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Hypoglycemia treatment

Question Type:
Intervention
Full Question:
Among adults and children with symptomatic hypoglycemia (P), does administration of dietary forms of sugar (I), compared with standard dose (15 - 20 gm) of glucose tablets (C), change time to resolution of symptoms, risk of complications (eg aspiration), blood glucose, Hypoglycaemia, hospital length of stay (O)?
Consensus on Science:
Dietary Sugars (I) Compared With Glucose Tablets (C) For the critical outcome of time to resolution of symptoms, none of the 4 studies identified(Brodows 1984, 3378; Slama 1990, 589; Husband 2010, 154; McTavish 2011, 381) showed that any form of dietary sugar or glucose tablets improved the blood glucose before 10 minutes. For the important outcome of hypoglycemia (clinical relief in 15 minutes or less), we identified low-quality evidence (downgraded for risk of bias and imprecision) from 3 randomized controlled studies(Slama 1990, 589; Husband 2010, 154; McTavish 2011, 381) with pooled data from 502 diabetic patients treated with dietary sugars (sucrose, fructose, orange juice, jelly beans, Mentos, and milk) and 223 treated with glucose tablets (15–20 g) that showed a benefit with glucose tablets, with slower resolution of symptoms 15 minutes after diabetic patients were treated with dietary sugars compared with glucose tablets (RR, 0.89; 95% CI, 0.83–0.96). For the important outcome of blood glucose (diabetic patients with at least a 20-mg/dL increase of blood glucose by 20 minutes), we found very-low-quality evidence (downgraded for risk of bias and imprecision) from 1 observational study(Brodows 1984, 3378) with 13 diabetic patients treated with dietary sugars and 9 treated with glucose tablets that showed a benefit with glucose tablets, with fewer diabetic patients demonstrating a 20-mg/dL increase in blood glucose level 20 minutes after treatment when treated with dietary sugars compared with glucose tablets (RR, 0.3; 95% CI, 0.1–0.85). For the critical outcome of time to resolution of symptoms, the important outcome of risk of complications (eg, aspiration), and the low-priority outcome of hospital length of stay, there were no human trials found. Sucrose (I) Compared With Glucose Tablets (C) For the important outcome of hypoglycemia (clinical relief in 15 minutes or less), we found low-quality evidence (downgraded for risk of bias and imprecision) from 2 RCTs(Slama 1990, 589; Husband 2010, 154) with pooled data from 177 diabetic patients treated with sucrose (165 with sucrose candy [Skittles] and 12 with sucrose tablets) and 171 treated with glucose tablets that showed no difference in their effects on blood glucose. Sucrose (either as sucrose candy [Skittles] or sucrose tablets) and glucose tablets were equivalent in providing clinical relief of hypoglycemia 15 minutes after ingestion (RR, 0.99; 95% CI, 0.91–1.07). For the important outcome of blood glucose (mean change in blood glucose [mmol/L] after 15 minutes), we found low-quality evidence (downgraded for risk of bias and imprecision) from 1 randomized controlled study(Slama 1990, 589) with 6 diabetic patients treated with sucrose (dissolved in water) and 6 treated with glucose tablets that showed a benefit to glucose administration, with the MD (mmol/L) in blood glucose 15 minutes after ingestion lower with sucrose (dissolved in water) than glucose tablets (MD, −0.9; 95% CI, −1.78 to −0.02). A second arm of this same study with 6 diabetic patients treated with sucrose (chewed) and 6 treated with glucose tablets showed no benefit, with the MD (mmol/L) in blood glucose 15 minutes after ingestion similar between sucrose (chewed) and glucose tablets (MD, 0.3; 95% CI, −0.8 to 1.41). For the critical outcome of time to resolution of symptoms, the important outcome of risk of complications (eg, aspiration), and the lower-priority outcome of hospital length of stay, there were no human trials found. Fructose (I) Compared With Glucose Tablets (C) For the important outcome of hypoglycemia (clinical relief in 15 minutes or less), we found low-quality evidence (downgraded for risk of bias and imprecision) from 1 RCT(Husband 2010, 154) with 165 diabetic patients treated with fructose (Fruit to Go) and 165 treated with glucose tablets that showed benefit with glucose, with a lower incidence of resolution of symptoms 15 minutes after treatment for diabetic patients treated with fructose compared with glucose tablets (RR, 0.77; 95% CI, 0.68–0.86). For the critical outcome of time to resolution of symptoms, the important outcomes of risk of complications (eg, aspiration) and blood glucose, and the low-priority outcome of hospital length of stay, there were no human trials found. Orange Juice (I) Compared With Glucose Tablets (C) For the important outcome of hypoglycemia (clinical relief in 15 minutes or less), we found very-low-quality evidence (downgraded for risk of bias, inconsistency, and imprecision) from 2 RCTs(Slama 1990, 589; McTavish 2011, 381) with the pooled data of 50 diabetic patients treated with orange juice and 58 treated with glucose tablets that showed no difference in the resolution of symptoms 15 minutes after treatment for diabetic patients treated with orange juice compared with glucose tablets (RR, 0.84; 95% CI, 0.69–1.02). For the important outcome of blood glucose, we identified very-low-quality evidence (downgraded for risk