|
Ai-Jun
Zhu, Jing-Sen Shi, Xue-Jun Sun, Department of General surgery,
The First Hospital of Xi’an Jiaotong University, Xi’an 710061,
Shaanxi Province, China
Correspondence to: Dr. Ai-Jun Zhu, Department of General
surgery, The First Hospital of Xi’an Jiaotong University, No.1
Jiankang Lu, Xi’an 710061, Shaanxi Province, China.
zhaj_1023@163.com
Telephone: +86-29-5323527
Received: 2003-03-20
Accepted: 2003-04-11
Abstract
AIM: To investigate the relationship between severe acute
pancreatitis (SAP) and organ failure.
METHODS:
Clinical data of 74 cases of SAP from Jan. 1993 to Dec. 2002 were
retrospectively reviewed, and the relationship between organ failure
and age, gender, etiology, extent of necrosis, infection of necrosis
and mortality was analyzed.
RESULTS:
A total of 47 patients (63.5 %) showed organ failure, 20 patients
(27.0 %) multiple organ failure, whereas 27 patients (36.5 %) with
dysfunction of a single organ system. Pulmonary failure was the most
common organ dysfunction (23.0 %) among single organ failures. There
were no significant differences in age, gender and gallstone
pancreatitis among patients with or without organ failure (P>0.05).
The incidence of organ failure in infected necrosis was not higher
compared with sterile necrosis, and patients with increased amount
of necrosis did not have an increased prevalence of organ failure (P>0.05).
Patients with organ failure had a higher mortality rate compared
with those without organ failure (P<0.05). The death of
SAP was associated with multiple organ failure (P<0.005),
pulmonary failure (P<0.005), cardiovascular dysfunction (P<0.05)
and gastrointestinal dysfunction (P<0.05).
CONCLUSION:
Organ failure is common in patients with SAP, and patients with
multiple organ failure and pulmonary failure have a higher mortality
rate. Prevention and active treatment of organ failure can improve
the outcome of patients with SAP.
Zhu
AJ, Shi JS, Sun XJ. Organ failure associated with severe acute
pancreatitis. World J Gastroenterol
2003; 9(11): 2570-2573
http://www.wjgnet.com/1007-9327/9/2570.asp
INTRODUCTION
Severe acute pancreatitis (SAP), as a common acute abdomen, is
characterized by complicated causes, lots of morbidities,
difficulties in the treatment, and high mortality[1-8].
The natural course of SAP progresses in two phases. The first 14
days are characterized by systemic inflammatory response syndrome
resulted from the release of inflammatory mediators. In patients
with SAP, organ failure is common and often occurs in the absence of
infection. The second phase, beginning approximately 2 weeks after
the onset of the disease, is dominated by sepsis-related
complications resulted from infection of pancreatic necrosis. This
is associated with multiple systemic complications, such as
pulmonary, renal, and cardiovascular failure[9-18].
Despite considerable improvements in understanding of the
pathophysiologic mechanisms and management of these patients,
mortality of SAP remains between 15-50 %[19-22]. Organ
failure is a severe complication of SAP and death occurs usually
only in patients with SAP and is commonly associated with failure of
at least one organ system[23-25]. From Jan. 1993 to Dec.
2002, a total of 74 patients with a diagnosis of SAP were admitted
to Department of Hepatobiliary Surgery, the First Hospital of
Xi’an Jiaotong University, 12 patients died in hospital. The aim
of this study was to analyze the relationship between extent of
necrosis, pancreatic infection, hospital death due to organ failure.
MATERIALS
AND METHODS
Patients
From Jan. 1993 to Dec. 2002, a total of 74 patients with a
diagnosis of SAP were admitted to Department of Hepatobiliary
Surgery, the First Hospital of Xi’an Jiaotong University.
