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Changes of CPK and CPK-MB levels after open and laparoscopic cholecystectomy
M. Safioleas, M.K. Stamatakos, G.J. Mouzopoulos, C. Manti, R. Iannescu, P. Skandalakis, A. Kostakis (Chirurgia, 101 (4): 401-405)

Introduction
Plasma-creatine kinase CPK is found primarily in heart and skeletal muscle as well as the brain. CPK has three cytoplasmic isoenzymes: the CK-BB (brain), CK-MB (myocardium), CK-MM (skeletal muscle) and a mitochondrial isoenzyme: the CK-Mt (1).
Plasma-creatine kinase (CPK) and its myocardial iso-enzyme CPK-MB are useful markers for the diagnosis of myocardial infarction (MI) (2). Since most of the released CPK after a myocardial infarction is CPK-MB, an increased ratio (more than 6%) of CPK-MB to total CPK may help in diagnosis of an acute infarction. Abnormally high levels of CPK-MB may indicated also alcoholism, brain trauma, convulsions, muscular dystrophy, polymyositis, dermatomyositis, shock, poisoning, hypothyroidism, acute psychosis, but in these cases CPK-MB counteracts in less than 6% of the total serum CPK (2).
It has been well established that total serum CPK levels rise after non-cardiac surgery, but little has been known concerning these changes after open or laparoscopic cholecystectomy (3).
This study was undertaken to compare the rise of the CPK-MB caused by tissue damage after open cholecystectomy with three types of incision (right oblique subcostal, right paramedial, vertical high midline) versus to laparoscopic cholecystectomy.

Materials and Methods
During the period from 2002 to 2004, 135 patients suffering from gallstones underwent an elective cholecystectomy and were included in our study. There were 52 men and 83 women, their age ranging between 18 and 72 years. Patient with coexistent diseases were excluded from the study.
Patients were divided into four groups according to type of surgical procedure, as follows:
Group I: a right oblique subcostal (Kocher's) incision was performe in 29 patients.
Group II: a right paramedian transrectal incision was performed in 52 patients.
Group III: a vertical high midline incision was performed in 17 patients.
Group IV: laparoscopic cholecystectomy in 37 patients.
The length of incision in open cholecystectomy varied between 11-15 cm (with a mean value of 11,9 cm). Laparoscopic cholecystectomy was evaluated by 3 holes in abdominal wall.
The technique of the remaining operation was always the same and there was the same degree of tissue damage in all patients. The duration of anaesthesia was no longer than 90 minutes and no serious postoperative complications, or deaths, occurred. Venous blood samples were taken in all patients postoperatively, and after 24, 72 and 120 hr. Total serum CPK and CPK-MB levels were measured by spectro-photometry.
Absolute values for total CPK and CPK-MB were recorded in International Units (IU/lt).
In all patients, resting 12-lead electrocardiograms were done preoperatively and on the 5th day postop, in order to rule out any cardiac contribution to the enzyme level increase. The mean values of CPK and CPK-MB increase, the standard deviation, the range of values and percentage of the increase were determined in all groups as shown in table 1, table 2, table 3, table 4 and table 5.
Furthermore, for every CPK value higher than the maximum normal limit, CPK-MB percentage was measured.
The T-test was used to analyze our data.

Results
The calculated values for the patients of each group are shown in table 1, table 2, table 3, table 4 and table 5.
We notice that a maximal increase was detected on the first postoperative day both for CPK and CPK-MB levels in all groups. These elevated levels remained high until the third postoperative day and returned to preoperative levels on the fifth postoperative day in all patients.
Comparing the CPK and CPK-MB changes in the four groups of patients we may observe a great increase occurring after a right oblique subcostal incision, and after a right paramedian transrectal incision, a smaller one after a vertical high midline incision and the smallest one after laparoscopic cholecystectomy. This is also evidenced in the graphs of Fig. 1 and 2.
Serum total CPK levels had a statistically significant increase in patients of group I as compared to patients of the other groups. In addition, serum CPK-MB levels had a statistically significant increase only in patients of group I as compared to group IV.
The rate of CPK-MB in total CPK never went over 6% in any group.
The mean percentage of CPK-MB in total CPK, the 1st and 3rd postoperative day is shown as well as the range of values.

