- Email: [email protected]
Classification and treatment of local septic complications in acute pancreatitis
Classification and Treatment of Local Septic Complications in Acute Pancreatitis Thomas J. Howard, MD, Eric A. Wiebke, MD, Geraldine Mogavero, MD, Kenyon Kopecky, MD, Joseph C. Baer, BS, Stuart Sherman, MD, Robert H. Hawes, MD, Glen A. Lehman, MD, Robert J. Goulet, MD, James A. Madura, MD, /ndianapo/is,lndiana
BACKGROUND: An international symposium on acute pancreatitis recently developed a clinical classification system tor severe acute pancreatitis that classifies all local septic complications into three groups: infected necrosis (IN), sterile necrosis (SN), and pancreatic abscess (PA). Despite the appeal of having three distinct, well-defined labels for this complex process, the clinical utility of this schema has yet to be determined. The purpose of this study was to investigate the prognostic and therapeutic utility of applying this clinical classification system to a iarge group of surgical patients with local septic complication from acute pancreatitis. PATIENTSAND METHODS: We reviewed the cases of 62 patients with complicated pancreatitis, classifying them into IN (n = 20), SN (n = 14), or PA (n = 28) groups. Ranson’s score, APACHE II score, and computed tomography grading were calculated within the first 48 hours of admission. Information on patient demographics, etiology of pancreatitis, operative procedures, timing of intervention, bacteriology, blood loss, intensive care unit days, ventilator days, and morbidity and mortality were also accrued and analyzed. RESULTS: Despite similar demographics and etiology of pancreatitis, patients with necrosis, both IN and SN, were more critically ill than were patients with PA (APACHE II score >15, 21% versus 0%, respectively), required earlier operative intervention (mean 14 days versus 29 days, P = 0.02), required necrosectomy with drainage (65% versus 4%, P
From the Departments of Surgety (TJH, EAW, JCB, RJG, JAM), Radiology (GM, KK), and Gastroenterology (SS, RHH, GAL), Indiana University School of Medicine, Indianapolis, Indiana. Requests for reprints should be addressed to Thomas J. Howard, MD, Emerson Hall #523, 545 Bamhill Drive, Indianapolis, Indiana 46202. Manuscript submitted June 6, 1994 and accepted in revised form October 20, 1994.
44
THE AMERICAN
JOURNAL
OF SURGERY@’ VOLUME
170
than either patients with SN or PA (P ~0.05). CONCLUSIONS: We conclude that this classification system allows ior the stratification of patients into three distinct groups-infected necrosis, sterile necrosk, and pancreatic abscess- and has both therapeutic and prognostic usefulness. Am J Surg, 1995;170:44-50.
S
evere acute pancreatitis generally declares itself shortly after onset with the production of systemic toxicity manifest by signs of organ failure.’ Aggressive fluid resuscitation, respiratory support, hemodynamic monitoring, and total parenteral nutrition (TPN) have dramatically reduced early mortality rates only to tender patients subject to delayed septic complications, which have emerged as the major cause of death. 2,3Accurate diagnosis and prompt treatment of these septic complications represents the cornerstone of surgical management.4 Recently, an intemational symposium on acute pancreatitis developed a clinically based classification system that defines all local septic complications from severe acute pancreatitis into three groups: infected necrosis (IN), sterile necrosis (SN), and pancreatic abscess ( PA).5 Despite the intuitive appeal of having three distinct, well-defined labels for this complex disease process, the utility of such a classification scheme has yet to be determined. The purpose of this study was to review a consecutive series of surgical patients with local septic complications from severe acute pancreatitis and classify them as IN, SN, or PA. To determine the usefulness of this schema, we evaluated all three groups with regards to severity of illness, surgical management, and morbidity and mortality rates. In addition, we investigated whether prognostic criteria (Ranson’s, APACHE II, or computed tomography [CT] grading) obtained within 48 hours of admission could discriminate between these three groups of patients. PATIENTS AND METHODS From 1977 to 1992, 1,179 patients were admitted to the Indiana University Hospital with the diagnosis of acute pancreatitis (n = 789) or an acute exacerbation of chronic pancreatitis (n = 390). Of these, 269 (23%) had operative procedures for local complications that occurred as a direct result of their current episode of pancreatitis. One hundred eighty-two patients (68%) had surgical drainage of noninfected pancreatic pseudocysts, the most frequent complication identified. Ten patients (4%) had successful percutaneous drainage of infected pancreatic collections. Eight patients (3%) developed infected pancreatic collections as JULY 1995
1 SEPTIC COMPLlCATlONS L
IN ACUTE PANCREATlTlSlHOWARD
ET AL
a result of prior attempts
at percutaneous or TABLE I endoscopic drainage of an initially sterile Comparison of Pancreatitis Patient Groups Classified as Infected collection. Seven patients (3%) had insuffiNecrosis (IN), Sterile Necrosis (SN), or Pancreatic Abscess (PA) cient data t’or analysis. That left 62 patients PA (%) IN (%) SN (%) (23%) who qualified for study. 20 14 28 No. of patients Patients were carefully classified by the 445 15 37* 12 Mean age (y) 45* 13 principal author according to the most re75125 50150 68132 Sex (% M/F) cent clinical consensus on pancreatitis as Comorbid disease having either IN, SN, or PA.’ Pancreatic 2 (10) 2 (14) 4 (14) Cardiovascular 0 1 (7) 0 Renal necrosis was defined as operatively docu1 (5) 1 (7) 1 (4) Diabetes mented pancreatic or peripancreatic tissue 0 2 (14) 3 (11) Pulmonaty necrosis. IN was distinguished from SN on Etiology the basis of cultures obtained intraopera7 (35) 3 (21) 6 (21) Alcohol tively. PA was defined as a localized collec3 (15) 3 (21) 5 (18) Gallstones tion of frank suppuration or turbid fluid that 2 (10) 2 (14) 2 (7) Steroids grew out pathogenic organisms on intraop1 (5) 1 (7) 2 (7) Hyperlipidemia erative culture, located in close proximity to 0 0 4 (14) Trauma the pancreas, containing little or no pancre3 (15) 2 (14) 2 (7) Postoperative 1 (5) 0 2 (7) Post-ERCP atic necrosis. All 62 patients who qualified 4 (20) 2 (14) 5 (18) Indeterminate for study were able to be classified into one of these three groups. ERCP = enodscopic retrograde cholang/opancreatography Multiple clinical, laboratory, and radiographic data were analyzed from both the medical records and radiology files. Patients TABLE II were classified by three separate prognostic Clinical Factors Related to Disease Severity pancreatitis: systems for acute staging SN PA Ranson’s,” APACHE II score,’ and CT grad(n = 14) (n r*O) (n = 28) ing.s Due to our status as a tertiary referral 5Ok IO 47 + 9 Hospital stay (d) 74 + 13’ center, many of our patients were treated ini25 + 8 11 +5’ ICU stay (d) 28 + 4 tially at an outside hospital during the first 10 f 4 6*3 Ventilator use (d) 22 * 8’ 48 hours of their illness. For these patients, 16 * 5 11 *3 Blood loss (units) 33 + 10’ 22 + 5 20 f 5 records from the outside hospitals were obTPN (d) 42 + 8’ tained and used to calculate Ranson’s and ‘P ~0 05. Student’s unpaired t-test mth Bonferronik correction APACHE II scores within the first 48 hours IN = infected necrosis: SN = sterile necrosis: PA = pancreatic abscess, ICU = mtenswe care of their hospitalization. When the initial abm/t: TPN = totai parental nutntion dominal CT scan was not available for re- Iview, the earliest CT scan to the initial onset of pancreatitis prior to operative intervention was used terval variables, and the one-tailed Fisher’s exact test was to determine the CT grade. In some instances, we were unused for analysis of proportions. Spearman’s rank-order corable to obtain an appropriate CT scan; these patients were relation was used to evaluate the relationship between excluded from CT grading, but were included in the reRanson’s and APACHE II scoring systems. maining analysis. Scans were graded by two of our radiology staff (GM, KK) who were blinded to the group to which RESULTS the patients were assigned. Of 62 patients available for analysis, 20 (32%) had IN, 14 Indications for operation in all patients were one of the (23%) had SN, and 28 (45%) had PA. The average age for following: clinical deterioration (n = 53), failure to improve patients in the entire series was 46 years (range 18 to 78); despite intensive medical management (n = 6), or a posithere were 39 men (63%) and 23 women (37%). There were tive gram stain or culture of a peripancreatic fluid collecno differences in age, sex, comorbid illnesses, or the etiology tion (n = 3). Mortality data are expressed as in-hospital morof pancreatitis between these three groups (Table I). The etitality and not as 300day postoperative mortality. All patients ologies for pancreatitis in this series are comparable to those have been observed to date by a review of their outpatient found in most large surgical series in the United States.“,“,‘* charts and records. The surgical procedures performed could The severity of illness in both groups was evaluated by their be classified into four general types: debridement and open average hospital days, intensive care unit (ICU) days, and packing (n = 4); debridement over drains (n = 24); pannumber of days the patient required mechanical ventilation. creatic resection over drains (n = 9); and simple drainage Patients with IN stayed, on average, 15 more hospital days (n = 25). and required mechanical ventilation for 13 more days than Statistical analysis was performed using Primer of patients with either SN or PA (Table II). Patients with IN Biostatistics software (McGraw-Hill, New York, New and SN had a similar number of ICU days, 28 and 25, reYork). Comparison between groups was made using spectively, both of which were significantly longer than ICU Student’s paired r-tesr with Bonferroni’s correction for indays for patients with PA (P ~0.05). Patients with IN reTHE AMERICAN
JOURNAL
OF SURGERY”
VOLUME
170
JULY 1995
45
1
iEPTlC COMPLICATIONS
IN ACUTE PANCREATlTlSlHOWARD
ET AL I
