The Timing of Biliary Surgery in Acute Pancreatitis JOHN H. C. RANSON, M.D.
The timing of biliary surgery remains controversial in patients with acute pancreatitis associated with cholelithiasis. Eighty hospital admissions for acute pancreatitis, occurring in 74 patients with cholelithiasis, have therefore been reviewed. Among 22 patients who underwent abdominal surgery during the first week of treatment, there were five deaths (23%) and four patients (18%) who required more than seven days of intensive care. Fifty-eight episodes of pancreatitis were managed nonoperatively during the first week of treatment, with no deaths, although six (10%) required more than seven days of intensive care. Biliary surgery was undertaken later during the same admission in 37 patients, with no deaths. Twenty-one patients were discharged without biliary operation, but seven (33%) developed further pancreatitis. Previously reported prognostic signs were used to divide pancreatitis into 57 "mild" episodes (1.8% mortality) and 23 "severe" episodes (17% mortality). Early (day 0-7) definitive biliary surgery was undertaken in 11 patients with "mild" pancreatitis, with one death (9%), and in six patients with "severe"I pancreatitis, with four deaths (67%). In three recent patients with "severe" pancreatitis, early biliary surgery was limited to cholecystostomy, with no deaths. These findings suggest that although early correction of associated biliary disease may be undertaken safely in many patients with "mild" acute pancreatitis, early definitive surgery is hazardous in "severe" pancreatitis and should, if possible, be deferred until pancreatitis has subsided. In most patients biliary surgery should precede hospital discharge.
PREVIOUS CLINICAL STUDIES of acute pancreatitis
have shown that the risk of death or major complications can be estimated by early objective findings and that early abdominal surgery does not reduce this risk.28-32 The etiologic associations of pancreatitis in these studies varied, but most patients gave a history of chronic alcohol abuse. In nonalcoholic patients, cholelithiasis is the most commonly recognized etiologic association of acute pancreatitis.13'38 The present study was therefore carried out to evaluate criteria for the identification of severe disease and to determine the role of biliary surgery in the management of patients who had acute pancreatitis associated with cholelithiasis. Presented at the Annual Meeting of the Southern Surgical Association, December 4-6, 1978, Hot Springs, Virginia. Reprint requests: John H. C. Ranson, M.D., Department of Surgery, New York University Medical Center, 560 First Avenue, New York, New York 10016. Submitted for publication: December 7, 1978.
From the Department of Surgery, New York University Medical Center, New York, New York
Materials and Methods Eighty admissions to Bellevue and New York University Hospitals for acute pancreatitis in patients with cholelithiasis have been reviewed. The admissions took place between January 1971 and May 1978 and involved 74 patients. There were 48 women and 26 men.
Second admissions for pancreatitis occurred in five women and one man. Age ranged from 14 to 92 years (mean 52 + 20 S.D.). Mean initial serum amylase was 2340 (+1902 S.D.) Somogyi units/100 ml (range 479000 S.U./100 ml); mean initial serum bilirubin was 2.6 (+2.6 S.D.) mg/100 ml (range 0.3- 12.5 mg/100 ml); and mean initial serum alkaline phosphatase was 17.8 (± 13.4 S.D.) King-Armstrong units/100 ml (range 3.272.6 K.-A. units/100 ml). Five patients gave a history of prolonged alcohol abuse. Cholelithiasis was documented in all patients either by operation or by radiographic studies. The diagnosis of acute pancreatitis was made on the basis of clinical, radiographic and biochemical findings in 21 cases. In this group, mean initial serum amylase was 2551 S. U./ 100 ml, and the mean lowest serum calcium level during the initial 48 hours of treatment was 8.3 mg/dl (range 6.5-10.8 mg/dl). Most of these patients had persistent generalized or left side abdominal pain or tenderness. Four developed severe respiratory insufficiency, one had hemorrhagic peritoneal fluid on paracentesis and one had marked residual fat necrosis at operation during a subsequent hospital admission. In 59 patients, acute pancreatitis was demonstrated at laparotomy during the same hospital admission. The operative diagnosis of pancreatitis was made in most patients on the basis of the presence of fat necrosis or pancreatic hemorrhage in addition to pancreatic inflammation. Patients with biliary disease and hyperamylasemia or mild pancreatic edema at operation but no other clinical or operative evidence of pancreatitis are not included.
