The incidence of both type 1 and type 2 diabetes mellitus in children is increasing in the United States (U.S.) (1,2), and management of these patients is becoming increasingly complex. Anesthesiologists must carefully consider not only the pathophysiology of the disease, but also each child’s specific diabetes treatment regimen, glycemic control, intended surgery, and anticipated postoperative care when devising an appropriate perioperative management plan. Because of the complexity and variability of current diabetes treatment options, the perioperative plan should be made in consultation with a pediatric endocrinologist. There is a paucity of literature on the perioperative management of children with diabetes (3–6), and to our knowledge, no recent reviews of this subject are in the American literature.
The advent of continuous insulin delivery devices, long- and rapid-acting insulin analogs, and an increasing prevalence of pediatric patients with type 2 diabetes have made the management of perioperative blood glucose levels a greater challenge for pediatric anesthesiologists. In this paper, we present an algorithm for the management of pediatric patients with either type 1 or type 2 diabetes mellitus presenting for surgery and anesthesia. We developed this algorithm to have a unified approach to the care of these patients at our institution, which manages an average of one to two diabetes patients per week who undergo a procedure requiring anesthesia. Because Children’s Hospital Boston, like many large institutions, has a perioperative assessment program to facilitate preoperative care of patients with medical comorbidities, use of an algorithm improves care and minimizes medical errors (7). For anesthesiologists either unfamiliar with diabetes treatments for children or with issues affecting their care, such as body size, pubertal development, and ability to tolerate nil per os status, this algorithm also serves as an instructive tool to highlight how such issues impact the perioperative care of these children. Studies in adults have demonstrated improved perioperative management of diabetes patients after the institution of standardized management protocols (8–10) without a significant increase in associated costs of management (10).
Classification and Epidemiology of Diabetes in American Children
Most diabetes in American children is attributed to either type 1 diabetes or type 2 diabetes (11,12). Type 1 diabetes is caused by pancreatic β cell destruction, usually immune-mediated, that results in absolute insulin deficiency (11,12). Type 2 diabetes, previously a disorder that predominantly affected middle-aged and elderly adults, results from a combination of insulin resistance and a relative deficiency of insulin (11,12). Children with type 2 diabetes are typically overweight and frequently have a family history of type 2 diabetes in a first- or second-degree relative (11). Rarer forms of diabetes encountered in children are listed in Table 1. Additional modifications to the perioperative treatment regimen may be required when diabetes is associated with genetic syndromes and/or other endocrinopathies. Whereas the specific modifications in each of these special circumstances are beyond the scope of this review, recognizing this heterogeneity is an important part of establishing an appropriate perioperative management plan.
The worldwide incidence of type 1 diabetes is highly variable (13), but it seems to be increasing in almost all populations throughout the world (1). In the U.S., data from the early 1990s suggest an annual incidence of type 1 diabetes in children less than or equal to 14 yr of age of 11.7 to 17.8 per 100,000 (13,14). The increased prevalence of obesity has also contributed to a progressive increase in the incidence and prevalence of type 2 diabetes in U.S. children (2). Based on the National Health and Nutrition Examination Survey III (1988–1994), approximately 100,000 U.S. adolescents aged 12 to 19 yr have diabetes with approximately 31% having type 2 diabetes (15).
Management Options for Diabetes Mellitus in Children
Type 1 diabetes always requires treatment with insulin. However, there are an increasing number of insulin preparations (Table 2). Insulin regimens incorporate a combination of intermediate-acting insulin (such as NPH or Lente) or long-acting insulin (such as Ultralente) with a short- or rapid-acting insulin (such as Regular, Novolog® [insulin aspart; Novo Nordisk Inc., Princeton, NJ], or Humalog® [insulin lispro; Eli Lilly and Co., Indianapolis, IN]) to provide prandial and postprandial glycemic coverage. Such regimens typically require two to three injections of insulin per day. A newer insulin, Lantus® (insulin glargine; Sanofi-Aventis, Bridgewater, NJ), is long-acting and provides a relatively constant 24-h basal level of circulating insulin without a pronounced peak (16). In conjunction with rapid-acting insulin administered with food, some studies have demonstrated superior glycemic control with glargine as compared with regimens using NPH and Regular insulin (17). More and more children and adolescents are managed with an insulin pump, a device which administers a continuous subcutaneous infusion of insulin (typically a rapid-acting insulin, such as insulin lispro or insulin aspart) at a basal rate that is supplemented by additional bolus doses of insulin given before meals and snacks and to correct hyperglycemia. In appropriately chosen patients, such management has also demonstrated potential superiority over injection regimens (18,19).