use of endoscopic retrograde cholangiopancreatography and sphincterotomy for this condition. In contrast to patients with IN and SN, those with PA were managed nonoperatively for a longer period of time, IN SN PA with half of the patients requiring surgical (n = 20) (n = 14) (n = 28) lime to intervention (d) 17 * 3 10 & 4’ 29 f 6 intervention after the 29th day from the Number of operations 2.6 f 0.3 1.9 * 0.4 1.1 f 0.5’ onset of their symptoms. Range l-7 l-6 l-3 The operative management of patients Surgical management with necrosis, both IN and SN, was ag DBbridement\open packing 3 (15%) 1 (7%) 0 gressive extirpation and debridement of inDBbridement\drains 13 (65%) 10 (71%) 1 (4%)+ fected and necrotic tissue (Table III). Pancreatic resection\drains 4 (20%) 2 (14%) 3 (11%) Thirty-three of 34 patients with IN and SN Simple drainage 0 1 (7%) 24 (86%)’ (97%) required debridement or resectional ‘P 4.05, Student’s unpaired t-test with Bonferroni’s correction therapy, whereas only 1 patient underwent tP ~0.001, Fisher’s exact test, one-failed. simple drainage of an infected intra-abdominal fluid collection. Patients with IN TABLE IV averaged 2.6 operations per patient (range Findings in 45 Patients With Bacteria or Fungus on lntraoperatlve Culture 1 to 7), whereas those with SN averaged of Peripancreatlc Fluid Collection or Necrotic Tissue Debris 1.9 (range 1 to 6). Four patients with necroOverall sis (3 IN, 1 SN) were managed by debride(n = :“o) (%) (n = E) (%) (n = 45) (%) ment and open packing, and 3 of these paSingle isolate 8 (40) 14 (56) 22 (49) tients (75%) subsequently died of sepsis and Multiple isolates 12 (60) 11 (44) 23 (51) multiple system organ failure. Patients with Bacterial isolates 39 36 73 PA required only 1 operation on average Pseudomonas 4 8 12 (16) (range 1 to 3) to gain adequate control of Enterobacter 7 4 11 (15) their intra-abdominal sepsis, and 24 of 28 Enterococcus 6 2 6 (11) patients (86%) were managed by simple exStaphylococcus 3 5 6 (11) ternal drainage of an infected fluid ollecKlebsiella 2 5 7 (10) tion. The only patient in this group reEscherichia co/i 3 4 7 (10) quiring dkbridement had a multiloculated Candida 4 2 6 (6) abscess extending through the transverse Proteus 4 0 4 (5) Citrobacter 2 1 3 (4) mesocolon with extensive mesenteric fat Streptococcus 0 3 3 (4) necrosis. Of the 3 patients with PA who reAnaerobes’ 4 2 6 (6) quired pancreatic resection, 2 had strictures of the main pancreatic duct and 1 had an ‘Anaerobes include Bacteroides, Peptostreptococcus, and Clostridia. IN = infected pancreatic necrosis; PA = pancreatic abscess. infected pseudocyst (Pseudo-) which could not be drained intemallv. Intraoperative cultures taken from all patient; were posiquired two to three times more blood transfusions per patient tive in 45 (75%). Bacteria or fungus was cultured from 20 than did patients with either SN or PA. All three patient patients with IN and from 25 patients with PA (Table IV). populations had prolonged gastrointestinal tract dysfunction Single isolates were recovered from 8 patients (40%) with and ileus; however, patients with IN required TPN signifiIN and 16 patients (57%) with PA, while multiple isolates cantly longer than did patients with either SN or PA (P were cultured in the remaining 12 patients (60%) with IN cO.05). and 12 (43%) with PA. Although many different types of Patients with IN (n = 20) became septic early, as manibacteria were found, the majority of isolates were coliforms, fest by spiking fevers, hypotension, and organ dysfunction with Pseudomonas, Enterobacter, and Enterococcus species that necessitated exploration, dkbridement, and drainage in being the most prevalent. Candida was found in 8% of isohalf the patients within 17 days of the onset of their symplates, and the incidence of anaerobic isolates in our series toms (Table III). Patients with SN (n = 14) were operated was extremely low (4%) despite the routine use of anaeroon even earlier in our series, with half being operated on bic specimen transport and culture techniques. This low inwithin 10 days from the onset of their symptoms. In this cidence of anaerobic bacteria in secondary pancreatic ingroup of patients, however, 6 (43%) underwent exploratory fections has been noted before.” laparotomy less than 10 days from the onset of their sympThe mortality rate in our series was 50% for patients with toms for several different indications: 2 patients were exSN, 25% for patients with IN, and 4% for patients with PA plored within 24 hours of presentation on the basis of an (P = 0.004; Table V). In the necrosis groups (IN and SN), acute abdomen and shock; 2 patients, immunosuppressed on 10 of 12 patients (83%) died of sepsis and multiple system steroids, were explored because of clinical deterioration organ failure directly attributable to their pancreatic insult. when the diagnosis of pancreatitis remained in doubt; and Of the 12 patients who died, 5 had IN and 7 had SN. Three 2 patients had impacted gallstones at the ampulla of Vater of 5 patients in the IN group and 5 of 7 patients in the SN with signs and symptoms of cholangitis prior to the routine TABLE
Ill
Surgical Timing, Number of Interventions, and Surgical Management of Patients With Infected Pancreatic Necrosis (IN), Sterile Pancreatic Necrosis (SN), or Pancreatic Abscess (PA)
46
THE AMERICAN
JOURNAL
OF SURGERY@
VOLUME
170
JULY 1995
1 SEPTIC COMPLICATIONS
IN ACUTE PANCREATITIS/HOWARD
ET AL
group had postmortem examination, and TABLE V all had peripancreatic fluid collection or Morbidity and Mortality Data necrosis that grew bacteria on culture. The PA IN SN lone death in the PA group was directly (n = 20) (n = 14) (n = 28) PValue’ attributable to the pancreatic insult and 5 (25%) 7 (50%) 1 (4%) 0.004 Death 11 (55%) 8 (57%) 17 (61%) 0.922 Morbidity was a patient who underwent simple 3 (15%) 2 (14%) 3 (11%) 0.895 Pancreatic fistula drainage of a PA followed by a long and 4 (14%) 0.769 Colonic fistula 2 (10%) 1 (7%) complex 72,day course in the surgical 3 (15%) 1 (7%) 2 (7%) 0.620 Small-bowel fistula ICU, resulting in systemic candidiasis and 0 0.175 Biliary fistula 0 1 (7%) multiple system organ failure. 2 (7%) 0.472 Hemorrhage 0 1 (7%) Morbidity was frequent but not signifi2 (10%) 2 (14%) 1 (4%) 0.451 Upper GI bleed cantly different between groups, occurring 0.540 Pulmonary embolism 0 0 1 (4%) in 11 patients (55%) with IN, 8 patients 1 (4%) 0.712 Bowel obstruction 1 (5%) 0 (57%) with SN, and 17 patients (61%) .FisherB exact test, one-tailed, was used to compare IN versus SN versus PA with PA. Pancreatic fistulas were common, IN = Infected necrosis; SN = stenle necrosis: PA = pancreatic abscess, Gi = gastro/ntest/nal occurring in 15% of IN, 14% of SN, and 11% of PA patients. Of the 8 patients in available for analysis, 87% of patients with IN and 88% of our series with pancreatic fistulas, 2 died of sepsis and mulpatients with SN had Balthazar grade E scans,” whereas only tiple system organ failure 2 and 4 weeks after their develop54% of patients with PA had scans graded with this score. ment. Both deaths were attributable to poor fistula control and persistent intra-abdominal sepsis. All 6 remaining panSimilarly, of the 7 patients with low-scoring scans (Balthazar A-C), 83% (5 of 6) were patients with PA, whereas only 1 creatic fistulas were adequately controlled, and 5 of these patient with SN had a scan given this grade. closed spontaneously after 3 to 9 weeks (mean 5). The remaining pancreatic fistula stayed open for 7 weeks, at which time endoscopic retrograde cholangiopancreatography reCOMMENTS Local septic complications in severe acute pancreatitis now vealed a complete pancreatic duct cut off in the neck of the gland without distal duct continuity. This patient underwent account for the vast majority of deaths associated with this operative closure of the fistula by distal pancreatectomy and disease process. ‘s Despite a wide variation in each patient’s clinical course and pancreatic morphology, prior to the insplenectomy. A total of 14 enterocutaneous fistulas occurred in 13 patroduction of the current international symposium’s classifitients in this series, and there was no difference between cation scheme, all septic complications in acute pancreatitis groups with regard to fistula incidence or location. There were grouped under the term “pancreatic abscess.“i4 Many were 7 colonic fistulas (2 IN, 1 SN, 4 PA), 6 small-bowel clinicians, realizing the unsatisfactory nature of a single title fistulas (3 IN, 1 SN, 2 PA), and 1 biliary fistula (1 SN). One for such a protean disease, coined more elaborate and depatient with IN had both a colonic and duodenal fistula, scriptive terms such as “phlegmon” and “hemorrhagic panwhich were repaired with a right hemicolectomy, ileotranscreatitis,” hoping to better elucidate and define subsets within verse colostomy, and primary repair of the duodenum with this complex pathophysiologic process.4J5 Unfortunately, a small-bowel serosal buttress 2 months after the initial rather than clarify, the use of these descriptive terms+-often episode c)f pancreatitis. Of the other 6 colonic fistulas, 3 used without adequate definition-left the literature replete closed spontaneously (at 2 ,4, and 6 weeks), whereas 3 rewith a vague lexicon leading to confusion and an inability to quired operative repair. Three of 6 small-bowel fistulas closed accurately classify patients in a useful manner. spontaneously (at 4, 7, and 12 weeks), and I patient with a Several recent observations have dramatically increased our duodenal fistula died of sepsis 4 weeks after the development understanding of this complex disease process. Based on both of pancreatitis. The remaining 2 patients with small-bowel clinical and experimental evidence, it is now well accepted fistulas required operative closure: 1 underwent vagotomy, that both the presence and extent of pancreatic necrosis dicantrectomy, and Billroth II gastrojejunostomy; and the other tate the clinical course of patients with severe acute pancrehad a small-bowel resection. The lone biliary fistula closed atitis.‘6J7 Furthermore, in patients with necrosis, the presence spontaneously at 8 weeks. of bacterial infection within the necrosis is an ominous event, Our prognostic staging data show that patients with necroaccounting for more than 80% of all deaths from acute sis (IN and SN) had higher Ranson’s, APACHE II, and CT pancreatitis. ‘3,‘6~17 These observations make the international grading scores when compared with the PA group (Table symposium’s classification system-which differentiates IN, VI). Thirty percent of patients with IN and 14% of patients SN, and PA-an attractive system, in that it should allow with SN had Ranson’s scores ~7, and 21% of both groups for an accurate stratification of patients with regard to their (IN and SN) had APACHE II scores >16. In contrast, paclinical course. tients with PA had extremely low scores, with 93% having To investigate the ability of this new classification system a Ranson’s score ~3 and an APACHE II score ~10. to stratify patients, we retrospectively classified 62 patients Furthermore, no patient in the PA group had a Ranson’s with complicated pancreatitis according to the symposium’s score >6 or an APACHE II score 214. There was a reasoncriteria into 20 patients with IN, 14 patients with SN, and able correlation (r = .68) between the Ranson’s and 28 patients with PA. Our data show that the most fulminate APACHE II sccjres in this series. Of the abdominal CT scans clinical course in severe acute pancreatitis occurs in patients THE AMERICAN
