The use of an insulin bolus in low-dose insulin infusion for pediatric diabetic ketoacidosis

The use of an initial bolus of insulin prior to the initiation of low-dose insulin infusion therapy was evaluated in 56 episodes of diabetic ketoacidosis (DKA) in 38 children. The cases were randomly assigned to a group that received a bolus of insulin (n = 24) and to a group that did not (n = 32). After the first hour of insulin therapy, the decline in serum glucose level and the changes in serum osmolality were statistically similar in the two groups, regardless of the degree of acidosis. The time required to reach a serum glucose level of less than 250 mg/dl and the total duration of insulin infusion likewise were similar in the two groups. The use of a bolus of insulin at the onset of treatment for DKA appears unnecessary.     

Comparison of 2 modes of treatment of diabetic ketoacidosis in children

In two groups of children with diabetic ketoacidosis, the effects of intramuscular insulin injections associated with intensive rehydration and alkalisation were compared with low-dose continuous intravenous infusion associated with well-controlled fluid and electrolyte therapy. Although correction of ketoacidosis was as effective with both methods, the second appeared to offer several advantages: 1. More progressive normalization of metabolic parameters; 2. Reduced risks of hypoglycemia and hypokaliemia; 3. Easier control of the decrease in plasma glucose levels; 4. Better correction of hyponatremia; 5. More gradual increase in pH values. These results confirmed that low-dose continuous insulin infusion with proper monitoring of fluid and electrolyte replacement was a safe, simple and effective treatment of diabetic ketoacidosis in children.     

Low-dose intravenous insulin infusion in patients with diabetic ketoacidosis: biochemical effects in children.

Twenty-five episodes of diabetic ketoacidosis in 20 children were treated with continuous low-dose intravenous insulin infusion. Stable serum immunoreactive insulin concentrations were produced, along with prompt falls in glucose, beta-hydroxybutyrate, and glucagon levels, and a steadily increasing bicarbonate level. Neither hypokalemia nor hypophosphatemia developed. Elevated serum alanine concentrations were found during ketoacidosis in contrast to the lowered concentrations found in adults, and were correlated inversely with plasma glucagon concentrations. The treatment regimen described is safe, easy to use, efficacious, and resulted in prompt correction of the observed biochemical alterations in children with diabetic ketoacidosis.     

Diabetic ketoacidosis and hyperosmolar diabetic coma in childhood. Low-dose continuous intravenous infusion of insulin (author's transl)]

Continuous intravenous infusion of low doses of insulin has been successfully used since 1972 in the treatment of "diabetic coma". The achieved levels of plasma insulin satisfy the transport of glucose and the inhibition of lipolysis. We are to report upon 8 children (mean age: 8.5 years), 6 with diabetic ketoacidosis and 2 with hyperosmolar diabetic coma. Blood sugar levels of 300 mg/dl or less were reached after averagely 8 hours of therapy and an average consumption of 0.8 U insulin/kg. Sodium and potassium levels, osmolality and acid base parameters for the first 24 hours are described. Low-dose continuous intravenous insulin infusion was effective, simple and safe in all cases. The presently recommended dosage of 0.1 insulin/kg x hour is to be used flexibly (range: 0.05--0.2 U/kg x hour). The administration of bicarbonate should be cautiously used for patients with severe acidosis. Infusion of hypotonic solutions as part of the treatment of the hyperosmolar diabetic coma can be dangerous. A new therapeutic regime based on our results is proposed.     

Effectiveness of low-dose continuous intravenous insulin infusion in diabetic ketoacidosis. A prospective comparative study.

Twenty pediatric patients with diabetic ketoacidosis were randomly assigned in equal numbers to receive insulin either as a low-dose continuous intravenous infusion or as high-dose intermittent subcutaneous injections. Blood was obtained hourly for determinations of total CO2, plasma glucose, and osmolality, and, in previously untreated patients, plasma insulin. Serum values of beta hydroxybutyrate, electrolytes, and acetone were monitored every two hours. Plasma insulin levels were in the therapeutically effective range with each method of administration. There were no statistically significant differences in rate of correction of ketoacidosis, rate of reduction of plasma glucose, or decline in plasma osmolality. The incidence and the severity of hypokalemia were increased in the patients receiving subcutaneous insulin. There was less variation in the rate of reduction of plasma glucose in the infusion group. Low-dose continuous intravenous infusion of insulin is at least as effective in treating diabetic ketoacidosis as the traditional high-dose intermittent subcutaneous injection of insulin and offers some definite advantages.     

