Left_Perioperative Glucose_diabetic and Nondiabetic

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Perioperative Glucose Control in the Diabeticor Nondiabetic PatientDawn D. Smiley, MD, and Guillermo E. Umpierrez, MD, FACP, FACE

Abstract: Patients with diabetes are more likely to undergo surgery

than nondiabetics, and maintaining glycemic control in subjects with

diabetes can be challenging during the perioperative period. Surgery

in diabetic patients is associated with longer hospital stay, higher

health care resource utilization, and greater perioperative mortality.In addition, several observational and interventional studies haveindicated that hyperglycemia is associated with adverse clinical out-comes in surgical and critically ill patients. This paper reviews thepathophysiology of hyperglycemia during trauma and surgical stressand will provide practical recommendations for the preoperative,intraoperative, and postoperative care of diabetic patients.

Key Words: hyperglycemia, surgery, complications, insulin infu-sion

Patients with diabetes are more likely to undergo surgerythan are people without diabetes.1,2 Maintaining glycemic

control in subjects with diabetes presents a challenging prob-lem during the perioperative period. Surgery in diabetic pa-tients is associated with longer hospital stay, higher healthcare resource utilization, and greater perioperative mortalitythan nondiabetic subjects.3–6 The higher morbidity and mor-tality relates in part to the heightened incidence of coronaryheart disease, hypertension, renal insufficiency, and increasedrates of postoperative complications.3,6,7 In addition, severalobservational and interventional studies have indicated thathyperglycemia per se is associated with adverse clinical out-comes in surgical and critically ill patients.8–12 In this paper,we review the pathophysiology of hyperglycemia duringtrauma and surgical stress and will provide practical recom-mendations for the preoperative, intraoperative, and postop-erative care of diabetic patients.

Metabolic Consequences of SurgicalStress and Anesthesia

The stress of surgery and anesthesia results in increasedsecretion of counterregulatory hormones (catecholamines,cortisol, glucagon, and growth hormone) and excessive re-lease of inflammatory cytokines, such as tumor necrosis fac-tor-�, interleukin-6 and interleukin-1�.13–18 The magnitudeof the counterregulatory response relates to the severity ofsurgery, as well as the type of anesthesia.5,19 The counter-regulatory response results in a number of alterations in car-bohydrate metabolism, including insulin resistance, increasedhepatic glucose production, impaired peripheral glucose uti-lization, and relative insulin deficiency.20 In the presence ofan absolute or relative deficiency of insulin, increased cat-echolamines and glucagon levels lead to increased glucone-ogenesis and glycogenolysis and inhibit glucose utilization inperipheral tissues.21–23 Epinephrine stimulates glucagon se-cretion and inhibits insulin release from pancreatic�-cells.24,25 High cortisol levels increase hepatic glucose pro-duction and stimulate protein catabolism and increased cir-

From the Division of Endocrinology, Metabolism and Lipids, Emory Uni-versity School of Medicine, Atlanta, GA.

Reprint requests to Guillermo Umpierrez, MD, FACP, FACE, AssociateProfessor of Medicine, Emory University School of Medicine, Director,Diabetes and Endocrinology, Grady Health System, 49 Jesse Hill JrDrive, Atlanta, GA 30303. Email: [email protected]

Accepted March 1, 2006.

Drs. Smiley and Umpierrez have no disclosures to declare.

Copyright © 2006 by The Southern Medical Association

0038-4348/0�2000/9900-0580

Key Points• The comprehensive operative risk assessment is an

important step in the management of the diabetic pa-tient before surgery.

• Surgery in diabetic patients is associated with longerhospital stay, higher health care resource utilization,and greater perioperative mortality than in nondia-betic subjects.

• Increasing evidence suggests that in hospitalized med-ical as well as surgical patients with and without di-abetes, the presence of hyperglycemia is associatedwith poorer clinical outcomes and aggressive glycemiccontrol positively impacts morbidity and mortality.

• Treatment recommendations are generally categorizedbased on the type of diabetes, nature and extent of thesurgical procedure, antecedent pharmacological ther-apy, and state of metabolic control prior to surgery.

• All patients with diabetes should receive continueddiabetes education and the outpatient treatment regi-men should be reviewed prior to discharge.

