lntraperitoneal Drains and Nasogastric Tubes In Elective Cholecystectomy A Controlled Clinical Trial
Gunnar Edlund, MD, htersund,
Sweden
Staffan Gedda, MD, bstersund,
Sweden
Willem van der Linden, MD, btersund,
Sweden
Cholecystectomy without intraperitoneal drainage was introduced by Spivack [I] as long ago as 1913. The pros and cons of drains have been debated ever since. Simple as the problem may seem, a consensus has not been reached. There has never been a shortage of prestigious opinions based on poorly construed theory or vague clinical impressions, but except to those who aired them, these opinions seemed of little avail. A number of large series of patients treated with [2,3] and without [4,5] a drain confused rather than enlightened the issue; both the proponents and opponents of drainage invariably reported excellent results with their respective methods. Retrospective studies from hospitals where both methods were used side by side [S-S] also turned out to be not very helpful. The objection against this type of study is that the choice between the methods may have depended on the patient’s condition [9], which invalidates any comparison. Efforts were made to avoid this objection by retrospective matching of patients. However, as Schwartz [IO] pointed out in a comment on one such study [6], the matching procedure proved unable to eliminate important differences between the groups that were compared. It should be obvious by now that the problem will never be solved unless we are willing to resort to studies performed according to the rules for controlled clinical trials. We have tried to perform such a study. As it was recently claimed that in elective cholecystectomy not only drainage but also nasogastric suction may be omitted [I I], we simultaneously put this claim to the test of a controlled clinical trial. From the Department of Surgery, Centrallasarettet, bstersund. Sweden. Reprint requests should be addressed to Wilfem van der Linden, MD. Lasarettet, S 83 10 1 dstersund 1, Sweden.
Volume 137, June 1979
Material and Methods Treatment Groups. One hundred consecutive patients submitted to elective cholecystectomy between November 1, 1977 and June 28,1978 entered into the trial. Patients with acute cholecystectomy and those with jaundice were excluded. If the common duct had to be explored, the patient was excluded again. In a strictly random fashion the 100 patients were allocated to four different treatment groups (groups A, B, C, and D) arranged in a 2 by 2 design (Figure 1). As can be seen, 50 patients (groups A and C) were treated with intraperitoneal drains, and in 50 (groups B and D) the drain was omitted. Similarly, 50 patients (groups A and B) were treated with a nasogastric tube and 50 patients (groups C and D) were not. Before the start of the trial 100 cards indicating the group to which the patient belonged were prepared in sealed envelopes. These envelopes were opened the morning after the operations had been divided among the surgeons of our department. Preoperative Management and Anesthesia. In patients in groups A and B the nasogastric tube was introduced in connection with premeditation. The tube was not connected to a suction apparatus but linked to a plastic bag in a closed circuit. All operations were performed in neurolept analgesia under pancuronium relaxation with 35 per cent oxygen and 62 per cent nitrogen. Routinely, 1,000 cc half isotone Ringer’s acetate in 5 per cent glucose (Rehydrex@) was given during the operation. Operatioe Technic. After a subcostal incision, cholecystectomy was performed according to a standard technic. Intraoperative cholangiography was performed in each patient. Closure of the gallbladder bed was performed when leakage of bile from the bed was suspected. The appendix was not removed. The operations were performed by registered specialists as well as by junior surgeons as part of their training program. In patients in groups A and C, a plastic drain was brought out through a stab wound and connected to a closed suction drainage system.
775
Edlund et al
Results Gastr.
Figure 1. Altocatlon of 100 patients to four groups. Gastr. = nasogastric.
Postoperative Management. Postoperatively all patients were again given 1,000 cc of Rehydrex followed by 1,000 cc of 15 per cent fructose with 5 per cent glucose. All patients were mobilized on the first postoperative day, and in patients with nasogastric tubes the tube was then removed. In patients with intraperitoneal drains the amount of discharge was noted daily and the drain was removed when this amount was less than 25 cc. Variables Studied. Preoperatively as well as on the second and fourth postoperative days serum was taken for the following determinations in our autoanalyzer. Bilirubin was determined according to the method of Gambino [ 121 with a maximal normal limit of 21 pmol/liter. Haptoglobin was determined according to Owen et al [13] with a maximal normal limit of 1.70 g/liter. Serum transaminase levels (ASAT and ALAT) were determined with the method of Reitman and Frankel[14] with a maximal normal limit of 0.80 pkatlliter. Fasting serum iron was determined according to Ichida et al [15] with minimal normal limits of 11 pmol/liter for females and 14 pmol/liter for males. Finally, serum albumin was determined according to the method of Schiradin and Ney [16] with normal limits between 37 and 52 g/liter. The duration of postoperative pyrexia was taken as the number of days on which a temperature above 37.6’ C was recorded. Postoperative complications, the length of hospital stay, the occurrence of vomiting, and the amount of fluid obtained via the intraperitoneal drain were noted on a card made out when the patient entered into the trial. Statistical Methods. Significance was tested with nonparametric tests as described by Siegel [17]. Calculations were performed with Hewlett-Packard calculator HP 65 using commercially available programs from Stat Pat 1.
