The incidence and severity of acute pancreatitis (AP) has increased, and the burden of pancreatic disorders is expected to increase over time (1,2). AP is one of the leading gastrointestinal causes of hospitalization in the United States (3), with mortality ranging from 3% in patients with interstitial pancreatitis (4), 15% in those with necrotizing pancreatitis, and up to 35% if associated with persistent organ failure (5). Impaired physical health-related quality of life is experienced in patients with AP, particularly when associated with multisystem organ failure (6). In an effort to optimize outcomes and provide care of the highest value, health systems and providers managing patients with AP should adhere to current evidence-based best practices and routinely identify gaps and opportunities for improvement.
Validated quality indicators (QIs), which assess process, outcome, appropriateness, efficiency, and structure of care metrics, can provide a quantitative basis for quality improvement (7). Using such metrics makes it possible to “document the quality of care; make comparisons (benchmarking) over time between facilities (e.g., hospitals and providers); make judgments and set priorities (e.g., choosing a hospital or surgery or organizing medical care); support accountability, regulation and accreditation; support quality improvement; and support patient choice of providers (8).” QIs are developed using evidence-based standards of care and are determined by an expert panel of health professionals in a consensus process.
Clinical practice guidelines are recommendations derived from systemic appraisal of the best available evidence for the purposes of advising both caregivers and patients about certain disease-specific management issues (7). Although there are many guidelines for diagnosis and management of AP, it is important to recognize that quality of such guidelines can be variable (9). QIs serve a different purpose than clinical practice guidelines; they are intended to emphasize the importance of outcomes with the goal of measuring performance in health care (10).
The burden of pancreatic disorders is expected to rise over time, and the future of health care requires tracking quality. Validated AP QIs could be used by hospitals and clinicians to assess their performance, set priorities, and develop specific initiatives to improve the quality of patient care and outcomes. The objective of this research was to formally develop a set of validated AP QIs using a robust, rigorous, and widely used methodology.
RAND/UCLA Appropriateness Methodology
AP QIs were developed using the RAND/UCLA Appropriateness Methodology (RAM), a well-defined and scientifically rigorous methodology that correlates with criteria set by national organizations, which specialize in the development and endorsement of clinical quality measurement (11–14). The RAM also reflects the approach of numerous studies across a spectrum of disease processes that have developed QIs (7,15–17). This methodology enables the combination of evidence-based recommendations with the collective judgment of clinical experts in their respective disease-specific specialties to determine the appropriateness of treatment options in clinical care. The modified Delphi methodology used in this study expounds on the original RAM by providing the experts the opportunity to discuss validity of QIs at a face-to-face meeting and rate the indicators in 3 rounds instead of 2, with the third round dedicated to establishing the necessity of indicators and establishing thresholds for adherence.
Valid indicators are defined as those that measure the quality of care and have the potential to improve clinical practices (18). “Necessary” indicators are those that identify practices that must exist in every scenario. Not “Not necessary” means only that the indicator is not universally required across health care systems (11). Therefore, an indicator can be “valid” and “not necessary.”
Establishment of the expert panel
The RAM recommended the use of multidisciplinary teams to reflect the variety of specialties involved in treatment decisions for patients with AP (11). The standards used to select the panel included having individuals who (i) are acknowledged leaders in their specialties, (ii) have an absence of conflicts of interest, and (iii) represent geographic and practice setting diversity (11). The nationally representative panel was made up of gastroenterologists, internists, and a surgeon. The study also recruited a panel moderator and established a research team made up of medical fellows and residents, a dietitian, a pancreatitis nurse navigator, a project manager/statistician, and a project coordinator.
Round 0: meeting
Round 0 was a face-to-face meeting (with an option for attendees to connect via webinar) held during the World Congress of Gastroenterology in Orlando, FL, on October 17, 2017. The purpose was to orient panelists to the study objectives, methodology, and project timeline. Panelists were also polled to gauge study-related preferences and needs.