0003-4932/79/0500/0654 $01.00 X J. B. Lippincott Company
654
Vol. 189.o NO. 5
BILIARY SURGERY TIMING
TABLE 1. Early Objective Signs to Estimate Severity of Pancreatitis At Admission or Diagnosis Age over 55 years White blood cell count over 16,000/cu mm Blood glucose over 200 mg/100 ml Serum lactic dehydrogenase over 350 I.U./liter Serum glutamic oxaloacetic transaminase over 250 Sigma Frankel units/100 ml During Initial 48 Hours Hematocrit fall greater than 10 percentage points Blood urea nitrogen rise more than 5 mg/100 ml Serum calcium level below 8 mg/100 ml Base deficit greater than 4 mEq/liter Estimated fluid sequestration more than 6000 ml Arterial Po2 below 60 mm Hg
655
blood glucose levels in patients with known diabetes mellitus. In this study there were 57 patients with less than three positive early signs, 19 with three or four positive signs, three patients with five or six positive signs and one patient with more than six signs (Fig. 1). Since the prognostic signs shown in Table 1 were developed in patients with pancreatitis of varied etiologies, the relationship between these measurements and morbidity has been evaluated in the present group of patients who had acute pancreatitis and cholelithiasis. Treatment of Acute Pancreatitis
Severity of Pancreatitis Previous studies28-31 in patients with acute pancreatitis of varied etiologies have demonstrated a relationship between the risk of death or major complication and 11 measurements made during the initial 48 hours after diagnosis. This relationship has been used to develop the 11 early prognostic signs which are listed in Table 1. The changes in hematocrit and in blood urea nitrogen levels represent the overall change from the initial value to the 48-hour value. Fluid sequestration was estimated by subtracting the total volume of nasogastric aspirate and urinary output from the volume of fluid administered intravenously during the initial 48-hour period. The only measurements which have been deliberately excluded from analysis are
All patients were treated with nasogastric suction, administration of intravenous fluids and antibiotics, usually ampicillin, 2 g intravenously every six hours. An indwelling urethral catheter was introduced to allow close monitoring of urinary output, and a central venous catheter usually was placed. Twenty-two patients underwent laparotomy during the first seven days of treatment (median, day 2). Cholecystectomy was carried out in 14 patients. In 12 of these the common bile duct was explored, and in five, transduodenal operations on the biliary sphincter were added. Two patients whose gallbladders had previously been removed underwent choledocholithotomy alone. In five patients early biliary surgery was limited to cholecystostomy, but peritoneal lavage catheters were placed in one of these patients, and a distal pancreatic resection was carried out in one. 100
100
100F BO z w FIG. 1. The morbidity of acute pancreatitis related to the number of positive
prognostic signs.
w ZL
DUF
40F20O
37
7.0 .. =zZ1 a 1.8
NUMBER OF POSITIVE EARLY SIGNS 0-2 NUMBER OF ADMISSIONS 57
3-4
5-6
7-8
19
3
1
656
RANSON
In one patient catheters were placed for peritoneal lavage, but no biliary surgery was performed. Fifty-eight episodes of acute pancreatitis were managed non-operatively during the first week of treatment, with the addition of percutaneous peritoneal lavage in two cases.32 Thirty-seven of these patients underwent biliary surgery later, during the same hospitalization, on the ninth to the forty-ninth day of treatment (median, day 16). In 22 patients cholecystectomy and common bile duct exploration were carried out, with transduodenal sphincteroplasty in three. Common bile duct exploration alone was carried out in one patient who had undergone previous cholecystectomy. Thirteen patients underwent cholecystectomy without surgical exploration of the common bile duct, and one underwent cholecystostomy. Twenty-two patients were discharged without biliary surgery, including one in whom early operation had been limited to laparotomy and placement of lavage catheters. Discharge without biliary surgery was determined by physician choice in 13, failure to document cholelithiasis in five and patient choice in four.