Most pediatric patients with type 2 diabetes are managed with insulin and/or metformin, the only oral drug approved for use in pediatric patients (20,21). Metformin’s primary action is to decrease hepatic glucose production and, secondarily, to increase insulin sensitivity in peripheral tissues. Occasionally, other oral drugs, including sulfonylureas, which promote insulin secretion, and thiazolidinediones, which increase insulin sensitivity in muscle and adipose tissue, are used in older adolescents (20). Understanding both the pharmacokinetic and pharmacodynamic properties of different insulin preparations and antihyperglycemic medications is critical to developing an appropriate perioperative plan.
The Metabolic Response to Surgery and Anesthesia
Trauma of any kind and surgery, in particular, causes a complex neuroendocrine stress response including suppression of insulin secretion and increased production of counterregulatory hormones, particularly cortisol and catecholamines (22,23). Insulin is the primary anabolic hormone that promotes glucose uptake in muscle and adipose tissue while suppressing glucose production (glycogenolysis and gluconeogenesis) by the liver. The counterregulatory hormones, including epinephrine, glucagon, cortisol, and growth hormone, have the opposite effects. They increase blood glucose concentration by stimulating glycogenolysis and gluconeogenesis in the liver, by increasing lipolysis and ketogenesis, and by inhibiting glucose uptake and use in muscle and fat. The result of these changes is increased catabolism, with increased hepatic glucose production, and breakdown of protein and fat. In the diabetic patient with absolute or relative insulin deficiency, the enhanced catabolism stimulated by surgical trauma can lead to marked hyperglycemia and even diabetic ketoacidosis (24). These metabolic effects may be compounded by the requisite period of starvation that precedes and accompanies surgery.
Adverse Consequences of Hyperglycemia
Hyperglycemia can impair wound healing by hindering collagen production, resulting in decreased tensile strength of the surgical wound (25). Hyperglycemia may also have adverse effects on neutrophil function, including decreased chemotaxis, phagocytosis, and bactericidal killing (26,27). Clinical studies have not consistently borne out the relationship between perioperative glycemic control and short-term risk of infection or morbidity (28,29). Golden et al. (30), however, demonstrated that postoperative hyperglycemia was an independent predictor of short-term infectious complications in 411 adult patients with diabetes undergoing coronary artery surgery, and Zerr et al. (31) showed that maintaining a postoperative mean blood glucose level <200 mg/dL significantly reduced the incidence of deep wound infections in diabetic patients undergoing open heart surgery. In critically ill patients treated in intensive care units, intensive glycemic control with insulin significantly reduced overall morbidity and mortality (32,33). Such studies support the generally accepted recommendation that maintaining blood glucose levels near to normal should be the standard of care in the perioperative management of patients with diabetes (34).
When feasible, elective surgery for children with diabetes should be delayed until metabolic control is acceptable (Fig. 1, Box 4); i.e., the child/adolescent does not have ketonuria, serum electrolytes are normal, and the HbA1c value is close to or within the ideal range for the child’s age. At our institution, the operational definition of ideal range for HbA1c for children younger than 5 yr is 7% to 9%, for age 5–13 yr is 6% to 8.5%, and for age 13 yr or older is 6% to 8%. In our management algorithm, we recommend that the preoperative consultation to assess metabolic control be scheduled at least 10 days before the procedure (Fig. 1, Box 3) and that surgery be delayed, if possible, when metabolic control is unsatisfactory. To reinforce the collaborative relationship between the anesthesia and endocrine services, we also recommend that both services participate in this assessment. Whenever possible, surgery for diabetes patients should be scheduled as the first case in the morning so that prolonged fasting is avoided and diabetes treatment regimens can be most easily adjusted.