580 © 2006 Southern Medical Association

culating amino acid concentration, providing precursors forgluconeogenesis.22,26 Increased counterregulatory hormonesduring stress also lead to enhanced lipolysis and increasedfree fatty acid (FFA) concentration.27,28 Increased FFA levelsproduce insulin resistance dose-dependently in diabetic andnondiabetic individuals29–31 and is an important factor in thedevelopment of stress hyperglycemia. Increased FFA levelshave been shown to inhibit insulin-stimulated glucose up-take,30–32 glycogen synthesis,29 and intracellular signalingcascade function in skeletal muscle.33

The type of anesthesia may influence the hyperglycemicresponse during surgery. General anesthesia has been shownto result in higher blood glucose concentration than local andepidural analgesia.5,24 Circulating catecholamines, cortisol,and glucagon concentration are higher in patients undergoinggeneral anesthesia.5,24,34 Volatile anesthetic agents inhibit in-sulin secretion35 and increase hepatic glucose production.36

In contrast, epidural analgesia has a minimal effect on car-bohydrate metabolism and levels of counterregulatory hor-mones are not significantly elevated.37 It should be noted thatthe reduced hyperglycemia associated with epidural analgesiais strictly limited to the operative period; afterwards, there isno difference in glycemic control. Several studies have in-vestigated the effect of opioids during general anesthesia onstress response, pain control and glycemic control during theperioperative period. Some studies have reported a reductionin the rate and severity of hyperglycemia with opioid anal-gesia,38 but others have not.39 Interestingly, several clinicaland experimental studies have suggested that diabetes or hy-perglycemia alters opioid responsiveness. A recent prospec-tive study evaluated the effect of diabetes mellitus on mor-phine requirements in the postoperative period of subjectsundergoing elective total abdominal hysterectomy.40 Postop-erative pain scores were higher in the diabetic group, and theyrequired more morphine for pain control than nondiabeticpatients. These findings suggest that the use of opioids duringgeneral anesthesia may reduce the rate of hyperglycemia dur-ing the perioperative period, but the analgesic effect of mor-phine is attenuated in diabetes, and larger doses of morphinemay be administered to diabetic patients for effective post-operative analgesia.40

Blood Glucose and PerioperativeOutcome

Increasing evidence suggests that in hospitalized patientswith and without diabetes, the presence of hyperglycemia isassociated with poor clinical outcomes8,9,11,41–44 and aggres-sive glycemic control positively impacts morbidity and mor-tality.10,11,43,45–50 We recently reported that one third of pa-tients admitted to general medicine and surgery wards in anurban general hospital had hyperglycemia, defined as an el-evated fasting glucose level � 126 mg/dL or 2 or more ran-dom blood glucose levels � 200 mg/dL.8 Of those patients,

26% had a known history of diabetes, and 12% had no historyof diabetes before admission. Stress or new hyperglycemiawas associated with higher in-hospital mortality rates (16%)compared with those patients with a prior history of diabetes(3%) and subjects with normoglycemia (1.7%).

Pomposelli et al9 determined the relationship betweenperioperative glucose control and postoperative infection ratesin 100 diabetic patients undergoing elective surgery. The au-thors found that a single blood glucose level �220 mg/dL onthe first postoperative day was a sensitive (87.5%) predictorof postoperative infection. Patients with blood glucose values�220 mg/dL had infection rates that were 2.7 times higherthan the rate for patients with lower blood glucose values(31.3% versus 11.5%, respectively). When minor infectionswere excluded, the relative risk for serious postoperative in-fection, including sepsis, pneumonia, and wound infections,was 5.7 times higher than those with glucose levels less than220 mg/dL.

In the United States, approximately 500,000 patients un-dergo coronary artery bypass grafting (CABG) each year,51

�20% of whom have diabetes.52,53 Diabetes is recognized asan independent risk factor in patients undergoingCABG.45,46,54,55 Perioperative hyperglycemia is associated witha higher risk of deep sternal wound infections and increasedmortality,45,46,54–56 and aggressive glucose control improves out-come in subjects undergoing CABG.3,8,45,46,48,53–56 In a pro-spective study of 1,499 consecutive patients undergoingCABG, Furnary et al54 reported that a conservative periop-erative insulin infusion protocol aimed at maintaining bloodglucose levels between 150 to 200 mg/dL was associated witha 59% reduction in deep sternal wound infections versus his-torical controls. In a subsequent report, they found that con-tinuous IV insulin therapy (mean blood glucose: 177 � 30mg/dL) compared with subcutaneous insulin (glucose: 213 �4 mg/dL) resulted in lower mortality, 2.5% versus 5.3%,respectively.45 In this study, patients with blood glucose lev-els � 250 mg/dL had a 14.5% mortality, compared with amortality rate of 0.9% in subjects with blood glucose � 150mg/dL.14 A different study assessed the perioperative glucosecontrol and outcome during the first 36 hours followingCABG surgery.55 Compared with patients in the lower quar-tile (121–206 mg/dL), the risk of infection was increased by17% for those with blood glucose between 207 to 229 mg/dL,by 78% in subjects with blood glucose between 253 to 352mg/dL, and by 86% for glucose levels between 230 to 252mg/dL.