Immediate metabolic response to a low dose of insulin in children presenting with diabetes

Seventeen new cases of diabetes in childhood were given an initial mean dose of insulin of 0-29 unit/kg body weight by intramuscular injection (mean age of patient 7-4 years). This resulted in a fall in blood glucose over the first 2 hours at a mean rate of 88 mg/100 ml per hour. Over the same time the mean total blood ketones fell from 3-23 to 2-3 mmol; and plasma insulin levels rose from a mean of 6 muU/ml to a mean of 65 muU/ml. Thus, with this small initial dose of insulin the 2-hour plasma insulin values were within the range which in adults has been associated with a maximum fall in blood glucose concentration. Three children with established diabetes presenting with ketoacidosis were also treated with a small initial dose of intramuscular insulin, 0-1 unit/kg in 2 of the patients and 0-5 unit/kg in the third. In 2 during a period of rehydration before insulin was given, blood glucose fell at a rate of 100 mg/100 ml per hour. Over the 2 hours after the initial dose of insulin the mean rate of fall of blood glucose for all 3 patients was 73 mg/100 ml per hour. None of these children developed hypoglycaemia nor hypokalaemia during treatment. We conclude that an initial intramuscular injection of soluble insulin in the dose range of 0-1-0-5 units/kg body weight may be more appropriate and possibly safer for the treatment of diabetic ketoacidosis in children than the currently recommended larger doses divided between intravenous and intramuscular routes. Adequate rehydration must, however, remain the first priority in the management of such cases.     

Immediate metabolic response to a low dose of insulin in children presenting with diabetes.

Seventeen new cases of diabetes in childhood were given an initial mean dose of insulin of 0-29 unit/kg body weight by intramuscular injection (mean age of patient 7-4 years). This resulted in a fall in blood glucose over the first 2 hours at a mean rate of 88 mg/100 ml per hour. Over the same time the mean total blood ketones fell from 3-23 to 2-3 mmol; and plasma insulin levels rose from a mean of 6 muU/ml to a mean of 65 muU/ml. Thus, with this small initial dose of insulin the 2-hour plasma insulin values were within the range which in adults has been associated with a maximum fall in blood glucose concentration. Three children with established diabetes presenting with ketoacidosis were also treated with a small initial dose of intramuscular insulin, 0-1 unit/kg in 2 of the patients and 0-5 unit/kg in the third. In 2 during a period of rehydration before insulin was given, blood glucose fell at a rate of 100 mg/100 ml per hour. Over the 2 hours after the initial dose of insulin the mean rate of fall of blood glucose for all 3 patients was 73 mg/100 ml per hour. None of these children developed hypoglycaemia nor hypokalaemia during treatment. We conclude that an initial intramuscular injection of soluble insulin in the dose range of 0-1-0-5 units/kg body weight may be more appropriate and possibly safer for the treatment of diabetic ketoacidosis in children than the currently recommended larger doses divided between intravenous and intramuscular routes. Adequate rehydration must, however, remain the first priority in the management of such cases.     

Outpatient management of diabetic ketoacidosis

An analysis of 63 pediatric diabetic patient visits to an emergency department for diabetic ketoacidosis was performed. Of 27 patients with a serum pH less than 7.20 or bicarbonate concentration less than 10 mmol/L (10 mEq/L) at admission, 25 (92%) had persistence of metabolic acidosis after three hours of outpatient therapy and were hospitalized. Of 36 patients with a serum pH greater than or equal to 7.20 or a bicarbonate concentration greater than or equal to 10 mmol/L (10 mEq/L) at admission, 34 (94%) had resolution of metabolic acidosis within three hours of initiating outpatient therapy and were discharged from the emergency department. The relapse rate in each group was similar. The initial serum glucose concentration accurately predicted duration of therapy necessary to resolve metabolic acidosis in the majority of patients discharged. Certain diabetic children can be treated for diabetic ketoacidosis with therapy administered in an outpatient setting. Most patients with an initial serum pH of 7.20 or higher or a bicarbonate concentration of 10 mmol/L (10 mEq/L) or higher will experience resolution of acidosis and tolerate feeding within three hours of initiating treatment.     

