|
 
 |
| REVIEW ARTICLE |
|
| Year : 2014 | Volume
: 28
| Issue : 1 | Page : 4-8 |
|
Perioperative management of diabetes mellitus
Ranabir Salam
Department of Medicine, Regional Institute of Medical Sciences, Imphal, Manipur, India
| Date of Web Publication | 24-Jun-2014 |
Correspondence Address:
Dr. Ranabir Salam
Department of Medcine, Regional Institute of Medical Sciences, Imphal, Manipur
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0972-4958.135214
Patients with diabetes mellitus undergo surgery more frequently than non-diabetics. Diabetics tend to have increased morbidity and longer hospital stay following surgery, which may be due to higher risk of infection and co-morbidities such as cardiovascular complications and nephropathy. Studies have shown that pre-operative glycemic control have a significant impact on the risk of infections. Glycosylated hemoglobin below 7% is the usual pre-operative target, but values between 8% and 9% may be acceptable depending on individual circumstances. Recent guidelines from Australia and UK no longer recommend withdrawal of oral hypoglycemic agents including metformin before surgery. Cardiac-related and overall mortality are greater with increased post-operative blood glucose levels. American Association of Clinical Endocrinologists and the American Diabetes Association recommends target glucose levels <180 mg/dL in critically ill patients and <140 mg/dL in non-critically ill patients. Insulin-glucose infusion is the preferred mode of insulin therapy until patient is able to take adequate calorie orally. Sliding scale insulin is no longer recommended and supplemental insulin protocol is more appropriate. Hypoglycemia is also a major contributor to an adverse outcome and severe hypoglycemia should be avoided. Keywords: Insulin-glucose infusion, Perioperative, Sliding scale insulin, Supplemental insulin, Wound infection
How to cite this article:
Salam R. Perioperative management of diabetes mellitus. J Med Soc 2014;28:4-8 |
| Perioperative Management of Diabetes Mellitus | |  |
In US, 18.8 million people have been diagnosed with diabetes and an additional 7 million are believed to be living with undiagnosed diabetes. [1] Diabetes afflicts around 62.4 million people in India. [2]
Patients with diabetes more frequently undergo surgical procedures than non-diabetic people. [3],[4] An estimated 25% of diabetic patients will require surgery. Major surgery leads to metabolic stress, which lead to an increase in catabolic hormones and inhibition of the anabolic hormone insulin. In non-diabetic patients this can lead to transient hyperglycemia. This initial inhibition of insulin secretion is followed post-operatively by a period of insulin resistance and hence that major surgery results in a state of functional insulin insufficiency. [5] People with type 1 diabetes have no insulin secretory capacity and are unable to respond to the increased demand for insulin with surgery. As people with type 2 diabetes has pre-existing insulin resistance with limited insulin reserve they have reduced capacity to respond to the increased demand. Poor perioperative glycemic control has a significant impact on the risk of post-operative infection. [6],[7] The stress response itself may precipitate diabetic crises such as diabetic ketoacidosis, hyperglycemic hyperosmolar syndrome during surgery or post-operatively. [8],[9]
Gastrointestinal instability provoked by anesthesia, medications and stress-related vagal dysfunction can lead to nausea, vomiting and dehydration compounding the volume contraction that may already be present from the osmotic diuresis induced by hyperglycemia. This may pose an increased risk for ischemic events and acute renal failure. Subtle to gross deficits in electrolytes such as potassium and magnesium may pose a risk for arrhythmia, which often is superimposed on coronary artery disease in middle-aged or older people with diabetes. It is therefore imperative that careful attention be paid to the metabolic status of diabetics undergoing surgical procedures. [10]
| Reasons for Adverse Outcomes in Diabetes | | |
Diabetes leads to increased morbidity and length of hospital stay of the surgical patient. The perioperative mortality rate is reported to be up to 50% higher than that of the population without diabetes. [11]
The reasons for these adverse outcomes are multifactorial:
- Multiple co-morbidities, including microvascular and macrovascular complications; [12],[12],[13],[14],[15],[17]
- Management errors when converting from the intravenous (IV) insulin infusion to usual medication;
- Perioperative infection. [11]
| Glycemic Control Matters Regardless of Diabetes Status | | |
Pre-operative glycemic control has a significant impact on the risk of infections including pneumonia, wound infection, urinary tract infection and sepsis in patients with diabetes across a variety of surgical procedures. [18] Post-operative glycemic control to a mean plasma glucose level <200 mg/dL in the immediate post-operative period significantly reduces the incidence of deep sternal wound infection after open heart surgery. [19] Among patients undergoing cardiothoracic surgery both cardiac-related and overall mortality are greater with increasing post-operative blood glucose (BG) levels. [20]
Hyperglycemia affects mortality regardless of diabetic status of the patient. In a study of 779 patients with acute myocardial infarction, mortality at 180 days was highly associated with hyperglycemia on admission independent of a history of diabetes. The highest mortality was among hyperglycemic patients without previously known diabetes. [21] Similarly, in a large study in intensive care unit (ICU) patients receiving insulin mortality in non-diabetic patients increased with median glucose level and was higher than mortality in diabetic patients. [22] Hence there is a need for vigilance in the perioperative and proper management of all patients with hyperglycemia, regardless of pre-admission diagnosis of diabetes, as they carry significant morbidity and mortality risk.