Figure 1A
Figure 1B
Figure 1C
Figure 1D

Discussion
Creatine phosphokinase is an enzyme which catalyzes the reversible reaction of creatine phosphorylation from ATP. The physiological role of kinase is rephosphorylation of ADP and formation of ATP, when excessive need for energy exists or when the classical route of ATP formation is interrupted. When cytosis exists, cytoplasmic kinase enters the circulation where it can be detected by biochemical methods (4).
The clinical value of creatine phosphokinase measurements is helpful in the diagnoses of myopathies and myocardial infarction (MI) (5). Its value increases within 12 hours following an acute MI and returns to normal levels in less than 72 hours.
Several studies have estimated CPK changes after surgery of the thorax, abdomen and myoskeletal system (6, 7).
Recent studies in orthopedics have shown that elevations of serum CPK and CPK-MB can occur in postoperative patients who have not undergone an MI (8). Wukich et al found that although more than 95% of total serum CPK rises, after major orthopedic operations, which is due to CPK-MM (skeletal muscle) isoenzyme, significant rise of CPK-MB also occurs on the 1st postoperative day in patients with no-signs of acute MI (9). This must be attributed to the fact that skeletal muscle contains small but detectable amounts of CPK-MB isoenzyme, and thus its presence in the serum of postoperative patients is not diagnostic of myocardial damage.
Akeson et al comparing CPK-MB/CPK ratio in 30 patients after total hip arthroplasty (THR) with 30 non surgical patients with acute myocardial infarction (MI), found that the highest value after THR exceeded the lowest value in MI (10).
In our study, we measured total serum CPK and CPK-MB changes after an elective cholecystectomy, one of the most common and short-lasting surgical operations. Maximal elevation of serum CPK and CPK-MB values were evaluated on the 1st postoperative day and declined to preoperative levels on the 5th postop day. A comparison between the four most common surgical procedures used in elective cholecystectomy, demonstrated the greatest increase in serum enzyme levels after a right oblique subcostal (Kocher's) incision, smaller after a right paramedian incision, smallest after a vertical high midline incision and minimal after laparoscopic cholecystectomy. In all cases, the CPK-MB rate never exceeded more than 6% of total CPK.
In an early study, Neumeier et al reported that in patients with a diagnosed postoperative acute MI this rate is higher and ranges between 6-25% (11).
Many studies support that for the first three postop days, the contribution of total serum CPK measurement in the diagnosis of MI is minimal (12,13). In our study, it is
evident that during the early postoperative period, the possibility of myocardial damage should be considered only if total serum CPK is elevated and the CPK-MB rate is higher than 6%.

Figure 2A
Figure 2B
Figure 2C
Figure 2D

References
1. Trask, R.V., Billadello, J.J. - Tissue specific distribution and developmental regulation of M and B creatine kinase mRNAs. Biochim. Biophys. Acta, 1990, 1049:182.
2. Galen, G.M. - The enzyme diagnosis of myocardial infarction. Hum. Pathol., 1975, 6:141.
3. Graeber, G.M. - Creatine kinase: its use in the evaluation of perioperative myocardial infarction. Surg. Clin. N. Am., 1985, 6:539.
4. Dawson, D.M., Fine, I.H. - Creatine kinase in human tissues. Arch. Neurol., 1967, 16:175.
5. Kar, N.C., Pearson, C.M. - Creatine phosphokinase isoenzymes in muscle in human myopathies. J. Clin. Pathol., 1965, 43:207.
6. Dixon, S.H., Fuchs, J.C., Ebert, P.A. - Changes in serum creatine phosphokinase activity following thoracic, cardiac and abdominal operations. Arch. Surg., 1971, 103: 66.
7. Penneys, R., Wilkinson, S.H. - Elevation of serum creatine kinase following amputation of the leg. Surg., 1970, 67:301.
8. Healey, J.H., Kagen, L.J., Velis, K.P., Levin, D.B. - Creatine kinase MB in skeletal muscle and serum of spine fusion patients. Clin. Orthop., 1985, 195:282.
9. Wukich, D.K., Callaghan, J.J., Graeber, G.M., Martyak, T., Savory, C.G., Lyon, J.J. - Cardiac isoenzyme values after total joint arthoplasty. Clin. Orthop., 1989, 242:232.
10. Akeson, I., Bostrom, P.A., Gustafson, C., Rosberg, B. - Serum CK-MB is useful in diagnosis of acute myocardial infarction after total hip arthroplasty. Acta Anaesthesiol. Scand., 1989, 33:435.
11. Neumeier, D., Prellwitz, W., Wurzburg, U., Brundobler, M., Olbermann, M., Just H.J., Knedel, M., Lang, H. - Determination of creatine kinase isoenzyme MB activity in serum using immunological inhibition of creatine kinase M subunit activity. Clin. Chim. Acta., 1976, 73:445.
12. Hobson, R.W., Conact, C., Mahoney, W.D. - Serum creatine phosphokinase analysis of postoperative changes. Am. J. Surg., 1972, 124:625.
13. Grace, D.M., Handerson, A.R. - Preoperative and postoperative changes in patients with gallstones. Surg. Gynecol. Obstet., 1978, 147:219.


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