Literature review and development of proposed quality indicators
The literature and proposed indicators were organized into 10 domains, outlining the plan of care for a patient with typical AP from diagnosis to disposition. These included Diagnosis, Etiology, Initial Assessment and Risk Stratification, Initial Management (baseline–72 hours), Endoscopic Retrograde Cholangiopancreatography (ERCP), Nutrition, Pharmacotherapy, Management of Early Complications (72 hours–4 weeks), Surgery, and Structure of Care. With some minor modifications, these domains were selected based on the established domains in the ACG Guidelines for Management of AP (19). The Structure of Care domain reflected the resources, infrastructure, and policies that a hospital or organization would need to have in place to have a quality program.
The literature review was extensive and a critical step to summarize and rate the available scientific evidence and provide a consistent body of evidence for expert panel members. This was the groundwork needed to resolve any potential disagreements, which may arise during expert panel ratings and/or during the face-to-face round 2 meeting (11).
A medical librarian and the study's research team were enlisted to access PubMed, Ovid, MEDLINE, Embase, and the Cochrane Database of Systematic Reviews/Cochrane Register of Controlled Trials for relevant articles. The literature review was restricted to original research and expert opinion manuscripts, a variety of medical subject headings (MeSH) and non-MeSH terms were used per AP domain, publication dates were limited from 1995 to present, and only English language articles were included. The 1995 cutoff year was elected by the expert panel during round 0 to focus the search on the most relevant clinical literature.
The research team developed proposed QIs based on the ongoing literature review.
For each proposed QI, the following descriptive information was documented:
- Relevant article citation(s) and identification of the research methodology used (e.g., randomized control trial [RCT], prospective cohort, case series) (11,12).
- Clinical recommendations/rationale, which lend support to the proposed QI (11,12).
- Indicator characteristics (i.e., type: process, outcome, appropriateness, efficiency, and/or structure of care) and level of measurement (i.e., hospital or patient) (7,8,11,13).
- Measure specifications (i.e., target population or exclusion criteria) (11,12).
- Performance targets identified, if available (17,20,21).
- Challenges in measurement or evidence gaps (11).
Expert panel members were divided into teams and assigned to 1 of the 10 AP domains. They were sent the literature review and proposed QIs and asked to reword/modify, delete, or suggest new indicators or literature for their assigned domain. Based on their feedback, a list of proposed QIs was revised and sent to the all panelists for round 1 rating.
Together, the literature review and descriptive information related to QIs identifies and organizes the quantity, quality, and consistency of the body of evidence and helps establish whether the evidence leads to desired health outcomes (13) (see Supplement I, Supplementary Digital Content 1, http://links.lww.com/AJG/A182).
Round 1: initial rating of proposed quality indicators
All panelists were sent via email a Qualtrics survey link with instructions on rating 71 proposed QIs for round 1. Based on guidance from the developers of RAM, panelists were given strict instructions stating (i) ratings should be based on their personal clinical judgments and available scientific evidence and not on what they think other panelists might say or believe; (ii) NOT to consider cost implications or feasibility of implementation; (iii) the indicators should be viewed from the perspective of an “average” patient who presents to an “average” physician at an “average” hospital; and (iv) indicators should not necessarily apply to any one specific patient, but rather should pertain to the overall care of patients with AP (11) (see Supplement II, Supplementary Digital Content 1, http://links.lww.com/AJG/A182).
For each proposed indicator, panelists were asked 4 required questions. The first 3 questions were “focusing questions.” According to guidance from the Agency for Healthcare Research and Quality (AHRQ), RAM, and similar studies (11,12,18), these focusing questions help ensure that the panelists consider similar issues when assigning their overall ratings to indicators. The responses to these questions were primarily used to facilitate discussion of QIs during round 2. Focusing questions included the following:
- Scientific evidence: Is the scientific evidence for the proposed QI sufficient? This was rated on a 9-point scale, where 1 = totally disagree and 9 = totally agree.
- Interpretability: Is the proposed indicator written such that it can be interpreted by clinicians? This was rated on a 9-point scale, where 1 = totally disagree and 9 = totally agree.
- Bias: To what extent is the indicator subject to bias? For example, some facilities/hospitals may be judged as poor performers on the indicator because they systematically differ from other hospitals in some aspect, such as severity of the case mix, which is not due to poor quality care. This was rated on a 9-point scale, where 1 = not at all biased and 9 = totally biased.