The landmark study by Van den Berghe et al. of intensive insulin therapy in surgical ICU patients demonstrated significant reductions in morbidity and mortality when glucose levels were controlled between 80 and 110 mg/dL compared with glycemic control of 180-200 mg/dL. [23] The benefit of intensive glycemic control was evident on the occurrence of sepsis, need for dialysis, need for blood transfusion and development of acute polyneuropathy. [24] However, a number of subsequent studies have clearly shown that as plasma glucose levels approach normoglycemia, the risks of hypoglycemia can offset the benefits of tight glycemic control. A follow-up study by Van den Berghe et al. in medical ICU failed to show a mortality benefit from tight glycemic control, though patients in the intensive control arm experienced less renal injury, faster weaning from ventilation and earlier discharge from the ICU and hospital. [25]
The more recent NICE-SUGAR study of aggressive glucose control in the ICU randomized patients to intensive group with target BG of 81-108 mg/dL or control group with target BG of 180 mg/dL or less. Mortality rates were higher in the intensive therapy group (27.5%) than in the control group (24.9%), which was driven by severe hypoglycemic events. [26] The conclusions from the available data would support a modified glycemic target in critically ill patients with strict avoidance of severe hypoglycemia. The recent consensus statement from the American Association of Clinical Endocrinologists and the American Diabetes Association recommends using insulin therapy if BG levels exceed 180 mg/dL, with target glucose levels <180 mg/dL in critically ill patients and <140 mg/dL in non-critically ill patients. [27] Development and implementation of safer insulin infusion algorithms and more frequent and accurate BG monitoring should enable to achieve better glycemic targets with lower risk.
| Pre-Operative Evaluation | | |
During pre-operative evaluation the type of diabetes is to be ascertained. The medication the patient is one is to be reviewed as this can have a bearing in the perioperative management. Glycemic control is to be ensured. The presences of complications of diabetes that might be adversely affected by or that might adversely impact upon the outcome of the proposed procedure have to be considered.
| What is the Acceptable Upper Limit of Hemoglobin (HBA1C) for Patients Undergoing Elective Surgery? | | |
Diabetes UK Position Statements and Care Recommendations states that there is insufficient evidence to recommend an upper limit of hemoglobin (HbA1c) prior to elective surgery and the risks associated with poor glycemic control should be balanced against the necessity for surgery. HbA1c between 8% and 9% (mean plasma glucose of 185-210 mg%) is acceptable, depending on individual circumstances. [28]
| Pre- and Intra-Operative Glycemic Management | | |
Until recently the consensus in patients with type 2 diabetes is that oral agents pose certain safety risks and should be discontinued prior to surgery. Sulfonylureas may induce hypoglycemia in patients who are placed on nil orally and should be held in patients who are fasting. Metformin can induce lactic acidosis if kidney function declines and should be withheld 1-2 days before planned surgery if a need for IV contrast is anticipated or the procedure could potentially lead to hemodynamic instability and reduced renal perfusion.