Patients presenting for emergent surgery, e.g., because of trauma or acute surgical conditions such as appendicitis, still require preoperative assessment with collaborative input from the endocrine and anesthesia services. However, surgery in these situations often cannot be delayed, even if metabolic control is inadequate. This has implications for the intraoperative management of such patients, as described below in Special Surgical Situations.
The regimen for managing diabetes before, during, and after a surgical or diagnostic procedure that requires the child to fast should aim to maintain near-normoglycemia, i.e., blood glucose of approximately 100–200 mg/dL. In this range, there will be a reduced risk of osmotic diuresis, dehydration, electrolyte imbalance, metabolic acidosis, infection, and of hypoglycemia in sedated patients who may be unaware of hypoglycemia or unable to communicate with staff (35). The child is admitted early in the morning on the day of the procedure. It is not the practice at our institution to admit patients to the hospital before the day of surgery because careful preoperative assessment should ensure that patients are in satisfactory metabolic control and that patients are prepared to make the appropriate adjustments to their diabetes regimen. However, other authors recommend considering admission to the hospital before major surgical procedures in children (3) and in adults to improve metabolic control (34). The patient should never undergo anesthesia without a blood glucose determination before the anesthetic is started. If the surgery has to be delayed for any reason, frequent blood glucose monitoring is mandatory to prevent hypoglycemia or severe hyperglycemia. On the morning of surgery, no rapid- or short-acting acting insulin is given unless the blood glucose is >250 mg/dL.
If the blood glucose is >250 mg/dL, a conservative dose of rapid-acting insulin (insulin lispro or insulin aspart) or short-acting (Regular) is administered to restore near-normoglycemia. This is achieved using the child’s usual sliding scale or a "correction factor." The insulin correction factor is the decrease in the blood glucose concentration expected after administering 1 U of rapid-acting or short-acting insulin and is calculated using the “1500 rule” by dividing 1500 by the child’s usual total daily dose of insulin. For example, if a child typically takes 30 U of insulin daily, this child’s correction factor would be 1500 ÷ 30 = 50; i.e., 1 U of rapid-acting or short-acting insulin would be expected to decrease the child’s blood glucose concentration by approximately 50 mg/dL. Various correction factors have been described including a 1500 rule for Regular insulin and an 1800 rule for rapid-acting insulin, such as insulin lispro (36), We opted for one correction factor calculation under all circumstances in our algorithm both for simplicity and because insulin resistance stimulated by surgical stress makes the 1500 rule appropriate in this setting, even with a rapid-acting insulin. To then calculate an appropriate corrective dose of insulin to restore near-normoglycemia, we aimed for a target blood glucose concentration of 150 mg/dL. For example, a patient presenting with a blood glucose concentration of 300 mg/dL, who has a correction factor of 1 U of rapid-acting or short-acting insulin to decrease blood glucose concentration by 50 mg/dL, will require (300–150) ÷ 50 = 3 U of insulin to correct the blood glucose concentration to approximately 150 mg/dL. The corrective dose is administered subcutaneously for patients receiving rapid-acting insulin and IV for those receiving short-acting (Regular) insulin and who will be managed with an IV insulin infusion during the procedure. For patients with type 2 diabetes who are not treated with insulin (but are insulin resistant), an insulin dose of 0.1 U/kg of rapid-acting insulin may be administered subcutaneously to correct blood glucose >250 mg/dL.
More detailed preoperative recommendations must be based on the individual child’s baseline treatment regimen. For most pediatric diabetes patients undergoing minor outpatient surgical procedures, insulin can still be provided perioperatively with subcutaneous injections. In adults, especially those with type 2 diabetes, this practice is frequently (35), although not universally (37), preferred. Our approach is at variance with recently published recommendations from the United Kingdom, which routinely recommend insulin infusions even for minor outpatient surgical procedures in children (3). Several reports in the literature suggest that better glycemic control can be achieved in the perioperative period with a continuous IV infusion rather than subcutaneous insulin administration (6,38,39). However, these studies were conducted before the availability of rapid-acting insulins whose rapid and reproducible effects after subcutaneous administration (40) may more closely match the ability to titrate IV-administered short-acting insulin. One recent study, for example, has even demonstrated comparable efficacy of subcutaneous insulin lispro compared with IV Regular insulin in the treatment of uncomplicated diabetic ketoacidosis in adults (41). Furthermore, simplified regimens consisting only of intermittent IV boluses of Regular insulin demonstrate comparable effectiveness in adult patients with type 2 diabetes compared with continuous infusions (42,43), further supporting simplified regimens without continuous IV insulin infusion for those undergoing minor surgical procedures.
