The influence of diabetes mellitus on postoperative infections

Crit Care Nurs Clin N Am 15 (2003) 125 – 135

The inf luence of diabetes mellitus on postoperative infections Daleen Aragon, PhD, CCRN, FCCM a,*, C. Allan Ring, BSN, RN b, Maureen Covelli, PhD, RN b a

Orlando Regional Healthcare System, 5428 Conway Oaks Court, Orlando, FL 32812, USA University of Central Florida School of Nursing, PO Box 162210, Orlando, FL 32816, USA

b

Diabetes mellitus (DM) affects 5.9% of the American population, or 17 million individuals in the United States [1]. It presents risks to individuals who have other pathologic states, such as cardiovascular, renal, and neurologic diseases. One important risk associated with DM and hyperglycemia is the development of infection and delayed or impaired wound healing [2 – 4]. Poor wound closure and wound infections are common in diabetic patients owing to a number of associated factors. Persons with DM do not heal as fast as individuals without DM [5] and are at risk for wounds in places particularly vulnerable to diminished circulation, such as in the feet [6]. Other comorbid factors may further reduce resistance to infection, such as age, malnutrition, obesity, perfusion deficits, and critical illness [2,4]. Diabetic patients may have an increased susceptibility to bacterial infections owing to an impaired host defense response [7]. This article summarizes the pathophysiologic processes that can occur with hyperglycemia and DM. The consequences of DM and hyperglycemia that can engender infection are reviewed, followed by a discussion of the effects of hyperglycemia on the body’s immune defense mechanisms. The additive nature of critical illness, stress, and surgery on infection in this population is explored. The results of studies and protocols that have yielded improved infectious outcomes

* Corresponding author. E-mail address: [email protected]. (D. Aragon).

in hyperglycemic patients and that have the potential to guide nursing interventions are summarized.

Association of infection with diabetes Despite widespread opinion that DM predisposes individuals to an increased susceptibility to infection, no strong evidence supports this assumption. Nevertheless, several specific infections are common in patients with DM, and some of these infections occur almost solely with the disease [3,8,9]. Experts generally agree that several defects are present in the defense mechanisms of the body in persons with DM. These patients can sustain changes in vascular and neurologic function that lead to a higher likelihood of infection. As McMahon and Bistrian [10] point out, although there is no proven causal link between hyperglycemia and infection, there are enough data to suspect elevated glucose levels as a culprit for an increased risk of infection. Risk of infection Jones and Huether [11] summarized five ways that DM might increase the risk of infection: (1) impaired perception, (2) hypoxia, (3) excess glucose, (4) reduced perfusion, and (5) impaired leukocyte function. Diminished sensitivity to pain and trauma in the lower extremities allows broken skin to go unnoticed, as does impaired vision. Hypoxia can be present owing to microvascular and macrovascular disease. Rayfield et al [12] point out that anaerobic microbes

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may grow better with reduced oxygen, and that leukocytes may function more poorly because their bactericidal activities are oxygen dependent. Infection may occur because gram-positive bacteria flourish in hyperglycemic serum [5], because fewer leukocytes may reach the affected area, or because depressed leukocyte function may lead to impaired chemotaxis and phagocytosis. The impaired perception of a diabetic patient has a role in the risk for infection. Neuropathy is a frequent complication of DM and affects 60% to 70% of patients. Although experts do not agree on the origins of impaired perception, chronic hyperglycemia is a common element [6]. Somatic and autonomic neuropathies may occur. The somatic sensorimotor manifestations of diabetic neuropathy are complex and may result in proprioceptive error, loss of sensation, muscle weakness, and atrophy [13]. Because these individuals have reduced pain sensation, they ignore warning signs of inflammation, thereby allowing injury, infection, and inflammation to develop further. Peripheral neuropathies also have a role in the development of foot and leg ulcers, which are ready sites for infection. Autonomic neuropathy diminishes gastrointestinal motility, cardiac function, and vascular contractility [6]. When autonomic neuropathy affects the bladder, urinary retention and stasis make urinary infections more likely [8,12]. Visual deficits, primarily owing to diabetic retinopathy, are another complication of DM. When coupled with peripheral neuropathy, visual deficits may represent a double sensory risk. The diabetic patient may not feel an injury and, with visual deficits, may not see the lesion after its occurrence. Other physiologic changes Several other physiologic derangements occur in DM, including macrovascular and microvascular disease and erythrocyte changes. DM is associated with the development of accelerated and premature atherosclerosis in the larger blood vessels. Lipid disorders common to diabetic persons, such as hypertriglyceridemia, low levels of high-density lipoproteins, high levels of low-density lipoproteins, and lipoprotein oxidation, may promote changes in vascular structure and atherogenesis. Immune mechanisms, altered macrophage function, and the effects of advanced glycation end products (AGEs) [6,11] lead to enhanced endothelial injury and microvascular and macrovascular disease. Atherosclerotic plaques form as a result of several physiologic processes. Over time, glycation, the binding of a glucose molecule to an amino acid, leads to the formation of AGEs.

