1. Dr Sawan Bopanna Preceptor:Dr Pramod Garg
ASSESSMENT OF SEVERITY OF ACUTE PANCREATITIS
Dr Sawan Bopanna Preceptor:Dr Pramod Garg

2. Acute pancreatitis- acute inflammatory process of the pancreas
Incidence of acute pancreatitis- Incidence of AP: 30-80/100,000 population
Indian data regarding incidence of acute pancreatitis lacking
Increasing trend of acute pancreatitis in the last two decades- likely due to
Increasing alcohol intake
Increasing obesity and thus gallstones

3. Acute pancreatitis is associated with 10–25% mortality
80% of patients with acute pancreatitis have mild disease
20%of patients develop severe acute necrotizing pancreatitis
The mortality in severe acute pancreatitis (SAP) is may reach 40%

4. PREDICTORS OF SEVERITY
WHY ARE THEY NEEDED?
There are important reasons to define and stratify the severity of acute pancreatitis
Appropriate Patient Triage:
Important to identify patients with potentially severe acute pancreatitis who require aggressive early treatment
In secondary care setting –for identification of those patients who need transfer to higher centres
Compare results of studies of the impact of therapy

5. WHEN ARE THEY NEEDED?
Optimally within first 24 hours
WHICH IS BEST?

6. WHETHER PATIENT WILL DEVELOP SAP ? WHETHER PATIENT WILL DIE ?
ASSESSMENT OF SEVERITY OF ACUTE PANCREATITIS ON THE DAY OF ONSET OF PAIN Questions?
WHETHER PATIENT WILL DEVELOP SAP ?
(SEVERITY)
WHETHER PATIENT WILL DIE ?
(MORTALITY)

7. Severity of acute pancreatitis :2 peaks
EARLY
LATE
CYTOKINES
SEPSIS

8. Usually lasts for the first week
TWO PHASES:
1.EARLY PHASE :
Usually lasts for the first week
Inappropriate systemic inflammatory response to acinar injury
Resulting cytokine storm – organ failure
Organ failure is a major determinant of severity in the early phase
Local complications may be identified but not the predominant determinant of severity.

9. 2. LATE PHASE: after the first week
Late phase occurs only in patients with moderately severe or severe acute pancreatitis
Local complications evolve during the late phase
Major determinant of severity in the late phase –sepsis related organ failure.

10. IDEAL PREDICTOR Rapid Reproducible Inexpensive Minimally invasive
Should assist in monitoring the progression of disease

11. Predictors of severity Day 1-3
Clinical assessment
SIRS
Organ failure asssessment
Biochemical parameters
Imaging
Multifactorial scoring systems

12. CLINICAL ASSESSMENT:
Clinical trials have evaluated the ability of clinicians to differentiate mild from severe acute pancreatitis.
Estimated that clinical assessment only identifies 34% to 44% of severe AP cases when performed by experts.
Therefore initial clinical assessment cannot predict the severity of AP reliably.
Wilson C, Heath DI, Imrie CW. Prediction of outcome in acute pancreatitis: a comparative study of APACHE II, clinical assessment and multiple factor scoring systems. Br J Surg 1990;77:1260–4

13. Patient characteristics: Obesity
Obesity to be an independent risk factor for severe outcome in patients with AP
Systemic complications were significantly more common among obese than nonobese patients .
Hypertensive or diabetic patients developed more systemic complications-multivariate analysis demonstrated that the presence of these underlying diseases did not modify the prognostic role of obesity in acute pancreatitis.
Martinez J, Sanchez-Paya J, Palazon JM, et al. Obesity: a prognostic factor of severity in acute pancreatitis. Pancreas 1999;19:15–20

14. Three trials could not show a significant effect of age on survival
Age > 70 years when admitted the hospital, 19% risk of mortality
Toh SK et al GUT 2000;46
Age cut off ranges from > 44 to > 70
Three trials could not show a significant effect of age on survival

15. 3. Diagnostic peritoneal lavage:
The presence, volume, and color of aspirated peritoneal fluid shortly after hospital admission- shown to be associated with severity in AP
Diagnostic peritoneal lavage after 8 hours –
superior to clinical assessment and as accurate as Ranson and Glasgow scores at 48 hours
Invasive and poorly tolerated by patients-no longer used.
McMahon MJ, Playforth MJ, Pickford IR. A Comparative study of methods for the prediction of severity of attacks of acute pancreatitis. Br J Surg 1980;67:22–5

