Management of severe acute pancreatitis

acute severe pancreatitis management
surgical and emergency journal
intensive care critical care
world journal of emergency surgery

1. 2019 WSES guidelines for the management of severe acute pancreatitis Fakhir Raza SIUT Leppäniemi A, Tolonen M, Tarasconi A, Segovia-Lohse H, Gamberini E, Kirkpatrick AW, Ball CG, Parry N, Sartelli M, Wolbrink D, van Goor H. 2019 WSES guidelines for the management of severe acute pancreatitis. World Journal of Emergency Surgery. 2019 Dec;14(1):1-20.

2. Causes of Pancreatitis

3. Timeline of Pacreatitis

4. Introduction B ile stones or excessive use of alcohol severe form comprising about 20–30% of the patients is a life-threatening hospital mortality rates of about 15% Mild: Interstitial edematous pancreatitis) – no organ failure, local or system complications, and usually resolves in the first week. Moderate: If there is transient (less than 48 h) organ failure, local complications or exacerbation of co-morbid disease Severe: Patients with persistent (more than 48 h) organ failure

5. Introduction Infection of the pancreatic and peripancreatic necrosis occurs in about 20–40% of patients with severe acute pancreatitis, and is associated with worsening organ dysfunctions Mortality rate I nfected necrosis and organ failure: 35.2% Sterile necrosis and organ failure: 19.8% I nfected necrosis without organ failure: 1.4%

6. Introduction A cute necrotic collection (ANC): during the first 4 weeks and containing variable amount of fluid and necrotic tissue involving the pancreatic parenchyma and/or peripancreatic tissues Walled off necrosis ( WON): Mature, encapsulated collection of pancreatic and/or peripancreatic necrosis with a well-defined, enhancing inflammatory wall. The maturation takes usually 4 weeks or more after the onset of acute pancreatitis

7. Method

8. Five main areas are discussed Diagnosis Antibiotic treatment Management in the Intensive Care Unit (ICU) Surgical and operative management Open abdomen

9. Diagnosis

10. Questions Which are the criteria to establish the diagnosis of severe acute pancreatitis? What is the appropriate imaging work-up in case of suspected severe acute pancreatitis? What is the role of magnetic resonance imaging (MRI), computed tomography (CT) scan, ultrasound (US), endoscopic ultrasound (EUS), and other ancillary tests? Which laboratory parameters should be considered in the diagnostic process? How do different etiologies affect the diagnostic workup? Which scores are indicated for risk assessment? What is the timing and the suitable test for early follow-up imaging?

11. Which are the criteria to establish the diagnosis of severe acute pancreatitis? Severe acute pancreatitis is associated with persistent organ failure (cardiovascular, respiratory, and/or renal), and high mortality. (1C). Patients who have persistent organ failure with infected necrosis have the highest risk of death (1C). Patients with organ failures should be admitted to an intensive care unit whenever possible (1C).

12. Diagnosis of Pancreatitis The diagnosis of AP requires at least the presence of two of the three following criteria ( i ) A bdominal pain consistent with the disease (ii) biochemical evidence of pancreatitis (serum amylase and/or lipase greater than three times the upper limit of normal) (iii) characteristic findings from abdominal imaging

13. Severity of Pancreatitis Revised Atlanta Classification (RAC) Mild acute pancreatitis (AP)  No organ failure  No local or systemic complications Moderately severe AP  Transient organ failure (< 48 h)  Local or systemic complications without persistent organ failure Severe AP  Persistent single or multiple organ  failure (> 48 h)

14. Severity of Pancreatitis Determinant-based classification (DBC) Mild AP  No organ failure AND  No (peri) pancreatic necrosis Moderate AP  Transient organ failure AND/OR  Sterile (peri) pancreatic necrosis Severe AP  Persistent organ failure OR  Infected (peri) pancreatic necrosis Critical AP  Persistent organ failure AND  Infected (peri) pancreatic necrosis

15. Statements (imaging) On admission, ultrasound (US) should be performed to determine the etiology of acute pancreatitis (biliary) (1C). When doubt exists, computed tomography (CT) provides good evidence of the presence or absence of pancreatitis (1C). All patients with severe acute pancreatitis need to be assessed with contrast-enhanced computed tomography (CE-CT) or magnetic resonance imaging (MRI). Optimal timing for first the CE-CT assessment is 72–96 h after onset of symptoms (1C). Magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasound should be considered to screen for occult common bile duct stones in patients with unknown etiology (1C).