TABLE I
Details of Four Groups
Details of Four Groups. The sex and age distribution of the four groups appears in Table I. As can be seen, there was little difference between the groups except that group C contained relatively few male patients. Also shown are the number of operations performed by senior and junior surgeons in the four groups; in this respect the groups differed little. Finally, this table gives the mean duration of the operation in the four groups. Again, there is little difference except for the low value in group C. However, when the patients are arranged into groups with and without drainage (groups A and C versus groups B and D) or into groups with and without a nasogastric tube (groups A and B versus groups C and D), the differences between the groups so constructed are not statistically significant. Mortality and Complications. There was one death in this series. In a 75 year old man in group D signs of peritonitis developed on the fourth postoperative day. At reexploration a perforated gastric ulcer was found. The patient died of cardiac insufficiency. One patient in group D had a wound infection, one in group C had postoperative bronchopneumonia, and one patient in group B had pancreatitis postoperatively. Postoperative Pyrexia. Table II gives the duration of postoperative fever in the four groups and values for patients with drainage (groups A and C!)and those without drainage (groups B and D). There was very little difference between the various groups. Hospital Stay. The mean length of hospital stay was 6.72 days for group A, 7.40 days for group B, 6.96 days for group C, and 6.63 days for group D. The differences were not significant. Amount and Duration of Drainage. The amount of fluid drained varied from 5 to 305 cc, with a mean value of 87.7 cc in group C and 85.8 cc in group A. As a rule, the intraperitoneal drain could be removed on the fourth postoperative day. Postoperative Serum Tests. The number of patients with a postoperative increase of serum bilirubin surpassing the maximal normal limit is shown in
Group A
No. of patients Males Females Age (yr) Mean Range Operating surgeon Senior Junior Duration of operation (min)
776
0
C
D
25
25
25
25
11 14
10 15
4 21
11 14
50.1 22-79
53.3 26-76
52.8 24-71
55.0 33-75
9 16
8 17
10 15
8 17
61
59.2
53
64.6
TABLE II
Duration of Postoperative Fever
No. of Days 55 6 or 7 Z-8 l
Groups With Drainage A c Total
Groups Without Drainage B D” Total
14 9 2
13 8 4
16 6 3
30 15 5
14 9 1
27 17 5
One death.
The American Journal of Surgery
Elective Choiecystectomy
Figure 2. An abnormal increase was observed in 7 of the 50 patients treated with a drain as compared with 17 of the 50 treated without drains. When subjected to the chi square test, the difference is significant at the 5 per cent level (x2 = 5.48; df = 1; 0.05 > p > 0.01). An increase in the transaminase level was seen in a number of patients, but there were no significant differences between the various groups. The number of patients with abnormally high postoperative serum haptoglobin levels is shown in Figure 3. As can be seen, an abnormal increase was observed in 22 of the 50 patients without drains compared with 12 of the 50 patients with drains. With the chi square test this difference is probably significant (x2 = 4.46; df = 1; 0.05 > p > 0.01). With the same test, the difference between patients with and without a gastric tube was not significant. Decreased serum iron values were observed in a number of patients, but there were no differences among the groups. Neither were there any group differences in serum albumin levels. Vomiting. The number of patients with postoperative vomiting is given in Figure 4. Vomiting occurred significantly more often in the 50 patients treated without a nasogastric tube than in the 50 patients treated with one (x” = 6.42; df = 1; 0.02 > p > 0.01). Comments
The basic rules for controlled clinical trials are randomization, replication, and unbiased assessment of results [18]. Strict randomization was applied in allocating the 100 patients to the four groups. However, even strict randomization does not guarantee that the groups will be exactly alike. Nothing can accomplish this. Therefore, it is essential to compare the groups. Comparison of sex and age and of other variables showed little difference between the groups except that group C (drainage but no nasogastric tube) contained few males. The mean duration of the operation was also shorter in this group than in the others (Table I). However, as the differences among the groups do not even approach the level of significance, the conclusion is that the groups can be used as a sound basis for comparisons. Apart from the aforementioned rules, there is in clinical trials another prerequisite that should be fulfilled. That is the precise identification of patients to whom the results may be applied. It is here that the difficulties start. Surgeons participating in a trial of this kind may feel inclined to exclude certain patients merely on the basis of clinical impressions gained during the operation. Therefore, before
Volume
137, June 1979
main Gastr.Tube NO
Tube
A
c
NO Drain
4
B
9
gD8 7
13 11
17
Figure 2. Number of patients with abnormally high postoperative serum bilirubin levels. Gastr. = nasogastric.