of bias and imprecision) from 1 RCT(Slama 1990, 589) with 6 diabetic patients treated with orange juice and 6 treated with glucose tablets that showed no benefit with glucose tablets, with the MD (mmol/L) in blood glucose 15 minutes after ingestion lower with orange juice than with glucose tablets (MD, −0.7; 95% CI, −1.55 to −0.15). Very-low-quality evidence (downgraded for risk of bias and imprecision) from 1 observational study(Brodows 1984, 3378) with 8 diabetic patients treated with orange juice and 9 treated with glucose tablets showed no difference in a diabetic patient’s likelihood of having a 20-mg/dL increase in blood glucose level 20 minutes after treatment with orange juice compared with glucose tablets (RR, 0.48; 95% CI, 0.18–1.26). For the critical outcome of time to resolution of symptoms, the important outcome of risk of complications (eg, aspiration), and the low-priority outcome of hospital length of stay, no human trials were found. Jelly Beans (I) Compared With Glucose Tablets (C) For the important outcome of hypoglycemia (clinical relief less in 15 minutes or less), we found very-low-quality evidence (downgraded for risk of bias and imprecision) from 1 RCT(McTavish 2011, 381) with 45 diabetic patients treated with jelly beans and 52 treated with glucose tablets that showed no difference in the resolution of symptoms 15 minutes after treatment, whether diabetic patients were treated with jelly beans or glucose tablets (RR, 0.85; 95% CI, 0.69–1.04). For the critical outcome of time to resolution of symptoms, the important outcomes of risk of complications (eg, aspiration) and blood glucose, and the low-priority outcome of hospital length of stay, no human trials were found. Mentos (I) Compared With Glucose Tablets (C) For the important outcome of hypoglycemia (clinical relief in 15 minutes or less), we found very-low-quality evidence (downgraded for risk of bias and imprecision) from 1 RCT(McTavish 2011, 381) with 48 diabetic patients treated with Mentos and 52 treated with glucose tablets that showed no difference in the resolution of symptoms 15 minutes after treatment, whether diabetic patients were treated with Mentos or glucose tablets (RR, 1.06; 95% CI, 0.92–1.21). For the critical outcome of time to resolution of symptoms, the important outcomes of risk of complications (eg, aspiration) and blood glucose, and the low-priority outcome of hospital length of stay, no human trials were found. Milk (I) Compared With Glucose Tablets (C) For the important outcome of blood glucose (diabetic patients with at least a 20-mg/dL increase of blood glucose by 20 minutes), we found very-low-quality evidence (downgraded for risk of bias and imprecision) from 1 observational study(Brodows 1984, 3378) that included 5 diabetic patients treated with whole milk and 9 treated with glucose tablets, showing no difference in likelihood of a 20-mg/dL increase in blood glucose level 20 minutes after treatment, whether diabetic patients were treated with milk or glucose tablets (RR, 0.11; 95% CI, 0.01–1.62). For the critical outcome of time to resolution of symptoms, the important outcomes of risk of complications (eg, aspiration) and hypoglycemia, and the low-priority outcome of hospital length of stay, no human trials were found. Glucose Gel (I) Compared With Glucose Tablets (C) For the important outcome of hypoglycemia (clinical relief in 15 minutes or less), we identified very-low-quality evidence (downgraded for risk of bias and imprecision) from 1 RCT(Slama 1990, 589) that included 6 diabetic patients treated with glucose gel and 6 treated with glucose tablets, finding no difference in the resolution of symptoms 15 minutes after treatment (RR, 0.5; 95% CI, 0.14–1.77). For the critical outcome of time to resolution of symptoms, the important outcomes of risk of complications (eg, aspiration) and blood glucose, and the low-priority outcome of hospital length of stay, no human trials were found. Glucose Solution (I) Compared With Glucose Tablets (C) For the important outcome of hypoglycemia (clinical relief in 15 minutes or less), we identified very-low-quality evidence (downgraded for risk of bias and imprecision) from 1 RCT(Slama 1990, 589) that included 6 diabetic patients treated with glucose solution and 6 treated with glucose tablets, finding no difference in the resolution of symptoms 15 minutes after treatment (RR, 1.25; 95% CI, 0.64–2.44). For the critical outcome of time to resolution of symptoms, the important outcomes of risk of complications (eg, aspiration) and blood glucose, and the low-priority outcome of hospital length of stay, no human trials were found. Cornstarch Hydrolysate (I) Compared With Glucose Tablets (C) For the important outcome of hypoglycemia (clinical relief in 15 minutes or less), we found very-low-quality evidence (downgraded for risk of bias and imprecision) from 1 RCT(Slama 1990, 589) that included 5 diabetic patients treated with cornstarch hydrolysate 15 g and 6 treated with glucose tablets, finding no difference in the resolution of symptoms 15 minutes after treatment (RR, 1.20; 95% CI, 0.59–2.45). For the critical outcome of time to resolution of symptoms, the important outcomes of risk of complications (eg, aspiration) and blood glucose, and the low-priority outcome of hospital length of stay, no human trials were found. • The following dietary sugars were evaluated in the included studies: • Skittles: ~90 g carbohydrate per 100 g, sugar (sucrose) corn syrup, partially hydrogenated soybean oil, fruit juice from concentrate (grape, strawberry, lemon, lime, orange), citric acid, dextrin, natural and artificial flavors, gelatin, food starch–modified coloring, ascorbic acid • Fruit to Go: apple pure concentrate; apple, cherry, and elderberry juice concentrates; wild berry concentrate (concentrated cherry, raspberry, blueberry, cranberry and boysenberry juices, natural flavor); citrus pectin; natural flavor; lemon juice concentrate • Mentos: 2.8 g carbohydrate in each mint (71% glucose and 29% oligosaccharides), 91.6 g carbohydrate per 100 g, 69.3 g sugar per 100 g, sugar, glucose syrup (corn), reconstituted fruit juices (strawberry, orange, lemon; 2.5%), hydrogenated vegetable oil (coconut), acid (citric acid), rice starch, thickeners (gum arabic, gellan gum, flavorings, glazing agent [carnauba wax]), emulsifier (sucrose esters of fatty acids), colors • Glucose gel: 15 g of glucose in 40 g of 40% dextrose gel (Hypostop, Novo Industries) • Glucose solution: 15 g of glucose dissolved in 150 mL of water • Cornstarch hydrolysate: 15 g of cornstarch hydrolysate containing 2% to 3% glucose, 6% to 8% maltose, 89% to 92% oligosaccharides and polysaccharides, and 0.15% protein (Glucides 19, Roquette Freres, Lestrem, France) diluted in 150 mL of water.
Treatment Recommendation:
We recommend that first aid providers administer glucose tablets for treatment of symptomatic hypoglycemia in conscious individuals (strong recommendation, low-quality evidence). We suggest that if glucose tablets are not available, various forms of dietary sugars such as Skittles, Mentos, sugar cubes, jelly beans, or orange juice can be used to treat symptomatic hypoglycemia in conscious individuals (weak recommendation, very-low-quality evidence). There is insufficient evidence to make a recommendation on the use of whole milk, cornstarch hydrolysate, and glucose solution, or glucose gels as compared with glucose tablets for the treatment of symptomatic hypoglycemia. Values, Preferences, and Task Force Insights In making this recommendation, we acknowledge the likelihood that glucose tablets will not always be available and that other dietary sugars are often more accessible. In the 4 studies, most individuals had symptom improvement 10 to 15 minutes after treatment. A rerun of the original literature search was performed in January 2015. No new studies were identified that subsequently altered the treatment recommendation. This review generated a number of excellent questions within the ILCOR task forces and via public commenting. Several of the comments asked if alternative forms of candy or dietary sugars could be substituted for those listed in the tables. Although alternative dietary sugars and candy may be effective in treating hypoglycemia, the forms of sugars listed in this review are the specific dietary sugars that have been evaluated, with the specific amount used (ie, number of candies or amount of orange juice) equating to glucose 15 to 20 g. Those who commented also asked if there is any harm from giving more than the tested amount of dietary sugars. While this review did not look at adverse effects of administering more sugar than needed, it is well known that providing more sugar than needed to diabetics with symptomatic hypoglycemia can lead to “overshooting” of blood glucose goals, which, when repeated over time, may be as harmful as recurrent episodes of hypoglycemia. Concern was expressed over administration of oral sugars to diabetics with symptomatic hypoglycemia, particularly if they have altered mental status. The recommendations made by this task force apply to individuals with symptomatic hypoglycemia who are conscious, able to follow commands, and able to swallow. If these criteria are not present, oral treatment should be withheld because there is risk of aspiration, and EMS (ie, 9-1-1 rescue services) should be contacted. The evidence reviewers for this topic were asked if some guidance could be provided in terms of the time required for resolution of symptoms of hypoglycemia after treatment using dietary sugar supplements as tested, to help determine when a repeat treatment may be necessary. For all tested dietary sugars, blood glucose levels did not improve substantially until 10 to 15 minutes after treatment (Figure 3). Glucose gels and paste are not directly equivalent to oral glucose tablets in terms of dosing and absorption, and, therefore, we did not include them in the control arm of this review. Instead, these agents were included as interventions compared with glucose tablets, with the finding of a single study with a very small number of subjects, showing them to be suboptimal as compared with oral glucose tablets. The task force strongly believes that further studies are needed with glucose gels and paste to determine if they are absorbed through the buccal mucosa or sublingually (versus swallowed), and to determine any dose equivalence to glucose tablets. We are aware of studies evaluating dextrose spray, gel, or paste for neonates or children, but without a glucose tablet comparison; thus, these studies were excluded from this review.
CoSTR Attachments:
Background Table dietary sugar vs. glucose tablets 11.25.14.docx    
CoSTR_hypoglycemia02-22-15.docx    
GRADE table 2.20.15.docx    

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