Pancreatic necrosis was defined by findings on CT scan or in
operation. There were 40 men and 34 women with a ratio of 1.18:1,
the average age of the patients was 49.3 years (range 14-94). The
presence of infected necrosis was determined by bacterial culture of
CT or ultrasonography-guided percutaneous aspiration and pancreatic
tissues debrided at surgery. Organ failure was defined according to
the Criteria of Clinical Diagnosis and Classification System for
Acute Pancreatitis (the second project, 1996, Pancreatic Surgery
Association of CMA)[26]. Causes of SAP were identified as
gallstone and non-gallstone. Initial management of these patients
included bowel rest, gastric secretions, intravenous fluid
resuscitation, suppression of pancreatic external secretion, and use
of prophylactic antibiotics. The indication for surgical treatment
was difined in the following instances, such as infection of
necrosis, pancreatic abscesses, cholangitis, obstructive jaundice
and pseudocyst formation for a long time.
Methods
The patients were divided into two groups according to
patients with or without organ failure within 2 weeks after
admission. The differences of age, gender, gallstone pancreatitis,
APACHE II scores, and mortality were analyzed. According to the
results of CT scan and findings in operation, the extent of
pancreatic necrosis was estimated to be (1) <33 %, (2) 33-50 %,
(3) >50 %. The relationship of organ failure to the extent of
pancreatic necrosis and infection of necrosis was analyzed. Finally,
the relationship between multiple organ failure and specific single
organ failure with infected necrosis and mortality was evaluated.
Statistics
Continuous data were evaluated by t test, and categorized
data were analyzed by Chi-square test. Significance was defined by P<0.05.
RESULTS
There were no significant differences in age, sex, gallstone
pancreatitis. Mortality and APACHE II scores were significantly
higher in patients with organ failure than in those without organ
failure (P<0.05 and P<0.001, respectively)
(Table 1).
Table
1 Characteristics of 74 patients with or without organ failure
|
Organ
failure(n=47) |
No
organ failure(n=27) |
Sig. |
| Age
(Y) |
4815 |
4915 |
NS |
| Gender
(M/F) |
26/21 |
14/13 |
NS |
| Etiology |
|
|
|
| Gallstones |
21 |
11 |
NS |
| Non-gallstones |
26 |
16 |
|
| APACHE
II scores |
297 |
233 |
<0.001 |
| Mortality
(%) |
12/47(25.5) |
0 |
<0.05 |
Among the 74 patients, 20 patients (27.0 %) showed multiple
organ failure (maximum 5 organ systems) and 9 of them died, 27
patients showed single organ failure. In patients suffering from
single organ failure, 17 patients (23.0 %) had pulmonary failure and
3 patients (17.6 %) died, 7 patients showed hepatic failure and 3
patients showed gastrointestinal failure, but none of these patients
died. No patient in this group was accompanied by cardiovascular
failure, renal failure, or neurologic failure (Table 2).
Table
2 Number of
patients with organ failure in 74 patients
| Organ
failure |
Morbidity(%) |
Mortality(%) |
| Multiple
organ failure |
20(27.0
%) |
9(45
%) |
| Specific
single organ failure |
|
|
| Pulmonary
failure |
17(23.0
%) |
3(17.6
%) |
| Renal
failure |
0 |
0 |
| Cardiovascular
failure |
0 |
0 |
| Hepatic
failure |
7(9.4
%) |
0 |
| Neurologic
failure |
0 |
0 |
| Gastrointestinal
failure |
3(4.1
%) |
0 |
As for the frequency of different specific single organ
failure, pulmonary failure occurred in 45.9 % (34/74), renal failure
in 16.2 % (12/74), cardiovascular failure in 17.6 % (13/74), hepatic
failure in 18.9 % (14/74), neurologic failure in 5.4 % (4/74) and
gastrointestinal failure in 10.8 % (8/74) (Table 3).