The fourth question asked panelists to rate the validity of the proposed QI:
- Validity: What is your overall validity rating of the indicator's ability to measure the quality of care and its potential to improve clinical practices (18)? This was rated on a 9-point scale, where 1 = definitely not valid and 9 = definitely valid. Indicators with median ratings between 7 and 9 that meet all criteria for agreement are considered valid (see the Statistical analysis section).
Panelists also had the opportunity to suggest wording changes to improve clarity or increase the potential validity of the QIs and propose new indicators and/or supporting literature.
Round 2: face-to-face meeting of the expert panel
Data from round 1 were analyzed. Panelists met on March 8–9, 2018, in Dallas, TX, for a face-to-face meeting. Each panel member was provided a summary book of their individual ratings and the aggregated round 1 ratings and comments. Panelists were oriented to the meeting objectives and given a brief methodology review, which included how agreement was determined. The panel moderator (R.H.H.) then led the group in discussions of each indicator (by domain) reviewing the aggregated data for scientific evidence, interpretability, bias, and validity. The panel discussed proposed wording changes and options to modify, combine, or eliminate indicators. There was a ≥80% vote required to eliminate an indicator, ultimately classifying it as “not valid.” New QIs were also proposed. After each domain was discussed, the panel rated the revised indicators again for validity based on a 9-point scale, where 1 = definitely not valid and 9 = definitely valid.
All panelists in attendance completed an after-meeting evaluation (17) (see Supplement III, Supplementary Digital Content 1, http://links.lww.com/AJG/A182).
Round 3: necessity rating and proposed performance thresholds
Data from round 2 were analyzed, and indicators were categorized as valid or not valid. All panelists were sent via email the round 2 results and a Qualtrics survey link with instructions on round 3, rating valid QIs for necessity and proposing performance thresholds.
Necessary indicators are those that identify practices that must exist in every scenario. Not necessary means only that the indicator is not universally required across health care systems (11). Panelists were informed that necessary indicators may be used to detect the underuse or overuse of a procedure or treatment; by hospitals and clinicians to quickly evaluate the quality of their AP programs and focus specifically on interventions or changes needed to fill critical gaps in care; and/or inform which indicators will be the focus of future research endeavors to develop quality measures from QIs (11). Panelists rated valid indicators for necessity based on a 9-point scale, where 1 = definitely not necessary and 9 = definitely necessary. The final classification of indicators could be (i) valid and necessary, (ii) valid and not necessary, or (iii) not valid.
Performance thresholds reflect the rate at which panelists recommend providers or health care systems (depending on the context of the QI) should fulfill the QIs in clinical practice (17). Most QIs can be applied to individual providers and/or systems. Performance thresholds represented a rate between 0 and 100. Indicators that recommend against a practice have a low median threshold and range, which suggests that the practice be avoided. A low median threshold is considered any rate between 0% and 40%. The suggested performance targets were determined by calculating the median and range (i.e., minimum target to maximum target) proposed by the expert panel.
Evidence summaries and GRADE classification
Expert panel members were informed of the final results and indicator classifications after round 3. They then drafted evidence summaries for their assigned domains and used the Grades of Recommendation Assessment, Development and Evaluation (GRADE) framework to evaluate supporting literature and identify the quality of evidence and strength of recommendation for each indicator (22). The evidence summaries are not exhaustive reviews of the literature. Instead, they are meant to represent an overview of the key concepts related to each care domain and may identify areas that deserve further clarification and/or the need for future research.
Validity was classified (i.e., valid or not valid) based on (i) the median rating and (ii) whether panelists agreed, as measured by the amount of dispersion of the ratings. Valid indicators had to have a median rating between 7 and 9 (on a scale of 1–9, where 1 = definitely not valid and 9 = definitely valid) and meet all 3 criteria for statistical agreement (which measure the dispersion of ratings). During round 2, there was a ≥80% vote required to eliminate an indicator, ultimately classifying it as “not valid.” Necessary indicators also had to have a median rating between 7 and 9 (on a scale of 1–9, where 1 = definitely not necessary and 9 = definitely necessary) and meet all 3 criteria for statistical agreement.