Low-dose continuous intravenous insulin infusion in childhood diabetic ketoacidosis.

We studied 58 children with diabetic ketoacidosis using a random, prospective protocol, with insulin administered either as a low-dose continuous infusion or as high-dose intermittent subcutaneous injections. There were no statistically significant differences between admission pH and glucose determinations or the time to metabolic correction. The incidence of hypoglycemia and hypokalemia was higher in patients receiving subcutaneous insulin. Insulin levels in the low-dose patients were 85--160 microU/ml. The insulin required to achieve metabolic recovery was 1.6 U/kg in the low-dose group and 4.5 U/kg in the high-dose group (p less than 0.01). Glucose administered at a rate of 3 to 4 g er unit of insulin infused in the low-dose group maintained a serum glucose of 150 to 250 mg/dl. Our studies suggest that low-dose intravenous insulin therapy is safe, as effective as high-dose intermittent subcutaneous injections and avoids the risks of hypoglycemia and hypokalemia. Meticulous attention to individual patient care, however, must remain the most important single variable.     

Continuous subcutaneous insulin infusion in diabetes mellitus. A year's prospective trial.

Thirteen children aged between 8 and 16 years were entered into a 12 month prospective trial comparing continuous subcutaneous insulin infusion with intensified conventional treatment. Two of seven children on insulin infusion withdrew after eight and nine weeks, and three of six children on conventional treatment withdrew after four to eight weeks. Withdrawals in both groups were related to dissatisfaction with the techniques. The group on insulin infusion treatment achieved a mean plasma glucose of 9.8 mmol/l (176.4 mg/100 ml), a median M value of 50 mmol/l (900 mg/100 ml) and a mean glycosylated haemoglobin of 9.1% during the year. This represents a significant improvement compared with the previous values, and also when compared with the conventional treatment group whose trial values of a mean plasma glucose of 15.5 mmol/l (279 mg/100 ml), median M value of 167 mmol/l (3006 mg/100 ml), and glycosylated haemoglobin of 10.4% were not significantly different from those before the trial. Two children on insulin infusion developed subcutaneous abscesses in the early months. There was an increased incidence of diabetic ketoacidosis in this group, but no difference in the incidence of serious hypoglycaemia between the two groups. The children reported improved well-being when using insulin infusion and continued with the technique after the trial finished. Insulin infusion offers an acceptable means of improving glycaemic control for some diabetic children.     

Practical management of diabetic ketoacidosis in childhood and adolescence

Diabetic ketoacidosis results from insulin deficiency and insulin resistance and is marked by hyperglycaemia, ketoacidosis, dehydration and electrolyte losses. Management includes correction of shock, dehydration, electrolyte deficits, hyperglycaemia, acidosis and sepsis (if present). Warning signs include severe dehydration, shock, pH <7.0, hypokalaemia, hypernatraemia, hyperosmolality, hyperlipidaemia, deterioration in consciousness and diabetic ketoacidosis in very young patients. The principles of treatment include (i) admission to a unit with paediatric experience, (ii) treatment of shock, (iii) rehydration over 24-36 h, or longer if the osmolality is >360 mmoll⁻¹, (iv) normal saline for rehydration unless the patient is hypernatraemic, (v) avoidance of bicarbonate unless acidosis is interfering with myocardial contractility, (vi) insulin infusion to achieve a fall in blood glucose levels of 5 mmol h⁻¹, (vi) potassium, (vii) use of 5% glucose when the blood glucose level falls <12 mmol 1⁻¹, (ix) treatment of any complications and (x) change to subcutaneous insulin when diabetic ketoacidosis is controlled.     

Low dose (0.05 units/kg/h) is comparable with standard dose (0.1 units/kg/h) intravenous insulin infusion for the initial treatment of diabetic ketoacidosis in children with type 1 diabetes—an observational study