Table
3 Frequency of
organ failure in 74 patients
| Organ
failure |
No.
organ failure |
Frequency
(%) |
| Multiple
organ failure |
20 |
27.0 |
| Pulmonary
failure |
34 |
45.9 |
| Renal
failure |
12 |
16.2 |
| Cardiovascular
failure |
13 |
17.6 |
| Hepatic
failure |
14 |
18.9 |
| Neurologic
failure |
4 |
5.4 |
| Gastrointestinal
failure |
8 |
10.8 |
No relationship was found between organ failure to the extent
of necrosis and infected necrosis (Tables 4, 5). No difference was
found between patients with infected necrosis and those with sterile
necrosis in the development of multiple organ failure and specific
organ failure (Table 6). Nevertheless patients died in hospital had
a significantly higher incidence rate of multiple organ failure,
pulmonary failure, cardiovascular failure and gastrointestinal
failure compared with survivors (Table 7).
Table
4 Relationship
between infected versus sterile necrosis and organ failure in 74
patients
| |
Organ
failure (%) |
No.
organ failure (%) |
| Sterile
necrosis |
31(66.0) |
16(34.0) |
| Infected
necrosis |
16(59.3) |
11(40.7) |
Note:
x2=0.3320, P>0.05.
Table
5 Relationship
between amount of necrosis and organ failure in 74 patients
| Amount
of necrosis (%) |
Organ
failure(n=47) |
No.
organ failure(n=27) |
| <33
% |
21(55.3
%) |
17(44.7
%) |
| 33-50
% |
11(64.7
%) |
6(35.3
%) |
| >50
% |
15(78.9
%) |
4(21.1
%) |
Note:
x2=3.0784, P>0.05.
Table
6 Relationship
between infected versus sterile necrosis and single organ failure in
74 patients
| Organ
failure (%) |
Sterile
necrosis(n=47) |
Infected
necrosis(n=27) |
x2 |
Sig. |
| Multiple
organ failure |
13(27.7
%) |
7(25.9
%) |
0.0261 |
NS |
| Pulmonary
failure |
24(51.1
%) |
10(37.0
%) |
1.3585 |
NS |
| Renal
failure |
6(12.8
%) |
6(22.2
%) |
1.1287 |
NS |
| Cardiovascular
failure |
10(21.3
%) |
3(11.1
%) |
1.2237 |
NS |
| Hepatic
failure |
7(14.9
%) |
7(25.9
%) |
1.3607 |
NS |
| Neurologic
failure |
4(8.5
%) |
0 |
|
NSa |
| Gastrointestinal
failure |
4(8.5
%) |
4(14.8
%) |
0.7068 |
NS |
a:
Fisher’s exact probabilities test.
Table
7 Relationship
between hospital death and organ failure in 74 patients
| Organ
failure |
Survivor(n=62) |
Nonsurvivor(n=12) |
x2 |
P
value |
| Multiple
organ failure |
11(17.7
%) |
9(75
%) |
16.7130 |
<0.005 |
| Pulmonary
failure |
22(35.5
%) |
12(100
%) |
16.8501 |
<0.005 |
| Renal failure |
8(12.9
%) |
4(33.3 %) |
1.7680 |
NS |
| Cardiovascular
failure |
8(12.9
%) |
5(41.7
%) |
3.9295 |
<0.05 |
| Hepatic
failure |
11(17.7
%) |
3(25
%) |
0.0342 |
NS |
| Neurologic
failure |
0 |
4(33.3 %) |
|
NSa |
| Gastrointestinal
failure |
4(6.5
%) |
4(33.3
%) |
5.0050 |
<0.05 |
a:
Fisher’s exact probabilities test.
DISCUSSION
Most of SAP mortality is associated with organ failure. In the
early courses, organ failure is resulted from inflammatory mediator
released by systemic inflammatory response syndrome even if in the
absence of infection. In the septic phase, organ failure occurs
because of sepsis, so organ failure is common in SAP. Previous study
showed that in SAP, organ failure occurred in 72-90.3 %, single
organ failure in 24.7-37 %, multiple organ failure in 35-65.6 %.