There is no consensus on the best statistical approach to measure dispersion, and different approaches may lead to different conclusions. To mitigate this issue/minimize variation and increase robustness, we used 3 versions (11): BIOMED classical, P value, and interpercentile range (IPR) adjusted for symmetry. The BIOMED classical definition of agreement sets the maximum number of responses that are allowed to fall outside the 3-point region (1–3, 4–6, and 7–9) containing the median to conclude agreement. For our panel sizes in rounds 1 and 3, this was ≤5 responses; for round 2, this was ≤4. The P value definition of agreement is simply the result of a binomial hypothesis test that 80% of the ratings are within the 3-point region containing the median. Finally, the interpercentile range adjusted for symmetry (IPRAS), a measure developed by the Carlos III Health Initiative (11), is based on the nonparametric measure of spread, which is the difference between the 70th and 30th percentiles (i.e., IPR). After adjusting for the lack of symmetry in responses, if the resulting IPR is less than the IPRAS, then the conclusion is that there is agreement.
Results of all questions from round 1 through 3 were provided to panelists. After round 1, panelists were provided a summary book of their individual and the aggregated round 1 rating responses and comments. For the focusing questions (scientific evidence, interpretability, and bias), this included (i) the median response, (ii) histogram of ratings, and (iii) the BIOMED classical measure of agreement. For the question of validity, this included (i) the median response, (ii) histogram of ratings, and (iii) 3 measures of agreement (i.e., IPRAS, BIOMED classical, and P value). After round 2, panelists were provided (i) median validity response, (ii) the count of responses in each 3-point region, (iii) 3 measures of agreement (i.e., IPRAS, BIOMED classical, and P value), and (iv) the classification of indicators (i.e., valid or not valid). After round 3, panelists were provided the (i) median necessity response, (ii) the count of responses in each 3-point region, (iii) 3 measures of agreement (i.e., IPRAS, BIOMED classical, and P value), (iv) the final classification of indicators (i.e., valid and necessary, valid and not necessary, or not valid), and (v) the median proposed performance threshold and range.
A 20-member nationally representative expert panel was convened. Nineteen (95%) participated in round 1, 15 (75%) participated in round 2, and 18 (90%) participated in round 3. At the end of round 1, 37 indicators were rated as valid, and 34 were rated as not valid. All indicators (valid and not valid) were discussed during round 2 and left as is or revised (n = 37), combined (resulting in n = 4), or eliminated (n = 25 ). After round 2, 41 indicators were rated as valid. After round 3, 40 valid indicators were all found to be necessary, and 1 indicator was eliminated from consideration, deeming it not valid. Table 1 shows the results following round 3. See Supplement IV (Supplementary Digital Content 1, http://links.lww.com/AJG/A182) for the list of 26 indicators deemed not valid.
The 40 final QIs were categorized by domain: Diagnosis (3 indicators), Etiology (6 indicators), Initial Assessment and Risk Stratification (3 indicators), Initial Management (3 indicators), ERCP (5 indicators), Nutrition (3 indicators), Pharmacotherapy (4 indicators), Management of Early Complications (5 indicators), Surgery (4 indicators), and Structure of Care (4 indicators) (Table 1).
Tables 2–11 list the QIs per domain including details about the type of QI, median performance target, and the quality of evidence and strength of recommendation of the indicator based on the GRADE classification criteria (22). An evidence summary follows for each AP care domain.
Diagnosis domain—evidence summary
Although severe upper abdominal pain is a principle component of AP, confirmation by objective data is required to ensure an accurate and specific diagnosis. Most commonly, the diagnosis of AP is supported by a 3-fold elevation in serum pancreatic enzymes (amylase and/or lipase) in the setting of characteristic epigastric pain. It is imperative that serum pancreatic enzymes be checked within 24 hours of pain onset; lipase levels tend to remain elevated for a longer period. Serum pancreatic enzymes may even be normal in some cases of AP (e.g., alcohol or hyperlipidemia) (23,24) or abnormal in some patients (e.g., type II diabetes) who are asymptomatic and do not have AP (25). Serum amylase and lipase may be elevated in cases of non–pancreatitis-related abdominal pain, particularly in the setting of renal insufficiency (26).