16. BIOCHEMICAL PARAMETERS H Repo et al BJS 2004
MARKERS
CUT OFF
SENSITIVITY
SPECIFICITY
TAP
10ng/ml
83%
72%
IL-6
>132pg/ml
73%
91%
CRP
>108mg/dl
70%
BUN
>5mmol
84%
66%
LDH
>750
77%
86%
APACHEII
>8
52%

17. OTHER MARKERS OF INFLAMMATION : Procalcitonin
Polymorphonuclear elastase
MARKER
SENSITIVITY
SPECIFICITY
ACCURACY
PMN-E 24 h/300 mcg/L 93 99 98
Procalcitonin(>1.1 ng/ml) 72 73 86

18. CYTOKINES: IL-6 IL-8 IL-1 MARKER SENSITIVITY SPECIFICITY ACCURACY
IL-6 (400 pg/mL)
89%
87%
88%
IL-8 (100 pg/mL)
50%
74%
IL-1 (1 pg/mL)
72%
82%
Inflammatory cytokines, C reactive protein, and procalcitonin in acute pancreatitis :Surgery 2004

19. C REACTIVE PROTEIN
CRP peak in serum is usually not maximal until about day 3 after the onset of pain
Detailed evaluation - determined CRP to
be a useful predictor of severe AP by 48 hours from the onset of symptoms
CRP is the best established and most popular single predictor of severity in AP because of its low cost and easy availability

20. A level of 150 mg/L is the standard for distinguishing mild from severe disease
CRP testing at 48 hours has shown a sensitivity ranging from 65% to 100% and a positive predictive value of 37% to 77%, which is similar to APACHE II
Triester SL, Kowdley KV. Prognostic factors in acute pancreatitis. J Clin Gastroenterol 2002;34:167–76

21. ROUTINE LABORATORY DATA AS PREDICTORS
Studies suggest that hemoconcentration on admission (hematocrit equal or greater than 47%) or failure of admission hematocrit to decrease at 24 hours -strong risk factor for the development of pancreatic necrosis
Baillargeon et al Am J Gastroenterol 1998;93:2130–4
Large trial that concluded that hemoconcentration does not correlate significantly with organ failure and mortality rate
Lankisch PG et al Am J Gastroenterol 2001;96:2081–5

22. Two general types of scoring systems have been applied to AP
The first correlates laboratory and pancreatitis-specific clinical markers with outcome Ex: Ransons criteria
The second correlates nonspecific physiological variables with outcome Ex: APACHE II

23. RANSONS CRITERIA
AT ADMISSION
ORIGINAL
GALLSTONE PANCREATITIS
Age at admission
>55
>70
WBC
>16000
>18000
Blood Glucose(mg/dl)
>200
>220
Lactic dehydrogenase
>350
>400
AST
>250
WITHIN 48 HOURS
Hematocrit decrease
>10
BUN
>5
>2
Serum Calcium(mg/dl)
<8
PaO2
<60
Base excess
< -4
< -5
Fluid Sequestration
>6
>4

24. Disadvantages ORIGINAL EVALUATION -Sensitivity 65% Specificity 99%
Requires a full 48 h to be completed, missing a potentially valuable early therapeutic window
It contains data not routinely ordered or collected during hospitalization at the current time (eg. lactate dehydrogenase, fluid sequestration, and base deficit)

25. GLASGOW/ IMRIE CRITERIA: From Glasgow, Scotland
Eight physiological and lab parameters within the first 48 hrs
Modified twice
Sensitivity of 56% and specificity of 83%
Imrie et al GUT 1984
Large number of studies analysing Imrie
Overall sensitivity of 80% and PPV of less than 70%

26. Glasgow/ Imrie criteria
Within 48 hours
Original
Modified
Blamey et al
Age (years)
>55
WBC(cells/mm3)
>15000
Blood glucose(mmol/l)
>10
Lactic dehydrogenase(U/L)
>600
Transaminases (U/L)
>100
omitted
Serum albumin(g/L)
<32
Blood Urea nitrogen(mmol/L)
>16
Serum calcium (mmol/L)
<2.0
PaO2
<60

27. APACHE II score :
Developed in Intensive Care Research group in Washington
Acute Physiology +age + chronic health evaluation score.
Calculate the prognosis in critically ill patients
In AP- scores > 8 Severe pancreatitis.

