In Brief to Practice Research From / With Acute Care of Patients Diabetes Pancreas transplantation is considered the best treatment option for patients with type 1 diabetes and renal failure. In this article, the authors describe peri- operative glucose control in patients undergoing pancreas or kidney-pancreas transplantation. Glucose Control During and After Pancreatic Transplantation After decades of controversy sur- graft survival rates are 72% for PAKT rounding the therapeutic validity of and 71% for PA.1,2 pancreas transplantation (PTX), the The Diabetes Control and Comp- M. Hosein Shokouh-Amiri, MD; procedure has become accepted as the lications Trial (DCCT) has clearly Robert J. Stratta, MD; Kashif A. preferred treatment for patients with shown that improved glycemic control Latif, MD; and Osama Gaber, MD insulin-requiring diabetes mellitus and lowers the risk of secondary diabetic advanced diabetic nephropathy. The complications.3 However, intensive trade-offs for normal glucose home- insulin therapy did not result in nor- ostasis are the operative risks of the malization of hemoglobin A1c (HbA1c) transplant procedure and the need for levels, was associated with a threefold chronic immunosuppression. Free islet increased risk of severe hypoglycemia, grafts have the same potential but do and was resource-intensive. The not approach PTX in terms of consis- results of the DCCT provide a strong tency of results. rationale for pancreas transplantation. From December 1966 to October 2000, more than 15,000 PTX proce- Recipient Selection dures were performed worldwide and Patient selection is aided by a compre- reported to the International Pancreas hensive medical evaluation before Transplant Registry (IPTR).1 In the transplantation (Tables 1 and 2) per- past decade, the majority (82%) of formed by a multidisciplinary team PTX procedures have been performed that confirms the diagnosis of dia- in combination with a kidney trans- betes, determines the patient’s ability plant (simultaneous kidney-pancreas to withstand the operative procedure, transplant [SKPT]) in patients with establishes the absence of any exclu- end-stage diabetic nephropathy. The sion criteria (Table 3), and documents current 1-year actuarial patient and end-organ complications for future kidney and pancreas (with complete tracking after transplantation.4 The insulin independence) graft survival primary determinants for recipient rates after SKPT are 95, 92, and 84%, selection are the presence of diabetic respectively.1,2 Solitary PTX proce- complications, degree of nephropathy, dures comprise the remaining activity, and cardiovascular risk (Table 1). including either sequential pancreas- With increasing experience, previ- after-kidney transplants (PAKT, 12%) ous absolute contraindications have or transplant of pancreas alone (PA, become relative contraindications, 6%). The current 1-year patient sur- and relative contraindications have vival rate after solitary PTX is 95%, become risk factors for PTX (Table and the 1-year actuarial pancreas 3). Binocular blindness or history of a 49 Diabetes Spectrum Volume 15, Number 1, 2002 otherwise and need to undergo an Table 1. Indications for Pancreas Transplantation: extensive cardiovascular and peripher- Eligibility Guidelines al vascular evaluation. Potential male recipients >100 kg and female recipi- I. Medical Necessity A. Presence of insulin-treated diabetes mellitus: ents >80 kg, depending on their height 1. Documentation of insulin dose and body habitus, have a higher rate 2. Type 1 or type 2 diabetes of surgical complications after PTX. B. Ability to withstand surgery and immunosuppression (as assessed by pretrans- For this reason, a BMI >30 kg/m2 is plant medical evaluation): considered an absolute contraindica- 1. Adequate cardiopulmonary function tion and BMI >27.5 kg/m2 is a relative a. Cardiac stress testing ± coronary angiography to rule out signifi- contraindication for solitary PTX. cant coronary artery disease or other cardiac contraindications b. Patients with significant coronary artery disease should have it Preoperative Preparations for corrected before transplant Pancreas Transplantation 2. Absence of other organ system failure (other than kidney) C. Emotional and sociopsychological suitability Patients are allowed nothing by D. Presence of well-defined diabetic complications (any two of the following): mouth once an organ becomes avail- 1. Proliferative retinopathy able. Patients’ blood glucose is 2. Nephropathy (hypertension, proteinuria, or decline in glomerular filtra- checked every 2 h, and insulin is sup- tion rate) plemented as needed to keep the 3. Symptomatic peripheral or autonomic neuropathy blood glucose between 100 and 150 4. Microangiopathy mg/dl. If blood glucose is