Is D50 Too Much of a Good Thing?: - Patient Care - @ JEMS.com


Is D50 Too Much of a Good Thing?:

A reappraisal of the safety of 50% dextrose administration in patients with hypoglycemia


 
 

Stephen P. Wood, MS, EMT-P | | Thursday, March 1, 2007


Every paramedic has a familiarity with dextrose solutions. They're commonly administered in the prehospital arena, primarily for the indication of all-cause hypoglycemia, and a bolus of dextrose often has rapid and impressive results. Other indications for the administration of dextrose include hyperkalemia, oral hypoglycemic agent overdose and, in some systems, coma of unknown origin.

However, use of this agent is not without complication or risk. Post-administration blood glucose concentration varies widely, with significant hyperglycemia commonly occurring.(1,2) Further, many co-morbid conditions increase morbidity and mortality in the setting of hyperglycemia, such as head injury, sepsis, myocardial infarction (MI) and stroke.(3,4,5,6) High concentrations of glucose can precipitate severe cerebral edema and death in children.(7,8) Other complications include thrombophlebitis and tissue necrosis.

Considering these risks, it may be time to reassess the method and dose by which we administer hypertonic dextrose.

Dextrose & Energy
Dextrose is the primary carbohydrate used by cells for the production of adenosine triphosphate (ATP), the main source of energy in the body. Also known as glucose, it's a six-carbon sugar that's taken into a cell by glucose-transporter proteins. These proteins are activated or stimulated by the hormone insulin, released by the beta cells of the pancreas.

Once in the cell, glucose undergoes a series of chemical reactions and is eventually reduced to a three-carbon molecule called pyruvate. Pyruvate subsequently enters the Krebs' cycle—the process in which the body turns carbohydrates, proteins and fats into carbon dioxide, water and energy—and is converted to a variety of substrates used throughout the body.

The last step is the electron transport chain, which ultimately results in the production of ATP. ATP is a highly energetic molecule because of the closely packed, negatively charged phosphates that are constantly repelling each other within it. It's used as an energy source throughout the body for a wide range of biochemical reactions. Lack of glucose in the blood or the inability of glucose to enter the cell will result in a reduction of ATP production and in energy stores, leading to enzymatic and organ dysfunction.

Hypoglycemia
Normal, random, non-fasting, serum blood glucose levels are 70-120 mg/dL.2 Levels remain fairly constant but will fluctuate depending on diet, exercise and related factors. The brain is one of the organs most sensitive to reductions in glucose availability, requiring a significant amount of glucose—approximately 25% of total body glucose utilization.(9)

The brain can't store glucose and is thus very susceptible to reductions in circulating glucose levels. Such reductions can occur with excess insulin administration, excess oral hypoglycemic administration, insulinoma, starvation and some toxic ingestions.

Cerebral hypoglycemia is postulated to result in a cascade of events, including local and global cerebral vascular constriction, reduction of important co-factors, and eventual neuronal death.(10,11) It can manifest as cerebral dysfunction. Clinical manifestations of hypoglycemia include mood change, coma, confusion, seizures and stroke-like symptoms. Activation of the sympathetic nervous system also occurs, manifesting diaphoresis, tachycardia and related symptoms.

These symptoms can occur at variable levels of serum glucose, but typically occur when serum glucose falls below 40 mg/dL.12 In the newborn, a plasma glucose level of less than 30 mg/dL in the first 24 hours of life, and less than 45 mg/dL thereafter constitutes hypoglycemia.(13,14) Some patients who have frequent episodes of hypoglycemia may be asymptomatic, even at levels of capillary glucose as low as 20 mg/dL.15

Treatment of hypoglycemia: Current practice in most prehospital systems encourages the use of point-of-care capillary blood glucose determinations on all patients with altered mental status, coma and seizures. These devices can rapidly and accurately determine blood glucose levels and thus are used to determine the presence or absence of hypoglycemia.