JOURNAL
OF SURGERYa
VOLUME
170
JULY 1995
47
)
;EPTIC COMPLICATIONS
IN ACUTE PANCREATlTlSlHOWARD
ET AL
-
necrosis. 16~18-20 In these instances, patients with necrosis are followed up closely with Evaluation of Ranson’s, APACHE II, and Balthazar Computed Tomography repeated investigations of their pancreatic (CT) Grading, Applied Within 48 Hours of Onset of Pancreatitis and peripancreatic fluid collections using CT-guided aspiration and culture.2* As Staging System (n = s4”) (%) (n = P, (%) (n = g) (%) long as the CT-guided aspirations reveal no Ranson’s criteria infection, patients are managed nonopera43 26 (93) 7 (35) 6 (43) tively. Indications for operation in these 4-6 7 (35) 6 (43) 2 (7) patients are either a positive culture on CT >7 0 2 (14) 6 (30) APACHE II score directed aspiration, or persistent symptoms <5 16 (57) 3 (15) 3 (21) of abdominal pain, systemic illness, pul5-10 10 (36) 6 (43) 8 (40) monary dysfunction, or the inability to eat 11-15 5 (25) 2 (14) 2 (7) after a period (usually 4 to 6 weeks) of med‘16-20 0 2 (141 4 (20) ical management (symptomatic necrosis). >21 0 0 1 (7) Our patients with SN occupied a middle CT grading’ a+ 15+ 13+ ground clinically between patients with A 0 0 1 (8) IN and those with PA. In a number of facB 0 0 2 (15) C 0 tors, including hospital days, ventilator 1 (13) 2 (15) D 0 2 (13) 1 (8) days, blood loss, and TPN days, patients E 13 (87) 7 (88) 7 (54) with SN closely resembled patients in the PA group. In terms of surgical manage‘Grade A = normal; grade B = focal or diffuse enlargement; grade C = intrinsic pancreatic abment-time to intervention, number of normalities; grade D = sing/e, ill-defined collection; grade E = t2 poorly defined collections. +On/y 15 IN patients (75%), 8 SN patients (57%), and 13 PA patients (46%). had computed operations, and type of operative managetomography scans available for analysis. ment (debridement versus drainage)-paIN = infected necrosis; SN = sterile necrosis; PA = pancreatic abscess; tients with SN more closely resembled patients in the IN group. The overall mortality rate for the entire series was 21%, with IN. These patients required operation within 17 days which is comparable to the 14% to 25% mortality rates for from the onset of their symptoms, averaged 74 days in hoscombined series reported in the literature.9J2~23 The morpital, 28 days in the ICU, 22 days on the ventilator, and tality rate in our subset of patients with SN (50%) is much were transfused 33 units of blood during their hospital stay. higher than the 8% to 17% mortality rates reported in most Not surprisingly, these data are nearly identical to those rerecent surgical series. 9~1o,24 Several reasons can be identified ported by Stanten and Frey9 in their series of 50 patients for the high mortality rate we observed in this group of pawith pancreatic necrosis. Patients with PA remained clinitients. First and foremost is the high disease severity found cally stable for a much longer period of time: they required in our group of patients with SN. Karimgani et alz5 identioperation within 28 days from the onset of their symptoms, fied several factors, including a high Ranson’s score, a high averaging 47 days in hospital, 11 days in the ICU, and 6 APACHE II score, shock, renal insufficiency, multiple sysdays on the ventilator, and were transfused only 6 units of temic complications, and a high body mass index, that were blood. This less precipitant disease course in patients with related to a fatal outcome in patients with SN. When one PA allowed for the localization, containment, and definianalyzes data from their patient group who died, the avertion of the inflammatory process to a discrete area of their age Ranson’s score (6.3 f 0.5), APACHE II score (16.5 f abdomen. This observation is supported by the fact that 26 3.0), and incidence of shock (90%) are not dissimilar from of 28 patients (93%) required only one operation to adethe average Ranson’s score (5.9 + 1.2), APACHE II score quately evacuate and drain their septic focus, and no pa(15.6 + 7), and incidence of shock (100%) found in our tient was managed by the open abdominal packing techpatients with SN who died. Furthermore, their overall 38% nique. In contrast, the diffuse, poorly localized nature of the mortality rate in a series of critically ill patients with SN is disease process in patients classified with necrosis is reflected similar to our 50% mortality rate in a comparable group. by the fact that they averaged 2.6 operations (range 1 to 7) An additional factor that may relate to our high mortalin IN, and 1.9 operations (range 1 to 6) in SN to adequately ity rate in patients with SN is the early timing of surgical control their intra-abdominal process. Furthermore, 5 paintervention that occurred in this group of patients. The tients in these two groups (3 IN, 2 SN) required open abrisk of early operation in patients with SN is converting the dominal packing. residual SN remaining after the initial necrosectomy into The distinction between IN and SN is important and relIN by secondary bacterial infection. If the necrotic tissue reevant. Although all patients with necrosis will have fever, mains sterile, overall mortality rates are generally quoted in leukocytosis, abdominal tenderness, renal insufficiency, or the range of 0% to 1 1%.17*22,25 If the necrotic tissue becomes pulmonary dysfunction, surgical debridement is necessary secondarily infected (IN), overall mortality rates jump to only in patients with IN. More and more patients with SN 14% to 50%.9J7J2 Had the diagnosis of SN been firm in are being successfully managed by aggressive medical treatthose patients who underwent early exploration (6 of 14 ment without the need for surgical intervention.‘(j In fact, [43%] explored less than 10 days from their onset of symp many pancreatic surgeons now base their clinical decision toms) , most would have been treated by a trial of aggressive for operation on the bacteriologic status of the pancreatic TABLE
48
VI
THE AMERICAN
JOURNAL
OF SURGERY-
VOLUME
170
JULY 1995
SEPTIC COMPLICATIONS
IN ACUTE PANCREATlTlSlHOWARD
ET AL 4
medical management, which may have reduced our 50% mortality rate. It is interesting to note, however, that of the 8 patients with SN in whom the diagnosis was firm, all were managed initially by aggressive medical management. These 8 patients were operated on an average of 24 days after presentation with symptomatic necrosis-ie, continued abdominal pain, inability to eat, or persistent pulmonary dysfunction and inability to wean from the ventilator. These 8 patients averaged 3.4 operations, 29 days in the ICU, 28 days on the ventilator, 26 days of TPN, and required 24 units of blood transfusion during their hospital stay, data not significantly different from patients with IN. Other factors involved in our high mortality rate include our lack of il standardized treatment algorithm for managing these complex patients and the fact that our study covers a 15-year period. With regard to a standardized treatment algorithm, other studies have shown excellent results when a standardized treatment protocol is followed.9?8~‘9~‘4 In addition to a standardized algorithm, most contemporary studies are reported by a single senior author who has a large experience in pancreatic surgery and has participated in the care of all patients reported. ‘XXV~ To support the benefits of a single experienced surgeon, Rattner et alz3 noted a wide difference in the incidence of recurrent abscesses and mortality between individual surgeons in their group treating this disease. Therefore, these previously reported studies have a standardization of judgment anJ technique that was not available in our study. Secondly, whereas our study covers a 15-year period (1977 to 1992), most of the excellent results reported in recent series have occurred over a S- to lo-year time frame.‘z~‘8~‘7When our series is broken down into 5-year periods, the mortality rates are as follows: 1977 to 1981, 29% (4 of 14); 1982 to 1986. 27% (6 of 22); and 1987 to 1992, 12% (3 of 26). This shows an increasing number of patients and decreasing mortality for each 5-year period. In our most recent 5-year period (1987 to 1992), the 12% mortality rate is comparable to other recently reported series.‘R,Z1,L4 An important observation macle by Bittner and coworkers17 and Beger anJ colleagues Zh is that the necrotic process in patients with necrosis is dynamic and continuous, sometimes continuing for as long as 2 weeks after the initial debridement. This knowledge has been used to advocate necrosectomy and open packing as a superior technique to necrosectomy and dkbridement over Jrains.12,“4 Despite the theoretical advantage of open abdominal packing to allow for multiple pancreatic dbbridements throughout the time course of this persistent necrosis, no compelling data are as yet available to suggest one method is superior to another.z7 In our experience, patients with the most extensive necrosis, anJ thus highest mortality, were manageil by the open packing technique. It is therefore not surprising that we found a 75% mortality rate in this group of patients. Careful evaluation of the literature suggests that competent use of either techniyue has resulted in similar morbidity and mortality rates in several different surgical series.y~10~‘z~2“ Complications in this series were both frequent and severe. Pancreatic fistula occurred with equal frequency (150/o, 14%, anJ 11%) in all patient groups. These findings support the notion that while glandular destruction occurs in all patients with severe pancreatitis, in patients with PA the process is
