Transplantation/immunology
Effect of Intraoperative Hyperglycemia During Liver Transplantation

https://doi.org/10.1016/j.jss.2007.02.019Get rights and content

Background

Intensive blood glucose management has been shown to decrease mortality and infections for intensive care patients. The effect of intraoperative strict glucose control on surgical outcomes, including liver transplantation, has not been well evaluated.

Materials and methods

A retrospective review of all adult liver recipients transplanted between January 1, 2004 and July 6, 2006 was performed. Donor and recipient demographics, intraoperative variables, and outcomes were collected. Intraoperative glucose measurements were performed by the anesthesiology team and treated with intravenous insulin bolus or continuous infusion. Patients with strict glycemic control (mean blood glucose <150 mg/dL) were compared with those with poor control (mean blood glucose ≥150 mg/dL).

Results

During the study period, a total of 184 patients met criteria for analysis. Recipients with strict glycemic control (n = 60) had a mean glucose of 135 mg/dL compared with 184 mg/dL in the poorly controlled group (n = 124). Other than recipient age (strict versus poor control, 47 ± 2 y versus 53 ± 1 y; P < 0.01), both groups had similar donor and recipient characteristics. Although the incidence of most postoperative complications were similar, poor glycemic control was associated with a significantly increased infection rate at 30 d posttransplant (48% versus 30%; P = 0.02), and also an increased 1 y mortality (21.9% versus 8.8%; P = 0.05).

Conclusions

Intraoperative hyperglycemia during liver transplantation was associated with an increased risk of postoperative infection and mortality. Strict intraoperative glycemic control, possibly using insulin infusions, may improve outcomes following liver transplantation.

Introduction

The first prospective, randomized, controlled study on the importance of strict glycemic control demonstrating improved morbidity and mortality in the critically ill postoperative patient was reported in 2001 [1]. Studies have also suggested that the blood glucose level, rather than the total insulin dose administered, confers the benefit [2]. After implementation of intensive insulin therapy to maintain strict glycemic control, the benefits of normoglycemia on morbidity and mortality were largely reproduced [3]. The advantage of strict glycemic control in the critically ill patient is now well accepted, and the Institute for Healthcare Improvement and Surviving Sepsis Campaign have set adequate glycemic control as part of the sepsis management bundle [4, 5].

The role of strict intraoperative glycemic control, however, is less well established. A prospective observational study showed that diabetic patients undergoing on-pump heart surgery had a decreased rate of severe postoperative morbidity if strict intraoperative glycemic control was maintained with aggressive insulin therapy [6]. A retrospective study of patients undergoing carotid endarterectomy demonstrated that an increased glucose concentration on the operative day blood draw was independently associated with perioperative stroke or transient ischemic attack, myocardial infarction, and death [7].

The current study examines the effect of intraoperative glycemic control in liver transplant recipients. Intraoperatively, liver transplantation incurs an acute stress state in the recipient for several hours, often with major blood loss, fluid shifts, an anhepatic phase, and a reperfusion phase. Recipients are also given large doses of glucocorticoids during induction of anesthesia or early in the procedure. Given these major metabolic derangements and stressors associated with an operation with a considerable morbidity and mortality, liver transplantation was used as a model to evaluate the effect of strict intraoperative glycemic control on postoperative outcomes.

Section snippets

Methods

A retrospective review of all adult liver recipients transplanted at the University of Michigan Health System between January 1, 2004 and July 6, 2006 was performed. Donor and recipient demographics, intraoperative variables (collected in real time by an automated intraoperative data manager), and postoperative outcomes were collected by chart review.

Intraoperative glucose measurements were performed by the anesthesiology team and treated by intravenous insulin bolus or continuous infusion.

Results

During the period from January 1, 2004 and July 6, 2006, a total of 184 patients underwent liver transplantation and were analyzed. Sixty recipients (32.6%) had strict intraoperative glycemic control while 124 (67.4%) were poorly controlled. Although recipients with poorly controlled intraoperative glycemia were significantly older, both groups were well matched with respect to gender, race, body mass index, incidence of coronary artery disease, need for preoperative hemodialysis, severity of

Discussion

In the present study, the effect of intraoperative glycemic control on postoperative outcomes in 184 liver transplant recipients was analyzed. Overall, both infectious complications and short-term mortality were improved in patients with a mean intraoperative blood glucose concentration of less than 150 mg/dL. As demonstrated in previous reports, benefit seemed to be conferred by the blood glucose concentration rather than by the amount of insulin administered [2, 8]. Maintaining blood glucose

References (52)

  • A.J. Garber et al.

    American College of Endocrinology position statement on inpatient diabetes and metabolic control

    Endocr Pract

    (2004)
  • G. van den Berghe et al.

    Intensive insulin therapy in the critically ill patients

    N Engl J Med

    (2001)
  • G. Van den Berghe et al.

    Outcome benefit of intensive insulin therapy in the critically ill: Insulin dose versus glycemic control

    Crit Care Med

    (2003)
  • R.P. Dellinger et al.

    Surviving sepsis campaign guidelines for management of severe sepsis and septic shock

    Crit Care Med

    (2004)
  • Institute for Healthcare Improvement....
  • A. Ouattara et al.

    Poor intraoperative blood glucose control is associated with a worsened hospital outcome after cardiac surgery in diabetic patients

    Anesthesiology

    (2005)
  • M.J. McGirt et al.

    Hyperglycemia independently increases the risk of perioperative stroke, myocardial infarction, and death after carotid endarterectomy

    Neurosurgery (Discussion)

    (2006)
  • S.J. Finney et al.

    Glucose control and mortality in critically ill patients

    JAMA

    (2003)
  • G. Van den Berghe et al.

    Intensive insulin therapy in the medical ICU

    N Engl J Med

    (2006)
  • G. Van den Berghe et al.

    Intensive insulin therapy in mixed medical/surgical intensive care units: Benefit versus harm

    Diabetes

    (2006)
  • A. Bruno et al.

    Admission glucose level and clinical outcomes in the NINDS rt-PA Stroke Trial

    Neurology

    (2002)
  • S.E. Capes et al.

    Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: A systematic overview

    Stroke J Cerebral Circ

    (2001)
  • K. Foo et al.

    A single serum glucose measurement predicts adverse outcomes across the whole range of acute coronary syndromes

    Heart (British Cardiac Society)

    (2003)
  • N. Kagansky et al.

    The role of hyperglycemia in acute stroke

    Arch Neurol

    (2001)
  • K. Malmberg

    Prospective randomized study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus

    Br Med J Clin Res Ed

    (1997)
  • K. Malmberg et al.

    Glycometabolic state at admission: Important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: long-term results from the Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study

    Circulation

    (1999)
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