Binding sites for AGEs on the vascular endothelium and smooth muscle cells give rise to atherosclerotic plaques [14 – 16], which reduce the vessel lumen diameter and tissue perfusion [2,4]. Common sites for the resulting atherosclerosis in diabetic patients are the deep femoral artery, distal tibial artery, and peroneal artery near the fibula [6]. The hallmark of microvascular disease in diabetic patients is thickening of the capillary basement membrane [5]. Researchers have proposed several ways in which thickening might occur. In one scenario, receptors in the capillary endothelium and macrophages react with AGEs and result in lesions and thickening of the capillary membrane with diminished perfusion, hypoxia, and ischemia [11]. Another possible contributor to membrane thickening may be related to type IV collagen, a principal component unique to the basement membrane, which is increased in DM [6]. When erythrocyte membranes are glycosylated, the cells become less deformable [5,6]. To deliver oxygen, they need flexibility to squeeze through the lumina of capillaries. Glycosylated hemoglobin (HbA1c) has impaired oxygen release [5]. These impairments to red blood cells may further alter perfusion and cellular oxygenation.

Physiologic effects of hyperglycemia on the immune system Immunocompetence is the ability of the immune system to respond to pathogenic organisms and tissue damage. DM and hyperglycemia can alter the immune function in several ways and expose diabetic patients to the risk of wound infections. Although experts disagree on the effect of DM on the inflammatory and immune process, some immune effects are well documented [8]. Role of chemotaxis Findings from animal and human studies indicate that elevated serum glucose has an effect on the antibacterial function of polymorphonuclear leukocytes [4,10,12]. A variety of factors may be involved. One feature of immunocompetence is the ability of phagocytes to respond to signals for attack through chemotaxis [11]. Chemotaxis is the process by which immune cells move to an area of inflammation because of the release of chemical mediators by neutrophils, monocytes, and injured tissues. Chemotaxis is thought to be impaired in hyperglycemia [8,10 – 12,17], and acidosis coupled with hyperglycemia further alters chemotaxis [4].

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The motility and phagocytic functions of white blood cells are associated with the fluidity of their cell membranes. In diabetic patients, the fluidity of the cell membrane is reduced, thereby decreasing the capacity of white blood cells for chemotaxis. The fluidity of the cell membrane is decreased significantly with increasing serum glucose in diabetic animals [17]. Hyperglycemia seems to be the most important mechanism for this change in the membrane. In addition to alterations in phagocytosis, some researchers have found alterations in bactericidal (cellular killing) activity in DM [4,8,10,12,17]. In animal studies, bactericidal activity in alveolar macrophages in insulin-deficient rats was markedly reduced, particularly the response to staphylococcus [7]. Once the rats underwent intensive insulin therapy, this abnormality was partially reversed. These findings were thought to be explained by cellular defects associated with insulin deficiency, and hyperglycemia was suggested as a marker for this phenomenon. Role of opsonization In the process of opsonization, components of the immune system, such as complement or immunoglobulins, coat foreign invaders such as bacteria to make them more susceptible to phagocytosis [11]. This process is particularly important for encapsulated bacteria. Opsonization, which allows for adherence of the bacteria to the surface of phagocytes, is impaired by hyperglycemia [10,17]. It is possible that glucose binds to the opsonic binding site, yielding a dysfunctional binding complex. This situation has been found to be true in infection with Candida albicans. Dysfunctional binding is thought to impair recognition by the phagocyte. Without opsonization and phagocytosis, bacteria are more likely to proliferate unchallenged in the diabetic patient. Immunoglobulin dysfunction Serum immunoglobulins or antibodies, such as immunoglobulin G (IgG), have a role in humoral immunity, the branch of the immune system responsible for immunoglobulin production. During hyperglycemia, nonenzymatic glycosylation (chemical linkage of glucose to proteins) occurs. Serum proteins such as hemoglobin, albumin, and immunoglobulins lose their function when glycosylated [18,19]. When IgG is nonenzymatically glycosylated, it has decreased immunologic function and may be entirely inactivated [18,19]. Researchers have suggested that the reduced function of IgG may be caused by reduced complement fixation [19].