In 2001, Van den Berghe et al10 reported a prospectivestudy of 1,548 adults randomized to intensive insulin therapyto maintain target blood glucose between 80 to 110 mg/dL(actual mean daily blood glucose � 103 mg/dL) or conven-tional therapy to maintain target blood glucose between 180to 200 mg/dL (actual mean daily blood glucose � 153 mg/dL). Two thirds of these patients underwent cardiac surgeryand the rest had noncardiac major surgical procedures. Inten-

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Southern Medical Journal • Volume 99, Number 6, June 2006 581

sive intervention reduced overall in-hospital mortality by 34%in patients with an ICU length of stay of more than 5 days andalso reduced requirements for antibiotics, red cell transfu-sions, kidney dialysis, and prolonged ventilatory support. Afurther analysis of the cohort41 reported that for each 20mg/dL glucose elevation above 100 mg/dL, the risk of ICUmortality was increased by 30%. The rate of hypoglycemia(defined as a blood glucose �40 mg/dL) occurred in 5.1% ofthe intensively treated patients.

The reasons for poor outcome with high blood glucoselevels during the perioperative period remain unclear. Muchof the attention has focused on the increased rate of infectionsand poor wound healing.57,58 Hyperglycemia is associatedwith impaired leukocyte function, including decreased phago-cytosis, impaired bacterial killing and chemotaxis.57,59,60

Other effects of hyperglycemia on the immune system in-clude inhibition of polymorphonuclear leukocyte respiratoryburst,61 diminished superoxide generation, inhibition of phos-pholipase D activity and altered complement function.60,62

Several prospective and well-designed studies have shownthat patients with a postoperative glucose greater than 200mg/dL have a 17 to 86% increased risk of infection,55 andthat reduction of blood glucose with insulin therapy improvesleukocyte function and lowers the risk of local and systemicinfections.10,45,63 Hyperglycemia has also been shown to im-pair collagen synthesis and to impair wound healing amongpatients with poorly controlled diabetes.64,65 In humans andin animal models of diabetes, hyperglycemia has been shownto cause multiple defects in wound healing, including reducedcollagen synthesis, reduced wound tensile strength, reducedneovascularization and capillary volume at the site of inju-ry.64,65 Advanced glycosylation end products accumulate indiabetes and may adversely affect extracellular matrix pro-duction, cell function, cytokine production and prevent woundhealing.66

In addition to the deleterious effects on wound healing,hyperglycemia results in a raised concentration of counter-regulatory hormones and cytokines which lead to increasedcirculating FFA levels.67,68 Elevated FFAs have been asso-ciated with arrhythmias, increased sympathetic overactivity,elevated blood pressure, a rise in oxidative stress, and endo-thelial dysfunction.69–71 They directly activate typical andatypical isoforms of protein kinase C (PKC).72 Activation ofPKC is involved in the regulation of vascular tone and vas-cular smooth muscle cell growth and may contribute to en-dothelial dysfunction. At the cellular level, there is evidencethat FFAs reduce nitric oxide bioavailability by inhibitingnitric oxide synthase activity and stimulating production ofreactive oxygen species (ROS).73 Reactive oxygen speciesare associated with activation of extracellular signal-regu-lated kinase (ERK), transcription factors, phospholipase A2,matrix metalloproteinases, increases in IGF-1 levels and de-creases in IGF binding proteins, DNA synthesis, and endo-thelial function. An acute increase in FFA also causes an

inflammatory response, as reflected in an increase in ROSgeneration and increased NF-�B binding activity in mononu-clear cells.74 Intensive insulin therapy has been shown toprevent excessive inflammation in critically ill patients.10,74

Insulin may exert direct anti-inflammatory effects through itssuppression of NF-�B–regulated pathways, including the pro-duction of inflammatory cytokines, such as TNF-�, macro-phage migration inhibitory factor, and the generation of su-peroxide.75–77

Preoperative Assessment of the DiabeticPatient: Risk Evaluation

The comprehensive operative risk assessment is an im-portant step in the management of the diabetic patient beforesurgery.24 The evaluation is oriented to identifying underly-ing cardiac, pulmonary and renal disease, electrolyte distur-bances, presence of macrovascular and microvascular com-plications, as well as the assessment of antecedent glycemiccontrol.

