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Front Page : Library : IVECCS 2005 : Metabolic : Pancreatitis: Consensus Update Back to Metabolic Back to Table of Contents
Pancreatitis: Consensus Update INTERNATIONAL VETERINARY EMERGENCY AND CRITICAL CARE SYMPOSIUM 2005 Shane Bateman, DVM, DVSc, DACVECC The Ohio State University Columbus, OH, USA 18285656
In April, 2004, an International Consensus Conference was held in Washington DC. The focus of the meeting, which is cosponsored by numerous international professional bodies, was management of human patients with severe acute pancreatitis. A jury of 10 clinicians representing the fields of critical care, internal medicine and surgery evaluated the presentations of 24 experts in the field of pancreatitis and developed consensus guidelines according to evidence-based medicine criteria. The expert presentations addressed specific questions regarding the management of patients that had been selected by the conference organizers and scientific advisors. Some of the questions addressed by the conference are relevant to veterinary patients and will be addressed in this lecture. New information regarding some of these questions has also been published since the conference guidelines were published and will also be addressed.
BACKGROUND
AND
DEFINITIONS
The severity of acute pancreatitis occupies a wide spectrum. Only a minority of human patients have severe disease that requires admission to an ICU. Severe cases such as these however have a 30-50% mortality rate and stay in the ICU for greater than one month. The incidence of severe pancreatitis in veterinary patients is not known. Severe Acute Pancreatitis (SAP) in humans is most often defined as patients with acute pancreatitis that have system manifestations and evidence of distant organ dysfunction that requires critical care. Some patients referred to veterinary specialists for care appear to be similar to humans with SAP and would meet the criteria for SAP of humans.
EVIDENCE BASED GRADE The jury evaluated all material and assigned their recommendations an evidence-based grade according to the following general scheme: Grade
Evidence Required*
A
consistent level 1 studies
B
consistent level 2 or 3 studies or extrapolations from level 1 studies
C
level 4 studies or extrapolations from level 2 or 3 studies
D
level 5 evidence or troublingly inconsistent or inconclusive studies of any level
*see http://www.cebm.net/levels_of_evidence.asp levels for further information
When should the patient admitted with acute pancreatitis be monitored in an ICU or a step-down unit? The first question that the jury dealt with was related to severity of disease, likelihood of progression of organ failure and thus prognosis. Several metrics are used to assess severity and predict outcome and include: scoring systems, biochemical markers, and diagnostic imaging to detect pancreatic necrosis. None of these metrics has been studied in small animal patients to date. Recommendations: Dynamic scoring systems that identify progressive organ dysfunction when combined with serial patient monitoring are more predictive of outcome (Level 5, Grade D).
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Biochemical markers such as C-reactive protein, procalcitonin and others are not recommended for routine use (Level 5, Grade D). Contrast enhanced CT for the detection of peripancreatic fluid accumulation, presence of intrapancreatic gas and pancreatic necrosis should be delayed for up to 72 hours to allow improved detection of necrosis (Level 5, Grade D). Should patients with SAP receive prophylactic antibiotics? Infection develops in about 30-50% of humans with pancreatic necrosis documented using CT or surgical biopsy. Patients with infected necrosis have the highest rates of organ failures and mortality. Infection is occasionally documented during the first week, but peaks during the third week of disease. Evidence is conflicted with one study (not methodologically sound) appearing to skew results towards used of antibiotics. Studies of this issue have enrolled heterogeneous patients, have not standardized management, or have utilized various antibiotic regimens with questionable pancreatic penetration. Intensive use of broad-spectrum antibiotics has shifted culture results to multi-resistant infections gram-negative, gram-positive and fungal infections. Necrosis has been documented in a large percentage of small animal patients with SAP at necropsy. The incidence of infection in small animal patients is unknown. Recommendations: Do not use routine antimicrobial prophylaxis (Level 2b, Grade B). Subsets of patients may benefit but require further study. What is the optimal mode and timing of nutritional support for the patient with SAP? Traditional approach to resting the gut and decreasing pancreatic secretions has resulted in a reliance on parenteral nutrition for many patients. The body of evidence is growing describing benefits of enteral feeding that include improved gut barrier and decreased risk of bacterial translocation and systemic infection. Recommendations: Use enteral feeding instead of parenteral feeding. Use jejunal feeding after initial resuscitation wherever possible (Level 1a, Grade A). Parenteral feeding should be used only after attempts at enteral feeding have failed after 5-7 days (Level 5, Grade D). Strict glycemic control should be enforced regardless of feeding method (Level 1b, Grade A). Parenteral nutrition should be enhanced with glutamine (Level 