Among the single organ failures, pulmonary failure was the most
commonly organ failure (39.1-63 %), followed by cardiovascular
failure (23-37.7 %), hepatic failure (20.7 %), renal failure (8.5-13
%)[27,28]. The present data showed that organ failure
occurred in 63.5 % (47/74), multiple organ failure in 27.0 %
(20/74), single organ failure in 36.5 % (27/74) (Table 2). No
relationship existed between organ failure and age, sex, gallstone
pancreatitis, but the severity (APACHE II scores) and mortality were
significantly higher in patients with organ failure than in those
without organ failure (Table 1). Pulmonary failure was the most
common single organ failure (23.0 %, 17/74) in SAP. The mortality
rate in patients with single pulmonary failure was 17.6 % (3/17),
followed by hepatic and gastrointestinal failure. No patient in this
group was accompanied by single renal failure, or cardiovascular
organ failure, or encephalic failure (Table 2). Among all the organ
failures, pulmonary failure was the most frequent organ failure
(45.9 %), the second was multiple organ failure (Table 3).
Conflicting
results about the relation between extent of necrosis, infected
necrosis and organ failure have been reported[28-31]. The
present study demonstrated that although the incidence of organ
failure in sterile necrosis was slightly higher than that in
infected necrosis (66.0 % vs 59.3 %), there was no difference in the
prevalence of organ failure in sterile necrosis compared with
infected necrosis (Table 4). The incidence of organ failure
increased with increased extent of necrosis, but patients with
increased amounts of necrosis did not have increased prevalence of
organ failure (Table 5).
As
to the relation between specific single organ failure and sterile
and infected necrosis, previous study showed that the incidence of
pulmonary failure was increased in infected necrosis compared with
sterile necrosis, and there was no difference in the prevalence of
renal failure, cardiovascular failure in infected necrosis compared
with sterile necrosis[31]. Our study showed that there
was no difference in the prevalence of specific single organ failure
in infected necrosis compared with sterile necrosis (Table 6).
The
mortality rate was 30 % in patients with multiple organ failure, and
was 8 % in those with single organ failure[31]. Our data
showed the mortality rate was 45 % (9/20) in patients with multiple
organ failure, and was 11 % (3/27) in those with single organ
failure (Table 2). Halonen et al[32] compared
multiple organ dysfunction (MOD) score, sequential organ failure
assessment (SOFA) score, and logistic organ dysfunction (LOD) score
in predicting hospital mortality rates of 178 SAP patients. The
results demonstrated that three different multiple organ dysfunction
scores showed good accuracy and were comparable with APACHE II in
predicting hospital mortality. In multiple logistic regression
analysis, only hepatic, renal, and cardiovascular failures were
independent risk factors for hospital mortality. Our study revealed
that non survivors had a significantly higher morbidity of multiple
organ failure, pulmonary failure, cardiovascular failure and
gastrointestinal failure compared with survivors, there was no
difference in the morbidity of renal failure, hepatic failure and
neurologic failure in nonsurvivors and survivors (Table 7). The
results demonstrated that the hospital mortality of SAP was
associated with multiple organ failure, pulmonary failure,
cardiovascular failure and gastrointestinal failure. Therefore,
prophylactic and active treatment of these organ failures are very
important in the treatment of SAP. Recently, hemoconcentration (hematocrit
≥44 % and/or failure of admission hematocrit to decrease at
approximately 24 hours)[33,34], plasma concentrations of
sTNF-Rs[35], activated polymorphonuclear leucocytes-elastase
(PMN-E) and IL-6[36] have been reported as early markers
for organ failure and necrotic pancreatitis. Patients coincident
with this standard should be treated with strong fluid resuscitation
and closely monitored in intensive care units, and new approaches
have to be found to counteract these severe complications.
REFERENCES
1
Wu XN. Management of severe acute pancreatitis. World J
Gastroenterol 1998; 4: 90-91
2
Qin RY, Zou SQ, Wu ZD, Qiu FZ. Experimental research on
production and uptake sites of TNFa
in rats with acute
hemorrhagic necrotic pancreatitis.