Adult subjects with diabetes should be considered high-risk for cardiac ischemia.78 The risk of coronary artery dis-ease is two to four times higher than in the correspondinggeneral population.79 Asymptomatic diabetic patients have anincidence of acute ischemic events similar to nondiabeticpatients with stable coronary artery disease.80 Diabetics withproven coronary artery disease have poorer long-term out-come after vascular surgery, with an increased probability ofcardiac death or myocardial infarction compared with non-diabetics with equivalent disease.81 In addition, myocardialinfarction and ischemia may be silent and frequently unrec-ognized because of the sympathetic denervation of theheart.82,83 A low threshold for cardiac testing has been rec-ommended in diabetics, especially those over 50 years of age,with obesity, physical inactivity, hypertension, albuminuria,dyslipidemia, and chronically elevated glucose (�200 mg/dL) and A1C levels (� 7%).84 The preoperative detection ofCAD in diabetic patients is difficult.85 The standard baselineelectrocardiogram has a value of 25% for predicting cardiacevents.86 Asymptomatic diabetic patients with multiple riskfactors should be investigated by stress testing if they have alow-functional capacity or if they are to undergo major orvascular surgery. The positive predictive value of all stresstests is modest (20–30%); however, their negative predictivevalue is excellent (95–100%).79 Stress tests with dipyridam-ole-thallium scintigraphy and dobutamine echocardiographyare dynamic investigations with better diagnostic accuracy.The American College of Cardiology (ACC) and AmericanHeart Association (AHA) have coauthored guidelines on pre-operative cardiac risk assessment.78,87,88 The ACC/AHAguidelines use major, intermediate, and minor clinical pre-dictors to stratify patients into different cardiac risk catego-ries. Patients with poor functional status or those undergoinghigh-risk surgery require further risk stratification via cardiac

Smiley and Umpierrez • Perioperative Glucose Control in the Diabetic or Nondiabetic Patient


stress testing. High-risk patients with unstable coronary syn-dromes, patients undergoing major surgery, or when consid-ering coronary revascularization, may merit from preoperativecardiac catheterization by the ACC/AHA guidelines.78,87,88

Autonomic neuropathy is a major complication of dia-betes, characterized by degeneration of afferent and efferentfibers of the sympathetic and parasympathetic nerves of theheart and peripheral vasculature.89,90 Cardiac autonomic neu-ropathy is reported in up to 20 to 40% of diabetic patientswith hypertension and appears to be independent of age, du-ration of diabetes, or the presence of microvascular compli-cations. Cardiac autonomic neuropathy explains the occur-rence of silent myocardial ischemia and the impairedcardiovascular response to exercise and stress24 and may pre-dispose to cardiovascular complications and perioperative hy-potension.91,92 The presence of resting tachycardia, posturalhypotension and loss of respiratory heart rate variabilityshould be sought during the examination.92 Besides cardiaccomplications, autonomic neuropathy may increase the riskof perioperative complications by decreasing esophageal mo-tility and causing gastroparesis that may lead to vomiting andaspiration of gastric content93 and by increasing the risk ofurinary track infection in the presence of neurogenic bladder.

Renal failure is the most common major complication inthe postoperative period and is associated with increased mor-bidity, mortality, and in-hospital resource utilization.94,95 Thereported incidence of renal dysfunction after cardiac surgeryis significantly influenced by the definition used in a givenstudy. The prevalence of renal dysfunction, defined as a post-operative serum creatinine level of � 177 �mol/L (�2.0mg/dL) and an increase in serum creatinine level of � 62�mol/L (�0.7 mg/dL) from the preoperative level, was ob-served in 171 (7.7%) of the 2,222 patients undergoing myo-cardial revascularization.95 Similarly, a prevalence of post-operative renal dysfunction of 7% has been reported inpatients undergoing general surgery.94 Risk factors for post-operative renal dysfunction include advanced age, type 1 di-abetes mellitus, preoperative hyperglycemia, a history of mod-erate to severe congestive heart failure, a previous coronaryartery bypass graft, or preexisting renal disease (as mani-fested by an elevated serum creatinine level).95 This risk ap-proximately doubles with one preoperative risk factor andquadruples with two risk factors. Before surgery, a urine anal-ysis is also recommended to rule out urinary tract infection94

and to determine the amount of proteinuria. The presence ofproteinuria is associated with a greater risk of developingacute renal failure in the postoperative period.