Results Five episodes of acute pancreatitis (6%) were fatal. Two deaths were due to cardiovascular collapse and occurred on days 6 and 12 of treatment. One death was due to respiratory failure and pulmonary sepsis and occurred on day 16 of treatment. Two deaths were related to intra-abdominal sepsis and occurred on days 10 and 60 of treatment. Ten other attacks of acute pancreatitis (13%) required more than seven days of treatment in the intensive care unit (range 8-16 days, mean 12.7 days). Estimation of Severity of Pancreatitis The relationship between morbidity and previously reported prognostic signs is shown in Figure 1. One (1L8%) of 57 patients with fewer than three positive signs died of respiratory complications. Three (5.3%) received more than seven days of treatment in the intensive care unit. In two cases, intensive care was required for cardiovascular instability, and in one it was necessitated by gastrointestinal bleeding which occurred on the thirty-eighth day of hospitalization, following late biliary surgery. Of 23 patients with more than three positive signs, four (17.4%) died, two following intra-abdominal sepsis and two from early cardiovascular collapse. Seven other patients (30%) required more than seven days of treatment in the intensive care unit. In one patient, this was for intraabdominal sepsis, and in six it was because of cardiovascular instability or respiratory failure.
Ann.
Surg. * May
1979
Thirteen patients who had less than three positive early signs underwent laparotomy during the first seven days of treatment. In this group no gross pancreatic hemorrhage or necrosis was noted. Nine patients who had three or more positive prognostic signs underwent laparotomy in the first week of treatment. In this group, four patients (44%) with an average of five positive signs had frank pancreatic hemorrhage or necrosis. Five patients (56%) with an average of 3.6 positive prognostic signs had no pancreatic hemorrhage or necrosis. Two additional patients with five positive prognostic signs had hemorrhagic fluid on early diagnostic paracentesis but did not undergo early laparotomy. The relationship between morbidity and prognostic measurements in this group of patients with acute pancreatitis and cholelithiasis is shown in Table 2. Significant relationships are demonstrated between morbidity and admission measurements: blood glucose, white blood cell count, serum lactic dehydrogenase and serum glutamic oxaloacetic transaminase; and between morbidity and initial 48-hour measurements: hematocrit fall, blood urea nitrogen change and lowest serum calcium. There was a tendency for increased age, early metabolic acidosis and fluid sequestration to be associated with morbidity, but this was not statistically significant in this sample. No relationship was demonstrated between prognosis and initial serum amylase, bilirubin and alkaline phosphatase levels or initial 48-hour lowest arterial Po2 values.
Timing of Biliary Surgery, Severity of Pancreatitis and Morbidity Among 22 patients who underwent abdominal operation during the first week of treatment, five (23%) died and four (18%) required more than seven days of treatment in the intensive care unit. Fifty-eight episodes of pancreatitis were managed non-operatively during the first week of treatment, with no deaths, although six (10%) required more than seven days of intensive care. "Severe" Pancreatitis. Twenty-three episodes of acute pancreatitis were associated with three or more positive, early prognostic signs and may be arbitrarily designated as "severe." In this group, nine patients (mean positive signs, 5.4) underwent laparotomy during the first seven days of treatment. In three (mean positive signs, 3.7), surgery was limited to cholecystostomy with the additional placement of catheters for postoperative peritoneal lavage in one. There were no deaths in this group, although all three were treated in the intensive care unit for more than seven days (mean,
Vol. 189 * No. 5
657
BILIARY SURGERY TIMING TABLE 2. Mean Value (±+S.D.) of Prognostic Signs in Patients wvith Acute Pancreatitis and Cholelithiasis
Number Recorded Number of admissions At Admission Age (years) Blood glucose (mg %) White cell count x103/cu mm Serum lactic dehydrogenase (IU/liter) Serum glutamic oxaloacetic transaminase (S.F.U. %) Initial 48 Hours Hematocrit fall (percentage points) BUN change
80
80 74 80
73 77
74
77
(mg %) Lowest calcium (mg %) Lowest Pao2 (mm Hg) Base deficit (mEq/liter) Estimated fluid
78
75
Died
74
6
73 46
80 66
63
p Live vs Died
51
61
±28
162 ±56 12.5 + 5.2 248 ± 153 222 ± 264
255 ±193 19.5 ± 4.7 346 ± 137 552 ± 942
4.0 ± 4.5 -4.9 ± 6.5 8.8 ± 0.9 72