World J Gastroenterol 1998; 4: 144-146
3
Zhao LG, Wu XX, Han EK, Chen YL, Chen C, Xu DQ. Protective
effect of YHI and HHI-I against experimental acute
pancreatitis in rabbits. World J
Gastroenterol 1998; 4: 256-259
4
Robert JH, Frossard JL, Mermillod B, Soravia C, Mensi N, Roth
M, Rohner A, Hadengue A, Morel P. Early prediction
of acute pancreatitis: prospective
study comparing computed tomography scans, Ranson, Glascow, Acute
Physiology
and Chronic Health Evaluation II
scores, and various serum markers. World J Surg 2002; 26: 612-619
5
Wu XN. Treatment revisited and factors affecting prognosis of
severe acute pancreatitis. World J Gastroenterol
2000; 6: 633-635
6
Chen DL, Wang WZ, Wang JY. Epidermal growth factor prevents
gut atrophy and maintains intestinal integrity in rats
with acute pancreatitis. World J
Gastroenterol 2000; 6: 762-765
7
Mao EQ, Tang YQ, Zhang SD. Effects of time interval for
hemofiltration on the prognosis of severe acute pancreatitis.
World J Gastroenterol 2003; 9:
373-376
8
Zhou ZG, Chen YD, Sun W, Chen Z. Pancreatic microcirculatory
impairment in experimental acute pancreatitis in
rats. World J Gastroenterol 2002; 8:
933-936
9
Norman J. The role of cytokines in the pathogenesis of acute
pancreatitis. Am J Surg 1998; 175: 76-83
10
Yi Y, Gao NR, Li ZL. Protective effects of ulinostatin on
acute lung injury induced by acute necrotizing pancreatitis in
rats. Shijie Huaren Xiaohua Zazhi
2002; 10: 558-561
11 Knoefel WT, Kollias N,
Warshaw AL, Waldner H, Nishioka NS, Rattner DW. Pancreatic
microcirculatory changes
in experimental pancreatitis of
graded severity in the rat. Surgery 1994; 116: 904-913
12
He L, Chen SF, Cao XH, Zhang LD, Pan LL, Zhou Z. Changes of
serum level of IL-15, IL-18 and sTNF-1R in patients
with acute pancreatitis. Shijie
Huaren Xiaohua Zazhi 2003; 11: 57-60
13 Schmid SW, Uhl W,
Friess H, Malfertheiner P, Buchler MW. The role of infection in
acute pancreatitis.
Gut 1999; 45: 311-316
14 Berger HG, Rau B,
Mayer J, Pralle U. Natural course of acute pancreatitis. World J
Surg 1997; 21: 130-135
15
Wu XZ. Therapy of acute severe pancreatitis awaits further
improvement. World J Gastroenterol 1998; 4: 285-286
16
Wu XN. Current concept of pathogenesis of severe acute
pancreatitis. World J Gastroenterol 2000; 6: 32-36
17
Slavin J, Ghaneh P, Sutton R, Hartley M, Rowlands P, Garvey
C, Hughes M, Neoptolemos J. Management of
necrotizing pancreatitis. World J
Gastroenterol 2001; 7: 476-481
18 Isenmann R, Rau B,
Berger HG. Early severe acute pancreatitis: characteristics of a new
subgroup. Pancreas
2001; 22: 274-278
19 Abu-Zidan FM, Bonham
MJ, Windsor JA. Severity of acute pancreatitis:a multivariate
analysis of oxidative stress
markers and modified Glasgow
criteria. Br J Surg 2000; 87: 10191023
20
Luo Y, Yuan CX, Peng YL, Wei PL, Zhang ZD, Jiang JM, Dai L,
Hu YK. Can ultrasound predict the severity of
acute
pancreatitis early by observing acute
fluid collection? World J Gastroenterol 2001; 7: 293-295
21
Pezzilli R, Mancini F. Assessment of severity of acute
pancreatitis: a comparison between old and most recent
modalities used to evaluate this
perennial problem. World J Gastroenterol 1999; 5: 283-285
22
Shi X, Gao NR, Guo QM, Yang YJ, Huo MD, Hu HL, Friess H.