localized, and subsequently Dissolves, suppurates, and is easily drained. This incidence of pancreatic fistula in this series is similar to the 19% to 36% rate previously reported in the literature.“.‘” Pancreatic fistulas in this setting require external drainage for control. Failure to adequately control the pancreatic output results in intra-abdominal sepsis, which, if not quickly corrected by reoperrttion or interventional radiographic drainage techniques, results in multiple system organ failure and death.” When properly controlled, the majority of external pancreatic fistulas will close nonoperatively within weeks to months, providing that pancreatic ductal continuity is present without proximal stricture or stenosis.“,‘? Enteric fistulas also occurred with an equal frequency in all three patient groups, and we found no relationship between the rates of intestinal fistulization anJ the type of surgical management used. Early identification of patients with necrosis (within 48 hours of admission) would allow for the close observation of that specific group of patients who are at the highest risk for morbidity and mortality. ‘.‘x” Toward that end, we evaluated the prognostic ability of Ranson’s scoring system, the APACHE II scoring system, and Balthazar’s CT grading system done within 48 hours of admission to correctly identify the subset of patients with necrosis (both IN and SN). We found that at high-scoring ranges both physiologic tests show a high degree of accuracy in predicting necrosis. In this series, all patients with Ranson’s score 26 or APACHE 11score ~14 had necrosis. Unfortunately, these physiologic scoring systems lost their discriminate ability to predict necrosis at lower scoring ranges (Ranson’s score ~6 or APACHE II score ~15). Therefore, the overall sensitivity and specificity of a Ranson’s score 13 in predicting pancreatic necrosis was only 62% and 93%, respectively, whereas an APACHE II score >lO was only 41% sensitive and 93% specific. The limitations of physiologic scoring systems in predicting hoth pancreatic necrosis and the incidence of complications have been noted by others. Tran and Cuesta’ showeJ that an APACHE II score >lO or a Ranson’s score >3 haJ a sensitivity of only 60% in predicting which patients with severe acute pancreatitis would develop complications or die. Larvin and McMahon? confirmed these findings by showing that APACHE 11 scores 19 and Ranson’s scores >2 at 48 hours had a sensitivity of only 75% in predicting outcome. Both of these papers failed to investigate the relationship between scoring systems and pancreatic necrosis. This relationship was studied by Nordback et al’” who found that multiple physiologic measurements, in&cling leukocyte count, platelet count, hematocrit, hlooci glucose concentration, and serum levels of sodium, potassium, calcium, triglycerides, creatinine, bilirubin, and transaminases, all &led to correlate with the extent of pancreatic necrosis in surgically resected glands. It seems clear, hoth from our Jata and that of Nordback, that while physiologic assessments are helpful in patient stratification and objectively quantifying the initial severity of illness, they Jo not proviJe sufficient accuracy to identify patients with necrosis, an essential variable neecled in classifying patients according to the international symposium’s system. Because identification of necrosis is so essential to proper patient classification in this schema, its ultimate clinical utility
THE AMERICAN
JOURNAL
OF SURGERY@’ VOLUME
170
JULY 1995
49
SEPTIC COMPLICATIONS
IN ACUTE PANCREATITISIHOWARD
ET AL 1
will depend on the ability to discern pancreatic necrosis nonoperatively.5 Despite numerous attempts to identify circulating serum markers released when the pancreas necroses, none of those investigated thus far has proven helpful.29 Dynamic contrast-enhanced CT is the current gold standard for the clinical diagnosis of pancreatic necrosis.-70 Focal or diffuse, well-marginated zones of nonenhanced pancreatic parenchyma that are larger than 3 cm or involve more than 30% of the area of the pancreas are the requisite criteria for CT diagnosis. 31Although the technique is not infallible, the overall accuracy of dynamic CT under these conditions is greater than 90%, and this technology remains the best method for identifying pancreatic necrosis nonoperatively.30-32 Unfortunately, our study spans a period (1977 to 1992) during which the vast majority of morphologic assessments of severe acute pancreatitis at our institution were carried out using regular nondynamic CT scanning. Consequently, we are unable to address the role of dynamic contrast CT in discriminating between patients with necrosis and PA at the time of hospital admission. To analyze our data morphologically, we opted to grade the CT scans based on a grading system developed by Balthazar and colleagues8 that has previously been shown to have clinical utility in predicting prognosis in severe pancreatitis. Although our data show that 96% of patients with necrosis had Balthazar grade D or E scans, these patients could not be reliably distinguished from the 62% of patients with PA who also had grade D or E scans. These data suggest that, in our hands, Balthazar’s classification system lacks the discriminate ability to predict necrosis in patients with severe pancreatitis. In summary, the international symposium’s clinical classification scheme for local septic complications of acute pancreatitis places patients into three discrete categoriesinfected necrosis, sterile necrosis, and pancreatic abscessand has both therapeutic and prognostic utility. Adoption of this system should allow for the standardization of interinstitutional data and provide a framework for more accurate and precise communication between clinicians. The ability to reliably identify patients with pancreatic necrosis, nonoperatively, early in the course of their disease remains the essential component in accurately applying this system prospectively.
REFERENCES 1. Tran DD. Cuesta MA. Evaluation of severitv in uatients with acute pamreatitisl Am J Gastmenterol. 1992;87:6&08. 2. Bjornson HS. Pancreatic “abscess”: diagnosis and management. Pnncreas. 1991;6:531S36. 3. Ranson JHC, Spencer FC. The role of peritoneal lavage in severe acute pancreatitis. Ann Surg. 1978;187:565-575. 4. Ranson JHC. The role of surgery in the management of acute pancreatitis. Ann Surg. 1990;211:382-393. 5, Bradley EL. A clinically based classification system for acute pancreatitis; summary of the international symposium on acute pancreatitis. Atlanta, GA; September 11-13, 1992. Arch Surg. 1993;128: 586-590. 6. Ranson JHC, Riikind KM, Rases DF, et al. Prognostic signs and the role of operative management in acute pancreatitis. Surg Gynecd Obsret. 1974;139:69-81.
50
THE AMERICAN
JOURNAL OF SURGERYa
VOLUME 170
7. Larvin M, McMahon MJ. APACHE-II score for assessment and monitoring of acute pancreatitis. Lancet. 1989;2:201-204. 8. Balthazar EJ, Ranson JHC, Naidich DP, et al. Acute pancreatitis: prognostic value of CT. Radiology. 1985;156:767-772. 9. Stamen R, Frey CF. Comprehensive management of acute necrotizing pancreatitis and pancreatic abscess. Arch Surg. 1990;125: 1269-1275. 10. Beger HG, Drautzberger W, Bittner R, et al. Results of surgical treatment of necrotizing pancreatitis. World J Surg. 1985;9:972-979. 11. Warshaw AL, Gongliang J. Improved survival in 45 patients with pancreatic abscess. Ann Surg. 1985;202:408-417. 12. Bradley EL. Management of infected pancreatic necrosis by open drainage. Ann Surg. 1987;206:542-550. 13. Renner IG, Savage WT III, Pantoja JL, et al. Death due to acute pancreatitis: a retrospective analysis of 405 autopsy cases. Dig IX Sci. 1985;30:1005-1018. 14. Warshaw AL. Pancreatic abscesses. NEJM. 1972;287:123+1236. 15. Sostre CF, FIournoy JG, Bova JG, et al. Pancreatic phlegmon. Dig Dis Sci. 1985;30:918-927. 16. Bradley EL, Allen K. A prospective longitudinal study of observation versus surgical intervention in the management of necrotizing pancreatitis. Am J Surg. 1991;161:19-25. 17. Bitmer R, Block S, Biichler M, Beger HG. Pancreatic abscess and infected pancreatic necrosis: different local septic complications in acute pancreatitis. Dig Dir Sci. 1987;32:1082-1087. 18. Howard JM. Delayed debridement and external drainage of massive pancreatic or peripancreatic necrosis. Surg Gynecot Obstet. 1989; 16825-29. 19. Reber HA. Surgical intervention in necrotizing pancreatitis. Gasrmenterology. 1986;91:479+82. 20. Beger HG, Btichler M, Bittner R, et al. Necrosectomy and postoperative local lavage in patients with necrotizing pancreatitis: results of a prospective clinical trial. Wmfd J Surg. 1988;12:255-262. 21. Gerrof SC, Banks PA, Robbins AH, et al. Early diagnosis of pancreatic infection by computed tomography-guided aspiration. Gasnoenterology. 1987;93:1315-1320. 22. San MG, Nagomey DM, Mucha P Jr, et al. Acute necrotizmg pancreatitis: management by planned staged pancreatic nectosectomy/debridement and delayed primary wound closure over drains. Br J Surg. 1991;78:576-581. 23. Ratmer DW, Legermate DA, Lee MJ, et al. Early surgical debridement of symptomatic pancreatic necrosis is beneficial irrespective of infection. Am J Surg. 1992;163:105-110. 24. Pemberton J, Nagomey DM, Becker JM, et al. Controlled open lesser sac drainage for pancreatic abscess. Ann Surg. 1986;203: 596-604. 25. Karimgani I, Porter KA, Langevin RE, Banks PA. Prognostic factors in sterile pancreatic necrosis. GastmenteroIo~. 1992;103: 1636-1640. 26. Beger HG, Bitmer R, Block S, BiichIer M. Bacterial contamina~ tion of pancreatic necrosis: a prospective clinical study. Gustroentero&y. 1986;91:433438. 27. Frey CF, Bradley EL III, Beger HG. Progress in acute pancreatitis. Surg Gynecol Obstet. 1988;167:282-286. 28. Nordback I, Pessi T, Auvinen 0, Aution V. Determination of necrosis in necrotizing pancreatitis. Br J Surg. 1985;72:225-227. 29. Aklridge MC. Diagnosis of pancreatic necrosis. Br J Surg. 1988; 75:99-X0. 30. Clavien PA, Hauyser H, Meyer I? Value of contrast-enhanced CT in the early diagnosis and prognosis of acute pancreatitis: a prospective study of 202 patients. Am J Surg. 1988;155:457466. 31. Balthazar EF, Robinson DL, Megibow AJ. Acute pancreatitis: value of CT in establishing prognosis. Radiology. 1990,174:331-336. 32. Bradley EL III, Murphy FC, Fetguson C. Prediction of pancteatic necrosis by dynamic pancreatography. Ann Surg. 1989;210:495-504.