54
±24
The timing of biliary surgery remains controversial in patients with acute pancreatitis associated with cholelithiasis. Eighty hospital admissions for acute pancreatitis, occurring in 74 patients with cholelithiasis, have therefore been reviewed. Among 22 patients who underwent abdominal surgery during the first week of treatment, there were five deaths (23%) and four patients (18%) who required more than seven days of intensive care. Fifty-eight episodes of pancreatitis were managed nonoperatively during the first week of treatment, with no deaths, although six (10%) required more than seven days of intensive care. Biliary surgery was undertaken later during the same admission in 37 patients, with no deaths. Twenty-one patients were discharged without biliary operation, but seven (33%) developed further pancreatitis. Previously reported prognostic signs were used to divide pancreatitis into 57 "mild" episodes (1.8% mortality) and 23 "severe" episodes (17% mortality). Early (day 0-7) definitive biliary surgery was undertaken in 11 patients with "mild" pancreatitis, with one death (9%), and in six patients with "severe"I pancreatitis, with four deaths (67%). In three recent patients with "severe" pancreatitis, early biliary surgery was limited to cholecystostomy, with no deaths. These findings suggest that although early correction of associated biliary disease may be undertaken safely in many patients with "mild" acute pancreatitis, early definitive surgery is hazardous in "severe" pancreatitis and should, if possible, be deferred until pancreatitis has subsided. In most patients biliary surgery should precede hospital discharge.
PREVIOUS CLINICAL STUDIES of acute pancreatitis
have shown that the risk of death or major complications can be estimated by early objective findings and that early abdominal surgery does not reduce this risk.28-32 The etiologic associations of pancreatitis in these studies varied, but most patients gave a history of chronic alcohol abuse. In nonalcoholic patients, cholelithiasis is the most commonly recognized etiologic association of acute pancreatitis.13'38 The present study was therefore carried out to evaluate criteria for the identification of severe disease and to determine the role of biliary surgery in the management of patients who had acute pancreatitis associated with cholelithiasis. Presented at the Annual Meeting of the Southern Surgical Association, December 4-6, 1978, Hot Springs, Virginia. Reprint requests: John H. C. Ranson, M.D., Department of Surgery, New York University Medical Center, 560 First Avenue, New York, New York 10016. Submitted for publication: December 7, 1978.
From the Department of Surgery, New York University Medical Center, New York, New York
Materials and Methods Eighty admissions to Bellevue and New York University Hospitals for acute pancreatitis in patients with cholelithiasis have been reviewed. The admissions took place between January 1971 and May 1978 and involved 74 patients. There were 48 women and 26 men.
Second admissions for pancreatitis occurred in five women and one man. Age ranged from 14 to 92 years (mean 52 + 20 S.D.). Mean initial serum amylase was 2340 (+1902 S.D.) Somogyi units/100 ml (range 479000 S.U./100 ml); mean initial serum bilirubin was 2.6 (+2.6 S.D.) mg/100 ml (range 0.3- 12.5 mg/100 ml); and mean initial serum alkaline phosphatase was 17.8 (± 13.4 S.D.) King-Armstrong units/100 ml (range 3.272.6 K.-A. units/100 ml). Five patients gave a history of prolonged alcohol abuse. Cholelithiasis was documented in all patients either by operation or by radiographic studies. The diagnosis of acute pancreatitis was made on the basis of clinical, radiographic and biochemical findings in 21 cases. In this group, mean initial serum amylase was 2551 S. U./ 100 ml, and the mean lowest serum calcium level during the initial 48 hours of treatment was 8.3 mg/dl (range 6.5-10.8 mg/dl). Most of these patients had persistent generalized or left side abdominal pain or tenderness. Four developed severe respiratory insufficiency, one had hemorrhagic peritoneal fluid on paracentesis and one had marked residual fat necrosis at operation during a subsequent hospital admission. In 59 patients, acute pancreatitis was demonstrated at laparotomy during the same hospital admission. The operative diagnosis of pancreatitis was made in most patients on the basis of the presence of fat necrosis or pancreatic hemorrhage in addition to pancreatic inflammation. Patients with biliary disease and hyperamylasemia or mild pancreatic edema at operation but no other clinical or operative evidence of pancreatitis are not included.