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Defects in chemotaxis, adherence, phagocytosis, and intracellular killing have been demonstrated in uncontrolled DM. Immune function may be compromised because of immunoglobulin dysfunction. These defects are reversible to some degree after aggressive treatment to maintain control of blood glucose [7,10]. This observation supports the theory that glycemic control may be important to reduce the risk of infection in the diabetic individual.

The role of the stress response In patients with injury [20] or stress, hyperglycemia and immunoincompetence often develop [18]. When the body is under stress, regardless of the cause (surgical, traumatic, critical illness), hormones are released that affect serum glucose levels [4,10]. These hormones are counterregulatory and drive hyperglycemia. Hormones that increase glucose include glucagon, epinephrine, norepinephrine, adrenocorticotropic hormone, and cortisol [20]. The simultaneous secretion of these hormones yields a synergistic effect on counterregulatory hormones during stressful events, elevating serum glucose levels [10]. The hormones cause hyperglycemia through gluconeogenesis, glycogenolysis, and lipolysis. Additionally, a primary insulin resistance occurs at the cellular level [4,18]. This response is a type of secondary DM in nondiabetic patients and aggravates glycemic control in patients with DM. The physiologic response to these hormones is increased hepatic release of glucose and decreased cellular uptake, leading to what is known as stress-induced DM. In diabetic individuals, this response is exaggerated further [10] in an augmented response, rendering it more difficult to control blood sugar in these patients [19]. Additionally, catecholamines can cause vasoconstriction in the microcirculation [4]. This response may further compromise diabetic patients with microvascular disease. Table 1 summarizes the pathophysiologic changes that occur with hyperglycemia and potential factors contributing to infection.

Surgical procedures and diabetes mellitus A surgical procedure creates tissue injury. The degree of injury depends on the type and location of the procedure. Surgical incisions alter the first line of defense for infection and, in patients with hyperglycemia, present a locus for infection. Surgical wounds typically heal by primary intention, an organized epithelial process [2]. After surgical injury, healing

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Macrovascular changes

Microvascular changes

Neuropathy

Immune response

Stress response

Physiologic events

Accelerated atherosclerosis

Thickening of the capillary membrane

Delayed sensory relay of pain Visual pathways impaired

Counterregulatory hormones promote glucose release and insulin resistance: catecholamines, gluconeogenesis, glycogenolysis

Physiologic consequences

Impaired blood flow

Effect on risk for infection

Reduced ability of serum elements to reach tissues Inadequate tissue oxygenation

Reduced tissue perfusion Impaired tissue oxygenation and ability of cellular elements to reach injured tissue

Impaired sensation and vision Reduced awareness of inflammation and wounds

Decreased function of PMLs Chemotaxis Phagocytosis Opsonization Cellular killing Complement activity impaired Impaired ability to fight off infection Infection develops Elevated glucose feeds bacteria Inflammatory process impaired

Abbreviations: PMLs, polymorphonuclear leukocytes.

Increased serum glucose Insulin resistance Increased available glucose for bacterial consumption Further exaggeration of hyperglycemic responses Impaired ability of cellular uptake of insulin