JULY 1995
BACKGROUND: An international symposium on acute pancreatitis recently developed a clinical classification system tor severe acute pancreatitis that classifies all local septic complications into three groups: infected necrosis (IN), sterile necrosis (SN), and pancreatic abscess (PA). Despite the appeal of having three distinct, well-defined labels for this complex process, the clinical utility of this schema has yet to be determined. The purpose of this study was to investigate the prognostic and therapeutic utility of applying this clinical classification system to a iarge group of surgical patients with local septic complication from acute pancreatitis. PATIENTSAND METHODS: We reviewed the cases of 62 patients with complicated pancreatitis, classifying them into IN (n = 20), SN (n = 14), or PA (n = 28) groups. Ranson’s score, APACHE II score, and computed tomography grading were calculated within the first 48 hours of admission. Information on patient demographics, etiology of pancreatitis, operative procedures, timing of intervention, bacteriology, blood loss, intensive care unit days, ventilator days, and morbidity and mortality were also accrued and analyzed. RESULTS: Despite similar demographics and etiology of pancreatitis, patients with necrosis, both IN and SN, were more critically ill than were patients with PA (APACHE II score >15, 21% versus 0%, respectively), required earlier operative intervention (mean 14 days versus 29 days, P = 0.02), required necrosectomy with drainage (65% versus 4%, P
From the Departments of Surgety (TJH, EAW, JCB, RJG, JAM), Radiology (GM, KK), and Gastroenterology (SS, RHH, GAL), Indiana University School of Medicine, Indianapolis, Indiana. Requests for reprints should be addressed to Thomas J. Howard, MD, Emerson Hall #523, 545 Bamhill Drive, Indianapolis, Indiana 46202. Manuscript submitted June 6, 1994 and accepted in revised form October 20, 1994.
44
THE AMERICAN
JOURNAL
OF SURGERY@’ VOLUME
170
than either patients with SN or PA (P ~0.05). CONCLUSIONS: We conclude that this classification system allows ior the stratification of patients into three distinct groups-infected necrosis, sterile necrosk, and pancreatic abscess- and has both therapeutic and prognostic usefulness. Am J Surg, 1995;170:44-50.
S
evere acute pancreatitis generally declares itself shortly after onset with the production of systemic toxicity manifest by signs of organ failure.’ Aggressive fluid resuscitation, respiratory support, hemodynamic monitoring, and total parenteral nutrition (TPN) have dramatically reduced early mortality rates only to tender patients subject to delayed septic complications, which have emerged as the major cause of death. 2,3Accurate diagnosis and prompt treatment of these septic complications represents the cornerstone of surgical management.4 Recently, an intemational symposium on acute pancreatitis developed a clinically based classification system that defines all local septic complications from severe acute pancreatitis into three groups: infected necrosis (IN), sterile necrosis (SN), and pancreatic abscess ( PA).5 Despite the intuitive appeal of having three distinct, well-defined labels for this complex disease process, the utility of such a classification scheme has yet to be determined. The purpose of this study was to review a consecutive series of surgical patients with local septic complications from severe acute pancreatitis and classify them as IN, SN, or PA. To determine the usefulness of this schema, we evaluated all three groups with regards to severity of illness, surgical management, and morbidity and mortality rates. In addition, we investigated whether prognostic criteria (Ranson’s, APACHE II, or computed tomography [CT] grading) obtained within 48 hours of admission could discriminate between these three groups of patients. PATIENTS AND METHODS From 1977 to 1992, 1,179 patients were admitted to the Indiana University Hospital with the diagnosis of acute pancreatitis (n = 789) or an acute exacerbation of chronic pancreatitis (n = 390). Of these, 269 (23%) had operative procedures for local complications that occurred as a direct result of their current episode of pancreatitis. One hundred eighty-two patients (68%) had surgical drainage of noninfected pancreatic pseudocysts, the most frequent complication identified. Ten patients (4%) had successful percutaneous drainage of infected pancreatic collections. Eight patients (3%) developed infected pancreatic collections as JULY 1995
1 SEPTIC COMPLlCATlONS L
IN ACUTE PANCREATlTlSlHOWARD
ET AL
a result of prior attempts
at percutaneous or TABLE I endoscopic drainage of an initially sterile Comparison of Pancreatitis Patient Groups Classified as Infected collection. Seven patients (3%) had insuffiNecrosis (IN), Sterile Necrosis (SN), or Pancreatic Abscess (PA) cient data t’or analysis. That left 62 patients PA (%) IN (%) SN (%) (23%) who qualified for study. 20 14 28 No. of patients Patients were carefully classified by the 445 15 37* 12 Mean age (y) 45* 13 principal author according to the most re75125 50150 68132 Sex (% M/F) cent clinical consensus on pancreatitis as Comorbid disease having either IN, SN, or PA.’ Pancreatic 2 (10) 2 (14) 4 (14) Cardiovascular 0 1 (7) 0 Renal necrosis was defined as operatively docu1 (5) 1 (7) 1 (4) Diabetes mented pancreatic or peripancreatic tissue 0 2 (14) 3 (11) Pulmonaty necrosis. IN was distinguished from SN on Etiology the basis of cultures obtained intraopera7 (35) 3 (21) 6 (21) Alcohol tively. PA was defined as a localized collec3 (15) 3 (21) 5 (18) Gallstones tion of frank suppuration or turbid fluid that 2 (10) 2 (14) 2 (7) Steroids grew out pathogenic organisms on intraop1 (5) 1 (7) 2 (7) Hyperlipidemia erative culture, located in close proximity to 0 0 4 (14) Trauma the pancreas, containing little or no pancre3 (15) 2 (14) 2 (7) Postoperative 1 (5) 0 2 (7) Post-ERCP atic necrosis. All 62 patients who qualified 4 (20) 2 (14) 5 (18) Indeterminate for study were able to be classified into one of these three groups. ERCP = enodscopic retrograde cholang/opancreatography Multiple clinical, laboratory, and radiographic data were analyzed from both the medical records and radiology files. Patients TABLE II were classified by three separate prognostic Clinical Factors Related to Disease Severity pancreatitis: systems for acute staging SN PA Ranson’s,” APACHE II score,’ and CT grad(n = 14) (n r*O) (n = 28) ing.s Due to our status as a tertiary referral 5Ok IO 47 + 9 Hospital stay (d) 74 + 13’ center, many of our patients were treated ini25 + 8 11 +5’ ICU stay (d) 28 + 4 tially at an outside hospital during the first 10 f 4 6*3 Ventilator use (d) 22 * 8’ 48 hours of their illness. For these patients, 16 * 5 11 *3 Blood loss (units) 33 + 10’ 22 + 5 20 f 5 records from the outside hospitals were obTPN (d) 42 + 8’ tained and used to calculate Ranson’s and ‘P ~0 05. Student’s unpaired t-test mth Bonferronik correction APACHE II scores within the first 48 hours IN = infected necrosis: SN = sterile necrosis: PA = pancreatic abscess, ICU = mtenswe care of their hospitalization. When the initial abm/t: TPN = totai parental nutntion dominal CT scan was not available for re- Iview, the earliest CT scan to the initial onset of pancreatitis prior to operative intervention was used terval variables, and the one-tailed Fisher’s exact test was to determine the CT grade. In some instances, we were unused for analysis of proportions. Spearman’s rank-order corable to obtain an appropriate CT scan; these patients were relation was used to evaluate the relationship between excluded from CT grading, but were included in the reRanson’s and APACHE II scoring systems. maining analysis. Scans were graded by two of our radiology staff (GM, KK) who were blinded to the group to which RESULTS the patients were assigned. Of 62 patients available for analysis, 20 (32%) had IN, 14 Indications for operation in all patients were one of the (23%) had SN, and 28 (45%) had PA. The average age for following: clinical deterioration (n = 53), failure to improve patients in the entire series was 46 years (range 18 to 78); despite intensive medical management (n = 6), or a posithere were 39 men (63%) and 23 women (37%). There were tive gram stain or culture of a peripancreatic fluid collecno differences in age, sex, comorbid illnesses, or the etiology tion (n = 3). Mortality data are expressed as in-hospital morof pancreatitis between these three groups (Table I). The etitality and not as 300day postoperative mortality. All patients ologies for pancreatitis in this series are comparable to those have been observed to date by a review of their outpatient found in most large surgical series in the United States.“,“,‘* charts and records. The surgical procedures performed could The severity of illness in both groups was evaluated by their be classified into four general types: debridement and open average hospital days, intensive care unit (ICU) days, and packing (n = 4); debridement over drains (n = 24); pannumber of days the patient required mechanical ventilation. creatic resection over drains (n = 9); and simple drainage Patients with IN stayed, on average, 15 more hospital days (n = 25). and required mechanical ventilation for 13 more days than Statistical analysis was performed using Primer of patients with either SN or PA (Table II). Patients with IN Biostatistics software (McGraw-Hill, New York, New and SN had a similar number of ICU days, 28 and 25, reYork). Comparison between groups was made using spectively, both of which were significantly longer than ICU Student’s paired r-tesr with Bonferroni’s correction for indays for patients with PA (P ~0.05). Patients with IN reTHE AMERICAN
JOURNAL
OF SURGERY”
VOLUME
170
JULY 1995
45
1
iEPTlC COMPLICATIONS
IN ACUTE PANCREATlTlSlHOWARD
ET AL I