In the presence of abdominal pain and normal serum pancreatic enzymes or elevated enzymes in the absence of abdominal pain, imaging is necessary for the diagnosis of AP. For example, cross-sectional imaging with computed tomography (CT) has been shown to be quite sensitive for both the diagnosis and staging of AP (27). The most widely accepted definition for the diagnosis of AP is the requirement of 2 of 3 of the following criteria (19,28–32):
- Acute, severe spontaneous pain in the upper abdomen
- Three-fold elevation of serum pancreatic enzymes (amylase and/or lipase)
- Cross-sectional imaging (e.g., CT) that reveals signs of AP
See Table 2 for details of QIs in this domain.
Etiology domain—evidence summary
A comprehensive assessment for potential etiology(-ies), including a careful history, physical examination, laboratory testing (liver chemistries, serum calcium, and serum triglycerides), and transabdominal ultrasound, is of paramount importance to guide immediate therapy and/or minimize recurrence. Etiologies that may require immediate etiology-based management include hypertriglyceridemia, biliary pancreatitis with ascending cholangitis, diabetic ketoacidosis, and hypercalcemic AP. Patients with AP are more likely to have recurrent attacks if the underlying etiology is not addressed including (i) counseling for smoking and alcohol cessation; (ii) discontinuation of high-risk medications that may be associated with AP (33); (iii) cholecystectomy or biliary sphincterotomy for gallstone-induced pancreatitis; and (iv) diet and medical intervention for hypertriglyceridemia (34) and management of genetic disorders. Because nearly 20% of individuals presenting with AP will develop 2 or more episodes in follow-up, recognition and intervention on etiologic factors is of utmost importance (35).
A contrast-enhanced cross-sectional imaging study with thin (approximately 1 mm) slice cuts obtained through the pancreas and surrounding structures and/or endoscopic ultrasonography is recommended in patients with AP without obvious etiologic factors. This is especially important in adults older than 40 years presenting with their first episode of AP because the prevalence of occult pancreatic ductal adenocarcinoma or other tumors is relatively higher (36). Diagnostic ERCP is not recommended because the yield is low (<10%) when high-quality cross-sectional imaging does not suggest a periampullary process or other obstructive lesions (e.g., main duct intraductal papillary mucinous neoplasm) and because there is risk of iatrogenic pancreatitis and other adverse events specific to ERCP.
An expanding number of pathogenic genetic susceptibility factors are believed to be common in patients with idiopathic AP and in those with recurrent AP with progression to chronic pancreatitis (37,38). Genetic testing is indicated in cases of idiopathic acute and acute recurrent pancreatitis; this should be coordinated by providers with experience in genetic counseling for pancreatitis risk genes and interpretation of the results. Pretest face-to-face counseling with a genetic counselor should be considered in proportion to the significance of test results, especially if the patient is younger (<35 years old), a family history of cystic fibrosis (39), hereditary pancreatitis (40), or in all patients being tested for pancreatic cancer risk (41). Posttest discussions are directed at helping the patient understand the test results and risk perception and developing a disease management plan with the treating physician.
The management of patients with idiopathic AP remains in evolution. However, because the risk of recurrence is substantial, especially after 2 or more episodes, treating physicians should have a low threshold for referral to a pancreatic center of excellence where advanced imaging, genetic testing, and state-of-the-art management approaches are available (42). See Table 3 for details of QIs in this domain.
Initial Assessment and Risk Stratification domain—evidence summary
Baseline intravascular volume status, assessment for evidence of hemoconcentration, and response to fluid resuscitation may influence both risk stratification and initial medical management (0–72 hours.) in patients with AP. Initial and then interval evaluation of hemodynamics, urine output, and renal function may be helpful to guide appropriate (goal-directed) early volume resuscitation (43) (see Initial Management domain). Volume depletion can be attributed to the attack of pancreatitis as a result of fluid loss (e.g., vomiting) and/or third-space losses. Ongoing volume depletion may promote further organ failure due to systemic hypoperfusion, renal insufficiency, hypoxia, and necrotizing pancreatitis. Persistent elevations of blood urea nitrogen (BUN) during the first 48 hours were reported to be associated with increased mortality (44). Clinical evidence of volume depletion (hemoconcentration) at baseline and during the first 24 hours might suggest risk of necrotizing pancreatitis (45,46), whereas the lack of hemoconcentration portends a low risk of necrosis (47,48).