Figure 3. Number of patients with abnormally high postoperative serum haptoglobin levels. Gastr. = nasogastric.
starting a trial on drainage, two things should be made clear. First, if the trial allows for patients to be excluded on clinical impressions, for instance, because of what the individual surgeon considers to be incomplete hemostasis, the results will become irreproducible and the trial will lose much of its value. The reason is that clinical impressions vary enormously. Second, it should be realized that the question of drainage in cholecystectomy is worth investigating or, alternatively, that the necessity of drainage can be determined by the individual surgeon on the basis of a clinical assessment during the operation and in that case the question is not worth investigating. Clearly, we cannot have it both ways. Any exclusion of patients, except for strictly defined reasons, is therefore not only detrimental to the trial’s success but also highly illogical. In the present trial we excluded patients with acute cholecystitis and those in whom the common duct was explored. Patients undergoing acute cholecystectomy were excluded because we have found that after those operations prolonged discharge of serofibrinous fluid occurs relatively frequently (191. Patients with common duct exploration were excluded because of the danger of biliary leakage. No patient was excluded for other reasons. Our results therefore apply to interval cholecystectomy without a common duct operation. There is at present only one study on drainage in elective cholecystectomy performed as a controlled trial, the study of Gordon et al 1201. In that study a number of patients were excluded on the basis of clinical assessments during the operation, mostly
777
Edlund et al
Gastr No
Figure 4. Number of pafients
with postoperative
vomiting.
Gasfr. = nasogasfric.
because of what was considered incomplete hemostasis. The category of patients to whom their results apply is therefore less strictly defined. However, as the number of such exclusions is small, a comparison of their results with ours is justified. Our results agree with those of Gordon et al [ZO]insofar as both trials failed to find a difference in postoperative pyrexia and length of hospital stay between patients with and those without drainage. It has been claimed on the basis of retrospective studies that omitting drainage shortens the duration of postoperative fever. Myers [21] even went so far as to introduce the concept of drain fever as a complication of drainage after cholecystectomy. As two successive controlled trials now have failed to find any difference in postoperative pyrexia, this concept can be refuted. Omitting drainage in the hope of shortening postoperative fever can no longer be defended. Systematic monitoring of a large number of serum values showed a difference in the way in which serum bilirubin reacted to operation with and without drainage (Figure 2). An abnormal postoperative increase was observed significantly more often in patients without a drain. As a rule, the increase was rapidly transient with many increased values already returning to normal on the fourth postoperative day. No similar difference was observed in serum transaminase levels. Most probably, therefore, the transient rise in the serum bilirubin level observed after cholecystectomy without drainage is due to resorption of bile that is otherwise discharged via the drain. However transient the rise may be, it should be regarded as an indication for the use of intraperitoneal drains. Our systematic checks also revealed a difference in the way serum haptoglobin reacted to cholecystectomy with and without a drain (Figure 3). Conditions such as infection, fever, and malignant disease and surgery are known to be capable of elevating serum haptoglobin levels [22,23]. The response df the haptoglobin level is immediate and the elevation is in proportion to the intensity of the traumatic stimulus. In the present study a rise to abnormal
778
levels was observed significantly more often in patients without intraperitoneal drains. The probable explanation is that omission of the drain adds to the operation’s traumatic effect. Finally, as perhaps could be expected, vomiting occurred significantly less often in patients with than in those without a nasogastric tube (Figure 4). We did not connect the tube to a suction apparatus, which perhaps is the reason that vomiting also occurred in a number of patients with a gastric tube. If such an apparatus had been used, the difference between the groups would probably have been even more marked. The results of this trial thus clearly favor the traditional management of patients subjected to cholecystectomy and lead us to recommend the use of intraperitoneal drains and nasogastric tubes. Summary