use of endoscopic retrograde cholangiopancreatography and sphincterotomy for this condition. In contrast to patients with IN and SN, those with PA were managed nonoperatively for a longer period of time, IN SN PA with half of the patients requiring surgical (n = 20) (n = 14) (n = 28) lime to intervention (d) 17 * 3 10 & 4’ 29 f 6 intervention after the 29th day from the Number of operations 2.6 f 0.3 1.9 * 0.4 1.1 f 0.5’ onset of their symptoms. Range l-7 l-6 l-3 The operative management of patients Surgical management with necrosis, both IN and SN, was ag DBbridement\open packing 3 (15%) 1 (7%) 0 gressive extirpation and debridement of inDBbridement\drains 13 (65%) 10 (71%) 1 (4%)+ fected and necrotic tissue (Table III). Pancreatic resection\drains 4 (20%) 2 (14%) 3 (11%) Thirty-three of 34 patients with IN and SN Simple drainage 0 1 (7%) 24 (86%)’ (97%) required debridement or resectional ‘P 4.05, Student’s unpaired t-test with Bonferroni’s correction therapy, whereas only 1 patient underwent tP ~0.001, Fisher’s exact test, one-failed. simple drainage of an infected intra-abdominal fluid collection. Patients with IN TABLE IV averaged 2.6 operations per patient (range Findings in 45 Patients With Bacteria or Fungus on lntraoperatlve Culture 1 to 7), whereas those with SN averaged of Peripancreatlc Fluid Collection or Necrotic Tissue Debris 1.9 (range 1 to 6). Four patients with necroOverall sis (3 IN, 1 SN) were managed by debride(n = :“o) (%) (n = E) (%) (n = 45) (%) ment and open packing, and 3 of these paSingle isolate 8 (40) 14 (56) 22 (49) tients (75%) subsequently died of sepsis and Multiple isolates 12 (60) 11 (44) 23 (51) multiple system organ failure. Patients with Bacterial isolates 39 36 73 PA required only 1 operation on average Pseudomonas 4 8 12 (16) (range 1 to 3) to gain adequate control of Enterobacter 7 4 11 (15) their intra-abdominal sepsis, and 24 of 28 Enterococcus 6 2 6 (11) patients (86%) were managed by simple exStaphylococcus 3 5 6 (11) ternal drainage of an infected fluid ollecKlebsiella 2 5 7 (10) tion. The only patient in this group reEscherichia co/i 3 4 7 (10) quiring dkbridement had a multiloculated Candida 4 2 6 (6) abscess extending through the transverse Proteus 4 0 4 (5) Citrobacter 2 1 3 (4) mesocolon with extensive mesenteric fat Streptococcus 0 3 3 (4) necrosis. Of the 3 patients with PA who reAnaerobes’ 4 2 6 (6) quired pancreatic resection, 2 had strictures of the main pancreatic duct and 1 had an ‘Anaerobes include Bacteroides, Peptostreptococcus, and Clostridia. IN = infected pancreatic necrosis; PA = pancreatic abscess. infected pseudocyst (Pseudo-) which could not be drained intemallv. Intraoperative cultures taken from all patient; were posiquired two to three times more blood transfusions per patient tive in 45 (75%). Bacteria or fungus was cultured from 20 than did patients with either SN or PA. All three patient patients with IN and from 25 patients with PA (Table IV). populations had prolonged gastrointestinal tract dysfunction Single isolates were recovered from 8 patients (40%) with and ileus; however, patients with IN required TPN signifiIN and 16 patients (57%) with PA, while multiple isolates cantly longer than did patients with either SN or PA (P were cultured in the remaining 12 patients (60%) with IN cO.05). and 12 (43%) with PA. Although many different types of Patients with IN (n = 20) became septic early, as manibacteria were found, the majority of isolates were coliforms, fest by spiking fevers, hypotension, and organ dysfunction with Pseudomonas, Enterobacter, and Enterococcus species that necessitated exploration, dkbridement, and drainage in being the most prevalent. Candida was found in 8% of isohalf the patients within 17 days of the onset of their symplates, and the incidence of anaerobic isolates in our series toms (Table III). Patients with SN (n = 14) were operated was extremely low (4%) despite the routine use of anaeroon even earlier in our series, with half being operated on bic specimen transport and culture techniques. This low inwithin 10 days from the onset of their symptoms. In this cidence of anaerobic bacteria in secondary pancreatic ingroup of patients, however, 6 (43%) underwent exploratory fections has been noted before.” laparotomy less than 10 days from the onset of their sympThe mortality rate in our series was 50% for patients with toms for several different indications: 2 patients were exSN, 25% for patients with IN, and 4% for patients with PA plored within 24 hours of presentation on the basis of an (P = 0.004; Table V). In the necrosis groups (IN and SN), acute abdomen and shock; 2 patients, immunosuppressed on 10 of 12 patients (83%) died of sepsis and multiple system steroids, were explored because of clinical deterioration organ failure directly attributable to their pancreatic insult. when the diagnosis of pancreatitis remained in doubt; and Of the 12 patients who died, 5 had IN and 7 had SN. Three 2 patients had impacted gallstones at the ampulla of Vater of 5 patients in the IN group and 5 of 7 patients in the SN with signs and symptoms of cholangitis prior to the routine TABLE
Ill
Surgical Timing, Number of Interventions, and Surgical Management of Patients With Infected Pancreatic Necrosis (IN), Sterile Pancreatic Necrosis (SN), or Pancreatic Abscess (PA)
46
THE AMERICAN
JOURNAL
OF SURGERY@
VOLUME
170
JULY 1995
1 SEPTIC COMPLICATIONS
IN ACUTE PANCREATITIS/HOWARD
ET AL
group had postmortem examination, and TABLE V all had peripancreatic fluid collection or Morbidity and Mortality Data necrosis that grew bacteria on culture. The PA IN SN lone death in the PA group was directly (n = 20) (n = 14) (n = 28) PValue’ attributable to the pancreatic insult and 5 (25%) 7 (50%) 1 (4%) 0.004 Death 11 (55%) 8 (57%) 17 (61%) 0.922 Morbidity was a patient who underwent simple 3 (15%) 2 (14%) 3 (11%) 0.895 Pancreatic fistula drainage of a PA followed by a long and 4 (14%) 0.769 Colonic fistula 2 (10%) 1 (7%) complex 72,day course in the surgical 3 (15%) 1 (7%) 2 (7%) 0.620 Small-bowel fistula ICU, resulting in systemic candidiasis and 0 0.175 Biliary fistula 0 1 (7%) multiple system organ failure. 2 (7%) 0.472 Hemorrhage 0 1 (7%) Morbidity was frequent but not signifi2 (10%) 2 (14%) 1 (4%) 0.451 Upper GI bleed cantly different between groups, occurring 0.540 Pulmonary embolism 0 0 1 (4%) in 11 patients (55%) with IN, 8 patients 1 (4%) 0.712 Bowel obstruction 1 (5%) 0 (57%) with SN, and 17 patients (61%) .FisherB exact test, one-tailed, was used to compare IN versus SN versus PA with PA. Pancreatic fistulas were common, IN = Infected necrosis; SN = stenle necrosis: PA = pancreatic abscess, Gi = gastro/ntest/nal occurring in 15% of IN, 14% of SN, and 11% of PA patients. Of the 8 patients in available for analysis, 87% of patients with IN and 88% of our series with pancreatic fistulas, 2 died of sepsis and mulpatients with SN had Balthazar grade E scans,” whereas only tiple system organ failure 2 and 4 weeks after their develop54% of patients with PA had scans graded with this score. ment. Both deaths were attributable to poor fistula control and persistent intra-abdominal sepsis. All 6 remaining panSimilarly, of the 7 patients with low-scoring scans (Balthazar A-C), 83% (5 of 6) were patients with PA, whereas only 1 creatic fistulas were adequately controlled, and 5 of these patient with SN had a scan given this grade. closed spontaneously after 3 to 9 weeks (mean 5). The remaining pancreatic fistula stayed open for 7 weeks, at which time endoscopic retrograde cholangiopancreatography reCOMMENTS Local septic complications in severe acute pancreatitis now vealed a complete pancreatic duct cut off in the neck of the gland without distal duct continuity. This patient underwent account for the vast majority of deaths associated with this operative closure of the fistula by distal pancreatectomy and disease process. ‘s Despite a wide variation in each patient’s clinical course and pancreatic morphology, prior to the insplenectomy. A total of 14 enterocutaneous fistulas occurred in 13 patroduction of the current international symposium’s classifitients in this series, and there was no difference between cation scheme, all septic complications in acute pancreatitis groups with regard to fistula incidence or location. There were grouped under the term “pancreatic abscess.“i4 Many were 7 colonic fistulas (2 IN, 1 SN, 4 PA), 6 small-bowel clinicians, realizing the unsatisfactory nature of a single title fistulas (3 IN, 1 SN, 2 PA), and 1 biliary fistula (1 SN). One for such a protean disease, coined more elaborate and depatient with IN had both a colonic and duodenal fistula, scriptive terms such as “phlegmon” and “hemorrhagic panwhich were repaired with a right hemicolectomy, ileotranscreatitis,” hoping to better elucidate and define subsets within verse colostomy, and primary repair of the duodenum with this complex pathophysiologic process.4J5 Unfortunately, a small-bowel serosal buttress 2 months after the initial rather than clarify, the use of these descriptive terms+-often episode c)f pancreatitis. Of the other 6 colonic fistulas, 3 used without adequate definition-left the literature replete closed spontaneously (at 2 ,4, and 6 weeks), whereas 3 rewith a vague lexicon leading to confusion and an inability to quired operative repair. Three of 6 small-bowel fistulas closed accurately classify patients in a useful manner. spontaneously (at 4, 7, and 12 weeks), and I patient with a Several recent observations have dramatically increased our duodenal fistula died of sepsis 4 weeks after the development understanding of this complex disease process. Based on both of pancreatitis. The remaining 2 patients with small-bowel clinical and experimental evidence, it is now well accepted fistulas required operative closure: 1 underwent vagotomy, that both the presence and extent of pancreatic necrosis dicantrectomy, and Billroth II gastrojejunostomy; and the other tate the clinical course of patients with severe acute pancrehad a small-bowel resection. The lone biliary fistula closed atitis.‘6J7 Furthermore, in patients with necrosis, the presence spontaneously at 8 weeks. of bacterial infection within the necrosis is an ominous event, Our prognostic staging data show that patients with necroaccounting for more than 80% of all deaths from acute sis (IN and SN) had higher Ranson’s, APACHE II, and CT pancreatitis. ‘3,‘6~17 These observations make the international grading scores when compared with the PA group (Table symposium’s classification system-which differentiates IN, VI). Thirty percent of patients with IN and 14% of patients SN, and PA-an attractive system, in that it should allow with SN had Ranson’s scores ~7, and 21% of both groups for an accurate stratification of patients with regard to their (IN and SN) had APACHE II scores >16. In contrast, paclinical course. tients with PA had extremely low scores, with 93% having To investigate the ability of this new classification system a Ranson’s score ~3 and an APACHE II score ~10. to stratify patients, we retrospectively classified 62 patients Furthermore, no patient in the PA group had a Ranson’s with complicated pancreatitis according to the symposium’s score >6 or an APACHE II score 214. There was a reasoncriteria into 20 patients with IN, 14 patients with SN, and able correlation (r = .68) between the Ranson’s and 28 patients with PA. Our data show that the most fulminate APACHE II sccjres in this series. Of the abdominal CT scans clinical course in severe acute pancreatitis occurs in patients THE AMERICAN