The split-mixed insulin regimen refers to patients managed with a combination of intermediate- or long-acting insulin, such as NPH, Lente, or Ultralente, and a rapid- or short-acting insulin. For these patients, 50% of the usual morning dose of intermediate- or long-acting insulin is administered on the morning of the procedure (Fig. 2). In contrast, for the child whose basal insulin is glargine, no additional insulin is given on the morning of surgery if the child has received a dose in the evening on the previous day (Fig. 3). However, if glargine is typically administered in the morning, the full dose should be administered on the day of the procedure. Because glargine provides only basal insulin coverage, the full dose is required to prevent ketosis.
Management of the child on an insulin pump depends on the duration of the surgical procedure (Fig. 4). Those having minor procedures expected to last for <2 h can usually continue to receive insulin via their pump with their usual basal rate for that time of day. However, this approach requires that the anesthesiology service at the institution is comfortable with the use of the pump in the operating room. Other protocols, for example, have suggested transitioning patients on insulin pumps to IV insulin infusions or subcutaneous insulin glargine (34). For procedures expected to last more than 2 h, we recommend transition to an IV insulin infusion as described below.
Pediatric patients with type 2 diabetes may be on insulin or one of several oral antihyperglycemic drugs (Fig. 5). Metformin should be discontinued 24 h before a procedure because of its long half-life and the risk of lactic acidosis in the setting of dehydration, hypoxemia, or poor tissue perfusion (44). Other oral drugs, such as sulfonylureas and thiazolidinediones, may be discontinued on the morning of the procedure. Figure 5 outlines additional recommendations that are required for type 2 diabetes patients who use split-mixed insulin, a common insulin regimen for such patients. Alternatively, if a type 2 diabetes patient is treated with insulin glargine, adjustments as in Figure 3 will be required. Adjustment for less common insulin regimens in type 2 diabetes should be determined in consultation with the endocrinology service. Whereas type 2 diabetes management issues may be familiar to adult anesthesiologists, the recently increased prevalence of this disorder in children makes this issue relatively novel for pediatric anesthesiologists. Treatment options for type 2 diabetes in children are a focus of active research, and modifications to the perioperative algorithm for these children are likely to be required in the future.
Major Surgery and IV Insulin Infusion
Stimulation of the sympathetic nervous system will have a direct effect on glucose homeostasis. Circulating epinephrine will stimulate α2 receptors, thus decreasing insulin release from the pancreas and increasing gluconeogenesis. To mitigate these additional variables impacting glycemic control, adequate surgical analgesia with minimal sympathetic stimulation is essential. For patients requiring major surgery, especially procedures anticipated to last longer than 2 h, IV insulin infusion is the preferred perioperative diabetes management plan (Fig. 6). Studies in children (6) and adults (8) have demonstrated the superiority of IV insulin infusion over subcutaneous injections in achieving optimal glycemic control under these circumstances. These patients should receive their usual dose of insulin on the day before the procedure. On the morning of the procedure, an IV infusion of 10% dextrose in half-normal saline is started at a maintenance rate, and an IV insulin infusion is provided to match the rate of dextrose infusion and to maintain blood glucose in the target range of 100–200 mg/dL (Fig. 6). The maintenance rate for IV fluids in a child depends on body size and can be calculated either based on body weight (4 mL·kg−1·h−1 for the first 10 kg of body weight, 2 mL·kg−1·h−1 for 11–20 kg, and 1 mL·kg−1·h−1 for each kilogram more than 20 kg) or body surface area (1.5 L/m2/d). Because prepubertal children are relatively more sensitive to insulin than pubertal adolescents (45), the insulin dose for children varies with age. In prepubertal children with type 1 diabetes, after the remission (honeymoon) period, the insulin requirement is typically 0.6–0.8 U·kg−1·d−1, whereas adolescents may require 1.0–1.5 U·kg−1·d−1. Patients with type 2 diabetes may have even larger insulin requirements because of their insulin resistance. With IV insulin, a suitable ratio of insulin to dextrose for prepubertal children (defined in our algorithm for simplicity as those ≤12 yr old) is typically 1 U per 5 g of IV dextrose and 1 U per 3 g of IV dextrose for adolescents (>12 yr old). Regular insulin, rather than rapid-acting insulins, should be used for IV infusions.