D. Aragon et al. / Crit Care Nurs Clin N Am 15 (2003) 125–135

Table 1 Pathophysiologic explanations of diabetes mellitus and infection

D. Aragon et al. / Crit Care Nurs Clin N Am 15 (2003) 125–135

begins in a sequential fashion and in phases, regardless of the type of healing that occurs. The initial period is the inflammatory phase that starts at the time of injury and extends 3 to 6 days afterwards [2]. Impaired immunocompetence during this phase may decrease the effectiveness of the inflammatory response. Early in the inflammatory process, simultaneous cascade systems are activated. In the previously noninfected patient, the first 24 to 48 hours following injury comprise the acute phase of inflammation, when mobilization of leukocytes, complement, and lymphocytes occurs [2]. If hyperglycemia is present during this phase, healing and the ability to fight foreign invaders may be impaired. In the immediate postoperative phase when the body is also subjected to the stress response of surgery, hyperglycemia may ensue. The impairment of immune function during hyperglycemia in the diabetic individual or nondiabetic individual may be important in the pathogenesis of infection [18]. Surgical stress may compound a derangement in glucose function in an already compromised host. Although the complete processes behind these derangements have not been fully explained, a synergistic effect of combined factors is associated with an increased infection rate. In diabetic patients, the control of glucose is also impaired during infection, and a vicious cycle of compromise ensues. The management of infection is problematic in the diabetic individual, and infections are associated with higher mortality rates [17]. Although a complete understanding of DM and infection is unclear, it is generally accepted that infections are more difficult to treat in diabetic patients, and that these infections tend to be more severe and prolonged than those occurring in the nondiabetic surgical population [7]. Diabetes mellitus and surgical wound infection Diabetes mellitus has been studied as a risk factor in surgical patients [8]. Surgical stress and critical illness impose a physiologic burden on all patients, but in patients with DM, these events may have an additive effect. Studies have been conducted in diabetic patients undergoing a variety of surgeries, such as median sternotomy, hip replacement, and vascular grafting [8]. Some of these studies have indicated an increased risk for postoperative infection with DM [12]. In nine studies of infection after cardiovascular surgery, seven found DM to be a predictor, whereas two did not. The subjects were not well matched across the studies, and definitions of infection varied greatly. Nonetheless, a possible connection between DM and infection warrants further investigation. Table 2 sum-

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marizes the results of these studies. DM, obesity [23], and the timing of antibiotic administration [26,32] were associated with infectious complications.

Clinical implications and recommendations By examining the physiologic changes that occur with hyperglycemia, clinicians can extrapolate many clinical recommendations. First, and most importantly, glycemic control may yield positive outcomes and reduction of complications. Many of the pathologic effects are partially reversible once hyperglycemia is corrected. Glycemic control A study conducted by the Diabetes Control and Complications Trial Research Group was a landmark example of the role of glycemic control in diabetic complications [10,32]. This multicenter, randomized, prospective study enrolled 1441 patients with type 1 DM and compared the effect of conventional versus intensive diabetic treatment on the development of diabetic complications. Outcomes from this study indicated that tighter control yielded a significant reduction in microvascular changes, retinopathy, neuropathy, and renal effects. Several other research studies have also presented data on current theories regarding glycemic control. In an intervention study, the investigators sought to determine the effect of tight glycemic control on sternal wound infections in the early postoperative period following open heart operations. In a prospective study of 2467 patients with types 1 and 2 diabetes, one group was treated with continuous intravenous insulin to maintain a blood glucose level of less than 200 mg/dL (11.1 mM/L), whereas a comparison group was treated with intermittent subcutaneous injections. Patients who were in the intravenous treatment group using the Portland protocol, as it is more widely known today, had a significant decrease in deep sternal wound infections (0.8% versus 2.0%) when compared with patients treated with intermittent subcutaneous infections. Obesity was also a factor associated with infection [33,34]. Other studies have reported similar findings. DeCherney et al [35] compared the effectiveness of fixed-rate doses of intravenous insulin versus an intermittent sliding scale insulin regimen on glycemic control in hyperglycemic postoperative coronary artery bypass graft patients. A higher continuous rate of intravenous insulin administration was effective in achieving

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Table 2 Studies of diabetes mellitus and surgical wound infection Population (n)

Aim of the study

Pertinent findings

Borger et al [21]

CABG, and other open heart procedures (12,267)

Determine risk factors for deep sternal wound infections

Casey et al [22]

High-risk patients undergoing vascular surgery operations (75)

Determine the relationship of immune and nutritional status to wound healing complications

Gadaleta et al [23]

CABG patients with obesity versus normal body weight (112)

Determine risk factors of morbid obesity on incidence of complications, including sternal wound infection

Golden et al [24]

CABG patients with type 1 and 2 DM (411)

Assess the relationship of perioperative glycemic control to the risk of infectious complications

McMahon and Bistrian [10]

Type 1 and 2 diabetic patients undergoing elective surgical procedures (100)

Monitored perioperative glucose control and development of postoperative infections