labile, then 5. Accelerated atherosclerosis (macroangiopathy) an insulin infusion is started. This 6. Glucose hyperlability, insulin resistance, or hypoglycemia unawareness consists of a mixture of 250 units of with a significant impairment in quality of life regular insulin in 250 cc of 50% E. Absence of any contraindications F. Financial resources saline, with a final concentration of 1 unit of insulin/ml of infusion fluid. II. Type of pancreas transplant The initial basal rate is 0.2–0.3 A. Specific entry criteria based on degree of nephropathy: unit/kg/h, which is then titrated with 1. Simultaneous kidney-pancreas transplant: creatinine clearance <30 ml/min blood glucose determinations every 2. Sequential pancreas after kidney transplant: creatinine clearance ≥40 1–2 h to maintain the blood glucose ml/min (on calcineurin inhibitor); >55 ml/min if not on calcineurin in the range noted above according to inhibitor the scale shown in Table 4. 3. Pancreas transplant alone: creatinine clearance >60–70 ml/min and 24-h protein excretion <2 g Intraoperative Monitoring B. Primary determinants for recipient selection are the presence of diabetic com- plications, degree of nephropathy, and cardiovascular risk Essentially the same regimen of infu- sion is followed intraoperatively as major amputation are not necessarily not contraindications for PTX, as the preoperative infusion, with the contraindications for PTX, provided excellent outcomes have been report- strict rule to maintain euglycemia. that the patient is well adjusted to ed in patients with previous cardiac Following a successful pancreas trans- these otherwise irreversible diabetic interventions.5 However, sudden car- plantation,8 the transplanted pancreas complications. Inclusion and exclu- diac death, in the absence of signifi- will take over glycemic control. sion criteria for PTX are listed in cant structural heart disease, contin- Tables 1 and 3. ues to be a major cause of cardiac Postoperative Management The cardiac status of each candi- mortality after PTX.6 For this reason, Insulin therapy, as outlined in Table date must be assessed carefully a number of centers are beginning to 4, can take one of two forms. The because significant (and silent) coro- test cardiac autonomic function in first involves instituting aggressive nary artery disease is not uncommon these patients, using laboratory- insulin therapy with the objective of in this population. The cardiac evalua- evoked cardiovascular tests and 24-h “complete” insulin replacement to tion consists of a noninvasive func- heart-rate variability measurements.7 “rest” the ␤-cells in the transplanted tional assessment, such as an exercise The new methodology may be able to pancreas for the first few days follow- or a pharmacological stress test, in detect alterations in autonomic func- ing surgery. The second is to let the addition to echocardiography. tion before the onset of disabling transplanted pancreas function as Coronary angiography is reserved for symptoms. soon as blood supply is restored to the specific indications such as age >45 In general, age >65 years, heavy transplanted organ. Each of these years, diabetes for >25 years, a posi- smoking, a left ventricular ejection approaches has its proponents. The tive smoking history, long-standing fraction <30%, recent MI, and severe advantages of each are discussed hypertension, previous major amputa- obesity (>150% ideal body weight or below. tion due to peripheral vascular disease, body mass index [BMI] >30 kg/m2) history of cerebrovascular disease, or are usually viewed as contraindica- Complete replacement cases in which the history, physical tions for PTX (Table 3).4 Most Some practitioners believe that pro- examination, or noninvasive cardiac patients <45 years of age are accept- viding complete replacement of studies reveal an abnormality.4 able candidates for PTX provided that insulin will “rest” the ␤-cells in the A history of previous myocardial no significant coronary artery disease transplanted pancreas and therefore infarction (MI), angioplasty, stenting, is present. Diabetic patients >45 years preserve their function and avoid or coronary artery bypass grafting are of age are not candidates until proven injury from acute stress. After 3–4 50 Diabetes Spectrum Volume 15, Number 1, 2002 vantage of this protocol is that the to Practice Research From / With Acute Care of Patients Diabetes Table 2. Evaluation of Pancreas Transplant Candidates precise status of the function and via- bility of the transplanted organ is dif- 1. Interviews and Consults ficult to judge when insulin produc- A. History and physical examination by nephrologist, endocrinologist, and transplant surgeon tion is suppressed due to exogenous B. Ophthalmology evaluation,