Intraoperative Management and Assessment
The insulin and fluid regimen during and after surgery depends on the duration of the procedure. If the procedure is likely to be brief (e.g., ≤1 h in duration) and one can reasonably anticipate that the child will be able to drink soon after the procedure, it may not be required to start an IV infusion. If the duration of fasting is likely to be more prolonged, an IV infusion should be given at a maintenance rate, as described above (Fig. 7). Intraoperative maintenance fluid should be replaced with a glucose-containing solution. However, insensible losses and replacement of intravascular volume caused by blood or other body fluid loss should be replaced with an appropriate isotonic solution (lactated Ringer’s solution or normal saline) to preserve intravascular volume.
Although other protocols may suggest inclusion of potassium chloride in the IV fluid solution (3,34,35), the anesthesia service at our institution avoids such supplementation because of the danger of inadvertent intraoperative administration of large volumes during fluid resuscitation. Patients beginning a short procedure with a normal serum potassium concentration and diabetes under good metabolic control have a small risk of hypokalemia. Those undergoing longer surgeries or emergent surgeries when metabolic decompensation is a higher risk require intraoperative assessment of electrolytes and appropriate adjustment of the electrolyte composition of their IV solution. In all cases, blood glucose concentration should be measured hourly, and either insulin or dextrose adjusted, as required, to maintain blood glucose in the target range of 100–200 mg/dL (Fig. 7).
As soon as the patient is able to resume drinking and eating normally, the usual diabetes regimen, including insulin and/or oral drugs, may be reinstituted, and the dextrose infusion, if applicable, is discontinued (Fig. 8). Patents on metformin should have normal renal function. For patients unable to eat and drink, IV dextrose and electrolyte solution is continued. The IV Regular insulin infusion or intermittent subcutaneous rapid-acting insulin is used to keep the blood glucose in the target range of 100–200 mg/dL. Frequent blood glucose monitoring and monitoring of blood or urine ketones is essential because of the variable effects of surgical trauma, inactivity, pain, nausea or vomiting with poor oral intake, medications, and postoperative infection. Patients being discharged should be given appropriate anticipatory guidance regarding these issues.
Special Surgical Situations
Diabetic patients who need urgent surgery must be fully assessed, clinically and biochemically. Often, the problem requiring surgery can lead to metabolic decompensation, which should first be corrected, unless the need for surgery is immediate. These patients may often be dehydrated and, in such a setting, rehydration in addition to insulin administration is critical in addressing the metabolic derangements. General management principles are as described above. In most cases, pediatric diabetes patients requiring emergent surgery should be managed with an IV infusion of insulin, as described above and in Figure 6.
Pediatric patients with diabetes are managed with increasingly complex regimens that have direct implications for their perioperative care. In addition to recognizing the relevant differences among diabetes treatment regimens, pediatric anesthesiologists must also consider a child’s metabolic control, age, size, pubertal development, the intended surgical procedure, and its length when devising a perioperative plan. Although there are multiple approaches to such care, we present one standardized algorithm developed for use at Children’s Hospital Boston that facilitates the comanagement of pediatric surgical patients by anesthesia, surgery, and endocrine services by systematically addressing these issues. As diabetes treatment options for children continue to change, such algorithms will need to be updated. Formal assessment of the impact of such algorithms on clinical outcomes, satisfaction with care, and cost of care would provide additional insight into their revision. Although the mechanism by which to achieve optimal diabetes control in the perioperative period may still be debated, recognition that hyperglycemia may have deleterious short-term as well as long-term consequences highlights the importance of consistently aiming for this goal in the perioperative period just as in the outpatient setting.
We thank Susan Klavon, MSSW, in the Children’s Hospital Boston Risk Management and Quality Improvement Department for her assistance with the development and formatting of this clinical practice guideline.