Incidence of sternal wound infection was 0.75%. Risk factors identified were as follows: DMa (OR = 2.6; CI, 1.7 – 4.0; P = 0.001), male gender (OR = 2.2; CI, 1.3 – 3.9; P = 0.007), and use of bilateral internal thoracic artery (BITA) grafts (OR = 3.2; CI, 1.1 – 8.9; P = 0.03). BITA and DMa were associated with a 14.3% risk of deep sternal wound infection ( P = 0.001). Male diabetics with BITA had a 20% incidence ( P = 0.001). 23/79 Patients had DMa; 38% (n = 14) of those with DM had wound complications. Patients with DM had significantly higher incidence of wound complications ( P<0.05) than those without DM. Serum albumin levels > 3 g/ dL were more likely to be associated with uncomplicated wound healing ( P<0.001). Serum transferrin level < 150 mg/dL was associated with more wound complications ( P<0.01) Incidence of sternal wound infection was 10.7% in obese patients and 0% in normal weight patients. Risk factors identified with complications were as follows: DMa ( P < 0.002) and BMI ( P < 0.05). Morbidly obese patients with diabetes had a longer length of stay ( P < 0.05) and were more likely to have >1 complication postoperatively ( P < 0.01) than nondiabetic obese patients. Incidence of leg wound infection was 10.9%; sternal wound infection, 5.6%; UTI, 6.6%; and pneumonia, 4.6%. Patients with higher mean capillary glucose were at increased risk for infections. Relative odds of infection (95% CI), were as follows: 1.17 (glucose, 207 – 229 mg/dL), 1.86 (glucose, 230 – 252 mg/dL [12.8 – 14 mM/L]), and 1.72 (glucose, 253 – 352 mg/dL [14.05 – 19.56 mM/L]) ( P = 0.05). Patients with higher glucose values on postoperative day 1 (glucose levels >12.2 mM [220 mg/dL] had infection rate 31.3% higher than the rate for those with levels < 12.2 mM. 2.7 times greater rate for infection was found in DM patients with higher serum glucose levels and a RR for development of serious postoperative infections of 5.9.

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Citation

CABG (77)

Determine the best surgical wound closure method for postoperative leg wound infection Determine risk factors for infection in vascular surgery patients

Richet et al [26]

Peripheral vascular surgery (561)

Spelman et al [27]

CABG retrospective chart review and historical controls (693)

Determine risk factors for surgical wound infection and septicemia

Trick et al [28]

CABG with radial artery harvest (309)

Determine risk factors for infection of the radial artery harvest site

Trick et al [29]

CABG (1796)

Determine risk factors for deep sternal wound infection

Vuorisalo et al [30]

CABG (884)

Identify preoperative and perioperative risk factors for surgical wound infection

Incidence of infection was 11.7% (minor and major). Risk factors identified were as follows: wound depth ( P = 0.03). DMa was not associated with infection. Incidence of surgical wound infection was 4.1%; lower respiratory tract infection, 3.9%; and UTI, 4.6%. Risk factors identified were as follows: surgery on lower extremities (RR = 231, P = 0.0001), delayed surgery (RR = 2, P = 0.001), IDDM (RR = 2.9; P = 0.03), past history of vascular surgery (RR = 1.7, P = 0.05), and short antimicrobial prophylaxis (RR = 1.6, P = 0.03) Incidence of infection was 9.38%. Risk factors identified were as follows: DMa (RR = 2.1; CI, 1.2 – 3.63; P = 0.009), obesity (RR = 2.82; CI, 1.58 – 5.03; P = 0.001), and previous cardiovascular intervention (RR = 2.6; CI, 1.15 – 5.65; P = 0.02). Incidence of infection was 11.3% overall (n = 35). Unilateral infection occurred in 5.5% (n = 17) and bilateral infection in 2.9% (n = 9). Risk factors identified were as follows: IDDM (OR = 2.8; CI, 0.7 – 4; P = 0.04), IDDM with blood glucose  200 mg/dL (11.1 mM/L) preoperatively (OR, 4.4; P = 0.01), all patients with blood glucose  200 mg/dL (OR = 4; CI, 1.2 – 14; P = 0.009), and surgery duration  5 hours (OR, 3.1; P = 0.02). Incidence of infection was 1.7%. Risk factors identified were as follows: cefuroxime receipt  2 hours preoperatively (OR = 5.0; CI, 1.4 – 17; P = 0.002); type 1 DM (OR = 2.6; CI, 1 – 6.7; P = 0.02) and 2 DM (OR = 3.7; CI, 1.1 – 13; P = 0.01) with blood glucose  200 mg/dL (11.1 mM/L) preoperatively (OR = 10.2; CI, 2.4 – 43; P = 0.008); all patients with blood glucose  200 mg/dL (OR = 5.0; CI, 1 – 26; P = 0.02); staples used for closure (OR = 4; CI, 1.4 – 13; P = 0.01). Incidence of actual or suspected infection was 19.5% until 30 days postoperatively.