16. Ultrasound Within 24 hours

17. CT and CECT After 72 hours

18. CT grade Grade score Definition A Normal pancreas B 1 Pancreatic enlargement C 2 Pancreatic inflammation and/or peripancreatic fat D 3 Single peripancreatic fluid collection E 4 ≥ 2 fluid collections and/or retroperitoneal air % of necrosis Necrosis score Definition  None Uniform pancreatic enhancement  < 30% 2 Non-enhancement of region(s) of gland equivalent in size of pancreatic head  30–50% 4 Non-enhancement of 30–50% of the gland  > 50% 6 Non-enhancement of over 50% of the gland CT Severity Index Morbidity Mortality  0–1  2–3 8% 3%  4–6 35% 6%  7–10 92% 17% CT severity Index = grade score (0–4) + necrosis score (0–6)

19. MRI and MRCP and Endoscopic US Allergic to iodinated contrast AKI and not a candidate of contrast Pregnant

20. Statement: Diagnostic laboratory parameters The cut-off value of serum amylase and lipase is normally defined to be three times the upper limit. C-reactive Protein level ≥ 150 mg/l at third day can be used as a prognostic factor for severe acute pancreatitis (2A). Hematocrit > 44% represents an independent risk factor of pancreatic necrosis (1B).

21. Statement: Diagnostic laboratory parameter 4. Urea > 20 mg/dl represents itself as an independent predictor of mortality (2B). 5. Procalcitonin is the most sensitive laboratory test for detection of pancreatic infection, and low serum values appear to be strong negative predictors of infected necrosis (2A). 6. In the absence of gallstones or significant history of alcohol use, serum triglyceride and calcium levels should be measured. Serum triglyceride levels over 11.3 mmol/l (1000 mg/dl) indicate it as the etiology (2C)

22. 6 24

23. Trypsinogen in Acute Pancreatitis Immediately Few hours Within 3 days

24. Blood test in acute pancreatitis Lipase is a preferred test over amylase (pancreatic and salivary) In the absence of gallstones or significant history of alcohol use, serum triglyceride should be measured and considered to be the etiology if the value is > 11.3 mmol/l (> 1000 mg/dl) CRP good indicator but rise after 48 hours. Can watch disease activity with this test Resistin for disease activity and prediction of necrosis and POF (persistent organ failure)

25. Blood test in acute pancreatitis BUN > 20 mg/dl (> 7.14 mmol/l) or rising BUN, hematocrit (HCT) > 44% or rising HCT lactate dehydrogenase (LDH), and procalcitonin for predicting infected necrosis in patients with confirmed pancreatic necrosis

26. Diagnostics in idiopathic pancreatitis

27. US exam, MRCP, EUS In idiopathic pancreatitis, biliary etiology should be ruled out with two ultrasound examinations, and if needed MRCP and/or endoscopic ultrasound EUS, to prevent recurrent pancreatitis (2B)

28. Risk scores

29. Bedside index of severity of acute pancreatitis (BISAP) score score one point for each of the following criteria   B lood urea nitrogen level > 8.9 mmol/L   I mpaired mental status   S ystemic inflammatory response syndrome is present   A ge > 60 years   P leural effusion on radiography A BISAP score of two was a statistically significant cutoff value for the diagnosis of severe acute pancreatitis, organ failure, and mortality

30. Risk factors BMI, obesity, and or overweight are independent risk factors for developing severe AP, local complications, or death Changes in intra-abdominal pressure (IAP) and BMI were significantly associated with the severity of AP

31. Takes at least 24 -48 hours Ranson criteria (1974), Glasgow-Imrie score (1978), Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score (SAPS II) (1984), Sequential Organ Failure Assessment (SOFA), CT severity index (CTSI), Bedside Index of Severity in Acute Pancreatitis (BISAP) score (2008), Japanese Severity Score

32. Predictors used age, organ failure or immunocompromise, previous history of chronic disease, temperature, blood pressure, pulse rate, respiratory rate, body mass index, consciousness level, presence of peritonitis, presence of acute renal failure, blood white cell count, blood hematocrit, blood platelet count, blood glucose, blood urea nitrogen, serum creatinine, serum aspartate transaminase, serum lactate dehydrogenase, serum calcium, serum electrolytes, serum bilirubin, plasma albumin, oxygen saturation, pH, and base deficit, multiple imaging modalities principally CT

33. significant cutoff values for prediction of severe AP Ranson ≥ 3, BISAP ≥ 2, APACHE-II ≥ 8, CTSI ≥ 3, CRP at 24 h ≥ 21 mg/dl (> 210 mg/l). A study of 161 patients evaluated the assessment and comparison of the early predictability of various parameters most widely used in AP

34. follow-up imaging

35. Statements In severe acute pancreatitis (computed tomography severity index ≥ 3), a follow-up CECT scan is indicated 7–10 days from the initial CT scan (1C). Additional CE-CT scans are recommended only if clinical status deteriorates or fails to show continued improvement, or when invasive intervention is considered (1C).