28. Acute Physiology Score
Variable +4 +3 +2 +1
TEMP
>41
<29.9
MAP
>160
70-109
50-69
<49 HR
>180 RR
>50
35-49
12-24 O2
>500
<200
Po2>70
PO2
61-70
pO2
55-60
<55 pH
>7.7
<7.15

29. +4 +3 +2 +1
sodium
>180
>160-
179
<110
Potassium
>7
6-6.9
3-3.4
<2.5
Creatinine
>3.5
2-3.4
0.6
Hct
>60
<20
WBC
>40
3-14.9
1-2.8
<1
GCS
15 – actual GCS

30. Chronic Health Points:
If patient has severe organ insufficiency or is immunocompromised:
For nonoperative or emergency postoperative patients(5 points)
For elective postoperative patients(2 points)
Age(yrs)
Points
<44
45-54 2
55-64 4
65-74 6
>75 8

33. ADVANTAGES OF APACHE II:
The ability to calculate a score on admission.
Earlier stratification to intensive care or enrollment onto clinical trials
Can be updated daily over the hospital course- allows for monitoring of disease progression and response to therapy
Range is from 0 to 72 points, more accurate selection of cut-off levels

34. DISADVANTAGES OF APACHE II:
Complexity – significant inconvenience
Requires the collection of a large number of parameters
Important measures such as pancreatic injury and significant regional complications are missed

35. New variables were added to APACHE II to improve its accuracy that lead to the development of APACHE III
APACHE III system does not appear to be as useful as APACHE II in distinguishing mild from severe attacks at the time of admission
Williams M, Simms HH. Prognostic usefulness of scoring systems in critically ill patients with severe acute pancreatitis. Crit Care Med 1999;27:901–7

36. BISAP :Bedside Index For Severity In Acute Pancreatitis
BUN >25
Impaired mental status (GCS <15)
SIRS defined as two or more of the following:
1.Temperature of <36 C or > 38 C
2. Respiratory rate >20 breaths/min or PaCO2 <32 mm hg
3. Pulse >90/min
4. WBC <4000 or >12000 cells/mm3
Age >60 years
Pleural effusion detected on imaging
1 point for each within 24 hr of presentation
Composite score 0-5

37. Claimed to be a simple system
Actual calculation requires measurement of more than 5 points.
Scores and mortality
3 = 5.3%
4 = 12.7%
5 = 22.5%

38. NEWER SCORING SYSTEMS

39. CT SEVERITY INDEX Pancreatic Inflammation: Normal Pancreas
Focal or diffuse enlargement of the gland 1
Intrinsic Pancreatic abnormalities with peripancreatic fat inflammation 2
Single ill defined collections or presence of gas in or adjacent to the pancreas 3
Two or more poorly defined collections or presence of gas in or adjacent to the pancreas 4
Pancreatic necrosis:
None
< 30 %
30 – 50 %
>50 % 6
Mild (0-3 points) Moderate (4-6 points) Severe (7-10points)

40. Interobserver agreement - excellent.
CT SEVERITY INDEX
Interobserver agreement - excellent.
Koenraad J. Mortele et al Gastrointestinal Imaging 2010
Severity:
CTSI of % CTSI of %
CTSI of %
CTSI of %
Balthazar EJ, Robinson DL, Megibow AJ, Ranson JH. Acute pancreatitis: value of CT in establishing prognosis. Radiology1990;174:331-6

41. IMPACT OF NECROSIS ON SEVERITY
Extent of pancreatic necrosis is associated with organ failure and death
AIIMS study, Clin Gastroenterol Hepatol 2005

42. Garg pk et al ,clinical gastroenterology and hepatology 2005

43. PROBLEMS WITH IMAGING
72 hours required for adequate assessment of necrosis
Cannot predict mortality accurately

44. Cut offs for SAP:
BISAP score ≥ 3
Ranson ’ s ≥ 3
APACHE-II ≥ 8
CTSI ≥ 3

46. PROBLEMS WITH SCORING SYSTEMS
LATE PREDICTION
CUMBERSOME
ALL PARAMETERS MAY NOT BE AVAILABLE
ACCURACY 80%

47. CHANGING CONCEPT OF SEVERITY IMPORTANT
SAP = Systemic + Local complications

48. Correlated with poorer survival
SIRS – EARLY PREDICTOR OF SEVERITY?
pulse >90 beats/min
rectal temperature <36º C or >38º C
white blood count <4000 or >12,000 per mm3
respirations >20/min or PCO2 <32 mm Hg
Persistent or developing SIRS in the first 48 h - associated with higher organ dysfunction scores
Correlated with poorer survival

