Asian Cardiovasc Thorac Ann 2002;10:115-118
© 2002 Asia Publishing EXchange Pte Ltd
Is Hyperamylasemia After Cardiac Surgery Due to Cardiopulmonary Bypass?
Wan Song, MD,
Ahmed A Arifi, MD,
Carmen SY Chan, BHSc,
Calvin SH Ng, MBBS,
Innes YP Wan, FRCS,
Lee Tak Wai, FRCS,
Anthony PC Yim, MD
|
Division of Cardiothoracic Surgery Department of Surgery The Chinese University of Hong Kong Prince of Wales Hospital Shatin, New Territories, Hong Kong People's Republic of China
|
|
|
Wan Song, MD Tel: 852 2632 2629 Fax: 852 2637 7974 email: swan{at}cuhk.edu.hk Division of Cardiothoracic Surgery, Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong, People's Republic of China.
|
 |
ABSTRACT
|
|---|
Although hyperamylasemia has been reported in a large proportion of patients undergoing cardiac surgery with cardiopulmonary bypass, its clinical significance and pathogenetic mechanisms remain poorly understood. The study was designed to investigate whether avoidance of cardiopulmonary bypass would limit amylase elevation. Serum levels of amylase and lipase were measured preoperatively as well as 24 and 48 hours postoperatively in 58 patients undergoing elective coronary artery bypass grafting. Three surgical approaches were used: cardiopulmonary bypass (n = 32) and off-pump through a median sternotomy (n = 14) or a left minithoracotomy (n = 12). There was no hospital mortality or postoperative abdominal complications. Transient hyperamylasemia occurred in 14 patients: 7 (22%), 5 (36%), and 2 (17%) in the respective groups. The increase in amylase levels was similar among the groups. However, no lipase elevation was detected in any patient. There was no clear correlation between hyperamylasemia and increased creatinine levels. Perioperative plasma calcium levels were normal in patients who had hyperamylasemia. Our results indicate that hyperamylasemia after bypass surgery is not related to the use of cardiopulmonary bypass or the mode of surgical access.
|
INTRODUCTION
|
|---|
Abdominal complications after cardiac surgery, with a reported incidence of only about 1%, carry a significantly high mortality.1–5 Acute pancreatitis, although even less frequently diagnosed, has been identified as one of the lethal complications.1,2 Pancreatic cellular injury after cardiopulmonary bypass (CPB) is not uncommon as hyperamylasemia of pancreatic origin was found in 27% of patients in a study.6 The overall incidence of hyperamylasemia was reported to be as high as 32% to 70% of patients undergoing surgery with CPB.7–9 More importantly, even non-pancreatic hyperamylasemia after CPB was associated with increased postoperative mortality.7 Although the exact pathogenetic mechanisms are poorly understood, increased perioperative administra-tion of calcium chloride6 or an impaired renal function after CPB9 may contribute to this "post-pump" amylase elevation.
Increased recognition of the important role of inflamma-tory responses in the development of post-CPB morbidity and mortality has recently heightened interest in off-pump cardiac surgery.10,11 It is still unknown, however, whether avoiding the use of CPB could reduce the incidence of postoperative hyperamylasemia. The purpose of this prospective study was to compare perioperative changes in serum levels of amylase and lipase in 3 groups of patients undergoing elective coronary artery bypass grafting (CABG) through 3 approaches: conventional CPB (on-pump through a median sternotomy), off-pump CABG (OPCAB, through a median sternotomy without using CPB), and minimally invasive direct CABG (MIDCAB, through a minithoracotomy without using CPB).
|
PATIENTS AND METHODS
|
|---|
This study was approved by the ethics committee of The Chinese University of Hong Kong. A total of 58 consecu-tive patients with coronary artery disease undergoing elective CABG were recruited. Those undergoing redo or emergency CABG, had preoperative renal failure or chronic liver dysfunction, or had a history of gastro-intestinal disease were excluded. Informed written consent was obtained from all participating patients. A MIDCAB procedure was indicated for patients with single left anterior descending coronary artery disease, utilizing the left internal mammary artery as the graft conduit. The choice of procedure was based mainly on the native coronary anatomy and the left ventricular function. Patients for OPCAB were selected only when complete revascu-larization was technically feasible. There were 32, 14, and 12 patients, respectively, in the CPB, OPCAB, and MIDCAB groups.