The effects of intraperitoneal drains and nasogastric tubes were studied in 100 consecutive patients undergoing elective cholecystectomy without exploration of the common duct. The study was performed as a randomized trial. Concurrent assessment of the effect of both the drain and the gastric tube was achieved with a 2 by 2 design. A large number of serum tests were systematically checked postoperatively. There was one death in a patient treated without either a drain or gastric tube. Apart from that, there were few complications. In accordance with the results of an earlier randomized trial, no difference in postoperative pyrexia and hospital stay was found between patients with and those without intraperitoneal drains. The concept of drainage fever is therefore refuted. An abnormal increase in the serum bilirubin level was found significantly more often after operations without an intraperitoneal drain. This transient rise is explained as being due to resorption of bile that would otherwise have been discharged via the drain. An abnormal rise in the haptoglobin level also occurred significantly more often in patients in whom intraperitoneal drains were not used. The suggested explanation is that omission of the drain adds to the operation’s traumatic effect. Vomiting occurred significantly more often in patients without nasogastric tubes. The use of intraperitoneal drains and nasogastric tubes is recommended. References 1. Spivack JL: The Surgical Technique of Abdominal Operations, 4th ed. Springfield, III, Charles C Thomas, 1946. 2. MC Kittrick JE, Yonehiro L, Latimer RG, Doane WH: In defense of drainage after cholecystectomy: an analysis of 246 cases.
The American Journal of Surgery
Elective
Chir Gastroenterol 10: 429, 1976. 3. Richter N: Routinemassige Drainage bei alleiniger Cholezystektomie. Zentralbl Chir 99: 41, 1974. 4. Carpentier WS, Kambouris AA, Allaben RD: Review of 555 cholecystectomies without drainage. Am Surg 44: 200, 1978. 5. Dreese WC: Cholecystectomy without drainage. J Int Co// Surg 40: 433, 1963. 6. Goldberg IM, Goldberg JP, Liechty RD, Buerk C, Eiseman 6, Norton L: Cholecystectomy with and without drainage. Am J Surg 130: 29, 1975. 7. Kambouris AA, Carpentier WS, Allaben RD: Cholecystectomy without drainage. Surg Gynecol Obstet 137: 613, 1973. 8. Neumann S: Zur Drainage und nicht Drainage in der Gallenchirurgie. Chirurg32: 414, 1961. 9. Armitage P: The construction of comparable groups, p 14. Controlled Clinical Trials (Hill AB, ed). Blackwell, Oxford, 1960. 10. Schwartz SI: Comment. The Yearbook of Surgery 1976, p 461. 11. Man B, Kraus L, Motovic A: Cholecystectomy without drainage, nasogastric suction and intravenous fluids. Am JSurg 133: 312, 1977. 12. Gambino SR: Bilirubin (modified Jendrassik and Grof)-provisional. Stand Methods C/in Chem 5: 55, 1965.
Volume 137, June 1979
Cholecystectomy
13. Owen JA, Better FC, Hoban J: A simple method for the determination of serum haptoglobin. J C/in fathol 13: 163, 1960. 14. Reitman S, Frankel S: A colorometric method for the determination of serum glutamic oxalectic and glutamic pyruvic transaminases. Am J Clin Pathol28: 56, 1957. 15. lchida T, Osaka T, Kojima K: A simple method for the determination of serum iron. C/in Chim Acta 22: 27 1, 1968. 16. Schirardin H, Ney J: Eine vereinfachte Mikromethode zur Bestimmung von Serum Albumin mit Hilfe von Bromkresolgrun. Z k/in Chem klin Biochem 10: 338, 1972. 17. Siegel S: Non-parametric Statistics. McGraw Hill, New York, 1956. 18. Hill AB: Controlled Clinical Trials, p 169. Blackwell, Oxford, 1960. 19. van der Linden W, Sunzel H: Early versus delsyed operation in acute cholecystitis. Am J Surg 120: 7, 1970. 20. Gordon AB, Bates T, Fiddian RV: A controlled clinical trial of drainage after cholecystectomy. Br J Surg 63: 278, 1976. 21. Myers MB: Drain fever, a complication of drainage after cholecystectomy. Surgery 52: 314, 1962. 22. Nyman M: Serum haptoglobin: methodological and clinical studies. Stand J C/in Lab /west [Suppl 391 11: 1, 1959. 23. Vickers M. Jr: Serum haptoglobin: a preoperative detector of metastatic renal carcinoma. J Ural 112: 310. 1974.