50. Clinical Predictors Of Multiorgan Failure

51. DYNAMICS OF ORGAN FAILURE
EARLY vs LATE
TRANSIENT vs PERSISTENT
SINGLE vs MULTIPLE

52. ORGAN FAILURE RELATED SCORING
Persistent Organ failure determinant of severity.
Marshall
SOFA
Evaluation of the six major organ systems Pulmonary, cardiac, renal, hepatic, neurologic, coagulation
Limited number of studies using these systems to assess survival or organ failure
Bassi et al Pancreatology 2005
Johnson et al GUT 2004

53. MARSHALL SCORE

54. MARSHALL SCORE
Simple to use
Universal applicability
Stratify disease severity

55. Sensitivity of 59% and specificity 91% within 72 hrs of admission
A score >2 for more than 2 days is associated with increased mortality
Sensitivity of 59% and specificity 91% within 72 hrs of admission
Comparable with APACHE II
Goris RJ et al Eur J Surg 1992

56. SOFA :SERIAL ORGAN FAILURE ASSESSMENT

57. SOFA :SEQUENTIAL ORGAN FAILURE ASSESSMENT
Scores over 4: Sensitivity 76.2% Specificity 69.2%
Scores over 8: Sensitivity 86.7 % Specificty 90%
Scoring systems in acute pancreatitis :Which on to use in ICU. Juneja D J Crit Care 2010

58. HOW DO YOU DETERMINE MORTALITY?
ORGAN FAILURE
INFECTED PANCREATIC NECROSIS
EARLY
PERSISTENT
SEVERE

59. Thus the presence of either indicates severe disease
The absolute influence of OF and IPN on mortality is comparable
Thus the presence of either indicates severe disease
The relative risk of mortality doubles when OF and IPN
are both present and indicates extremely severe disease or critical acute pancreatitis

60. TIMING OF ONSET OF ORGAN FAILURE
60% of patients with AP die of organ failure within the first week
Onset of organ failure within 7 days- Early severe acute pancreatitis
Overall mortality - 42–54% in the first week
Rapidity of development of organ failure- predictor of severity

61. Fulminant Subset-Organ failure within 72 hrs of onset of pancreatitis
Subfulminant subset–Organ failure between 4 and 7 days

62. MORTALITY

63. Early severe organ failure-risk of pancreatic infection increases
Timing of onset of organ failure- predictor of severity of acute pancreatitis
Severe OF within 72 h of onset of AP suggests intense systemic onslaught at a time when necrosis and pancreatic infection have not even evolved
Early severe organ failure-risk of pancreatic infection increases
Rau BM, Bothe A, Kron M, et al. Role of early multisystem organ failure as major risk factor for pancreatic infections and death in severe acute pancreatitis. Clin Gastroenterol Hepatol 2006;4:1053–61

65. Transient organ failure Worsening of pre-existing organ dysfunction
MILD ACUTE PANCREATITIS
No organ failure
No local or systemic complications
MODERATELY SEVERE ACUTE PANCREATITIS
Transient organ failure
Worsening of pre-existing organ dysfunction
Local complications
SEVERE ACUTE PANCREATITIS
Persistence of organ failure(48 hours)
Single/multiple organ failure

66. LOCAL COMPLICATIONS Acute Pancreatitis Interstitial Pancreatitis
Necrotizing
APFC <4 weeks
ANC
Resolve
Pseudocyst
>4 weeks
Resolve
WON > 4weeks
Sterile
Infected

67. Limitations: Moderate category:
All local complications including infected pancreatic necrosis placed under this category
Organ Failure:
Prognostic relevance of early organ failure not clearly defined

68. SUMMARY
There is no single tool that serves as the optimal predictor of severity
CRP –most useful single marker.
MULTIPARAMETER SCORING SYSTEMS
APACHE II scoring is used most often as it gives early and continuous monitoring of severity
Ranson/ Imrie –historical significance.
BISAP- newer,easier to calculate
No clear data on one scoring to be better than the other.

69. RADIOLOGICAL SCORING:
Useful in assessing severity
Value of CT in predicting severity – No different than other scores
Does not help in predicting mortality
The Revised Atlanta Classification – allows classification and management but has its limitations

70. ASSESSMENT OF SEVERITY WHICH ONE TO USE

71. SEVERITY ASSESSMENT INITIAL LATE IPN SIRS 1 WEEK DAY 1 ORGAN FAILURE