All patients received a similar balanced anesthetic regimen, including fentanyl and midazolam. Muscle relaxation was achieved with pancuronium. Anesthesia was maintained by a continuous infusion of propofol (4 to 6 mg•kg-1•h-1). Cefuroxime (Zinacef; GlaxoWellcome, Greenford, Middlesex, UK) was given intravenously for antimicrobial prophylaxis at a dose of 1.5 g at the induction of anesthesia, followed by 0.75 g every 8 hours for 24 hours. No patients received corticosteroids before, during, or after surgery. As a routine practice, every patient was monitored by intraoperative transesophageal echocardiography (TEE). The TEE probe was inserted after anesthesia induction and removed at the end of surgery.
Our techniques for CPB, OPCAB, and MIDCAB have been described previously.11,12 In the CPB setting, the extracorporeal circuit consisted of a roller pump (Sarns 9000; 3M Health Care, Ann Arbor, MI, USA) and a membrane oxygenator (Turbo; 3M Health Care, Ann Arbor, MI, USA). Standard systemic heparinization (3 mg•kg-1) was performed, and an activated clotting time of more than 480 seconds was maintained during CPB. The pump flow was set at 2.4 L•min-1•m-2. Patients were slightly cooled to 35°C to 36°C during CPB, and intermittent antegrade normothermic blood cardioplegia was induced with a mixture of 400 to 600 mL of oxygenated blood with graduated doses of potassium-magnesium solution. In the non-CPB setting, following either a standard median sternotomy in the OPCAB group or a small left anterior thoracotomy in the MIDCAB group, patients received a reduced heparin dose (1 mg•kg-1). The coronary artery was temporarily occluded on either side of the anastomotic site with 2 pieces of silicone elastomer surgical tape (Quest Medical, Allen, TX, USA). Stabilization of the target arteries was accomplished with a CTS Stabilizer (CardioThoracic Systems, Cupertino, CA, USA). The technique for an-astomosis was identical among the groups. Proximal anastomosis of the venous graft was always performed while the aorta was partially clamped. Heparin was routinely neutralized with protamine sulfate on discontinuation of CPB in the CPB group or after all anastomoses were completed in the OPCAB and MIDCAB groups.
Blood samples were collected from each patient before operation as well as 24 and 48 hours after surgery. The serum of each sample was stored at –70°C and assayed within 4 weeks. Amylase activity in serum was determined using Sigma Amylase Reagent (Sigma Diagnostics, St. Louis, MO, USA). Serum lipase levels were measured using Sigma Lipase Substrate (Sigma Diagnostics, St. Louis, MO, USA). Meanwhile, perioperative plasma levels of creatinine and calcium were also monitored and recorded.
Data were analyzed using StatView Software (Brainpower Inc., Calabasas, CA, USA). Unpaired 2-tailed t test was used for comparing clinical variables between groups. A 2-way analysis of variance for repeated measures was used for comparison of amylase and lipase levels between the CPB group and the non-CPB group (including both OPCAB and MIDCAB groups) at each time point. Clinical data are shown as mean ± standard deviation, while values of the biochemical parameters are presented as mean ± standard error of the mean. Differences were considered statistically significant if p < 0.05.
|
RESULTS
|
|---|
There were no differences among the 3 groups of patients with respect to age, gender, symptoms, or functional class (Table 1
). Two patients in the CPB group and 1 in the OPCAB group required reexploration for bleeding after surgery. Nevertheless, there was no hospital mortality or major complications, including abdominal complications, in either group.
Serum amylase levels were normal (below 125 U•L-1) in all patients before surgery. Transient postoperative hyperamylasemia, defined as a serum amylase level exceeding 250 U•L-1 24 hours after surgery which decreases thereafter, occurred in 14 patients, of whom 7 (22%) were in the CPB group, 5 (36%) in the OPCAB group, and 2 (17%) in the MIDCAB group. The degree of amylase elevation was similar between the CPB and the non-CPB groups (Figure 1). However, no lipase elevation was detected in any of the patients.