Glycemic Goal During the PerioperativePeriod

Although there are still no proven mechanisms to explainthe detrimental effects of hyperglycemia, there are increasingefforts worldwide to improve and maintain appropriate gly-

cemic control during the perioperative period and in criticallyill patients.10,69,96 A recent position statement of the Ameri-can Association of Clinical Endocrinologists and the Amer-ican Diabetes Association recommended glycemic targets be-tween 80 to 110 mg/dL for critical patients in the intensivecare unit (ICU). For patients with noncritical illness, a pre-prandial blood glucose less than 110 mg/dL and a randomblood glucose level less than 180 mg/dL were recommend-ed.97 These glucose control parameters applied to surgicalpatients in the surgical ICU, in particular after CABG proce-dures. In surgical patients discharged from the ICU to loweracuity units, it was recommended that glucose levels shouldbe maintained as close as possible to normoglycemic levels,either by intensive subcutaneous insulin therapy or by con-tinuation of IV insulin therapy. Recently, several groups haveraised concerns about this position statement, including thefact that the AACE position paper was based primarily onfindings from a single surgical ICU and the fact that therewere no differences on mortality in patients with an ICUlength of stay less than 5 days or in patients after vascularsurgery.98 Several large prospective international studies arecurrently under way that will provide definitive evidence onintensified insulin therapy in critical illness in the ICU.

Intensified glucose control is associated with an increasedrisk of hypoglycemia.99,100 Hypoglycemia is commonly en-countered in hospitalized patients with altered cognitive sta-tus, due to the effects of age, illness, or psychotropic medi-cations. In such patients, the typical symptoms of impendinghypoglycemia are not properly perceived. Although most hy-poglycemic events are mild and without significant clinicalconsequences,10,101 in the cardiac patient, hypoglycemia mayresult in excess catecholamine release that may aggravatemyocardial ischemia or have proarrhythmogenic consequenc-es.98,102,103 The risk benefit ratio of strict glycemic control inall hospitalized patients must take into account the negativeimplications of more frequent hypoglycemic events.10,12,20,96

Continued staff education and the use of frequent blood glu-cose monitoring facilitate early detection and treatment ofhypoglycemic events.12,20,96

Approaches to ManagementGeneral Principles

Treatment recommendations are generally categorizedbased on the type of diabetes, nature and extent of the sur-gical procedure, antecedent pharmacological therapy, andstate of metabolic control before surgery.104 A key factor forsuccess of any regimen requires frequent blood glucose mon-itoring to allow early detection of any alterations in metaboliccontrol. In general, all patients with type 1 diabetes under-going minor or major surgical procedures require insulin dur-ing the perioperative period (Table 1). In such patients, thestress of surgery may result in the development of diabeticketoacidosis or hyperosmolar hyperglycemic nonketotic syn-

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drome, with negative prognostic consequences.104–107 Pa-tients with type 2 diabetes undergoing major surgery andcoronary revascularization procedures are also candidates forintensive perioperative diabetes management.23,108,109 Insu-lin, given either intravenously as a continuous infusion orsubcutaneously, is currently the only available agent for ef-fectively controlling glycemia in the hospital. The best methodof providing insulin during surgery is debatable. There are amyriad of protocols for the management of this problem, butthere are none with clear superiority. Any good regimenshould attempt to maintain good glycemic control, avoidingboth hyperglycemia and hypoglycemia, should be easy tounderstand, and should be applicable to different settings (op-erating room, recovery room, general medicine and surgicalwards). Concerns about hypoglycemia due to altered nutrition

during the perioperative period is the leading limiting factorin maximizing glycemic control in patients with diabetes.12,

110–112 Fear of hypoglycemia frequently leads to the inappro-priate practice of holding a patient’s previous outpatient di-abetic regimen and initiating “sliding scale” insulin coverage,a practice associated with limited therapeutic success.113–115

The use of sliding scale should never be the sole regimen inpatients with type 1 diabetes or in patients with type 2 dia-betes undergoing major surgical procedures.