5, Grade D). What are the indications for surgery in SAP and what is the optimal timing of intervention? What are the roles for less invasive approaches? Apart from catastrophic indications for surgical intervention, controversy surrounds which features of SAP warrant surgical intervention. Advancement in non-invasive techniques have allowed less invasive surgery to be performed with acceptable results. Infected necrosis is still considered a surgical disease, but delayed surgical intervention may allow infection to progress into abscess that may be treated non-invasively. The incidence of infection has not been studied in veterinary patients. Recommendations: CT or US guided FNA should be performed (repeatedly if required) to determine if necrosis is sterile or infected (Level 4, Grade C). Do not debride or drain sterile necrosis (Level 4, Grade C). Surgical or non-invasive (in selected patients) debridement/drainage should occur in infected necrosis (Level 4, Grade C). If the patient is otherwise stable, operative intervention for debridement of infected necrosis should be delayed until week 2-3 (Level 4, Grade C). Is there a role for therapy targeting the inflammatory response in the patient with SAP? The host response to SAP and the presence of infection is complex. Many anti-inflammatory mediators may play a role. Increasingly, the inflammatory response has been recognized to compartmentalize into a potent local pro-inflammatory actions, while systemic anti-inflammatory activity predominates. This may increase the risk of secondary bacterial infection. Several anti-inflammatory mediators have been studied, but the results are inconclusive due to small size or lack of effect documented. The use of fresh frozen plasma in human patients has been shown to be ineffective. Current interest in the use of rh-APC is emerging in light of the beneficial effect documented in severe sepsis. SAP patients meeting criteria for severe sepsis (infection documented) may benefit from the use of rh-APC, but the use of rh-APC has not been studied in patients with SAP without evidence of severe sepsis. The use of fresh frozen plasma is still recommended by many for treatment of pancreatitis in small animal patients. Recommendations: General supportive measures should be employed such as early volume resuscitation (Level 1b, Grade A) and lung protective ventilation strategies in patients with
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respiratory failure (Level 1b, Grade A). If the patient with SAP meets criteria for severe sepsis then management according to current sepsis guidelines should be initiated and include: use of rh-APC (Level 1b, Grade A) and low dose corticosteroids for pressor-dependent shock (Level 1b, Grade B). The use of other immune-modulating therapies is not recommended (Level 1b, Grade A for PAF antagonist lexipafant; Level 5, Grade D for all others).
OPPORTUNITIES
FOR FURTHER STUDY TO CLARIFY MANAGEMENT OF HUMAN
SAP
Large randomized, multi-center trials of sufficient power to generate clear evidence are needed to answer the following questions: The benefits of intravenous prophylactic antimicrobial therapy The merits of enteral and parenteral nutrition when strict glycemic control is included The consequences of gastric versus jejunal feeding The benefit of novel immune-modulating therapies
APPLICATION
OF
HUMAN GUIDELINES
TO
SMALL ANIMAL VETERINARY
PATIENTS
Important differences should be deliberated when the application of these guidelines are considered for small animal veterinary patients. Most importantly, the incidence of infection in our patients is NOT known. Traditionally, the course of hospitalization has been one week or less on average. The duration of hospitalization appears to be an important factor relating to infection in humans. With increasingly complex care and the ability to keep patients alive longer, infection may play an increasingly important part of the pathophysiology of this disease in our patients. Although there is scanty evidence in our literature to suggest that infection does not play an important role, we haven't been looking for infection. Although we have become increasingly adept at documenting pancreatic necrosis, no study has looked for the incidence of infection. The use of color-flow Doppler ultrasound or contrast enhanced CT evaluation of small animal patients with SAP is warranted to document the presence and severity of pancreatic necrosis. Increasingly, we need to utilize serial FNA as a tool to document the infection of sterile pancreatic necrosis. The use of prophylactic antibiotics in veterinary patients with SAP appears to be widespread with no good evidence to support their use. Further study is desperately needed to base future treatment recommendations upon. References 1. Clancy TE, Benoit EP, Ashley SW. Current management of acute pancreatitis. Journal Of Gastrointestinal Surgery 2005;9(3):440-452. 2. Eatock FC, Chong P, Menezes N, et al. A Randomized study of early nasogastric versus nasojejunal feeding in severe acute pancreatitis. American Journal Of Gastroenterology 2005;100(2):432-439. 3. Nathens AB, Curtis JR, Beale RJ, et al. Management of the critically ill patient with severe acute pancreatitis. Critical Care Medicine 2004;32(12):2524-2536.
SPEAKER INFORMATION (click the speaker's name to view other papers and abstracts submitted by this speaker) Shane Bateman, DVM, DVSc, DACVECC he Ohio State University Columbus, OH
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