View larger version (16K):
[in this window]
[in a new window]
|
Figure 1. Serum amylase activity before surgery and 24 and 48 hours after surgery in patients with transient hyperamylasemia after coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB), or after non-CPB procedures of off-pump CABG and minimally invasive direct CABG.
|
|
Temporary renal dysfunction, defined as the presence of a normal plasma creatinine level before surgery which increases to above 130 µmol•L-1 within 48 hours after CABG, was noted in 5 patients (16%) in the CPB group and 1 patient each in the OPCAB (7%) and the MIDCAB (8%) groups. There was no clear correlation between hyperamylasemia and increased creatinine levels. More-over, perioperative plasma calcium levels were within the normal range in patients who had hyperamylasemia.
|
DISCUSSION
|
|---|
In healthy subjects, the pancreas and the salivary gland account for almost all of the serum amylase activity. Because serum amylase has a relatively short half-life of about 2 hours, its concentration reflects the in-and-out balance of this enzyme in the circulatory system.13 Thus, hyperamylasemia may be due to either an increased release of amylase into the circulation and/or a decreased metabolic clearance of this enzyme.
Hyperamylasemia of pancreatic origin often represents pancreatic cellular injury6 or, not as often, results from perforation or ischemia of the gut, which can lead to absorption of pancreatic amylase from the intestinal lumen.13 Hyperamylasemia also may be a consequence of temporary renal dysfunction since it has been suggested that reduced tubular reabsorption of amylase is a nonspecific response of the kidneys to any significant stress.13 Paajanen and associates9 recently showed that hyperamylasemia after CABG was mainly due to elevated pancreatic amylase levels, although there was no change in serum concentrations of pancreatic phospholipase A2. They also suggested that decreased fractional excretion of pancreatic and salivary isoamylases, rather than enhanced amylase production, is the major cause of hyperamylasemia after CPB. Findings from the present study indirectly indicate that the frequently noticed hyperamylasemia after cardiac surgery may be due to reduced renal clearance of amylase, as a common response to major stress, even in the absence of evident renal dysfunction. Nevertheless, since the kidneys account for the removal of only half of the body's amylase,13 it is still possible that some other factors are also involved in postoperative hyperamylasemia. For instance, situations such as enhanced absorption of pancreatic amylase from the intestines could not be totally excluded. Perioperative administration of calcium chloride was also noted to result in a dose-related increase in pancreatic amylase levels,6 but this was not investigated in the current study.
Our data indicate that hyperamylasemia after CABG is not related to the use of CPB. A comparable incidence, as well as similar levels of amylase elevation, was observed following conventional CPB, OPCAB, and MIDCAB procedures, suggesting that inadequate perfusion during CPB may not be the principal cause of hyperamylasemia as previously suspected.14 Although some other parameters have been recently proposed to be more disease-specific and predictive in determining pancreatic cellular injury,15 amylase and lipase values are still widely used in the clinical setting as the primary diagnostic means.16 Since none of our patients suffered from postoperative abdominal complications, moderate hyperamylasemia without an accompanying increase in lipase levels, thus, may not be a reliable marker of pancreatic cellular injury, which is in agreement with a previous observation.16 Although the mechanisms involved in postoperative hyperamylasemia await further exploration, it seems clear in this study that the phenomenon is far more common than the incidence of pancreatic cellular injury after cardiac surgery.9
On the contrary, hyperamylasemia of salivary isoamylase can be observed in many conditions such as lactic acidosis and mild injury to the salivary glands,13 which often occur during or after surgery. In fact, intraoperative TEE monitoring could potentially enhance the release of salivary isoamylase. Therefore, it might be interesting to compare the elevation of pancreatic and salivary isoamylases in patients undergoing OPCAB with or without TEE monitoring. Whether a relatively long period of mechanical ventilation could induce some sort of inflammatory injury to the salivary glands may also deserve investigation. Although the 2 isoamylases were not measured in the present study to further distinguish the potential source of hyperamylasemia, and the number of patients in each group was relatively small, our obser-vation may improve the understanding of the underlying mechanisms in hyperamylasemia following CABG.