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Mullen et al [25]

(continued on next page)

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Population (n)

Aim of the study

Pertinent findings

Vuorisalo et al [30]

CABG (884)

Identify preoperative and perioperative risk factors for surgical wound infection

Whang and Bigger [31]

CABG with ejection fraction < 0.36 (900)

Determine relationship between DM (types 1 and 2) and outcomes in patients with severe left ventricular dysfunction

Incidence of actual or suspected infection was 19.5% until 30 days postoperatively. Chest wound infections occurred in 5.3%. Donor site infections occurred in 15.4%. Risk factors identified were as follows: in chest area, DM (types 1 and 2) ( P = 0.003), extreme BMI ( P = 0.01); at donor site, female gender ( P = 0.003). DM was not associated with a higher mortality rate. DM was associated with a higher readmission rate ( P < 0.001), superficial sternal wound infection (OR = 3.31, P = 0.02), and BMI >30% (OR = 2.08, P = 0.001).

Abbreviations: BMI, body mass index; CABG, coronary artery bypass grafting surgery; CI, 95% confidence interval; DM, diabetes mellitus; IDDM, insulin-dependent DM; OR, odds ratio; RR, relative risk; UTI, urinary tract infection. a Type of DM not specified.

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Table 2 (continued ) Citation

D. Aragon et al. / Crit Care Nurs Clin N Am 15 (2003) 125–135

satisfactory control over blood glucose and was superior to the sliding scale regimen. Other studies support the need for stringent glycemic control. In a prospective, randomized, controlled study of 1548 patients in a surgical intensive care unit, the patients were randomized to two levels of glycemic control (80 – 100 mg/dL [4.44 – 5.56 mM/L] or 180 – 200 mg/dL [10 – 11.1 mM/L]). Patients received the glycemic control protocol regardless of whether they were diabetic. A more normoglycemic level of control was associated with a lower mortality rate during the intensive care unit stay (8% versus 4.6%), particularly in patients who were in the intensive care unit for more than 5 days (20.2% versus 10.6%). The largest reduction in mortality was seen in patients who received intensive insulin therapy who died of multiple organ failure with a proven septic focus. This effect was true in diabetic patients and in patients who experienced hyperglycemia without DM. Intensive glycemic control reduced overall hospital mortality by 34% and septicemia by 46% [36]. Although few clinical studies have estimated the effect of glycemic control on surgical wound infection, some evidence suggests that glycemic control yields fewer instances of infection, septicemia, and bacteremia, and reduces morbidity and mortality. A strong link exists among hyperglycemia, DM, and infection, in general, and surgical wound infection, in particular. The findings from clinical studies indicate that tighter glycemic control results in improved patient outcomes in the general and surgical populations. The implications for clinical practice include the need for better identification of patients at risk and the necessity of early and stringent management of serum glucose. The best range for glycemic control remains unanswered. Interventional studies to control glucose levels have used different parameters for target ranges for insulin administration. Subjects in the study performed by van den Berghe et al [36] had the tightest control at near-normal glucose levels (107 mg/dL), whereas subjects in the study by Furnary et al [33] (Portland protocol) had a higher glucose target level (150 – 200 mg/dL). Perhaps glycemic control should be considered in diabetic and nondiabetic critically ill or major surgical patients to avoid infection and sepsis. The studies mentioned herein did not include the measurement of preoperative HbA1c, most likely because that measure is not completed routinely in the preoperative period. Assays of HbA1c measure the degree of long-term glucose control, whereas preoperative glucose levels reflect the level of control at the time of surgery and have more clinical applicability [29].