Puttha R, Cooke D, Subbarayan A, Odeka E, Ariyawansa I, Bone M, Doughty I, Patel L, Amin R. Low dose (0.05 units/kg/h) is comparable with standard dose (0.1 units/kg/h) intravenous insulin infusion for the initial treatment of diabetic ketoacidosis in children with type 1 diabetes—an observational study
Objective: To compare low dose (0.05 units/kg/h) with standard dose (0.1 units/kg/h) intravenous insulin infusion for the treatment of diabetic ketoacidosis (DKA) in children with type 1 diabetes.
Study design: Data from five paediatric centres were compared in children who received 0.05 (41 episodes) or 0.1 units/kg/h (52 episodes).
Results: In the low vs. standard dose group, at 6 h following admission, the fall in blood glucose levels [11.3 (95% confidence interval 8.6 to 13.9) vs. 11.8 (8.4 to 15.2) mmol/L, p = 0.86] and rise in pH [0.13 (0.09 to 0.18) vs. 0.11 (0.07 to 0.15), p = 0.78] were similar. These changes were comparable between doses in relation to: severity of initial acidosis, children newly diagnosed with diabetes or aged less than 5 years. After adjustment for other clinical and biochemical covariates, insulin dose was unrelated to the change in pH and blood glucose levels at 6 h following admission. Comparisons of safety data, particularly in relation to abnormal Glasgow Coma Score, were inconclusive.
Conclusion: In this observational study, low dose was as effective as standard dose intravenous insulin infusion in the initial treatment (less than 6 h) of DKA in children with type 1 diabetes. A randomised controlled trial is required to show true equivalence between doses and to evaluate potential safety benefits.     

Care in diabetic emergencies

A review is presented on the care of three diabetic emergencies : diabetic ketoacidosis (DKA), hypoglycemias and sick days. A treatment scheme, based on low-dose insulin regime and i.v. insulin administration is presented. Plenty of emphasis is laid on fluid and electrolyte therapy. It is stressed that the primary goal in the treatment of DKA is not to reduce blood glucose, but to correct the fluid and electrolyte deficit and by administering insulin to correct the metabolic acidosis and change catabolism into anabolism. The use of bicarbonate in severe DKA is discouraged, and the risk of cerebral edema as a complication of the treatment is stressed. A diabetic child being treated for DKA needs particularly love and care. The three categories of hyperglycemias, mild, moderate, and severe, are briefly reviewed. In severe hypoglycemia (hypoglycemic shock) the treatment is either i.m. glucagon or i.v. glucose. In acute illnesses the use of extra doses of regular insulin is emphasized, in order to prevent DKA     

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目的探讨儿童糖尿病酮症酸中毒并发脑水肿的临床特征及危险因素。方法对重庆医科大学附属儿童医院1993—2005年住院治疗的糖尿病酮症酸中毒并发脑水肿患儿的临床特征及病因进行分析,并与未并发者进行对照比较。结果在71例酮症酸中毒患儿中,有6例临床表现符合脑水肿的诊断标准,临床确定为并发脑水肿,并发率为8·4%。6例均为重型酮症酸中毒。与未发生脑水肿同等程度的重型酮症酸中毒患儿相比较,并发脑水肿患儿酸中毒更为严重,在治疗期间血钠上升缓慢及持续低钠血症,尿素氮水平升高。6例患儿中有5例应用碳酸氢盐治疗,用量大于未并发者。结论糖尿病儿童并发重型酮症酸中毒易发生脑水肿。严重酸中毒、血钠上升缓慢或持续低钠血症、血尿素氮升高及碳酸氢盐的使用有可能增加脑水肿发生的危险性。     

Low-dose intravenous insulin infusion versus subcutaneous insulin injection: a controlled comparative study of diabetic ketoacidosis.

Fourteen paients, 5 to 17 years old, with 18 episodes of uncomplicated diabetic ketoacidosis were randomly allocated and studied prospectively. The study group received 0.1 units of insulin per kilogram of body weight per hour as a continuous intravenous infusion; the control group received insulin subcutaneously. In both groups, a gradual fall in serum glucose and ketone levels was achieved. Serum ketones persisted longer in the intravenous group. No complications were encountered. The study suggests that both regimens of insulin administration are equally effective, but a low-dose constant infusion may provide more simplified and controlled management than the standard subcutaneous regimen.     

TREATMENT OF DIABETIC COMA IN CHILDREN

Abstract. A short review is given on current aspects of the low-dose insulin therapy of diabetic ketoacidosis, and briefly on the other aspects of the treatment. Frequent intramuscular administration of low doses of regular insulin leads to plasma insulin concentrations, sufficient for maximal insulin biologic activity. The intravenous and subcutaneous routes of insulin administration are suitable as well in the low-dose insulin therapy. The author described results from a retrospective study comparing the efficacy of large and small insulin doses in the treatment of diabetic precoma and coma in children (1). The i.m. administration of insulin, 0.5 U/kg initially, followed by 0.25 U/kg at intervals of 1/22 hours led to as rapid disappearance of the signs and symptoms of ketoacidosis as with previously used larger insulin doses. The tendency to hypoglycemia and hypokalemia was milder with the smaller insulin dose. With such a modified low-dose insulin therapy it is essential to initiate i.v. glucose administration rather early. The responsiveness to insulin may vary from one child to another, and infections may increase the need for insulin. Therefore, careful individual monitoring of the treatment is important even when using the low-dose insulin therapy.     