1. Onkamo P, Vaananen S, Karvonen M, Tuomilehto J. Worldwide increase in incidence of Type I diabetes–the analysis of the data on published incidence trends. Diabetologia 1999;42:1395–403.
2. Fagot-Campagna A, Pettitt DJ, Englelgau MM, et al. Type 2 diabetes among North American children and adolescents: an epidemiologic review and a public health perspective. J Pediatr 2000;136:664–72.
3. Chadwick V, Wilkinson KA. Diabetes mellitus and the pediatric anesthetist. Paediatr Anaesth 2004;14:716–23.
4. Kirschner RM. Diabetes in pediatric ambulatory surgical patients. J Post Anesth Nurs 1993;8:322–6.
5. Holvey SM. Surgery in the child with diabetes. Pediatr Clin North Am 1969;16:671–9.
6. Kaufman FR, Devgan S, Roe TF, Costin G. Perioperative management with prolonged intravenous insulin infusion versus subcutaneous insulin in children with type I diabetes mellitus. J Diabetes Complications 1996;10:6–11.
7. Ferrari LR. Preoperative evaluation of pediatric surgical patients with multisystem considerations. Anesth Analg 2004;99:1058–69.
8. Gonzalez-Michaca L, Ahumada M, Ponce-de-Leon S. Insulin subcutaneous application vs. continuous infusion for postoperative blood glucose control in patients with non-insulin-dependent diabetes mellitus. Arch Med Res 2002;33:48–52.
9. Markovitz LJ, Wiechmann RJ, Harris N, et al. Description and evaluation of a glycemic management protocol for patients with diabetes undergoing heart surgery. Endocr Pract 2002;8:10–8.
10. Vora AC, Saleem TM, Polomano RC, et al. Improved perioperative glycemic control by continuous insulin infusion under supervision of an endocrinologist does not increase costs in patients with diabetes. Endocr Pract 2004;10:112–8.
11. American Diabetes Association. Type 2 diabetes in children and adolescents. Diabetes Care 2000;23:381–9.
12. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2004;27:S5–10.
13. Karvonen M, Viik-Kajander M, Moltchanova E, et al. Incidence of childhood type 1 diabetes worldwide: Diabetes Mondiale (DiaMond) Project Group. Diabetes Care 2000;23:1516–26.
14. Lipman TH, Chang Y, Murphy KM. The epidemiology of type 1 diabetes in children in Philadelphia 1990-1994: evidence of an epidemic. Diabetes Care 2002;25:1969–75.
15. Fagot-Campagna A, Saaddine JB, Flegal KM, Beckles GL. Diabetes, impaired fasting glucose, and elevated HbA1c in U.S. adolescents: the Third National Health and Nutrition Examination Survey. Diabetes Care 2001;24:834–7.
16. Owens DR, Griffiths S. Insulin glargine (Lantus). Int J Clin Pract 2002;56:460–6.
17. Murphy NP, Keane SM, Ong KK, et al. Randomized cross-over trial of insulin glargine plus lispro or NPH insulin plus regular human insulin in adolescents with type 1 diabetes on intensive insulin regimens. Diabetes Care 2003;26:799–804.
18. Weintrob N, Benzaquen H, Galatzer A, et al. Comparison of continuous subcutaneous insulin infusion and multiple daily injection regimens in children with type 1 diabetes: a randomized open crossover trial. Pediatrics 2003;112:559–64.
19. Willi SM, Planton J, Egede L, Schwarz S. Benefits of continuous subcutaneous insulin infusion in children with type 1 diabetes. J Pediatr 2003;143:796–801.
20. Gahagan S, Silverstein J. Prevention and treatment of type 2 diabetes mellitus in children, with special emphasis on American Indian and Alaska native children: American Academy of Pediatrics Committee on Native American Child Health. Pediatrics 2003;112:e328.
21. Rapaport R, Silverstein JH, Garzarella L, Rosenbloom AL. Type 1 and type 2 diabetes mellitus in childhood in the United States: practice patterns by pediatric endocrinologists. J Pediatr Endocrinol Metab 2004;17:871–7.
22. Halter JB, Pflug AE. Relationship of impaired insulin secretion during surgical stress to anesthesia and catecholamine release. J Clin Endocrinol Metab 1980;51:1093–8.