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Patient assessment Diabetic patients who present for elective surgical procedures may be at a higher risk for wound healing complications and infections than are nondiabetic patients. In this ‘‘controlled trauma’’ situation of surgery, every effort must be made to recognize and prevent wound healing problems, because their development typically leads to poor outcomes. Careful assessment and a high index of suspicion assist the critical care nurse in making judgments to limit infection. Preoperative glucose levels should be evaluated in any patient scheduled for surgery. Postoperative monitoring of serum glucose and implementing strategies to promote normoglycemia are potential means for preventing infections and other complications in surgical patients. The use of early and continuous monitoring of glucose, particularly within the first 48 hours postoperatively, and the use of intravenous insulin may be warranted. Other risk factors for infection related to diabetes, such as retinopathy and neuropathy, should be assessed and addressed early in the postoperative course. The effect of hyperglycemia on the development of infection is best evaluated from a multifactorial standpoint. Hyperglycemia has been shown to impair phagocytic function, even at modest levels of 200 – 270 mg/dL [10]. Values in this range are common in critically ill hospitalized patients, particularly in the postoperative period. Other infections encountered in hospitalized patients include line sepsis from central line catheters and total parenteral nutrition and ventilator-associated nosocomial infections. All of these factors may predispose the diabetic patient to infection.

Summary Clinicians and researchers are linking elevated glucose levels with potential infectious outcomes. Physiologic processes to fight foreign agents are potentially impaired during periods of hyperglycemia. Some of these responses, such as immune function and the inflammatory response, are impaired when they are needed most, such as during the recovery from surgical procedures. Investigators have demonstrated the importance of control of serum glucose postoperatively. Outcomes are improved when tighter glycemic control is practiced. The current literature challenges practitioners to become more cognizant of serum glucose in surgical patients and patients who are critically ill. Implementing protocols to gain tighter control of serum glucose

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in the diabetic patient seems warranted based on currently available data, and control of serum glucose in any patient may be appropriate. Further investigation of glycemic control in surgical and other populations will reinforce research findings in this area. Studies should be performed on surgical patients who are particularly vulnerable to DM, glycemic alterations, and postoperative infections, such as patients undergoing peripheral vascular surgery. Further investigations are also needed on the role of hyperglycemia and outcomes in nondiabetic individuals, and on the similarities or differences in glycemic control in types 1 and 2 DM. To increase the generalizability of the study findings, definitions used across studies, such as the type of diabetes, should be standardized. When these studies determine optimal glycemic control practices in a variety of patient populations, clinicians will be able to determine the best practice guidelines to optimize patient care and limit adverse infectious outcomes.

[12]

[13]

[14]

[15] [16]

[17]

[18]

References [1] American Diabetes Association. Facts and figures. Available at: www.diabetes.org. Accessed May 1, 2002. [2] Flynn MB. Wound healing and critical illness. Crit Care Clin 1996;8(2):115 – 23. [3] Joshi N, Caputo GM, Weitekamp MR, Karchmer AW. Infections in patients with diabetes mellitus. N Engl J Med 1999;341(25):1906 – 12. [4] Meyer JS. Diabetes and wound healing. Crit Care Clin 1996;8(2):195 – 201. [5] Silhi N. Diabetes and wound healing. J Wound Care 1998;7(1):47 – 51. [6] Kamal K, Powell RJ, Sumpio BE. The pathobiology of diabetes mellitus: implications for surgeons. J Am Coll Surg 1996;183(3):271 – 89. [7] Sima AAF, O’Neill SJ, Naimark D, et al. Bacterial phagocytosis and intracellular killing by alveolar macrophages in BB rats. Diabetes 1988;37:544 – 9. [8] Boyko EJ, Lipsky BA. Infection and diabetes. In: Harris MI, Cowie CC, Stern MP, et al, editors. Diabetes in America (NIH Publication No. 95 – 1468). 2nd edition. Washington, DC: US Government Printing Office; 1995. p. 485 – 99. [9] Lo¨e H, Genco RJ. Oral complications in diabetes. In: Harris MI, Cowie CC, Stern MP, et al, editors. Diabetes in America (NIH Publication No. 95 – 1468). 2nd edition. Washington, DC: US Government Printing Office; 1995. p. 501 – 6. [10] McMahon MM, Bistrian BR. Host defenses and susceptibility to infection in patients with diabetes mellitus. Infect Dis Clin North Am 1995;9(1):1 – 9. [11] Jones RE, Huether SE. The immune system. In:

[19]

[20]

[21]

[22]

[23]

[24]

[25]

[26]

[27]

