Diabetes Mellitus
The endocrine condition most frequently encountered in the perioperative period in children is diabetes mellitus. Diabetes mellitus is the result of an absolute or functional deficiency of insulin production by the pancreas. In type 1 diabetes, this deficiency is caused by an autoimmune process, mediated by autoantibodies including anti-GAD (glutamic acid decarboxylase) and insulinoma-associated antibody. Insulin deficiency results in abnormalities of glucose transport and storage and of lipid and protein synthesis. Over time, these metabolic derangements result in the vascular pathology that leads to end-stage complications of renal, cardiac, and eye disease; diseases that typically do not occur in childhood. The anesthetic implications of type 1 diabetes in children differ from those in adults with the same disease, for whom the primary concern is the type and severity of end organ disease. Perioperative insulin administration is essential to control glucose and to promote an anabolic state, which is most conducive to speedy healing and metabolic homeostasis.
Type 2 diabetes, insulin resistance without evidence of autoimmunity, has been increasing in the pediatric population by 4.8% per year.
Children with insulin-dependent diabetes may be treated with various types of insulin on a daily basis to maintain tight blood glucose control, with the aid of frequent or constant blood glucose monitoring. Currently, all Food and Drug Administration (FDA)-approved insulin preparations are produced using recombinant DNA technology with laboratory-cultivated bacteria or yeast. Animal-sourced insulin has not been produced in the United States since the manufacturers voluntarily discontinued production of beef insulin in 1998 and porcine insulin in 2006. Insulin products called insulin analogs are produced so the structure differs slightly from human insulin (by one or two amino acids) to change onset and peak of action. Examples of analogs include lispro (Humalog), aspart (Novolog), and glulisine (Apidra), ultrashort-acting insulins that may be given only 15 minutes before a meal or even within 20 minutes of beginning a meal ( Table 10.1 ). The peak and duration of action of these analogs parallel the glucose rise that results from carbohydrate ingestion.
| Insulin | Trade Name | Route | Onset (h) | Peak (h) | Effective Duration (h) |
|---|---|---|---|---|---|
| Rapid-Acting | |||||
| Lispro | Humalog | SC | 0.25 | 0.5–1.5 | 3–4 |
| Aspart | Novolog | SC | 0.25 | 1–3 | 3–5 |
| Glulisine | Apidra | SC | 0.25–0.5 | 0.5–1 | 4 |
| Short-Acting | |||||
| Regular | Humulin, Novolin | IV/SC | 0.5–1.0 | 2–3 | 3–6 |
| Long-Acting | |||||
| Glargine | Lantus | SC | 1.0 | 2–3 | 24 |
| Detemir | Levemir | SC | 1.0 | 3–6 | 20* |
Glargine (Lantus, Basaglar) and detemir (Levemir), which almost mimic an insulin pump’s basal infusion, provide a 24-hour, continuous low background level of insulin with only one subcutaneous daily injection. Twice-daily injections may be superior to once-daily with detemir. Both of these agents are used in combination with ultrashort-acting analogs to mimic endogenous insulin secretion seen in nondiabetics.
An increasing number of children are being managed with continuous subcutaneous insulin infusion (CSII) via an external insulin pump, which provides a background (basal) infusion of insulin and the ability to give boluses before meals and for correction of hyperglycemia. The newest insulin pumps incorporate feedback from continuous glucose monitoring systems (CGMS) to adjust insulin delivery according to the patient’s blood sugar using a hybrid closed-loop system (HCLS).
Type 2 diabetes in children and adolescents may be controlled with diet and exercise, but these children also may be taking metformin (Glucophage).
Preoperative Optimization
Because of the effects of surgical stress on glucose homeostasis, insulin-dependent diabetic children are at risk for acute fluctuations in blood glucose, even when their preoperative glucose control is good. Poorly controlled or noncompliant diabetic patients have additional problems, including an increased risk for perioperative hypoglycemia or hyperglycemia, osmotic diuresis with resultant hypovolemia, and altered mental status. Coordination and cooperation among the patient, parents, pediatrician, endocrinologist, and anesthesiologist are essential to prepare for the perioperative period.
Preoperative anesthesia evaluation for elective procedures, informed by contemporaneous endocrine assessment of adequacy of glucose control, should be completed 7 to 10 days before the scheduled date of surgery to allow adjustment of treatment regimen or delay of procedure if control is not optimal. The International Society for Pediatric and Adolescent Diabetes published a comprehensive review of concerns and perioperative management of pediatric diabetic patients; it features useful clinical practice guidelines, incorporating both preoperative assessment and perioperative insulin regimens.
The preoperative evaluation should include a review of recent measurements of glucose levels over a period of days or weeks because a single, isolated value does not indicate the adequacy or quality of glycemic control. A hemoglobin A 1C level (i.e., glycosylated hemoglobin assay), although a useful index of long-term (i.e., over the preceding 2–3 months) glucose control, is unlikely to affect the anesthetic plan and is not an essential preoperative test. With the rise of continuous glucose monitoring systems, time in range (TIR) has become a useful and clinically meaningful metric and outcome measure. TIR has been defined as the percentage of blood glucose readings in the target range of 70 to 180 mg/dL per unit of time. Compared with Hb A 1C , TIR captures all glucose levels, including hypoglycemia and hyperglycemia, over a given time frame and is more likely to reveal the impact of acute interventions and changes in diabetes management.