JOURNAL
OF SURGERYa
VOLUME
170
JULY 1995
47
)
;EPTIC COMPLICATIONS
IN ACUTE PANCREATlTlSlHOWARD
ET AL
-
necrosis. 16~18-20 In these instances, patients with necrosis are followed up closely with Evaluation of Ranson’s, APACHE II, and Balthazar Computed Tomography repeated investigations of their pancreatic (CT) Grading, Applied Within 48 Hours of Onset of Pancreatitis and peripancreatic fluid collections using CT-guided aspiration and culture.2* As Staging System (n = s4”) (%) (n = P, (%) (n = g) (%) long as the CT-guided aspirations reveal no Ranson’s criteria infection, patients are managed nonopera43 26 (93) 7 (35) 6 (43) tively. Indications for operation in these 4-6 7 (35) 6 (43) 2 (7) patients are either a positive culture on CT >7 0 2 (14) 6 (30) APACHE II score directed aspiration, or persistent symptoms <5 16 (57) 3 (15) 3 (21) of abdominal pain, systemic illness, pul5-10 10 (36) 6 (43) 8 (40) monary dysfunction, or the inability to eat 11-15 5 (25) 2 (14) 2 (7) after a period (usually 4 to 6 weeks) of med‘16-20 0 2 (141 4 (20) ical management (symptomatic necrosis). >21 0 0 1 (7) Our patients with SN occupied a middle CT grading’ a+ 15+ 13+ ground clinically between patients with A 0 0 1 (8) IN and those with PA. In a number of facB 0 0 2 (15) C 0 tors, including hospital days, ventilator 1 (13) 2 (15) D 0 2 (13) 1 (8) days, blood loss, and TPN days, patients E 13 (87) 7 (88) 7 (54) with SN closely resembled patients in the PA group. In terms of surgical manage‘Grade A = normal; grade B = focal or diffuse enlargement; grade C = intrinsic pancreatic abment-time to intervention, number of normalities; grade D = sing/e, ill-defined collection; grade E = t2 poorly defined collections. +On/y 15 IN patients (75%), 8 SN patients (57%), and 13 PA patients (46%). had computed operations, and type of operative managetomography scans available for analysis. ment (debridement versus drainage)-paIN = infected necrosis; SN = sterile necrosis; PA = pancreatic abscess; tients with SN more closely resembled patients in the IN group. The overall mortality rate for the entire series was 21%, with IN. These patients required operation within 17 days which is comparable to the 14% to 25% mortality rates for from the onset of their symptoms, averaged 74 days in hoscombined series reported in the literature.9J2~23 The morpital, 28 days in the ICU, 22 days on the ventilator, and tality rate in our subset of patients with SN (50%) is much were transfused 33 units of blood during their hospital stay. higher than the 8% to 17% mortality rates reported in most Not surprisingly, these data are nearly identical to those rerecent surgical series. 9~1o,24 Several reasons can be identified ported by Stanten and Frey9 in their series of 50 patients for the high mortality rate we observed in this group of pawith pancreatic necrosis. Patients with PA remained clinitients. First and foremost is the high disease severity found cally stable for a much longer period of time: they required in our group of patients with SN. Karimgani et alz5 identioperation within 28 days from the onset of their symptoms, fied several factors, including a high Ranson’s score, a high averaging 47 days in hospital, 11 days in the ICU, and 6 APACHE II score, shock, renal insufficiency, multiple sysdays on the ventilator, and were transfused only 6 units of temic complications, and a high body mass index, that were blood. This less precipitant disease course in patients with related to a fatal outcome in patients with SN. When one PA allowed for the localization, containment, and definianalyzes data from their patient group who died, the avertion of the inflammatory process to a discrete area of their age Ranson’s score (6.3 f 0.5), APACHE II score (16.5 f abdomen. This observation is supported by the fact that 26 3.0), and incidence of shock (90%) are not dissimilar from of 28 patients (93%) required only one operation to adethe average Ranson’s score (5.9 + 1.2), APACHE II score quately evacuate and drain their septic focus, and no pa(15.6 + 7), and incidence of shock (100%) found in our tient was managed by the open abdominal packing techpatients with SN who died. Furthermore, their overall 38% nique. In contrast, the diffuse, poorly localized nature of the mortality rate in a series of critically ill patients with SN is disease process in patients classified with necrosis is reflected similar to our 50% mortality rate in a comparable group. by the fact that they averaged 2.6 operations (range 1 to 7) An additional factor that may relate to our high mortalin IN, and 1.9 operations (range 1 to 6) in SN to adequately ity rate in patients with SN is the early timing of surgical control their intra-abdominal process. Furthermore, 5 paintervention that occurred in this group of patients. The tients in these two groups (3 IN, 2 SN) required open abrisk of early operation in patients with SN is converting the dominal packing. residual SN remaining after the initial necrosectomy into The distinction between IN and SN is important and relIN by secondary bacterial infection. If the necrotic tissue reevant. Although all patients with necrosis will have fever, mains sterile, overall mortality rates are generally quoted in leukocytosis, abdominal tenderness, renal insufficiency, or the range of 0% to 1 1%.17*22,25 If the necrotic tissue becomes pulmonary dysfunction, surgical debridement is necessary secondarily infected (IN), overall mortality rates jump to only in patients with IN. More and more patients with SN 14% to 50%.9J7J2 Had the diagnosis of SN been firm in are being successfully managed by aggressive medical treatthose patients who underwent early exploration (6 of 14 ment without the need for surgical intervention.‘(j In fact, [43%] explored less than 10 days from their onset of symp many pancreatic surgeons now base their clinical decision toms) , most would have been treated by a trial of aggressive for operation on the bacteriologic status of the pancreatic TABLE
48
VI
THE AMERICAN
JOURNAL
OF SURGERY-
VOLUME
170
JULY 1995
SEPTIC COMPLICATIONS
IN ACUTE PANCREATlTlSlHOWARD
ET AL 4
medical management, which may have reduced our 50% mortality rate. It is interesting to note, however, that of the 8 patients with SN in whom the diagnosis was firm, all were managed initially by aggressive medical management. These 8 patients were operated on an average of 24 days after presentation with symptomatic necrosis-ie, continued abdominal pain, inability to eat, or persistent pulmonary dysfunction and inability to wean from the ventilator. These 8 patients averaged 3.4 operations, 29 days in the ICU, 28 days on the ventilator, 26 days of TPN, and required 24 units of blood transfusion during their hospital stay, data not significantly different from patients with IN. Other factors involved in our high mortality rate include our lack of il standardized treatment algorithm for managing these complex patients and the fact that our study covers a 15-year period. With regard to a standardized treatment algorithm, other studies have shown excellent results when a standardized treatment protocol is followed.9?8~‘9~‘4 In addition to a standardized algorithm, most contemporary studies are reported by a single senior author who has a large experience in pancreatic surgery and has participated in the care of all patients reported. ‘XXV~ To support the benefits of a single experienced surgeon, Rattner et alz3 noted a wide difference in the incidence of recurrent abscesses and mortality between individual surgeons in their group treating this disease. Therefore, these previously reported studies have a standardization of judgment anJ technique that was not available in our study. Secondly, whereas our study covers a 15-year period (1977 to 1992), most of the excellent results reported in recent series have occurred over a S- to lo-year time frame.‘z~‘8~‘7When our series is broken down into 5-year periods, the mortality rates are as follows: 1977 to 1981, 29% (4 of 14); 1982 to 1986. 27% (6 of 22); and 1987 to 1992, 12% (3 of 26). This shows an increasing number of patients and decreasing mortality for each 5-year period. In our most recent 5-year period (1987 to 1992), the 12% mortality rate is comparable to other recently reported series.‘R,Z1,L4 An important observation macle by Bittner and coworkers17 and Beger anJ colleagues Zh is that the necrotic process in patients with necrosis is dynamic and continuous, sometimes continuing for as long as 2 weeks after the initial debridement. This knowledge has been used to advocate necrosectomy and open packing as a superior technique to necrosectomy and dkbridement over Jrains.12,“4 Despite the theoretical advantage of open abdominal packing to allow for multiple pancreatic dbbridements throughout the time course of this persistent necrosis, no compelling data are as yet available to suggest one method is superior to another.z7 In our experience, patients with the most extensive necrosis, anJ thus highest mortality, were manageil by the open packing technique. It is therefore not surprising that we found a 75% mortality rate in this group of patients. Careful evaluation of the literature suggests that competent use of either techniyue has resulted in similar morbidity and mortality rates in several different surgical series.y~10~‘z~2“ Complications in this series were both frequent and severe. Pancreatic fistula occurred with equal frequency (150/o, 14%, anJ 11%) in all patient groups. These findings support the notion that while glandular destruction occurs in all patients with severe pancreatitis, in patients with PA the process is