Patients Treated with Diet AlonePatients whose diabetes is well controlled by a regimen

of diet and physical activity may require no special preoper-ative intervention for diabetes.104 Fasting blood glucoseshould be measured on the morning of surgery, and bloodglucose could be controlled with small doses of supplementalshort-acting insulin. In contrast, hospitalized patients withpoor metabolic control on diet alone (blood glucose �180mg/dL) should received IV insulin therapy (Table 1).

Patients Treated with Oral AntidiabeticAgents

Of the three primary categories of oral agents—secreta-gogues, biguanides, and thiazolidinediones—none have beensystematically studied during the perioperative period.12,116

In general, oral agents should be discontinued one day beforesurgery. Sulfonylureas increase the risk of hypoglycemia; inaddition, a longstanding controversy exists regarding the vas-cular effects of sulfonylureas in patients with cardiac andcerebral ischemia.117–120 Sulfonylureas inhibit ATP-sensitivepotassium channels, resulting in cell membrane deporaliza-tion and increased intracellular calcium concentration.121,122

This mechanism may inhibit ischemic preconditioning andmay lead to increased risk of vascular events.123 Althoughmetformin has a short half-life of approximately 6 hours, it isprudent to temporarily withhold therapy 1 to 2 days beforesurgery, especially in patients undergoing procedures that in-crease the risk for renal hypoperfusion, tissue hypoxia, andlactate accumulation.124,125 Thiazolidinediones increase in-travascular volume and may precipitate or worsen congestiveheart failure and peripheral edema.125,126

In patients with good metabolic control after discontin-uation of oral agents, blood glucose could be controlled withsmall subcutaneous doses (4–10 U) of short-acting insulin(Table 2). Most antidiabetic medications can be restarted oncepatients start eating, with the exception of metformin, whichshould be withheld for 48 to 72 hours following surgery oriodinated radiocontrast procedures. Metformin therapy can berestarted after documentation of normal renal function. Pa-tients with poor metabolic control or those scheduled to un-dergo major surgery should be treated with an IV infusion ofinsulin and dextrose during the perioperative period.

Table 1. Perioperative management of patients withdiabetes

I) Minor surgery in DM2 patients not treated with insulin

● Hold oral agents the day of surgery

● Patients with “fair” metabolic control (fasting blood glucose � 180mg/dL)—cover with regular insulin or rapid-acting (lispro, aspart,glulisine) insulin as needed (see Table 3)

● Patients with “poor” metabolic control (fasting blood glucose � 180mg/dL)—start continuous insulin infusion.

● Goals: avoid excessive hyperglycemia (blood glucose �180 mg/dL)and hypoglycemia (blood glucose � 80 mg/dL)

II) Minor surgery in DM1 and DM2 patients treated with insulin

● Hold oral agents (if treated with combination therapy) the day ofsurgery

● Patients in “fair” metabolic control (fasting blood glucose � 180 mg/dL):

– Give half of intermediate-acting insulin (NPH) the morning of thesurgery

– While NPO, infuse dextrose 5% saline plus KCl (10-20 mEq/L) at100 mL/hour

– Check blood glucose every 4 to 6 hours while NPO andsupplement with short-acting insulin (see Table 3)

– Patient treated with basal (glargine) insulin should receive theirusual basal insulin dose. Similarly, patients treated with continuousinsulin infusion therapy (insulin pump) should receive their usualbasal infusion rate

– Restart preadmission insulin therapy once food intake is tolerated

● Patients in “poor’ control (fasting blood glucose � 180 mg/dL)—start continuous insulin infusion

III) Major surgery in DM1 and DM2 patients treated with insulin

● Hold oral agents the day of surgery

● Start continuous insulin infusion prior to surgery and continue duringperioperative period (Table 3)

● Goals: Maintain blood glucose � 180 mg/dL during surgery, andblood glucose between 80 to 120 mg/dL during the perioperativeperiod in the surgical intensive care unit. Start subcutaneous insulintwo hours prior to discontinuation of insulin infusion. In non-ICUsettings, avoid excessive hyperglycemia (blood glucose �180 mg/dL)and hypoglycemia (blood glucose � 80 mg/dL)

DM1, type 1 diabetes; DM2, type 2 diabetes; NPO, nothing per oral route,fasting; ICU, intensive care unit.