36. Antibiotic treatment

37. Questions Which are the indications for an antimicrobial therapy in case of severe acute pancreatitis? Is antibiotic prophylaxis effective in sterile severe acute pancreatitis? What is the correct timing to introduce an antimicrobial therapy? Which antimicrobial regimen should be used? What is the correct duration of antimicrobial therapy?

38. Prophylactic antibiotics Recent evidences have shown that prophylactic antibiotics in patients with acute pancreatitis are not associated with a significant decrease in mortality or morbidity. Thus, routine prophylactic antibiotics are no longer recommended for all patients with acute pancreatitis (1A)

39. Infected necrosis and antibiotics Antibiotics are always recommended to treat infected severe acute pancreatitis. However the diagnosis is challenging due to the clinical picture that cannot be distinguished from other infectious complications or from the inflammatory status caused by acute pancreatitis (2A) Serum measurements of procalcitonin (PCT) may be valuable in predicting the risk of developing infected pancreatic necrosis (1B) A CT-guided fine-needle aspiration (FNA) for Gram stain and culture can confirm an infected severe acute pancreatitis and drive antibiotic therapy but is no longer in routine use (1B)

40. Type of antibiotics In patients with infected necrosis, antibiotics known to penetrate pancreatic necrosis should be used (1B) In patients with infected necrosis, the spectrum of empirical antibiotic regimen should include both aerobic and anaerobic Gram-negative and Gram-positive microorganisms. Routine prophylactic administration of antifungal is not recommended in patients with infected acute pancreatitis, although Candida spp. are common in patients with infected pancreatic necrosis and indicate patients with a higher risk of mortality (1B)

41. Which antibiotic Aminoglycoside Third generation cephalosporins piperacillin/tazobactam Quinolones (ciprofloxacin and moxifloxacin) and carbapenems Metronidazole

42. Intensive care unit

43. Questions Which are the indications for intensive care unit (ICU) admission? When is fluid resuscitation indicated and which fluid should be used? What is the optimal fluid infusion rate and response measurement for initial resuscitation? What is the preferred pharmacologic approach to persistent shock? What is the correct approach for pain control? Which are the indications for mechanical ventilation? What is the medical approach to the abdominal compartment syndrome? What is the role of medications such as Gabexate Mesilate and somatostatin analogues? Enteral nutrition: which are the indications, what type of nutrition should be used, and which is the best way to administer enteral nutrition?

44. Admit in ICU for monitoring Continuous vital signs monitoring in high dependency care unit is needed if organ dysfunction occurs. Persistent organ dysfunction or organ failure occurrence despite adequate fluid resuscitation is an indication for ICU admission (1C)

45. Fluid resuscitation Early fluid resuscitation is indicated to optimize tissue perfusion targets, without waiting for hemodynamic worsening. Fluid administration should be guided by frequent reassessment of the hemodynamic status, since fluid overload is known to have detrimental effects. Isotonic crystalloids are the preferred fluid (1B)

46. Pain control No evidence or recommendation about any restriction in pain medication is available. Non-steroidal anti-inflammatory drugs (NSAID) should be avoided in acute kidney injury (AKI). Epidural analgesia should be an alternative or an agonist with intravenous analgesia, in a multimodal approach. Patient-controlled analgesia (PCA) should be integrated with every described strategy. (1C) Hydromorphone ( Dilaudid ) is preferred over morphine or fentanyl in the non-intubated patient

47. Mechanical ventilation Mechanical ventilation must be instituted if oxygen supply, even with high flow nasal oxygen, or continuous positive airway pressure became ineffective in correcting tachypnea and dyspnea. Both non-invasive and invasive techniques can be used, but invasive ventilation is mandatory when bronchial secretions clearance start to be ineffective and/or the patient is tiring or predicted to tire. Lung-protective strategies should be used when invasive ventilation is needed (1C)

