Therapeutic
Intranasal Drug DeliveryIntranasal glucagon for severe hypoglycemia
Introduction
On a year to year basis, between 10% and 30% of patients on insulin therapy suffer severe hypoglycemia requiring external assistance.[1] Current treatment modalities include oral glucose (which may be poorly tolerated in the unconscious patient), intramuscular glucagon and intravenous dextrose. The later two options require injections of the medications and are difficult skills for family members to master. Therefore, emergency medical services (EMS) are frequently contacted to respond to these patients and to administer appropriate therapies to increase the patient’s blood sugar. If it were possible to administer glucagon intranasally without the need for an injection, family members could resuscitate their diabetic relatives much more easily and EMS calls would decrease.[2] This treatment option would also be attractive to the EMS workers themselves – reducing the risk of a needle stick in a patient population that is often confused and combative.
Literature overview and discussion
A moderate amount of literature exists demonstrating that intranasal glucagon is effective in treating hypoglycemia. Most of this literature suggests that nasal glucagon is optimally absorbed if mixed with a surfactant additive (such as sodium glycocholate rather than the sterile water diluent that comes with the package) to enhance absorption. The literature is also fairly clear in showing that intramuscular or subcutaneous glucagon leads to more rapid rises in blood glucose with longer effect.[3, 4] Pontiroli and colleagues have published the majority of data on this topic.[4-7] Other authors have also confirmed the effectiveness of IN glucagon when mixed with absorptive enhancers.[8, 9]
Despite the majority of published data noting improved results with a surfactant additive, there are studies that simply used standard glucagon solubilized in the packaged diluent (sterile water) as an intranasal spray and noted effective results. Hvidberg et al found that 2 mg of IN glucagon solution was effective in raising blood glucose levels of hypoglycemic patients, though not as quickly as that found with 1 mg of intramuscular glucagon.[10] Pacchioni et al found IN glucagon as effective as IV glucagon at stimulating gut motility for radiologic procedures.[11] Rosenfalck et al compared 1 mg and 2 mg doses of intranasal glucagon to 1 mg does of intramuscular glucagon in hypoglycemic adults. They found all three methods more effective at raising blood glucose than observation alone. Furthermore they found the 2 mg IN dose to be equal to the 1 mg IM dose, suggesting a potential role for intranasal glucagon in the treatment of accidental hypoglycemia, especially if higher doses were used.[12] Numerous discussions exist on the Internet demonstrating that paramedics are using intranasal glucagon in unconscious patients with hypoglycemia. These discussions suggest that this method is of interest to EMS workers, but as of mid 2008 no published data exists to demonstrate the results of their experiences.
In summary, intranasal glucagon is effective for the treatment of hypoglycemia, especially if it is solubilized with an absorptive enhancer such as sodium glycocholate. It is less clear how effective IN glucagon is when solubilized in sterile water. In the current packaging, which uses sterile water as the solubilization medium, several small studies do suggest intranasal glucagon is superior to placebo when given in doses of 2 mg. There may be a role for this medication (as intranasal formulation) in home therapy and in combative patients with severe hypoglycemia since it can be given without an injection – an advantage that would likely enhance its use in the home setting.[2] It would be nice to see this role confirmed with research data from EMS agencies.
Personal insights from experienced clinicians
This section awaits users input
Treatment protocol
Indications: For use on patients with documented hypoglycemia
Procedure:
- Assess ABC’s – Airway, Breathing, Circulation
- For pulseless patients, proceed to ACLS guidelines
- If hypoxemia or apnea exists– Establish oral airway and begin bag ventilation with 100% oxygen
- Check finger stick blood glucose.
- Consider other rapidly reversible causes of coma (opiate overdose, hypoxemia)
- If hypoglycemia is documented by finger stick blood glucose, continue as below:
- Solubilize 2 mg of glucagon (2 vials) in a total volume of 1 ml of diluent (1/2 ml per vial). If possible obtain sodium glycocholate as the diluent, if not use that which comes with the package.
- Load syringe with 2 mg of glucagon and attach a nasal atomizer.
- Place atomizer within the nostril
- Briskly compress syringe to administer 1/2 of atomized spray.
- Remove and repeat in other nostril, so the entire 2 mg of medication are administered.
- Simultaneously administer glucose paste under lip and tongue to further enhance blood sugar elevation.
- Continue ventilating patient as needed
Teaching materials
None at this time, please submit any personal insights you have to be posted here on this web site (see links for contact e-mail address)
Bibliography (click here for abstracts)
1. Carstens, S. and I. Andersen, [Intranasal glucagon in the treatment of hypoglycemia. A therapeutic possibility in the future]. Ugeskr Laeger, 1994. 156(30): p. 4339-42.
2. Yanai, O., et al., IDDM patients' opinions on the use of glucagon emergency kit in severe episodes of hypoglycemia. Practical Diabetes, 2005. 14(2): p. 40-42.
3. Stenninger, E. and J. Aman, Intranasal glucagon treatment relieves hypoglycaemia in children with type 1 (insulin-dependent) diabetes mellitus. Diabetologia, 1993. 36(10): p. 931-5.
4. Pontiroli, A.E., et al., Nasal administration of glucagon and human calcitonin to healthy subjects: a comparison of powders and spray solutions and of different enhancing agents. Eur J Clin Pharmacol, 1989. 37(4): p. 427-30.
5. Pontiroli, A.E., M. Alberetto, and G. Pozza, Metabolic effects of intranasally administered glucagon: comparison with intramuscular and intravenous injection. Acta Diabetol Lat, 1985. 22(2): p. 103-10.
6. Pontiroli, A.E., et al., Intranasal glucagon as remedy for hypoglycemia. Studies in healthy subjects and type I diabetic patients. Diabetes Care, 1989. 12(9): p. 604-8.
7. Pontiroli, A.E., et al., Pharmacokinetics of intranasal, intramuscular and intravenous glucagon in healthy subjects and diabetic patients. Eur J Clin Pharmacol, 1993. 45(6): p. 555-8.
8. Freychet, L., et al., Effect of intranasal glucagon on blood glucose levels in healthy subjects and hypoglycaemic patients with insulin-dependent diabetes. Lancet, 1988. 1(8599): p. 1364-6.
9. Slama, G., et al., A new non-invasive method for treating insulin-reaction: intranasal lyophylized glucagon. Diabetologia, 1990. 33(11): p. 671-4.
10. Hvidberg, A., R. Djurup, and J. Hilsted, Glucose recovery after intranasal glucagon during hypoglycaemia in man. Eur J Clin Pharmacol, 1994. 46(1): p. 15-7.
11. Pacchioni, M., et al., The hypotonic effect of intranasal and intravenous glucagon in gastrointestinal radiology. Abdom Imaging, 1995. 20(1): p. 44-6.
12. Rosenfalck, A.M., et al., Nasal glucagon in the treatment of hypoglycaemia in type 1 (insulin-dependent) diabetic patients. Diabetes Res Clin Pract, 1992. 17(1): p. 43-50.