However, recent guidelines from UK [28] and Australia [29] no longer recommend withdrawal on oral hypoglycemic agents (OHA) before surgery. Australian guideline recommends stopping OHA on the day of surgery. Patients receiving OHAs (metformin, sulfonylureas, repaglinide, acarbose, glitazones and dipeptidyl peptidase-4 inhibitors) as well as glucagon-like peptide-1 agonists such as exenatide can continue their diabetes medications on the day prior to surgery. However, these should be omitted on the morning of surgery. Once they resume their meals, OHAs can be restarted, with the possible exception of Metformin and the thiazolidinediones following cardiac surgery (given their risk of precipitating cardiac failure in patients with significant cardiac disease). [29]
UK guideline recommends that, for patients undergoing a short starvation period (one missed meal only), metformin can be continued unless the patient is on a 3-times/day regimen, when the middle dose should be omitted. In renal impairment metformin should be stopped when the pre-operative fast begins and restarted post-operatively once the patient is eating again. [28]
Depending on whether the surgery is major or minor perioperative management differ. Major surgery is defined as any surgical procedure that requires an overnight admission to hospital or duration of surgery is >4 h. This includes cardiothoracic surgery, some orthopedic and neurosurgical procedures, intra-abdominal surgery such as cholecystectomy, laparotomy and Minor surgery is defined as day-only procedures where the duration of surgery is short. Afternoon procedures are not ideal for insulin-treated patients as they are more disruptive to their glycemic control.
For major surgery the usual insulin doses and diet to be maintained till the day before the surgery and fast from midnight. Usual morning insulin (and OHA) is to be omitted. Glucose potassium insulin (GKI) infusion or preferably separate infusions of insulin and glucose with potassium to be commenced prior to induction of anesthesia or by 10.00 am at the latest if the operation is scheduled later. Several different algorithms for IV regular insulin therapy are in use. Some are static, such as those of Markovitz et al. [30] and Stockton et al., [31] while others are dynamic as the "Yale protocol" of Goldberg et al. [32] BG is to be measured at least hourly during the intra-operative period. Serum potassium is to be monitored 4-6 hourly to prevent hypokalemia resulting from intracellular shift from the extracellular compartment. Infusion is to be continued for at least 24 h post-operatively and until the patient is capable of resuming an adequate oral intake.
Minor surgery has minimal impact on glycemic control, recovery is quick and resumption of the patient's usual diet and routine occurs within a short period of time. Insulin therapy is dependent on the timing and duration of the procedure and the resumption of the patient's usual diet. The usual morning dose of insulin is to be delayed provided that the procedure is completed and the patient is ready to eat by 10.00 am. After the procedure the patient can have a late breakfast after the usual dose of insulin is given. For later procedures, a reduced dose of insulin is to be given in the morning in the form of intermediate or long-acting insulin if possible. If the plasma glucose remains elevated >180 mg%, a GKI infusion or glucose and insulin infusions should be commenced.
| Post-Operative Glycemic Management | | |
GKI infusion or infusions of glucose-potassium and insulin should be continued until the patients can resume an adequate diet. Infusion should ideally be stopped after breakfast and a dose of subcutaneous insulin (or OHA) is given before breakfast. Insulin must be replaced according to physiologic needs, which requires that a long-/intermediate acting basal insulin be used regardless of oral intake status, regular/rapid-acting insulin be given to cover prandial or nutritional needs and supplemental regular/rapid-acting insulin be used to correct hyperglycemia.
In the transition from IV insulin, basal insulin replacement can begin at any time if long acting and peak less insulin such as glargine is used. When solid food is commenced, the patient's usual dose of subcutaneous insulin is to be given prior to the meal and the infusion can then be ceased 1-2 h afterwards (allowing for some overlap between IV and the absorption of the subcutaneous insulin) as IV insulin has a half-life of 7 min. In type 1 diabetes, this transition ensures basal insulin coverage and minimizes the risk of developing ketonemia and ketoacidosis. In type 2 diabetes, it can ensure a more stable transition and better glycemic control.