0003-4932/79/0500/0654 $01.00 X J. B. Lippincott Company
654
Vol. 189.o NO. 5
BILIARY SURGERY TIMING
TABLE 1. Early Objective Signs to Estimate Severity of Pancreatitis At Admission or Diagnosis Age over 55 years White blood cell count over 16,000/cu mm Blood glucose over 200 mg/100 ml Serum lactic dehydrogenase over 350 I.U./liter Serum glutamic oxaloacetic transaminase over 250 Sigma Frankel units/100 ml During Initial 48 Hours Hematocrit fall greater than 10 percentage points Blood urea nitrogen rise more than 5 mg/100 ml Serum calcium level below 8 mg/100 ml Base deficit greater than 4 mEq/liter Estimated fluid sequestration more than 6000 ml Arterial Po2 below 60 mm Hg
655
blood glucose levels in patients with known diabetes mellitus. In this study there were 57 patients with less than three positive early signs, 19 with three or four positive signs, three patients with five or six positive signs and one patient with more than six signs (Fig. 1). Since the prognostic signs shown in Table 1 were developed in patients with pancreatitis of varied etiologies, the relationship between these measurements and morbidity has been evaluated in the present group of patients who had acute pancreatitis and cholelithiasis. Treatment of Acute Pancreatitis
Severity of Pancreatitis Previous studies28-31 in patients with acute pancreatitis of varied etiologies have demonstrated a relationship between the risk of death or major complication and 11 measurements made during the initial 48 hours after diagnosis. This relationship has been used to develop the 11 early prognostic signs which are listed in Table 1. The changes in hematocrit and in blood urea nitrogen levels represent the overall change from the initial value to the 48-hour value. Fluid sequestration was estimated by subtracting the total volume of nasogastric aspirate and urinary output from the volume of fluid administered intravenously during the initial 48-hour period. The only measurements which have been deliberately excluded from analysis are
All patients were treated with nasogastric suction, administration of intravenous fluids and antibiotics, usually ampicillin, 2 g intravenously every six hours. An indwelling urethral catheter was introduced to allow close monitoring of urinary output, and a central venous catheter usually was placed. Twenty-two patients underwent laparotomy during the first seven days of treatment (median, day 2). Cholecystectomy was carried out in 14 patients. In 12 of these the common bile duct was explored, and in five, transduodenal operations on the biliary sphincter were added. Two patients whose gallbladders had previously been removed underwent choledocholithotomy alone. In five patients early biliary surgery was limited to cholecystostomy, but peritoneal lavage catheters were placed in one of these patients, and a distal pancreatic resection was carried out in one. 100
100
100F BO z w FIG. 1. The morbidity of acute pancreatitis related to the number of positive
prognostic signs.
w ZL
DUF
40F20O
37
7.0 .. =zZ1 a 1.8
NUMBER OF POSITIVE EARLY SIGNS 0-2 NUMBER OF ADMISSIONS 57
3-4
5-6
7-8
19
3
1
656
RANSON
In one patient catheters were placed for peritoneal lavage, but no biliary surgery was performed. Fifty-eight episodes of acute pancreatitis were managed non-operatively during the first week of treatment, with the addition of percutaneous peritoneal lavage in two cases.32 Thirty-seven of these patients underwent biliary surgery later, during the same hospitalization, on the ninth to the forty-ninth day of treatment (median, day 16). In 22 patients cholecystectomy and common bile duct exploration were carried out, with transduodenal sphincteroplasty in three. Common bile duct exploration alone was carried out in one patient who had undergone previous cholecystectomy. Thirteen patients underwent cholecystectomy without surgical exploration of the common bile duct, and one underwent cholecystostomy. Twenty-two patients were discharged without biliary surgery, including one in whom early operation had been limited to laparotomy and placement of lavage catheters. Discharge without biliary surgery was determined by physician choice in 13, failure to document cholelithiasis in five and patient choice in four.