McCance KL, Huether SE, editors. Pathophysiology: the biologic basis for disease in adults and children. 4th edition. St. Louis: Mosby; 2002. p. 640 – 57. Rayfield EJ, Ault MJ, Keusch GT, et al. Infection and diabetes: the case for glucose control. Am J Med 1982; 72:439 – 50. Eastman RC. Neuropathy in diabetes. In: Harris MI, Cowie CC, Stern MP, et al, editors. Diabetes in America (NIH Publication No. 95 – 1468). 2nd edition. Washington, DC: US Government Printing Office, 1995. p. 339 – 48. Friedman EA. Advanced glycosylated end products and hyperglycemia in the pathogenesis of diabetic complications. Diabetes Care 1999;22:B65 – 71. Furth AJ. Glycated proteins in diabetes. Br J Biomed Sci 1997;54:192 – 200. Sano H, Nagai R, Matsumoto K, et al. Receptors for proteins modified by advanced glycation end products (AGE) – their functional role in atherosclerosis. Mech Ageing Dev 1999;107:333 – 46. Masuda M, Murakami T, Egawa H, Murata K. Decreased fluidity of polymorphonuclear leukocyte membrane in streptozocin-induced diabetic rats. Diabetes 1990;39:466 – 70. Black CT, Hennessey PJ, Andrassy RJ. Short-term hyperglycemia depresses immunity through nonenzymatic glycosylation of circulating immunoglobulin. J Trauma 1990;30(7):830 – 3. Hennessey PJ, Black CT, Andrassy RJ. Nonenzymatic glycosylation of immunoglobulin G impairs complement fixation. Journal of Parenteral and Enteral Nutrition 1991;15(1):60 – 3. Foster DW, McGarry DJ. Glucose, lipid, and protein metabolism. In: Griffin JE, Ojeda SR, editors. Textbook of endocrine physiology. New York: Oxford University Press; 2000. p. 393 – 419. Borger MA, Rao V, Weisel RD, et al. Deep sternal wound infection: risk factors and outcomes. Ann Thorac Surg 1998;65(4):1050 – 6. Casey J, Flinn WR, Yao JS, et al. Correlation of immune and nutritional status with wound complications in patients undergoing vascular operations. Surgery 1983;93(6):822 – 7. Gadaleta D, Risucci DA, Nelson RL, et al. Effects of morbid obesity and DM mellitus on risk of coronary artery bypass grafting. Am J Cardiol 1992;70(20): 1613 – 4. 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(9):1408 – 14. Mullen JC, Bentley MJ, Mong K, et al. Reduction of leg wound infections following coronary artery bypass surgery. Can J Cardiol 1999;15(1):65 – 8. Richet HM, Chidiac C, Prat A, et al. Analysis of risk factors for surgical wound infections following vascular surgery. Am J Med 1991;91(3B):170S – 2S. Spelman DW, Russo P, Harrington G, et al. Risk factors for surgical wound infection and bacteraemia fol-

D. Aragon et al. / Crit Care Nurs Clin N Am 15 (2003) 125–135

[28]

[29]

[30]

[31]

[32]

lowing coronary artery bypass surgery. Aust N Z J Surg 2000;70(1):47 – 51. Trick WE, Scheckler WE, Tokars JI, et al. Risk factors for radial artery harvest site infection following coronary artery bypass graft surgery. Clin Infect Dis 2000; 30(2):270 – 5. Trick WE, Scheckler WE, Tokars JI, et al. Modifiable risk factors associated with deep sternal site infection after coronary artery bypass grafting. J Thorac Cardiovasc Surg 2000;119(1):108 – 14. Vuorisalo S, Haukipuro K, Pokela R, Syrja¨la¨ H. Risk features for surgical-site infections in coronary artery bypass surgery. Infect Control Hosp Epidemiol 1998; 19(4):240 – 7. Whang W, Bigger JTJ. Diabetes and outcomes of coronary artery bypass graft surgery in patients with severe left ventricular dysfunction: results from The CABG Patch Trial database. The CABG Patch Trial Investigators and Coordinators. J Am Coll Cardiol 2000;36(4):1166 – 72. The effect of intensive treatment of diabetes on the

[33]

[34]

[35]

[36]

135

development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329(14):977 – 86. 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(2):352 – 60. 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(2):356 – 61. DeCherney GS, Maser RE, Lemole GM, et al. Intravenous insulin infusion therapies for postoperative coronary artery bypass graft patients. Del Med J 1998; 70(9):399 – 404. van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med 2001;345(19):1359 – 67.