During the post-operative period, insulin requirements may fluctuate, depending on the metabolic impact of the procedure, the presence of pain or infection and the adequacy of oral intake. While the insulin requirement is difficult to predict, the best approach following major surgery is to resume the patient's usual diabetes medication after ceasing the insulin infusion and to provide additional treatment (insulin if rquired) should glycemic thresholds be exceeded. It is essential that BG be monitored more frequently during this period and treatment requirements be reviewed on a daily basis. If oral intake is not adequate and hypoglycemia occur, the next dose of insulin should not be omitted (otherwise hyperglycemia and possible ketosis may occur). Rather, the dose of insulin could be reduced by ∼10% and insulin regimen reviewed. When oral intake is variable or unreliable, a basal-bolus insulin regimen is more appropriate, as the basal insulin can be continued and the timing and doses of short-acting insulin adapted according to the patients carbohydrate intake. [29]
"Sliding scale insulin" is NOT recommended for the post-operative management of diabetes when used as sole therapy. [28],[29] A "supplemental insulin protocol," which is given in addition to the patient's usual diabetes medication regimen, is more appropriate. [33]
| Determining the Basal Insulin Dose | | |
The starting dose of basal insulin should be 50-80% of the prior IV insulin total daily dose, if stable glycemic control had been achieved with IV insulin. [34] Alternatively, a calculation called the "Miami 4/12 rule" can be used, whereby the basal insulin replacement dose is equal to the patient's weight in kilograms divided by 4. It is recommended that basal insulin replacement be given either once daily or divided twice daily as a long-acting insulin analog (e.g., insulin glargine or insulin detemir). If cost is a concern neutral protamine Hagedorn insulin can be used twice daily but there is a higher risk of hypoglycemia.
| Switching to Subcutaneous Supplemental Insulin | | |
Instructions must be given for switching to subcutaneous supplemental doses of insulin. Glycemic targets generally from <130 to 150 mg/dL must be established. The recommendation on the frequency of finger stick testing is as follows:
- If the patient is being fed enterally or parenterally, blood glucose monitoring by glucometer is recommended every 4-6 h if a rapid-acting insulin analog is used and every 6 h if regular insulin is used
- If the patient is eating, blood glucose monitoring by glucometer should be performed before meals and at bedtime.
Supplemental insulin to correct hyperglycemia can be individualized based on a patient's perceived sensitivity to insulin. Adjustments in supplemental doses are needed to maintain glycemic targets. [33]
Use of a basal/bolus insulin regimen appears to be more beneficial than supplemental-scale regular insulin in hospitalized patients with type 2 diabetes. According to a recent randomized trial which compared the two approaches in 130 patients with BG levels >140 mg/dL, patients in the basal/bolus group received a higher total daily insulin dose than those in the supplemental-scale group (mean of 42 U/day vs. 13 U/day). Mean daily BG levels were 27 mg/dL lower in patients who received basal/bolus therapy compared with the supplemental-scale group. However there was no difference between groups in the risk of hypoglycemia. More patients randomized to basal/bolus therapy achieved the glycemic goal of <140 mg/dL (66% vs. 38%). Nearly 14% of patients assigned to supplemental scale insulin had values persistently >240 mg/dL and had to be switched to the basal/bolus regimen. [33]
| Covering Nutritional Requirements | | |
Nutrition-related insulin needs depend on the type of caloric intake prescribed:
In patients receiving total parenteral nutrition (TPN), 1 U of regular insulin (placed in the bag) for every 10-15 g of dextrose in the TPN mixture is to be started.
In patients receiving enteral nutrition, regular insulin every 6 h or a rapid-acting insulin analog every 4 h subcutaneously is to be used. One unit of insulin subcutaneously for every 10-15 g of delivered carbohydrates is to be started. For example, if a patient is receiving 10 g of carbohydrates per hour, a short or rapid-acting insulin given at a dose of 4 U every 4 h (1 U/10 g of carbohydrates) should adequately cover enteral feedings. For any bolus feedings, subcutaneous insulin injection as a bolus 15-20 min in advance, based on the carbohydrate content of the feeding is to be administered.