779
Gunnar Edlund, MD, htersund,
Sweden
Staffan Gedda, MD, bstersund,
Sweden
Willem van der Linden, MD, btersund,
Sweden
Cholecystectomy without intraperitoneal drainage was introduced by Spivack [I] as long ago as 1913. The pros and cons of drains have been debated ever since. Simple as the problem may seem, a consensus has not been reached. There has never been a shortage of prestigious opinions based on poorly construed theory or vague clinical impressions, but except to those who aired them, these opinions seemed of little avail. A number of large series of patients treated with [2,3] and without [4,5] a drain confused rather than enlightened the issue; both the proponents and opponents of drainage invariably reported excellent results with their respective methods. Retrospective studies from hospitals where both methods were used side by side [S-S] also turned out to be not very helpful. The objection against this type of study is that the choice between the methods may have depended on the patient’s condition [9], which invalidates any comparison. Efforts were made to avoid this objection by retrospective matching of patients. However, as Schwartz [IO] pointed out in a comment on one such study [6], the matching procedure proved unable to eliminate important differences between the groups that were compared. It should be obvious by now that the problem will never be solved unless we are willing to resort to studies performed according to the rules for controlled clinical trials. We have tried to perform such a study. As it was recently claimed that in elective cholecystectomy not only drainage but also nasogastric suction may be omitted [I I], we simultaneously put this claim to the test of a controlled clinical trial. From the Department of Surgery, Centrallasarettet, bstersund. Sweden. Reprint requests should be addressed to Wilfem van der Linden, MD. Lasarettet, S 83 10 1 dstersund 1, Sweden.
Volume 137, June 1979
Material and Methods Treatment Groups. One hundred consecutive patients submitted to elective cholecystectomy between November 1, 1977 and June 28,1978 entered into the trial. Patients with acute cholecystectomy and those with jaundice were excluded. If the common duct had to be explored, the patient was excluded again. In a strictly random fashion the 100 patients were allocated to four different treatment groups (groups A, B, C, and D) arranged in a 2 by 2 design (Figure 1). As can be seen, 50 patients (groups A and C) were treated with intraperitoneal drains, and in 50 (groups B and D) the drain was omitted. Similarly, 50 patients (groups A and B) were treated with a nasogastric tube and 50 patients (groups C and D) were not. Before the start of the trial 100 cards indicating the group to which the patient belonged were prepared in sealed envelopes. These envelopes were opened the morning after the operations had been divided among the surgeons of our department. Preoperative Management and Anesthesia. In patients in groups A and B the nasogastric tube was introduced in connection with premeditation. The tube was not connected to a suction apparatus but linked to a plastic bag in a closed circuit. All operations were performed in neurolept analgesia under pancuronium relaxation with 35 per cent oxygen and 62 per cent nitrogen. Routinely, 1,000 cc half isotone Ringer’s acetate in 5 per cent glucose (Rehydrex@) was given during the operation. Operatioe Technic. After a subcostal incision, cholecystectomy was performed according to a standard technic. Intraoperative cholangiography was performed in each patient. Closure of the gallbladder bed was performed when leakage of bile from the bed was suspected. The appendix was not removed. The operations were performed by registered specialists as well as by junior surgeons as part of their training program. In patients in groups A and C, a plastic drain was brought out through a stab wound and connected to a closed suction drainage system.
775
Edlund et al
Results Gastr.
Figure 1. Altocatlon of 100 patients to four groups. Gastr. = nasogastric.
Postoperative Management. Postoperatively all patients were again given 1,000 cc of Rehydrex followed by 1,000 cc of 15 per cent fructose with 5 per cent glucose. All patients were mobilized on the first postoperative day, and in patients with nasogastric tubes the tube was then removed. In patients with intraperitoneal drains the amount of discharge was noted daily and the drain was removed when this amount was less than 25 cc. Variables Studied. Preoperatively as well as on the second and fourth postoperative days serum was taken for the following determinations in our autoanalyzer. Bilirubin was determined according to the method of Gambino [ 121 with a maximal normal limit of 21 pmol/liter. Haptoglobin was determined according to Owen et al [13] with a maximal normal limit of 1.70 g/liter. Serum transaminase levels (ASAT and ALAT) were determined with the method of Reitman and Frankel[14] with a maximal normal limit of 0.80 pkatlliter. Fasting serum iron was determined according to Ichida et al [15] with minimal normal limits of 11 pmol/liter for females and 14 pmol/liter for males. Finally, serum albumin was determined according to the method of Schiradin and Ney [16] with normal limits between 37 and 52 g/liter. The duration of postoperative pyrexia was taken as the number of days on which a temperature above 37.6’ C was recorded. Postoperative complications, the length of hospital stay, the occurrence of vomiting, and the amount of fluid obtained via the intraperitoneal drain were noted on a card made out when the patient entered into the trial. Statistical Methods. Significance was tested with nonparametric tests as described by Siegel [17]. Calculations were performed with Hewlett-Packard calculator HP 65 using commercially available programs from Stat Pat 1.
