  Mahadevan SV, Garmel GM, eds. An Introduction to Clinical Emergency Medicine. 2nd ed. New York, NY: Cambridge University Press; 2012;276
6. Kuwahara T, Asanami S, Kubo S. Experimental infusion phlebitis: tolerance osmolality of peripheral venous endothelial cells. Nutrition. 1998;14(6):496-501. 
7. Wiegand R, Brown J. Hyaluronidase for the management of dextrose extravasation. Am J Emerg Med. 2010;28(2):257.e1-2. 
8. Reddick A, Ronald J, Morrison W. Intravenous fluid resuscitation: was Poiseuille right? Emerg Med J. 2011;28(3):201-202. 
9. Kiefer MV, Gene Hern H, Alter HJ, Barger JB. Dextrose 10% in the treatment of out-of-hospital hypoglycemia. Prehosp Disaster Med. 2014 Apr;29(2):190-4. doi: 10.1017/S1049023X14000284. Epub 2014 Apr 15. PMID: 24735872.

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