23. Allison SP, Tomlin PJ, Chamberlain MJ. Some effects of anaesthesia and surgery on carbohydrate and fat metabolism. Br J Anaesth 1969;41:588–93.
24. Hirsch IB, McGill JB. Role of insulin in management of surgical patients with diabetes mellitus. Diabetes Care 1990;13:980–91.
25. Rosenberg CS. Wound healing in the patient with diabetes mellitus. Nurs Clin North Am 1990;25:247–61.
26. Delamaire M, Maugendre D, Moreno M, et al. Impaired leucocyte functions in diabetic patients. Diabet Med 1997;14:29–34.
27. Marhoffer W, Stein M, Maeser E, Federlin K. Impairment of polymorphonuclear leukocyte function and metabolic control of diabetes. Diabetes Care 1992;15:256–60.
28. MacKenzie CR, Charlson ME. Assessment of perioperative risk in the patient with diabetes mellitus. Surg Gynecol Obstet 1988;167:293–9.
29. Hjortrup A, Sorensen C, Dyremose E, et al. Influence of diabetes mellitus on operative risk. Br J Surg 1985;72:783–5.
30. Golden SH, Peart-Vigilance C, Kao WH, Brancati FL. Perioperative glycemic control and the risk of infectious complications in a cohort of adults with diabetes. Diabetes Care 1999;22:1408–14.
31. Zerr KJ, Furnary AP, Grunkemeier GL, et al. Glucose control lowers the risk of wound infection in diabetics after open heart operations. Ann Thorac Surg 1997;63:356–61.
32. van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in the critically ill patients. N Engl J Med 2001;345:1359–67.
33. Krinsley JS. Effect of an intensive glucose management protocol on the mortality of critically ill adult patients. Mayo Clin Proc 2004;79:992–1000.
34. Glister BC, Vigersky RA. Perioperative management of type 1 diabetes mellitus. Endocrinol Metab Clin North Am 2003;32:411–36.
35. Schiff RL, Welsh GA. Perioperative evaluation and management of the patient with endocrine dysfunction. Med Clin North Am 2003;87:175–92.
36. Klingensmith GJ, ed. Intensive diabetes management. 3rd ed. Alexandria, VA: American Diabetes Association, 2003.
37. Marks JB. Perioperative management of diabetes. Am Fam Physician 2003;67:93–100.
38. Christiansen CL, Schurizek BA, Malling B, et al. Insulin treatment of the insulin-dependent diabetic patient undergoing minor surgery: continuous intravenous infusion compared with subcutaneous administration. Anaesthesia 1988;43:533–7.
39. Meyer EJ, Lorenzi M, Bohannon NV, et al. Diabetic management by insulin infusion during major surgery. Am J Surg 1979;137:323–7.
40. ter Braak EW, Woodworth JR, Bianchi R, et al. Injection site effects on the pharmacokinetics and glucodynamics of insulin lispro and regular insulin. Diabetes Care 1996;19:1437–40.
41. Umpierrez GE, Latif K, Stoever J, et al. Efficacy of subcutaneous insulin lispro versus continuous intravenous regular insulin for the treatment of patients with diabetic ketoacidosis. Am J Med 2004;117:291–6.
42. Hemmerling TM, Schmid MC, Schmidt J, et al. Comparison of a continuous glucose-insulin-potassium infusion versus intermittent bolus application of insulin on perioperative glucose control and hormone status in insulin-treated type 2 diabetics. J Clin Anesth 2001;13:293–300.
43. Raucoules-Aime M, Labib Y, Levraut J, et al. Use of i.v. insulin in well-controlled non-insulin-dependent diabetics undergoing major surgery. Br J Anaesth 1996;76:198–202.
44. Mercker SK, Maier C, Neumann G, Wulf H. Lactic acidosis as a serious perioperative complication of antidiabetic biguanide medication with metformin. Anesthesiology 1997;87:1003–5.
© 2005 International Anesthesia Research Society
45. Roemmich JN, Clark PA, Lusk M, et al. Pubertal alterations in growth and body composition. VI. Pubertal insulin resistance: relation to adiposity, body fat distribution and hormone release. Int J Obes Relat Metab Disord 2002;26:701–9.