48. Increased intra-abdominal pressure Limitation of sedation, fluids, and vasoactive drugs to achieve resuscitative goals at lower normal limits is suggested. Deep sedation and paralysis can be necessary to limit intra-abdominal hypertension if all other nonoperative treatments including percutaneous drainage of intraperitoneal fluid are insufficient, before performing surgical abdominal decompression (1B)

49. Pharmacological treatment No specific pharmacological treatment except for organ support and nutrition should be given (1B)

50. Enteral nutrition Enteral nutrition is recommended to prevent gut failure and infectious complications. Total parenteral nutrition (TPN) should be avoided but partial parenteral nutrition integration should be considered to reach caloric and protein requirements if enteral route is not completely tolerated. Both gastric and jejunal feeding can be delivered safely (1A)

51. Surgical and operative management

52. Questions Which are the indications for emergent ERCP in case of severe acute pancreatitis? Which is the correct operative/surgical strategy in severe acute pancreatitis? Which are the indications for percutaneous/endoscopic drainage of pancreatic collections (i.e., sterile necrosis, infected necrosis, others)? Which are the indications for surgical intervention?

53. Questions What is the timing for surgery and what is the appropriate surgical strategy (i.e., laparoscopy vs. laparotomy, intraperitoneal vs. extraperitoneal, early vs. delayed)? When is cholecystectomy recommended and what is the correct timing?

54. Indications for emergent ERCP Routine ERCP with acute gallstone pancreatitis is not indicated (grade 1A). ERCP in patients with acute gallstone pancreatitis and cholangitis is indicated (grade 1B). ERCP in acute gallstone pancreatitis with common bile duct obstruction is indicated (grade 2B). ERCP in patients with predicted severe acute gallstone pancreatitis without cholangitis or common bile duct obstruction cannot be recommended at this time (grade 2B).

55. Urgent endoscopic retrograde cholangiopancreatography with sphincterotomy versus conservative treatment in predicted severe acute gallstone pancreatitis (APEC): a multicentre randomised controlled trial Published:July 18, 2020DOI: https://doi.org/10.1016/S0140-6736(20)30539-0 Background It remains unclear whether urgent endoscopic retrograde cholangiopancreatography (ERCP) with biliary sphincterotomy improves the outcome of patients with gallstone pancreatitis without concomitant cholangitis. We did a randomised trial to compare urgent ERCP with sphincterotomy versus conservative treatment in patients with predicted severe acute gallstone pancreatitis. Methods In this multicentre , parallel-group, assessor-masked, randomised controlled superiority trial, patients with predicted severe (Acute Physiology and Chronic Health Evaluation II score ≥8, Imrie score ≥3, or C-reactive protein concentration >150 mg/L) gallstone pancreatitis without cholangitis were assessed for eligibility in 26 hospitals in the Netherlands . Patients were randomly assigned (1:1) by a web-based randomisation module with randomly varying block sizes to urgent ERCP with sphincterotomy (within 24 h after hospital presentation) or conservative treatment. The primary endpoint was a composite of mortality or major complications (new-onset persistent organ failure, cholangitis, bacteraemia , pneumonia, pancreatic necrosis, or pancreatic insufficiency) within 6 months of randomisation . Analysis was by intention to treat. This trial is registered with the ISRCTN registry, ISRCTN97372133.

56. APEC Findings Between Feb 28, 2013, and March 1, 2017, 232 patients were randomly assigned to urgent ERCP with sphincterotomy (n=118) or conservative treatment (n=114). One patient from each group was excluded from the final analysis because of cholangitis (urgent ERCP group) and chronic pancreatitis (conservative treatment group) at admission. The primary endpoint occurred in 45 (38%) of 117 patients in the urgent ERCP group and in 50 (44%) of 113 patients in the conservative treatment group (risk ratio [RR] 0·87, 95% CI 0·64–1·18; p=0·37). No relevant differences in the individual components of the primary endpoint were recorded between groups, apart from the occurrence of cholangitis (two [2%] of 117 in the urgent ERCP group  vs  11 [10%] of 113 in the conservative treatment group; RR 0·18, 95% CI 0·04–0·78; p=0·010). Adverse events were reported in 87 (74%) of 118 patients in the urgent ERCP group versus 91 (80%) of 114 patients in the conservative treatment group. Interpretation In patients with predicted severe gallstone pancreatitis but without cholangitis, urgent ERCP with sphincterotomy did not reduce the composite endpoint of major complications or mortality, compared with conservative treatment. Our findings support a conservative strategy in patients with predicted severe acute gallstone pancreatitis with an ERCP indicated only in patients with cholangitis or persistent cholestasis .