Results Five episodes of acute pancreatitis (6%) were fatal. Two deaths were due to cardiovascular collapse and occurred on days 6 and 12 of treatment. One death was due to respiratory failure and pulmonary sepsis and occurred on day 16 of treatment. Two deaths were related to intra-abdominal sepsis and occurred on days 10 and 60 of treatment. Ten other attacks of acute pancreatitis (13%) required more than seven days of treatment in the intensive care unit (range 8-16 days, mean 12.7 days). Estimation of Severity of Pancreatitis The relationship between morbidity and previously reported prognostic signs is shown in Figure 1. One (1L8%) of 57 patients with fewer than three positive signs died of respiratory complications. Three (5.3%) received more than seven days of treatment in the intensive care unit. In two cases, intensive care was required for cardiovascular instability, and in one it was necessitated by gastrointestinal bleeding which occurred on the thirty-eighth day of hospitalization, following late biliary surgery. Of 23 patients with more than three positive signs, four (17.4%) died, two following intra-abdominal sepsis and two from early cardiovascular collapse. Seven other patients (30%) required more than seven days of treatment in the intensive care unit. In one patient, this was for intraabdominal sepsis, and in six it was because of cardiovascular instability or respiratory failure.
Ann.
Surg. * May
1979
Thirteen patients who had less than three positive early signs underwent laparotomy during the first seven days of treatment. In this group no gross pancreatic hemorrhage or necrosis was noted. Nine patients who had three or more positive prognostic signs underwent laparotomy in the first week of treatment. In this group, four patients (44%) with an average of five positive signs had frank pancreatic hemorrhage or necrosis. Five patients (56%) with an average of 3.6 positive prognostic signs had no pancreatic hemorrhage or necrosis. Two additional patients with five positive prognostic signs had hemorrhagic fluid on early diagnostic paracentesis but did not undergo early laparotomy. The relationship between morbidity and prognostic measurements in this group of patients with acute pancreatitis and cholelithiasis is shown in Table 2. Significant relationships are demonstrated between morbidity and admission measurements: blood glucose, white blood cell count, serum lactic dehydrogenase and serum glutamic oxaloacetic transaminase; and between morbidity and initial 48-hour measurements: hematocrit fall, blood urea nitrogen change and lowest serum calcium. There was a tendency for increased age, early metabolic acidosis and fluid sequestration to be associated with morbidity, but this was not statistically significant in this sample. No relationship was demonstrated between prognosis and initial serum amylase, bilirubin and alkaline phosphatase levels or initial 48-hour lowest arterial Po2 values.
Timing of Biliary Surgery, Severity of Pancreatitis and Morbidity Among 22 patients who underwent abdominal operation during the first week of treatment, five (23%) died and four (18%) required more than seven days of treatment in the intensive care unit. Fifty-eight episodes of pancreatitis were managed non-operatively during the first week of treatment, with no deaths, although six (10%) required more than seven days of intensive care. "Severe" Pancreatitis. Twenty-three episodes of acute pancreatitis were associated with three or more positive, early prognostic signs and may be arbitrarily designated as "severe." In this group, nine patients (mean positive signs, 5.4) underwent laparotomy during the first seven days of treatment. In three (mean positive signs, 3.7), surgery was limited to cholecystostomy with the additional placement of catheters for postoperative peritoneal lavage in one. There were no deaths in this group, although all three were treated in the intensive care unit for more than seven days (mean,
Vol. 189 * No. 5
657
BILIARY SURGERY TIMING TABLE 2. Mean Value (±+S.D.) of Prognostic Signs in Patients wvith Acute Pancreatitis and Cholelithiasis
Number Recorded Number of admissions At Admission Age (years) Blood glucose (mg %) White cell count x103/cu mm Serum lactic dehydrogenase (IU/liter) Serum glutamic oxaloacetic transaminase (S.F.U. %) Initial 48 Hours Hematocrit fall (percentage points) BUN change
80
80 74 80
73 77
74
77
(mg %) Lowest calcium (mg %) Lowest Pao2 (mm Hg) Base deficit (mEq/liter) Estimated fluid
78
75
Died
74
6
73 46
80 66
63
p Live vs Died
51
61
±28
162 ±56 12.5 + 5.2 248 ± 153 222 ± 264
255 ±193 19.5 ± 4.7 346 ± 137 552 ± 942
4.0 ± 4.5 -4.9 ± 6.5 8.8 ± 0.9 72
54
±24