TABLE I
Details of Four Groups
Details of Four Groups. The sex and age distribution of the four groups appears in Table I. As can be seen, there was little difference between the groups except that group C contained relatively few male patients. Also shown are the number of operations performed by senior and junior surgeons in the four groups; in this respect the groups differed little. Finally, this table gives the mean duration of the operation in the four groups. Again, there is little difference except for the low value in group C. However, when the patients are arranged into groups with and without drainage (groups A and C versus groups B and D) or into groups with and without a nasogastric tube (groups A and B versus groups C and D), the differences between the groups so constructed are not statistically significant. Mortality and Complications. There was one death in this series. In a 75 year old man in group D signs of peritonitis developed on the fourth postoperative day. At reexploration a perforated gastric ulcer was found. The patient died of cardiac insufficiency. One patient in group D had a wound infection, one in group C had postoperative bronchopneumonia, and one patient in group B had pancreatitis postoperatively. Postoperative Pyrexia. Table II gives the duration of postoperative fever in the four groups and values for patients with drainage (groups A and C!)and those without drainage (groups B and D). There was very little difference between the various groups. Hospital Stay. The mean length of hospital stay was 6.72 days for group A, 7.40 days for group B, 6.96 days for group C, and 6.63 days for group D. The differences were not significant. Amount and Duration of Drainage. The amount of fluid drained varied from 5 to 305 cc, with a mean value of 87.7 cc in group C and 85.8 cc in group A. As a rule, the intraperitoneal drain could be removed on the fourth postoperative day. Postoperative Serum Tests. The number of patients with a postoperative increase of serum bilirubin surpassing the maximal normal limit is shown in
Group A
No. of patients Males Females Age (yr) Mean Range Operating surgeon Senior Junior Duration of operation (min)
776
0
C
D
25
25
25
25
11 14
10 15
4 21
11 14
50.1 22-79
53.3 26-76
52.8 24-71
55.0 33-75
9 16
8 17
10 15
8 17
61
59.2
53
64.6
TABLE II
Duration of Postoperative Fever
No. of Days 55 6 or 7 Z-8 l
Groups With Drainage A c Total
Groups Without Drainage B D” Total
14 9 2
13 8 4
16 6 3
30 15 5
14 9 1
27 17 5
One death.
The American Journal of Surgery
Elective Choiecystectomy
Figure 2. An abnormal increase was observed in 7 of the 50 patients treated with a drain as compared with 17 of the 50 treated without drains. When subjected to the chi square test, the difference is significant at the 5 per cent level (x2 = 5.48; df = 1; 0.05 > p > 0.01). An increase in the transaminase level was seen in a number of patients, but there were no significant differences between the various groups. The number of patients with abnormally high postoperative serum haptoglobin levels is shown in Figure 3. As can be seen, an abnormal increase was observed in 22 of the 50 patients without drains compared with 12 of the 50 patients with drains. With the chi square test this difference is probably significant (x2 = 4.46; df = 1; 0.05 > p > 0.01). With the same test, the difference between patients with and without a gastric tube was not significant. Decreased serum iron values were observed in a number of patients, but there were no differences among the groups. Neither were there any group differences in serum albumin levels. Vomiting. The number of patients with postoperative vomiting is given in Figure 4. Vomiting occurred significantly more often in the 50 patients treated without a nasogastric tube than in the 50 patients treated with one (x” = 6.42; df = 1; 0.02 > p > 0.01). Comments
The basic rules for controlled clinical trials are randomization, replication, and unbiased assessment of results [18]. Strict randomization was applied in allocating the 100 patients to the four groups. However, even strict randomization does not guarantee that the groups will be exactly alike. Nothing can accomplish this. Therefore, it is essential to compare the groups. Comparison of sex and age and of other variables showed little difference between the groups except that group C (drainage but no nasogastric tube) contained few males. The mean duration of the operation was also shorter in this group than in the others (Table I). However, as the differences among the groups do not even approach the level of significance, the conclusion is that the groups can be used as a sound basis for comparisons. Apart from the aforementioned rules, there is in clinical trials another prerequisite that should be fulfilled. That is the precise identification of patients to whom the results may be applied. It is here that the difficulties start. Surgeons participating in a trial of this kind may feel inclined to exclude certain patients merely on the basis of clinical impressions gained during the operation. Therefore, before
Volume
137, June 1979
main Gastr.Tube NO
Tube
A
c
NO Drain
4
B
9
gD8 7
13 11
17
Figure 2. Number of patients with abnormally high postoperative serum bilirubin levels. Gastr. = nasogastric.