Perioperative Management
Various regimens for managing insulin therapy perioperatively have been proposed, including frequent blood sugar monitoring without altering the patient’s usual regimen and relying upon either a long-acting insulin analog or the patient’s subcutaneous infusion insulin pump to provide a basal level of insulin, intravenous (IV) insulin infusion, and the “classic” regimen ( Table 10.2 ).
| Regimen | Morning of Surgery Procedure |
|---|---|
| Classic regimen |
|
| Continuous insulin infusion |
|
| Insulin- and glucose-free regimen (for operative procedures of short duration) |
|
Regardless of the regimen chosen, it is ideal to schedule elective surgery for the diabetic child as early as possible in the day to minimize fasting times and thus reduce the risk for hypoglycemia. The fasting interval should be the same as that recommended for nondiabetic patients: no solid food or milk for 6 hours (or 8 hours, depending on institutional practice and policy). Children with diabetes should be encouraged to continue to drink clear liquids up until the time allowed by institutional policy. The sugar content of the clear liquid will depend on the chosen perioperative insulin regimen. With type 2 diabetes, metformin should be stopped 48 hours before surgery based on reports of lactic acidosis in patients who remain on the drug and are in a fasting state perioperatively.
Although some investigators have recommended the withholding of preoperative sedation from diabetic patients to better monitor for signs of hypoglycemia, premedication is recommended in children. The use of agents such as benzodiazepines, opioids, or barbiturates does not alter glucose metabolism, and a mild rise in blood sugar (caused by the catecholamine response to anxiety) might actually occur with avoidance of these agents.
Based on blood glucose level determined on arrival to the preoperative facility and before implementation of the regimens discussed below, glucose and/or insulin should be administered according to a sliding scale scheme ( Table 10.3 ). With the proliferation of long-acting insulin analogs and subcutaneous insulin infusion pumps, perioperative insulin therapy often does not require major deviation from the patient’s usual regimen.
| Blood Glucose Level | Management |
|---|---|
| <80 mg/dL | 2 mL/kg D10W followed by glucose infusion |
| 80–250 mg/dL | D5/0.45 NS or D10/0.45 NS solution at maintenance if IV insulin is to be administered; 0.9 NS if short case without insulin infusion |
| >250 mg/dL | Administer rapid-acting (lispro) or short-acting (regular) insulin SC to reduce blood sugar; use correction factor from patient’s endocrine provider or 0.2 unit/kg SC |
| >350 mg/dL | Consider canceling or postponing surgery, especially if ketonuria is present |
Long-Acting Insulin Analogs and Subcutaneous Infusion Insulin Pumps
Patients who are maintained on a home regimen involving once- (or twice-) daily subcutaneous injections of a long-acting analog (e.g., glargine or detemir) can take their normal dose the night before and/or on the morning of surgery. Insulin pump basal infusions can be maintained at their normal rate. If morning hypoglycemia is an issue or concern, the dose or basal rate can be reduced slightly (up to one-third of normal), but this carries the risk for hyperglycemia and ketosis that may be more problematic than mild hypoglycemia. Parents should be advised to check their child’s blood sugar upon arising that morning and correct hyperglycemia according to their usual routine, and blood sugar should be rechecked upon arrival to the hospital or surgical facility. Hypoglycemia should be treated with clear, glucose-containing fluids (e.g., apple juice, white grape juice, Pedialyte) to avoid delaying the anesthetic, because clear liquids may be allowed up until 1 hour before the induction of anesthesia.
Increasing numbers of pediatric patients with type 1 diabetes are being managed with external insulin pumps capable of subcutaneous administration of both continuous and bolus doses of insulin. Such pumps afford excellent control, with changes in administration coordinated with eating, exercise, and stress. The increasing adoption of CSII technology is an indication of the added convenience and quality of glucose control for patients in the outpatient setting, and these benefits can be observed in the inpatient and hospital setting as well. The use of insulin pumps throughout the perioperative period, including intraoperatively, has become widely accepted as standard practice, regardless of the anticipated duration of the procedure or anesthetic. The use of insulin pumps in the MRI suite or magnetoencephalography (MEG) is contraindicated, but for short studies (under 1–2 hours), the pump can be disconnected with little effect on blood glucose levels and reconnected immediately at the cessation of the study; any hyperglycemia can be corrected at that time. Most manufacturers recommend against the use of insulin pumps in the setting of ionizing radiation (e.g., x-rays, fluoroscopy, computed tomography [CT] scan), but many practitioners will use lead aprons to shield the pump in those cases. In surgical cases requiring electrocautery, either bipolar cautery should be used or the grounding pad should be placed between the surgical site and the infusion set.
Because of the rapid development and advances in technology, CGMS and HCLS ( Fig. 10.1 ) have not yet been studied extensively in the perioperative setting. Nevertheless, these systems likely will provide superior perioperative glucose management compared with intermittent fingersticks and/or fixed basal infusion rates, in conjunction with frequent monitoring of the CGM values and close attention to pump alarms.
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