localized, and subsequently Dissolves, suppurates, and is easily drained. This incidence of pancreatic fistula in this series is similar to the 19% to 36% rate previously reported in the literature.“.‘” Pancreatic fistulas in this setting require external drainage for control. Failure to adequately control the pancreatic output results in intra-abdominal sepsis, which, if not quickly corrected by reoperrttion or interventional radiographic drainage techniques, results in multiple system organ failure and death.” When properly controlled, the majority of external pancreatic fistulas will close nonoperatively within weeks to months, providing that pancreatic ductal continuity is present without proximal stricture or stenosis.“,‘? Enteric fistulas also occurred with an equal frequency in all three patient groups, and we found no relationship between the rates of intestinal fistulization anJ the type of surgical management used. Early identification of patients with necrosis (within 48 hours of admission) would allow for the close observation of that specific group of patients who are at the highest risk for morbidity and mortality. ‘.‘x” Toward that end, we evaluated the prognostic ability of Ranson’s scoring system, the APACHE II scoring system, and Balthazar’s CT grading system done within 48 hours of admission to correctly identify the subset of patients with necrosis (both IN and SN). We found that at high-scoring ranges both physiologic tests show a high degree of accuracy in predicting necrosis. In this series, all patients with Ranson’s score 26 or APACHE 11score ~14 had necrosis. Unfortunately, these physiologic scoring systems lost their discriminate ability to predict necrosis at lower scoring ranges (Ranson’s score ~6 or APACHE II score ~15). Therefore, the overall sensitivity and specificity of a Ranson’s score 13 in predicting pancreatic necrosis was only 62% and 93%, respectively, whereas an APACHE II score >lO was only 41% sensitive and 93% specific. The limitations of physiologic scoring systems in predicting hoth pancreatic necrosis and the incidence of complications have been noted by others. Tran and Cuesta’ showeJ that an APACHE II score >lO or a Ranson’s score >3 haJ a sensitivity of only 60% in predicting which patients with severe acute pancreatitis would develop complications or die. Larvin and McMahon? confirmed these findings by showing that APACHE 11 scores 19 and Ranson’s scores >2 at 48 hours had a sensitivity of only 75% in predicting outcome. Both of these papers failed to investigate the relationship between scoring systems and pancreatic necrosis. This relationship was studied by Nordback et al’” who found that multiple physiologic measurements, in&cling leukocyte count, platelet count, hematocrit, hlooci glucose concentration, and serum levels of sodium, potassium, calcium, triglycerides, creatinine, bilirubin, and transaminases, all &led to correlate with the extent of pancreatic necrosis in surgically resected glands. It seems clear, hoth from our Jata and that of Nordback, that while physiologic assessments are helpful in patient stratification and objectively quantifying the initial severity of illness, they Jo not proviJe sufficient accuracy to identify patients with necrosis, an essential variable neecled in classifying patients according to the international symposium’s system. Because identification of necrosis is so essential to proper patient classification in this schema, its ultimate clinical utility
THE AMERICAN
JOURNAL
OF SURGERY@’ VOLUME
170
JULY 1995
49
SEPTIC COMPLICATIONS
IN ACUTE PANCREATITISIHOWARD
ET AL 1
will depend on the ability to discern pancreatic necrosis nonoperatively.5 Despite numerous attempts to identify circulating serum markers released when the pancreas necroses, none of those investigated thus far has proven helpful.29 Dynamic contrast-enhanced CT is the current gold standard for the clinical diagnosis of pancreatic necrosis.-70 Focal or diffuse, well-marginated zones of nonenhanced pancreatic parenchyma that are larger than 3 cm or involve more than 30% of the area of the pancreas are the requisite criteria for CT diagnosis. 31Although the technique is not infallible, the overall accuracy of dynamic CT under these conditions is greater than 90%, and this technology remains the best method for identifying pancreatic necrosis nonoperatively.30-32 Unfortunately, our study spans a period (1977 to 1992) during which the vast majority of morphologic assessments of severe acute pancreatitis at our institution were carried out using regular nondynamic CT scanning. Consequently, we are unable to address the role of dynamic contrast CT in discriminating between patients with necrosis and PA at the time of hospital admission. To analyze our data morphologically, we opted to grade the CT scans based on a grading system developed by Balthazar and colleagues8 that has previously been shown to have clinical utility in predicting prognosis in severe pancreatitis. Although our data show that 96% of patients with necrosis had Balthazar grade D or E scans, these patients could not be reliably distinguished from the 62% of patients with PA who also had grade D or E scans. These data suggest that, in our hands, Balthazar’s classification system lacks the discriminate ability to predict necrosis in patients with severe pancreatitis. In summary, the international symposium’s clinical classification scheme for local septic complications of acute pancreatitis places patients into three discrete categoriesinfected necrosis, sterile necrosis, and pancreatic abscessand has both therapeutic and prognostic utility. Adoption of this system should allow for the standardization of interinstitutional data and provide a framework for more accurate and precise communication between clinicians. The ability to reliably identify patients with pancreatic necrosis, nonoperatively, early in the course of their disease remains the essential component in accurately applying this system prospectively.
REFERENCES 1. Tran DD. Cuesta MA. Evaluation of severitv in uatients with acute pamreatitisl Am J Gastmenterol. 1992;87:6&08. 2. Bjornson HS. Pancreatic “abscess”: diagnosis and management. Pnncreas. 1991;6:531S36. 3. Ranson JHC, Spencer FC. The role of peritoneal lavage in severe acute pancreatitis. Ann Surg. 1978;187:565-575. 4. Ranson JHC. The role of surgery in the management of acute pancreatitis. Ann Surg. 1990;211:382-393. 5, Bradley EL. A clinically based classification system for acute pancreatitis; summary of the international symposium on acute pancreatitis. Atlanta, GA; September 11-13, 1992. Arch Surg. 1993;128: 586-590. 6. Ranson JHC, Riikind KM, Rases DF, et al. Prognostic signs and the role of operative management in acute pancreatitis. Surg Gynecd Obsret. 1974;139:69-81.
50
THE AMERICAN
JOURNAL OF SURGERYa
VOLUME 170
7. Larvin M, McMahon MJ. APACHE-II score for assessment and monitoring of acute pancreatitis. Lancet. 1989;2:201-204. 8. Balthazar EJ, Ranson JHC, Naidich DP, et al. Acute pancreatitis: prognostic value of CT. Radiology. 1985;156:767-772. 9. Stamen R, Frey CF. Comprehensive management of acute necrotizing pancreatitis and pancreatic abscess. Arch Surg. 1990;125: 1269-1275. 10. Beger HG, Drautzberger W, Bittner R, et al. Results of surgical treatment of necrotizing pancreatitis. World J Surg. 1985;9:972-979. 11. Warshaw AL, Gongliang J. Improved survival in 45 patients with pancreatic abscess. Ann Surg. 1985;202:408-417. 12. Bradley EL. Management of infected pancreatic necrosis by open drainage. Ann Surg. 1987;206:542-550. 13. Renner IG, Savage WT III, Pantoja JL, et al. Death due to acute pancreatitis: a retrospective analysis of 405 autopsy cases. Dig IX Sci. 1985;30:1005-1018. 14. Warshaw AL. Pancreatic abscesses. NEJM. 1972;287:123+1236. 15. Sostre CF, FIournoy JG, Bova JG, et al. Pancreatic phlegmon. Dig Dis Sci. 1985;30:918-927. 16. Bradley EL, Allen K. A prospective longitudinal study of observation versus surgical intervention in the management of necrotizing pancreatitis. Am J Surg. 1991;161:19-25. 17. Bitmer R, Block S, Biichler M, Beger HG. Pancreatic abscess and infected pancreatic necrosis: different local septic complications in acute pancreatitis. Dig Dir Sci. 1987;32:1082-1087. 18. Howard JM. Delayed debridement and external drainage of massive pancreatic or peripancreatic necrosis. Surg Gynecot Obstet. 1989; 16825-29. 19. Reber HA. Surgical intervention in necrotizing pancreatitis. Gasrmenterology. 1986;91:479+82. 20. Beger HG, Btichler M, Bittner R, et al. Necrosectomy and postoperative local lavage in patients with necrotizing pancreatitis: results of a prospective clinical trial. Wmfd J Surg. 1988;12:255-262. 21. Gerrof SC, Banks PA, Robbins AH, et al. Early diagnosis of pancreatic infection by computed tomography-guided aspiration. Gasnoenterology. 1987;93:1315-1320. 22. San MG, Nagomey DM, Mucha P Jr, et al. Acute necrotizmg pancreatitis: management by planned staged pancreatic nectosectomy/debridement and delayed primary wound closure over drains. Br J Surg. 1991;78:576-581. 23. Ratmer DW, Legermate DA, Lee MJ, et al. Early surgical debridement of symptomatic pancreatic necrosis is beneficial irrespective of infection. Am J Surg. 1992;163:105-110. 24. Pemberton J, Nagomey DM, Becker JM, et al. Controlled open lesser sac drainage for pancreatic abscess. Ann Surg. 1986;203: 596-604. 25. Karimgani I, Porter KA, Langevin RE, Banks PA. Prognostic factors in sterile pancreatic necrosis. GastmenteroIo~. 1992;103: 1636-1640. 26. Beger HG, Bitmer R, Block S, BiichIer M. Bacterial contamina~ tion of pancreatic necrosis: a prospective clinical study. Gustroentero&y. 1986;91:433438. 27. Frey CF, Bradley EL III, Beger HG. Progress in acute pancreatitis. Surg Gynecol Obstet. 1988;167:282-286. 28. Nordback I, Pessi T, Auvinen 0, Aution V. Determination of necrosis in necrotizing pancreatitis. Br J Surg. 1985;72:225-227. 29. Aklridge MC. Diagnosis of pancreatic necrosis. Br J Surg. 1988; 75:99-X0. 30. Clavien PA, Hauyser H, Meyer I? Value of contrast-enhanced CT in the early diagnosis and prognosis of acute pancreatitis: a prospective study of 202 patients. Am J Surg. 1988;155:457466. 31. Balthazar EF, Robinson DL, Megibow AJ. Acute pancreatitis: value of CT in establishing prognosis. Radiology. 1990,174:331-336. 32. Bradley EL III, Murphy FC, Fetguson C. Prediction of pancteatic necrosis by dynamic pancreatography. Ann Surg. 1989;210:495-504.
JULY 1995