Type 1 or Type 2 Diabetes Treated withInsulinMinor Surgery

Most patients receiving insulin before admission can betreated with conventional subcutaneous insulin therapy. If thesurgery is to be performed in the morning in a patient treatedwith intermediate-acting (NPH) insulin, one half of the totalmorning dose of NPH insulin should be adminis-tered.3,19,23,127 While the patient remains NPO, a 5% dex-trose-potassium infusion is infused at a rate of 100 mL/h. Thedextrose infusion should be discontinued once oral intake isreinitiated. If needed, blood glucose can be controlled withsmall doses of supplemental short-acting insulin. In patientstreated with basal/bolus insulin combination—glargine andrapid acting insulin analogs (lispro, aspart, glulisine) - thedose of glargine should be continued, but premeal bolus dosesshould be held until meals are tolerated. Similarly, patientstreated with continuous insulin infusion therapy (insulinpumps) should receive their usual basal infusion rate.

Major SurgeryIV infusion of insulin is the standard therapy for the

perioperative management of diabetes, especially in type 1diabetic patients and patients with type 2 diabetes undergoingmajor procedures.12,19,100 Several reports have emphasizedthe advantages of the insulin infusion regimen over subcuta-

neous delivery.12,19,100 Insulin-treated patients undergoingmajor elective surgery should be monitored carefully duringthe period before admission, aiming for an HbA1c less than7%. The patient should be admitted the evening before sur-gery or at least several hours before surgery, especially ifglycemic control is suboptimal (hemoglobin A1c �8%). Thiswill allow sufficient time to perform a complete clinical as-sessment and start insulin infusion before surgery.

Institutions around the world use a variety of insulininfusion algorithms that can be implemented by nursing staff.Recently, several insulin infusion protocols have been re-ported in the literature.10,42,45,96 These algorithms facilitatecommunication between physicians and nurses, achieve cor-rection of hyperglycemia in a timely manner, and provide amethod to determine the insulin infusion rate required tomaintain blood sugars within a defined target range.12,101 Inmost insulin infusion protocols, orders to “titrate drip” aregiven to achieve a target blood glucose range using an estab-lished algorithm or by the application of mathematical rulesby nursing staff.12,101 Two main methods of insulin deliveryhave been used either combining insulin with glucose andpotassium in the same bag (GIK regimen) or giving insulinseparately with an infusion pump. The GIK is initiated at arate of 100 mL/h in a solution of 500 mL of 10% dextrose, 10mmol of potassium, and 15 U of insulin. Adjustments in theinsulin dose are made in 5 U increments according to bloodglucose measurements performed at least every 2 hours.3 Po-tassium is added to prevent hypokalemia and is monitored at6-hour intervals. The combined GIK infusion is efficient,safe, and effective but does not permit selective adjustment ofinsulin delivery without changing the bag. In the UnitedStates, separate continuous glucose and insulin infusions areused more frequently than the glucose-potassium-insulin in-fusion.10,42,45,96

A proposed regimen for separate IV insulin infusion forperioperative diabetes management is shown in Table 3 . Inpatients with type 2 diabetes treated with diet or oral antidi-abetic agents, we recommend starting continuous insulin in-fusion when blood glucose levels are � 140 mg/dL; however,patients with type 1 diabetes or with known diabetes treatedwith insulin can be started on continuous insulin infusionwhen blood glucose is � 70 mg/dL. The initial insulin rate iscalculated by dividing the blood glucose level (mg/dL) by100, then rounding it to nearest 0.5 U (eg, if the initial bloodglucose is 260 mg/dL, 260 � 100 � 2.5, start drip at 2.5 U/h).An initial IV insulin bolus is frequently used for patients withsignificant hyperglycemia (blood glucose � 200 mg/dL). Theinfusions should be continued postoperatively until oral in-take is established, after which the usual diabetes treatmentcan be resumed.

Adequate glucose should be provided to prevent catab-olism, starvation ketosis, and insulin-induced hypoglycemia.The physiologic amount of glucose required to prevent ca-tabolism in the average nondiabetic adult is 120 g/d (or 5

Table 2. Supplemental sliding scale insulin

● Type of insulin: regular or rapid-acting insulin (lispro, aspart,glulisine) to be given before each meal and at bedtime.

● Each column represents the number of units of insulin to be added toscheduled insulin dose.

– “Sensitive” column: elderly, cachectic, renal and liver failure, andpatients with poor oral intake or NPO.