Figure 3. Number of patients with abnormally high postoperative serum haptoglobin levels. Gastr. = nasogastric.
starting a trial on drainage, two things should be made clear. First, if the trial allows for patients to be excluded on clinical impressions, for instance, because of what the individual surgeon considers to be incomplete hemostasis, the results will become irreproducible and the trial will lose much of its value. The reason is that clinical impressions vary enormously. Second, it should be realized that the question of drainage in cholecystectomy is worth investigating or, alternatively, that the necessity of drainage can be determined by the individual surgeon on the basis of a clinical assessment during the operation and in that case the question is not worth investigating. Clearly, we cannot have it both ways. Any exclusion of patients, except for strictly defined reasons, is therefore not only detrimental to the trial’s success but also highly illogical. In the present trial we excluded patients with acute cholecystitis and those in whom the common duct was explored. Patients undergoing acute cholecystectomy were excluded because we have found that after those operations prolonged discharge of serofibrinous fluid occurs relatively frequently (191. Patients with common duct exploration were excluded because of the danger of biliary leakage. No patient was excluded for other reasons. Our results therefore apply to interval cholecystectomy without a common duct operation. There is at present only one study on drainage in elective cholecystectomy performed as a controlled trial, the study of Gordon et al 1201. In that study a number of patients were excluded on the basis of clinical assessments during the operation, mostly
777
Edlund et al
Gastr No
Figure 4. Number of pafients
with postoperative
vomiting.
Gasfr. = nasogasfric.
because of what was considered incomplete hemostasis. The category of patients to whom their results apply is therefore less strictly defined. However, as the number of such exclusions is small, a comparison of their results with ours is justified. Our results agree with those of Gordon et al [ZO]insofar as both trials failed to find a difference in postoperative pyrexia and length of hospital stay between patients with and those without drainage. It has been claimed on the basis of retrospective studies that omitting drainage shortens the duration of postoperative fever. Myers [21] even went so far as to introduce the concept of drain fever as a complication of drainage after cholecystectomy. As two successive controlled trials now have failed to find any difference in postoperative pyrexia, this concept can be refuted. Omitting drainage in the hope of shortening postoperative fever can no longer be defended. Systematic monitoring of a large number of serum values showed a difference in the way in which serum bilirubin reacted to operation with and without drainage (Figure 2). An abnormal postoperative increase was observed significantly more often in patients without a drain. As a rule, the increase was rapidly transient with many increased values already returning to normal on the fourth postoperative day. No similar difference was observed in serum transaminase levels. Most probably, therefore, the transient rise in the serum bilirubin level observed after cholecystectomy without drainage is due to resorption of bile that is otherwise discharged via the drain. However transient the rise may be, it should be regarded as an indication for the use of intraperitoneal drains. Our systematic checks also revealed a difference in the way serum haptoglobin reacted to cholecystectomy with and without a drain (Figure 3). Conditions such as infection, fever, and malignant disease and surgery are known to be capable of elevating serum haptoglobin levels [22,23]. The response df the haptoglobin level is immediate and the elevation is in proportion to the intensity of the traumatic stimulus. In the present study a rise to abnormal
778
levels was observed significantly more often in patients without intraperitoneal drains. The probable explanation is that omission of the drain adds to the operation’s traumatic effect. Finally, as perhaps could be expected, vomiting occurred significantly less often in patients with than in those without a nasogastric tube (Figure 4). We did not connect the tube to a suction apparatus, which perhaps is the reason that vomiting also occurred in a number of patients with a gastric tube. If such an apparatus had been used, the difference between the groups would probably have been even more marked. The results of this trial thus clearly favor the traditional management of patients subjected to cholecystectomy and lead us to recommend the use of intraperitoneal drains and nasogastric tubes. Summary