Although protocols vary, most EMS systems will recommend the administration of dextrose for a blood glucose level < 60 mg/dL with corresponding alteration in mental status. A dextrose bolus is typically administered as a 10%, 25% or 50% concentration, depending on patient age. The 10% and 25% concentrations are used in the neonatal and pediatric population, and the 50% concentration is administered to adolescents and adults.(7,10)

Neonates (birth to one month) can receive 2-4 mL/kg of 10% dextrose. Children less than eight years old can receive 5 mg/kg of 25% dextrose; adolescents and adults typically receive 0.5 g/kg of 50% dextrose (D50).(14)

In practice, most adolescents and adults receive the full 50 g dose, regardless of actual weight. Rises in serum glucose after the administration of dextrose occur rapidly, with the duration of action dependent on serum glucose levels at administration, serum insulin levels and other related factors.

The half-life of D50 varies, averaging 30 minutes in healthy adults, although this is likely to be variable in patients with hypoglycemia.1 Elevations in serum glucose can vary, with a range of 37–370 in one human trial using a cohort with altered mental status presenting to the emergency department (ED).(1)

Thus, dextrose administration can result in rapid and prolonged hyperglycemia. The effects of this rapid peak, as well as the resultant hyperglycemia in a model of bolus dextrose in the setting of hypoglycemia, is unknown. However, providers should be aware of potential deleterious sequelae that might occur.

Complications of Hyperglycemia
Commercially prepared D50 is typically 25 g of dextrose monohydrate in 50 mL of water without preservatives. It's a hypertonic solution with an osmolarity of approximately 2,525 mOsm/L and a pH between 3.5 and 6.5.

Most IV infusion resources recommend infusing medications with an osmolarity > 900 via a central vein, such as the subclavian vein.16 These recommendations are based on clinical and physiological evidence of increased rates of phlebitis and thrombophlebitis of drugs with osmolarities > 900 mOsm/L. Thus, local venous irritation and/or thrombophlebitis can occur with dextrose administration. Extravasation of dextrose can result in significant tissue necrosis, and several cases of amputation after dextrose extravasation have been reported.(17)

In contrast, 10% dextrose has an osmolarity of 506 mOsm/L and is within the range of safer peripheral administration. Glucagon, an alternative to IV dextrose, is administered subcutaneously or intramuscularly and carries little risk of tissue injury.

Hyperglycemia, both acute and long-term, has been associated with deleterious sequelae in a variety of disorders, including stroke, head injury, post-resuscitation and sepsis. Hyperglycemia is significantly associated with worse morbidity and mortality in both head injury and stroke.(3,4)

A meta-analysis by Capes et al demonstrated the relative risk of death in stroke patients with blood glucose > 110-126 mg/dL was 3.28 (95% CI, 2.32-4.64).(18) The relative risk is a statistical value that looks at the risk of developing a disease for a given exposure; in this case, it's for stroke patients exposed to a blood glucose value > 110 mg/dL. A confidence interval (CI) of 95 % is a statistic used to state that there's a 95% probability that the real value—here, the relative risk of death—will fall between two numbers; in this case, it's 2.32 and 4.64.

The impact of hyperglycemia was also the focus of a retrospective analysis of head-injured patients by Jeremitsky et al. These researchers demonstrated that hyperglycemia was associated with lower post-injury Glasgow Coma Scale scores, prolonged length of stay and death.(4) Efron et al reported a case of a neonate with profound iatrogenic hyperglycemia who suffered significant cerebral injury.(8) Thus this injurious mechanism could occur in all populations.

Hyperglycemia has also been associated with worse outcomes in MI.5 In one study evaluating MI, hyperglycemia on admission had an increased risk of 180-day mortality, independent of a history of diabetes.17 Hyperglycemia in sepsis is also associated with worse outcomes.(6)

In the diabetic population, rapid elevation of serum glucose may exacerbate chronic issues as well as make subsequent control of blood glucose difficult, at least in the short-term. The glucose fluctuations that occur may result in secondary hypoglycemia or, in contrast, persistent hyperglycemia.