Relationship between overexpression of NK-1R, NK-2R
and intestinal mucosal damage in
acute necrotizing pancreatitis. World J Gastroenterol 2003; 9:
160-164
23 Baron TH, Morgan DE.
Acute necrotizing pancreatitis. N Engl J Med 1999; 340: 1412-1417
24
Yuan YZ, Gong ZH, Lou KX, Tu SP, Zhai ZK, Xu JY. Involvement
of apoptosis of alveolar epithelial cells in acute
pancreatitis-associated lung injury.
World J Gastroenterol 2000; 6: 920-924
25 Blum T, Maisonneuve P,
Lowenfels AB, Lankisch PG. Fatal outcome in acute pancreatitis: its
occurrence and early
prediction. Pancreatology 2001; 1:
237-241
26 Pancreatic Surgery
Association of CMA. The Criteria of Clinical Diagnosis and
Classification System for Acute
Pancreatitis (the second project,
1996,). Zhonghua Waike Zazhi 1997; 35: 773-775
27 Buchler MW, Gloor B,
Muller CA, Friess H, Seiler CA, Uhl W. Acute necrotizing
pancreatitis: Treatment strategy
according to the status of infection.
Ann Surg 2000; 232: 619-626
28 Gotzinger P, Sautner
T, Kriwanek S, Beckerhinn P, Barlan M, Armbruster C, Wamser P,
Fugger R. Surgical treatment
for severe acute pancreatitis: extent
and surgical control of necrosis determine outcome. World J Surg
2002; 26: 474-478
29 Lankisch PG,
Pflichthofer D, Lehnick D. No strict correlation between necrosis
and organ failure in acute pancreatitis.
Pancreas 2000; 20: 319-322
30 Tenner S, Sica G,
Hughes M, Noordhoek E, Feng S, Zinner M, Banks PA. Relationship of
necrosis to organ failure in
severe acute pancreatitis.
Gastroenterology 1997; 133: 899-903
31 Isenmann R, Rau B,
Beger HG. Bacterial infection and extent of necrosis are
determinants of organ failure in patients
with acute necrotizing pancreatitis.
Br J Surg 1999; 86: 1020-1024
32 Halonen KI, Pettila V,
Leppaniemi AK, Kemppainen EA, Puolakkainen PA, Haapiainen RK.
Multiple organ dysfunction
associated with severe acute
pancreatitis. Crit Care Med 2002; 30: 1274-1279
33 Brown A, Orav J, Banks
PA. Hemoconcentration is an early marker for organ failure and
necrotizing pancreatitis.
Pancreas 2000; 20: 367-372
34 Jiang CQ, Ai ZL, Liu
ZS, He YM, Sun Q, Xu R, Fan LF. Hemoconcentration as an early risk
factor for severe acute
pancreatitis. Zhongguo Shiyong Waike
Zazhi 2001; 21: 666-667
35 Hirota M, Nozawa F,
Okabe A, Shibata M, Beppu T, Shimada S, Egami H, Yamaguchi Y, Ikei
S, Okajima T, Okamoto
K, Ogawa M. Relationship between
plasma cytokine concentration and multiple organ failure in patients
with acute
pancreatitis. Pancreas 2000; 21:
141-146
36 Ikei S, Ogawa M,
Yamaguchi Y. Blood concentrations of polymorphonuclear leucocyte
elastase and interleukin-6 are
indicators for the occurrence of
multiple organ failures at the early stage of acute pancreatitis. J
Gastroenterol
Hepatol 1998; 13: 1274-1283
Edited
by Zhao
M and Wang XL
| |