– “Usual” column: for most patients who are expected to eat all ormost of their meals.

– “Insulin Resistant” column: for patients not controlled with “usual”column dose, or receiving glucocorticoids, obesity (BMI � 30 kg/m2), or patients with diabetes receiving �80 units/day of insulin.

Blood Glucose □ □ □

(mg/dL) Insulin Sensitive Usual Insulin Resistant

� 150 0 0 0

151-180 1 2 4

181-220 2 3 4

221-260 3 4 5

261-300 4 5 6

301-340 5 6 7

341-380 6 7 8

380-420 7 8 9

� 420 8 9 10

**Check appropriate column below and cross out other columns

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g/h). With preoperative fasting, surgical stress, and ongoinginsulin therapy, the caloric requirement in most diabetic pa-tients averages 5 to 10 g/h of glucose. This can be given as5% or 10% dextrose. An infusion rate of 100 mL/h with 5%dextrose delivers 5 g/h of glucose. If fluid restriction is nec-essary, the more concentrated 10% dextrose can be used.Fluids containing lactate (ie, Ringer lactate, Hartmann solu-tion) cause exacerbation of hyperglycemia.3

Discharge RecommendationsAll patients with newly diagnosed diabetes should re-

ceive diabetes education, and the outpatient treatment regi-men should be discussed before discharge.30 Arrangementsshould be made for follow-up with a health care professionalwho will oversee the patient’s diabetes management. Thepatient or caregiver should receive appropriate instruction onproper dietary therapy, as well as home glucose monitoringtechniques. The patient should also be educated on the signsand symptoms of hypoglycemia and hyperglycemia. Finally,patients should be educated on ‘sick day’ management with afocus on the importance of insulin administration during anillness, blood glucose goals and the use of supplemental shortor rapid-acting insulin.

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Table 3. Continuous insulin infusion (CII) protocol

I) Initiating continuous insulin infusion (CII):

● Prepare solution: 1 unit (U) per 1 mL of 0.9% normal saline.

● Start continuous insulin infusion (CII) when blood glucoselevel � 140 mg/dL (x 2). Patients with known diabetes treated withinsulin can start CII when blood glucose � 70 mg/dL.

● Initial rate: divide blood glucose level (mg/dL) by 100, then round tonearest 0.5 U

II) Insulin infusion rate change:

Blood

Glucose (mg/dL) instructions:

� 200 1 rate by 2 U/h

� 160–200 1 rate by 1.0 U/h

� 120–160 1 rate by 0.5 U/h

80–120 No change in rate

60–80 If � 10% lower blood glucose, 2 rate by 1 U/h,� BG within 30 min

If � 10% lower blood glucose, 2 rate by 50%,� BG within 30 min

� 60 Stop infusion (give IV dextrose 12.5 g IV bolus),� blood glucose within 30 min. When blood glucose� 100 mg/dL, restart infusion at 50% of previous rate

III) Patient monitoring:

● Check capillary blood glucose every hour until it is within goal rangefor 2 hours, and then decrease to every 2 hours.

● Hourly monitoring may be indicated for critically ill patients even ifthey have stable blood glucose. If a patient is eating, hourly bloodglucose monitoring is necessary for at least 3 hours after eating.

● Decrease insulin infusion rate by 50% if nutritional therapy (e.g. totalparenteral nutrition or tube feeds) are discontinued or significantlyreduced.

IV) Treatment of Hypoglycemia (BG�60 mg/dL)

● Turn off insulin infusion.

● Blood glucose level 40–60 mg/dL: give 12.5 g (25 mL) IV bolus ofdextrose 50% solution. For blood glucose � 40 mg/dL, or if a patientis not awake, give 25 g (50 mL) IV bolus of dextrose 50% solution.

● Recheck BG every 20 minutes, repeat 25 mL of 50% dextrose IV ifBG �60mg/dL.

● Restart infusion once BG is �80 mg/dL.

V) Notify the physician:

● For any blood glucose change greater than 100 mg/dL in one hour.

● For blood glucose � 40 mg or �360 mg/dL.

● For hypoglycemia which has not resolved within 20 min ofadministering 50 mL of 50% dextrose.

CII, continuous insulin infusion; BG, blood glucose.

Conversion factors to SI units: serum glucose (mg/dL) � 0.055 mmol/L.



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Please see Ann S. Reed’s editorial on page 557 ofthis issue.

No man may make another free.––Zora Neale Hurston

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