Research on Dextrose Administration
Several studies have investigated the effects of dextrose administration in humans. Balentine et al used a prospective interventional study to determine the effects of 25 g of D50 in healthy subjects.19 The main outcome of this study was the determination of post-glucose administration serum glucose levels at five predetermined time intervals. The mean increase in serum glucose was 244.4 (+/− 44.6 mg/dL) at five minutes, with a return to baseline within a mean of 30 minutes.

A serum glucose level of 244 mg/dL is significantly high, despite the fact that levels returned to baseline in 30 minutes. Because the study involved healthy subjects with presumably normally functioning pancreases, these results can't be extrapolated to patients with diabetes mellitus, patients taking exogenous insulin or oral hypoglycemic agents. In these patient populations, high serum glucose may persist even longer.

Several prehospital studies have evaluated the administration of glucose. Carstens et al randomized patients presenting to EMS to receive D50 either as a 25 g bolus or 1 mg of glucagon.20 The aim of the study was to compare the time to recovery in both groups.

Recovery time was significantly quicker in the glucose group versus the glucagon (one to three minutes as compared with eight to 21 minutes respectively). However, fluctuation of glucose levels was significantly greater in the glucose group, representing a low but present risk for secondary hypoglycemia.

Moore and Woolard investigated randomizing patients to receive either 10% dextrose or D50 for the prehospital management of hypoglycemia.(21) Their cohort included 51 patients, with 25 receiving 10% dextrose and 26 receiving 50% dextrose. Median time to recovery was eight minutes in each group.

Of significance, the mean recovery serum glucose level was 6.2 mmol/L (111.6 mg/dL) in the 10% group and 9.4 mmol/L (169.2 mg/dL) in the 50% group. Post-treatment hypoglycemia within 24 hours was equal (four patients in each group): 10% dextrose delivers a significantly lower dose of dextrose (10 g) and is additionally less hypertonic than D50. Thus, 10% dextrose may be a safer, equally efficacious alternative to 50% dextrose.

Considering the research, re-evaluation of the practice of hypertonic dextrose administration seems prudent. Although dextrose administration is a vital component of prehospital pharmacology, prolonged hypoglycemia can result in significant morbidity and even death.

The method of administration and doses currently used in the prehospital setting are not without risk. These risks can easily be tempered with simple changes in the concentration of dextrose used and the dosing schedule.

Utilizing a 10% solution reduces the hypertonicity and total dose of glucose administered and thus potentially reduces the risks of vessel injury and tissue damage from extravasation. A 50 mL dose of 10% solution delivers only 10 g of dextrose versus 50 g in the 50% solution. Clinical trials have demonstrated that 10% and 50% dextrose each demonstrate similar recovery times from hypoglycemic episodes. A benefit, however, of the 10%/10 g dose is that glucose fluctuations are much less significant. This helps control patient blood glucose, as well as minimize of the risk of secondary or rebound hypoglycemia.

Hyperosmolar glucose solutions carry a significant risk of thrombophlebitis, as well as tissue injury if extravasation occurs from peripheral administration. Less hyperosmolar than D50, 10% dextrose thereby reduces these risks. Glucagon, which is administered in small volumes subcutaneously or intramuscularly, carries even less risk, but the onset of action is much more prolonged.

Conclusion
Clearly, additional clinical trials investigating dextrose administration are called for. The current evidence demonstrates that a 10%/10 g bolus is as efficacious as a 50%/50 g bolus, with the advantage that excessive hyperglycemia and glucose fluctuations are minimized, and a reduction in hypertonicity reduces vascular and tissue risks.

Evidence further supports changing the current practice of administering 25 g of 50% dextrose to the alternative of either glucagon or a 10 g/10% solution. Current literature suggests that this practice would be equally efficacious and safer from a range of standpoints.