In patients who are eating, regular insulin or a rapid acting insulin analog before meals can be used. Again, 1 U of insulin subcutaneously is to be started for every 10-15 g of carbohydrates, or the prandial portion of the Miami 4/12 rule. For example, in a 60-kg patient one would start with 5 U (60 ÷ 12) of a short or rapid-acting insulin before each meal. [34]
| Choice of Perioperative Fluid for Patients Requiring Variable Rate IV Insulin Infusion | | |
Use of 0.45% saline with 5% glucose and 0.15% potassium chloride is advocated as the first choice solution. But as this fluid is not widely available dextrose saline can be used with Potassium chloride added. Insulin is preferably given in a separate line by syringe infusion pump. Use of GKI solution leads to increased nursing workload and difficulties in maintaining accurate fluid balance charts with constant changes of fluid bags according to capillary BG [28] so is a poorer option. Again intermittent use of insulin glucose infusion alternate with normal saline or Ringer lactate solution is to be avoided as it can lead to marked swings in BG.
| Conclusion | | |
Elective surgery in people with uncontrolled diabetes should preferably be scheduled after acceptable glycemic control has been achieved. Admission to the hospital 1-2 days before a scheduled surgery is advisable for such patients. The actual treatment recommendations for a given patient should be individualized, based on diabetes classification, usual diabetes regimen, state of glycemic control, nature and extent of surgical procedure and available expertise. Some general rules can be applied, however. Whenever possible, ketoacidosis, hyperosmolar state and electrolyte derangements should be searched for and corrected pre-operatively and the surgery itself should be scheduled early in the day, to avoid protracted fasting.
| References | | |
| 1. | Centers for Disease Control and Prevention. National diabetes fact sheet: National estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2011. www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf. 
|
| 2. | Anjana RM, Pradeepa R, Deepa M, Datta M, Sudha V, Unnikrishnan R, et al. Prevalence of diabetes and prediabetes (impaired fasting glucose and/or impaired glucose tolerance) in urban and rural India: Phase I results of the Indian Council of Medical Research-INdia DIABetes (ICMR-INDIAB) study. Diabetologia 2011;54:3022-7.
|
| 3. | Galloway JA, Shuman CR. Diabetes and surgery. A study of 667 cases. Am J Med 1963;34:177-91.
|
| 4. | Goldmann DR. Surgery in patients with endocrine dysfunction. Med Clin North Am 1987;71:499-509.
|
| 5. | Desborough JP. The stress response to trauma and surgery. Br J Anaesth 2000;85:109-17.
|
| 6. | 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.
|
| 7. | Furnary AP, Zerr KJ, Grunkemeier GL, Starr A. Continuous intravenous insulin infusion reduces the incidence of deep sternal wound infection in diabetic patients after cardiac surgical procedures. Ann Thorac Surg 1999;67:352-60.
|
| 8. | Brenner WI, Lansky Z, Engelman RM, Stahl WM. Hyperosomolar coma in surgical patients: An latrogenic disease of increasing incidence. Ann Surg 1973;178:651-4.
|
| 9. | Walker M, Marshall SM, Alberti KG. Clinical aspects of diabetic ketoacidosis. Diabetes Metab Rev 1989;5:651-63.
|
| 10. | Dagogo-Jack S, Alberti KG. Management of diabetes mellitus in surgical patients. Diabetes Spectr 2002;15:44-8.
|
| 11. | Frisch A, Chandra P, Smiley D, Peng L, Rizzo M, Gatcliffe C, et al. Prevalence and clinical outcome of hyperglycemia in the perioperative period in noncardiac surgery. Diabetes Care 2010;33:1783-8.
|
| 12. | Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care 1993;16:434-4.
|
| 13. | Lee TH, Marcantonio ER, Mangione CM, Thomas EJ, Polanczyk CA, Cook EF, et al. Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation 1999;100:1043-9.
|
| 14. | Gordois A, Scuffham P, Shearer A, Oglesby A, Tobian JA. The health care costs of diabetic peripheral neuropathy in the US. Diabetes Care 2003;26:1790-5.
|
| 15. | Veglio M, Chinaglia A, Cavallo-Perin P. QT interval, cardiovascular risk factors and risk of death in diabetes. J Endocrinol Invest 2004;27:175-81.