The effects of intraperitoneal drains and nasogastric tubes were studied in 100 consecutive patients undergoing elective cholecystectomy without exploration of the common duct. The study was performed as a randomized trial. Concurrent assessment of the effect of both the drain and the gastric tube was achieved with a 2 by 2 design. A large number of serum tests were systematically checked postoperatively. There was one death in a patient treated without either a drain or gastric tube. Apart from that, there were few complications. In accordance with the results of an earlier randomized trial, no difference in postoperative pyrexia and hospital stay was found between patients with and those without intraperitoneal drains. The concept of drainage fever is therefore refuted. An abnormal increase in the serum bilirubin level was found significantly more often after operations without an intraperitoneal drain. This transient rise is explained as being due to resorption of bile that would otherwise have been discharged via the drain. An abnormal rise in the haptoglobin level also occurred significantly more often in patients in whom intraperitoneal drains were not used. The suggested explanation is that omission of the drain adds to the operation’s traumatic effect. Vomiting occurred significantly more often in patients without nasogastric tubes. The use of intraperitoneal drains and nasogastric tubes is recommended. References 1. Spivack JL: The Surgical Technique of Abdominal Operations, 4th ed. Springfield, III, Charles C Thomas, 1946. 2. MC Kittrick JE, Yonehiro L, Latimer RG, Doane WH: In defense of drainage after cholecystectomy: an analysis of 246 cases.
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Elective
Chir Gastroenterol 10: 429, 1976. 3. Richter N: Routinemassige Drainage bei alleiniger Cholezystektomie. Zentralbl Chir 99: 41, 1974. 4. Carpentier WS, Kambouris AA, Allaben RD: Review of 555 cholecystectomies without drainage. Am Surg 44: 200, 1978. 5. Dreese WC: Cholecystectomy without drainage. J Int Co// Surg 40: 433, 1963. 6. Goldberg IM, Goldberg JP, Liechty RD, Buerk C, Eiseman 6, Norton L: Cholecystectomy with and without drainage. Am J Surg 130: 29, 1975. 7. Kambouris AA, Carpentier WS, Allaben RD: Cholecystectomy without drainage. Surg Gynecol Obstet 137: 613, 1973. 8. Neumann S: Zur Drainage und nicht Drainage in der Gallenchirurgie. Chirurg32: 414, 1961. 9. Armitage P: The construction of comparable groups, p 14. Controlled Clinical Trials (Hill AB, ed). Blackwell, Oxford, 1960. 10. Schwartz SI: Comment. The Yearbook of Surgery 1976, p 461. 11. Man B, Kraus L, Motovic A: Cholecystectomy without drainage, nasogastric suction and intravenous fluids. Am JSurg 133: 312, 1977. 12. Gambino SR: Bilirubin (modified Jendrassik and Grof)-provisional. Stand Methods C/in Chem 5: 55, 1965.
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Cholecystectomy
13. Owen JA, Better FC, Hoban J: A simple method for the determination of serum haptoglobin. J C/in fathol 13: 163, 1960. 14. Reitman S, Frankel S: A colorometric method for the determination of serum glutamic oxalectic and glutamic pyruvic transaminases. Am J Clin Pathol28: 56, 1957. 15. lchida T, Osaka T, Kojima K: A simple method for the determination of serum iron. C/in Chim Acta 22: 27 1, 1968. 16. Schirardin H, Ney J: Eine vereinfachte Mikromethode zur Bestimmung von Serum Albumin mit Hilfe von Bromkresolgrun. Z k/in Chem klin Biochem 10: 338, 1972. 17. Siegel S: Non-parametric Statistics. McGraw Hill, New York, 1956. 18. Hill AB: Controlled Clinical Trials, p 169. Blackwell, Oxford, 1960. 19. van der Linden W, Sunzel H: Early versus delsyed operation in acute cholecystitis. Am J Surg 120: 7, 1970. 20. Gordon AB, Bates T, Fiddian RV: A controlled clinical trial of drainage after cholecystectomy. Br J Surg 63: 278, 1976. 21. Myers MB: Drain fever, a complication of drainage after cholecystectomy. Surgery 52: 314, 1962. 22. Nyman M: Serum haptoglobin: methodological and clinical studies. Stand J C/in Lab /west [Suppl 391 11: 1, 1959. 23. Vickers M. Jr: Serum haptoglobin: a preoperative detector of metastatic renal carcinoma. J Ural 112: 310. 1974.
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