In conclusion, we have observed that the use of CPB is not the major factor responsible for hyperamylasemia following CABG, as previously believed by many. Moreover, our findings support the opinion that hyper-amylasemia alone is unlikely to be a reliable marker of pancreatic cellular injury after cardiac surgery.
|
Acknowledgments
|
|---|
This study was supported by a Research Grant Council Earmarked Grant (CUHK 4091/00M), Hong Kong.
|
REFERENCES
|
|---|
-
Krasna MJ, Flancbaum L, Trooskin SZ, Fitzpatrick JC, Scholz PM, Scott GE, et al. Gastrointestinal complications after cardiac surgery. Surgery
1988;104:773–80.[Medline]
-
Huddy SP, Joyce WP, Pepper JR. Gastrointestinal complications in 4473 patients who underwent cardio-pulmonary bypass surgery. Br J Surg
1991;78:293–6.[Medline]
-
Ohri SK, Desai JB, Gaer JA, Roussak JB, Hashemi M, Smith PL, et al. Intraabdominal complications after cardiopulmonary bypass. Ann Thorac Surg
1991;52: 826–31.[Abstract]
-
Johnston G, Vitikainen K, Knight R, Annest L, Garcia C. Changing perspective on gastrointestinal complications in patients undergoing cardiac surgery. Am J Surg
1992; 163:525–9.[Medline]
-
Tsiotos GG, Mullany CJ, Zietlow S, van Heerden JA. Abdominal complications following cardiac surgery. Am J Surg
1994;167:553–7.[Medline]
-
Fernandez-del Castillo C, Harringer W, Warshaw AL, Vlahakes GJ, Koski G, Zaslavsky AM, et al. Risk factors for pancreatic cellular injury after cardiopulmonary bypass. N Engl J Med
1991;325:382–7.[Abstract]
-
Rattner DW, Gu ZY, Vlahakes GJ, Warshaw AL. Hyperamylasemia after cardiac surgery. Incidence, significance, and management. Ann Surg
1989;209: 279–83.[Medline]
-
Svensson LG, Decker G, Kinsley RB. A prospective study of hyperamylasemia and pancreatitis after cardiopulmonary bypass. Ann Thorac Surg
1985;39:409–11.[Abstract]
-
Paajanen H, Nuutinen P, Harmoinen A, Poyhonen M, Pitkanen O, Nordback I, et al. Hyperamylasemia after cardiopulmonary bypass: pancreatic cellular injury or impaired renal excretion of amylase? Surgery
1998; 123:504–10.[Medline]
-
Wan S, LeClerc JL, Vincent JL. Inflammatory response to cardiopulmonary bypass: mechanisms involved and possible therapeutic strategies. Chest
1997;112:676–92.[Abstract/Free Full Text]
-
Wan S, Izzat MB, Lee TW, Wan IYP, Tang NLS, Yim APC. Avoiding cardiopulmonary bypass in multivessel CABG reduces cytokine response and myocardial injury. Ann Thorac Surg
1999;68:52–6.[Abstract/Free Full Text]
-
Izzat MB, Khaw KS, Atassi W, Yim AP, Wan S, El-Zufari MH. Routine intraoperative angiography improves the early patency of coronary grafts performed on the beating heart. Chest
1999;115:987–90.[Abstract/Free Full Text]
-
Pieper-Bigelow C, Strocchi A, Levitt MD. Where does serum amylase come from and where does it go? Gastroenterol Clin North Am
1990;19:793–810.[Medline]
-
Moneta GL, Misbach GA, Ivey TD. Hypoperfusion as a possible factor in the development of gastrointestinal complications after cardiac surgery. Am J Surg
1985; 149:648–50.[Medline]
-
Rau B, Cebulla M, Uhl W, Schoenberg MH, Beger HG. The clinical value of human pancreas-specific protein procarboxypeptidase B as an indicator of necrosis in acute pancreatitis: comparison to CRP and LDH. Pancreas
1998;17:134–9.[Medline]
-
Chase CW, Barker DE, Russell WL, Burns RP. Serum amylase and lipase in the evaluation of acute abdominal pain. Am Surg
1996;62:1028–33.[Medline]
TOP
ABSTRACT
INTRODUCTION