|
| 16. | Cuthbertson BH, Amiri AR, Croal BL, Rajagopalan S, Brittenden J, Hillis GS. Utility of B-type natriuretic peptide in predicting medium-term mortality in patients undergoing major non-cardiac surgery. Am J Cardiol 2007;100:1310-3.
|
| 17. | O′Brien MM, Gonzales R, Shroyer AL, Grunwald GK, Daley J, Henderson WG, et al. Modest serum creatinine elevation affects adverse outcome after general surgery. Kidney Int 2002;62:585-92.
|
| 18. | Dronge AS, Perkal MF, Kancir S, Concato J, Aslan M, Rosenthal RA. Long-term glycemic control and postoperative infectious complications. Arch Surg 2006;141:375-80.
|
| 19. | Zerr KJ, Furnary AP, Grunkemeier GL, Bookin S, Kanhere V, Starr A. Glucose control lowers the risk of wound infection in diabetics after open heart operations. Ann Thorac Surg 1997;63:356-61.
|
| 20. | Furnary AP, Gao G, Grunkemeier GL, Wu Y, Zerr KJ, Bookin SO, et al. Continuous insulin infusion reduces mortality in patients with diabetes undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg 2003;125:1007-21.
|
| 21. | Ainla T, Baburin A, Teesalu R, Rahu M. The association between hyperglycaemia on admission and 180-day mortality in acute myocardial infarction patients with and without diabetes. Diabet Med 2005;22:1321-5.
|
| 22. | Rady MY, Johnson DJ, Patel BM, Larson JS, Helmers RA. Influence of individual characteristics on outcome of glycemic control in intensive care unit patients with or without diabetes mellitus. Mayo Clin Proc 2005;80:1558-67.
|
| 23. | van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, et al. Intensive insulin therapy in critically ill patients. N Engl J Med 2001;345:1359-67.
|
| 24. | Van den Berghe G, Wouters PJ, Kesteloot K, Hilleman DE. Analysis of healthcare resource utilization with intensive insulin therapy in critically ill patients. Crit Care Med 2006;34:612-6.
|
| 25. | Van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, et al. Intensive insulin therapy in the medical ICU. N Engl J Med 2006;354:449-61.
|
| 26. | NICE-SUGAR Study Investigators, Finfer S, Chittock DR, Su SY, Blair D, Foster D, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009;360:1283-97.
|
| 27. | Moghissi ES, Korytkowski MT, DiNardo M, Einhorn D, Hellman R, Hirsch IB, et al. American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Diabetes Care 2009;32:1119-31.
|
| 28. | Dhatariya K, Levy N, Kilvert A, Watson B, Cousins D, Flanagan D, et al. NHS Diabetes guideline for the perioperative management of the adult patient with diabetes. Diabet Med 2012;29:420-33.
|
| 29. | Australian Diabetes Society. Peri-operative Diabetes Management Guidelines. ; 2012. http://www.diabetessociety.com.au
|
| 30. | Markovitz LJ, Wiechmann RJ, Harris N, Hayden V, Cooper J, Johnson G, et al. Description and evaluation of a glycemic management protocol for patients with diabetes undergoing heart surgery. Endocr Pract 2002;8:10-8.
|
| 31. | Stockton L, Baird M, Cook CB, Osburne OC, Reid J, McGowan K, et al. Development and implementation of evidence-based guidelines for IV insulin: A statewide collaborative approach. Insulin 2008;3:67-77. (Elsevier publication)
|
| 32. | Goldberg PA, Siegel MD, Sherwin RS, Halickman JI, Lee M, Bailey VA, et al. Implementation of a safe and effective insulin infusion protocol in a medical intensive care unit. Diabetes Care 2004;27:461-7.
|
| 33. | Umpierrez GE, Smiley D, Zisman A, Prieto LM, Palacio A, Ceron M, et al. Randomized study of basal-bolus insulin therapy in the inpatient management of patients with type 2 diabetes (RABBIT 2 trial). Diabetes Care 2007;30:2181-6.
|
| 34. | Meneghini LF. Perioperative management of diabetes: Translating evidence into practice. Cleve Clin J Med 2009;76 Suppl 4:S53-9.
|
|
Search Pubmed for