Treatment of diabetic coma in children.

A short review is given on current aspects of the low-dose insulin therapy of diabetic ketoacidosis, and briefly on the other aspects of the treatment. Frequent intramuscular administration of low doses of regular insulin leads to plasma insulin concentrations, sufficient for maximal insulin biologic activity. The intravenous and subcutaneous routes of insulin administration are suitable as well in the low-dose insulin therapy. The author described results from a retrospective study comparing the efficacy of large and small insulin doses in the treatment of diabetic precoma and coma in children (1). The i.m. administration of insulin, 0.5 U/kg initially, followed by 0.25 U/kg at intervals of 1/2-3 hours led to as rapid disappearance of the signs and symptoms of ketoacidosis as with previously used larger insulin doses. The tendency to hypoglycemia and hypokalemia was milder with the smaller insulin dose. With such a modified low-dose insulin therapy it is essential to initiate i.v. glucose administration rather early. The responsiveness to insulin may vary from one child to another, and infections may increase the need for insulin. Therefore, careful individual monitoring of the treatment is important even when using the low-dose insulin therapy.     

Low-dose intravenous insulin in the treatment of diabetic ketoacidosis.

Continuous slow intravenous infusion of insulin was used in 52 episodes of diabetic ketoacidosis. No complications of therapy, ie, hypoglycemia, induced hypokalemia, insulin resistance, or cerebral edema, were encountered. Potassium phosphate was given to 47 of the 52 patients. Sodium bicarbonate was administered to only one patient. The hyperglycemia frequently resolved more rapidly than the systemic acidosis; this was managed by adding glucose to the intravenous fluids when the blood sugar concentration decreased to approximately 250 mg/dL; insulin infusion, however, was continued until the acidosis was corrected (venous standard bicarbonate greater than 14 mEq/L). We have found this method of treatment to be safe and simple to administer, and we believe it is the preferred treatment of patients with diabetic ketoacidosis.     

Prediction of Starting Dose for Conventional Insulin Treatment (Using the Practical Closed-Loop System)

This study was undertaken in 10 newly diagnosed diabetic children to assess the usefulness of the practical closed-loop system in determining insulin doses in conventional treatment. During application of this system of continuous intravenous insulin infusion, the infusion dose was changed according to the hourly monitored blood glucose values. Conventional insulin treatment was started, based on the daily insulin profile obtained by the practical close-loop system. This consisted of two daily injections of a mixture of short- and intermediate-acting insulins. There was no significant difference in mean blood glucose, M-value or mean amplitude of glycemic excursions between the two treatments. Compared with the previous insulin regimen in which conventional insulin treatment was performed following the initial treatment for diabetic ketoacidosis without this practical closed-loop system, good glycemic control was obtained in a shorter period by using this system. Thus, the practical closed-loop system could be helpful in predicting the starting insulin dose for conventional insulin treatment.     

Care in diabetic emergencies

A review is presented on the care of three diabetic emergencies : diabetic ketoacidosis (DKA), hypoglycemias and sick days. A treatment scheme, based on low-dose insulin regime and i.v. insulin administration is presented. Plenty of emphasis is laid on fluid and electrolyte therapy. It is stressed that the primary goal in the treatment of DKA is not to reduce blood glucose, but to correct the fluid and electrolyte deficit and by administering insulin to correct the metabolic acidosis and change catabolism into anabolism. The use of bicarbonate in severe DKA is discouraged, and the risk of cerebral edema as a complication of the treatment is stressed. A diabetic child being treated for DKA needs particularly love and care. The three categories of hyperglycemias, mild, moderate, and severe, are briefly reviewed. In severe hypoglycemia (hypoglycemic shock) the treatment is either i.m. glucagon or i.v. glucose. In acute illnesses the use of extra doses of regular insulin is emphasized, in order to prevent DKA