57. Indications for percutaneous/endoscopic drainage of pancreatic collections Clinical deterioration with signs or strong suspicion of infected necrotizing pancreatitis is an indication to perform intervention (percutaneous/endoscopic drainage)

58. After 4 weeks after the onset of the disease On-going organ failure without sign of infected necrosis On-going gastric outlet, biliary, or intestinal obstruction due to a large walled off necrotic collection Disconnected duct syndrome Symptomatic or growing pseudocyst

59. After 8 weeks after the onset of the disease On-going pain and/or discomfort

60. Indications for surgical intervention As a continuum in a step-up approach after percutaneous/endoscopic procedure with the same indications Abdominal compartment syndrome Acute on-going bleeding when endovascular approach is unsuccessful Bowel ischaemia or acute necrotizing cholecystitis during acute pancreatitis Bowel fistula extending into a peripancreatic collection

61. Timing of surgery Postponing surgical interventions for more than 4 weeks after the onset of the disease results in less mortality (2B) 72 h, 12 days, and 30 days – late surgery has clear benefit

62. Surgical strategy In infected pancreatic necrosis, percutaneous drainage as the first line of treatment (step-up approach) delays the surgical treatment to a more favorable time or even results in complete resolution of infection in 25–60% of patients and it is recommended as the first line of treatment (1A) Minimally invasive surgical strategies, such as transgastric endoscopic necrosectomy or video-assisted retroperitoneal debridement (VARD), result in less postoperative new-onset organ failure but require more interventions (1B)

63. Considering mortality, there is insufficient evidence to support open surgical, mini-invasive, or endoscopic approach (1B) In selected cases with walled-off necrosis and in patients with disconnected pancreatic duct, a single-stage surgical transgastric necrosectomy is an option (2C) A multidisciplinary group of experts should individualize surgical treatment taking local expertize into account (2C)

64. Timing of cholecystectomy Laparoscopic cholecystectomy during index admission is recommended in mild acute gallstone pancreatitis (1A). When ERCP and sphincterotomy are performed during the index admission, the risk for recurrent pancreatitis is diminished, but same admission cholecystectomy is still advised since there is an increased risk for other biliary complications (1B). In acute gallstone pancreatitis with peripancreatic fluid collections, cholecystectomy should be deferred until fluid collections resolve or stabilize and acute inflammation ceases (2C)

65. Open abdomen

66. Questions Which are the indications for open abdomen in case of severe acute pancreatitis? What is the best temporary abdominal closure system for open abdomen? What is the correct timing for dressing changes? What is the correct timing for abdominal closure?

67. Open abdomen (OA) In patients with severe acute pancreatitis unresponsive to conservative management of IAH/ACS, surgical decompression and use of open abdomen are effective in treating the abdominal compartment syndrome (2C). We suggest that clinicians should be cautious not to over-resuscitate patients with early SAP and measure intra-abdominal pressure regularly (1C). We suggest that the open abdomen (OA) be avoided if other strategies can be used to mitigate or treat severe intra-abdominal hypertension in SAP (1C). We recommend not to utilize the OA after necrosectomy for SAP (unless severe IAH mandates OA as a mandatory procedure) (1C). We recommend not to debride or undertake early necrosectomy if forced to undertake an early OA due abdominal compartment syndrome or visceral ischemia (1A).

68. Open abdomen management and temporary abdominal closure We recommend the use of negative pressure peritoneal therapy for OA management (1B). We suggest fascial traction be added to NPWT methods (2B). We suggest that further controlled studies be conducted on intra-peritoneal osmotic therapies in SAP (no recommendation)

69. Timing of dressing changes pen abdomen re-exploration should be conducted no later than 24–48 h after the index and any subsequent operation, with the duration from the previous operation shortening with increasing degrees of patient non-improvement and hemodynamic instability (1C)

70. Timing for abdominal closure Early fascial and/or abdominal definitive closure should be the strategy for management of the open abdomen once any requirements for on-going resuscitation have ceased, the source control has been definitively reached, no concern regarding intestinal viability persist, no further surgical re-exploration is needed, and there are no concerns for abdominal compartment syndrome (1B)