References

1. Adler PM . “Serum glucose changes after administration of 50% dextrose solution: Pre- and in-hospital calculations.” . American Journal of Emergency Medicine . 1986;4(6):504–506

2. “Endocrinology and Metabolism.” . In:  Kasper D ,  Braunwald E ,  Fauci A , et al. editor. Harrison's Principles of Internal Medicine . 14th edition. New York: McGraw-Hill; 1998;p. 1965–2214

3. Garg R , Chaudhuri A , Munschauer F , et al.   “Hyperglycemia, insulin and acute ischemic stroke: A mechanistic justification for a trial of insulin infusion therapy.” . Stroke . 2006;37(1):267–273

4. Jeremitsky E , Omert LA , Dunham CM , et al.   “The impact of hyperglycemia on patients with severe brain injury.” . The Journal of Trauma . 2005;58(1):47–50

5. Ainla T , Baburin A , Teesalu R . “The association between hyperglycemia on admission and 180-day mortality in acute myocardial infarction patients with and without diabetes.” . Diabetic Medicine . 2005;22(10):1321–1325

6. Andersen SK , Gjedsted J , Christiansen C , et al.   “The roles of insulin and hyperglycemia in sepsis pathogenesis.” . Journal of Leukocyte Biology . 2004;75(3):413–421

7. “Hypoglycemia in infants and children.” . In:  Reid SR ,  Losek JD ,  Bosker G editor. The Textbook of Primary and Acute Care Medicine . Thomson American Health Consultants; 2003;

8. Efron D , South M , Volpe JJ . “Cerebral injury in association with profound iatrogenic hyperglycemia in a neonate.” . European Journal of Paediatric Neurology . 2003;7(4):167–171

9. Kety SS , Schmidt CF . “The nitrous oxide method for the quantitative determination of cerebral blood flow in man: theory, procedure, and normal values.” . Journal of Clinical Investigation . 1948;27(4):476–483

10. Service FJ . “Hypoglycemic disorders.” . New England Journal of Medicine . 1995;332(17):1144–1152

11. Suh SW , Aoyama K , Matsumori Y , et al.   “Pyruvate administered after severe hypoglycemia reduces neuronal death and cognitive impairment.” . Diabetes . 2005;54(5):1452–1458

12. National Diabetes Information Clearinghouse . http://diabetes.niddk.nih.gov/dm/pubs/hypoglycemia/index.htm

13. Cornblath M , Hawdon JM , Williams AF , et al.   “Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds.” . Pediatrics . 2000;105(5):1141–1145

14. Halamek LP , Benaron DA , Stevenson DK . “Neonatal hypoglycemia, Part I: Background and definition.” . Clinical Pediatrics . 1997;36(12):675–680

15. Cryer PE . “Hypoglycemia-associated autonomic failure in diabetes.” . American Journal of Physiology. Endocrinology and metabolism . 2001;281(6):E1115–E11121

16. Kuwahara T , Asanami S , Kubo S . “Experimental infusion phlebitis: Tolerance osmolality of peripheral venous endothelial cells.” . Nutrition . 1998;14(6):496–501

17. Kumar RJ , Pegg SP , Kimble RM . “Management of extravasation injuries.” . ANZ Journal of Surgery . 2001;71(5):285–289

18. Capes SE , Hunt D , Malmberg K . “Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients.” . Stroke . 2001;32(10):2426–2432

19. Balentine JR , Gaeta TJ , Kessler D . “Effect of 50 milliliters of 50% dextrose in water administration on the blood sugar of euglycemic volunteers.” . Academic Emergency Medicine . 1998;5(7):691–694

20. Carstens S , Sprehn M . “Prehospital treatment of severe hypoglycaemia: a comparison of intramuscular glucagon and intravenous glucose.” . Prehospital and Disaster Medicine . 1998;13(2–4):44–50

21. Moore C , Woolard M . “Dextrose 10% or 50% in the treatment of hypoglycaemia out of hospital? A randomised controlled trial.” . Emergency Medicine Journal . 2005;22(7):512–515

Stephen P. Wood, MS, EMT-P, has been a paramedic for 15 years. He is currently the EMS coordinator at the Beth Israel Deaconess Medical Center in Boston, a flight paramedic with Boston MedFlight, and an adjunct faculty member at the New Hampshire Technical Institute.




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Related Topics: Patient Care, Medical Emergencies, dextrose 50, dextrose 10, dextrose administration, hypoglycemia

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