Fortunately, most attacks of AP are self-limited and uncomplicated. Meeting criteria (absence of rebound tenderness/guarding and normal creatinine and hematocrit) for the Harmless Acute Pancreatitis Score is predictive (98%) for having a mild attack (49). Such low-risk patients might be candidates for brief observation and early discharge. Risk stratification is helpful to determine strategies related to early resuscitation and guide triage (intensive care unit [ICU] or ward) decisions. The ability to predict the severity of AP remains challenging, in part because most cases will be mild in severity. Studies comparing the many clinical scoring systems concluded that ability to predict severe AP is limited (50,51). Recognition of patient baseline intrinsic risk factors (e.g., age and comorbidities) and early evidence of clinical deterioration (organ failure and systemic inflammatory response syndrome [SIRS]) despite initial fluid resuscitation seem to be most important (19,52,53). The Bedside Index of Severity in Acute Pancreatitis (BISAP) score (BUN, impaired mental status, SIRS, age >60 years, and pleural effusion) (54) is simple and considered to be an accurate predictor for severe AP (55–57). Organ failure and meeting SIRS criteria are the principle factors associated with severe AP (58,59). It is recommended that patients with hemodynamic instability and/or SIRS (>2 criteria) be admitted to the ICU (19). See Table 4 for details of QIs in this domain.
Initial Management (baseline–72 hours) domain—evidence summary
Early fluid resuscitation with crystalloid solutions remains the cornerstone of initial management for AP, while recognizing that currently available data lack clarity to support a specific strategy (43,60). Intravascular volume depletion in AP occurs for multiple reasons including reduced oral intake, vomiting, insensible losses, and third-space fluid sequestration. The primary goals of initial management are to replete intravascular volume depletion and maintain end-organ perfusion with fluid resuscitation regardless of the clinical setting, severity of the attack, or patient comorbidities.
Adding to the complexity, there is risk of fluid overload due to overly aggressive fluid resuscitation resulting in end-organ damage (e.g., pulmonary edema, hemodilution/tissue hypoxia, and abdominal compartment syndrome). For example, fluid sequestration is associated with worse outcomes (necrosis, fluid collections, and organ failure) in AP (61). However, fluid sequestration may indicate the need for aggressive intravascular fluid resuscitation and is associated with an increased risk of adverse outcomes (e.g., abdominal compartment syndrome). As such, studies regarding fluid resuscitation and AP are potentially subject to reverse causation bias whereby the outcome (fluid sequestration) precedes the intervention (intravenous fluids [IVFs]) (62).
It is challenging to draw firm conclusions from studies of fluid resuscitation in patients with AP because results are often divergent. For example, 1 retrospective cohort study reported that early aggressive fluid resuscitation was associated with improved clinical outcomes (63), whereas another concluded that increased IVFs were associated with adverse outcomes (64). Two prospective studies have also suggested worse outcomes with early aggressive IVF resuscitation (65,66). However, another prospective study reported that early aggressive fluid resuscitation was beneficial even in patients predicted to have mild AP (67).
Although most practitioners and experts can agree that IVF resuscitation is important, several important questions are relevant: (i) What is the optimal initial strategy for resuscitation in terms of bolus and rate of fluid? (ii) How should the response to resuscitation efforts in terms of markers, frequency, and duration be monitored? and (iii) What type of IVFs should be administered?
Limited data suggest that there is an early therapeutic window in AP during which aggressive fluid resuscitation in the emergency department (62) and/or within the first 24 hours of presentation (68–70) can result in meaningfully improved clinical outcomes. Thereafter, a reactive (goal-directed) rather than dogmatic strategy to manage ongoing resuscitation efforts should be adopted based on patient responsiveness to hydration and especially in severe AP (43). It is recommended that monitoring physiologic (mean arterial pressure and urine output) and laboratory parameters (BUN and HCT) over the first 48 hours should guide decisions regarding fluid resuscitation (71). Lactated Ringer solution is the preferred fluid for resuscitation in AP. Compared with normal saline, the anti-inflammatory effect of lactated Ringer solution has been associated with reduced SIRS and CRP levels (72–74).
Current recommendations for fluid resuscitation are based on the sparse body of evidence derived from expert opinion, translational trials, and inconsistent retrospective and prospective clinical studies. Thus, further high-quality prospective trials are needed to further clarify the best strategy for initial hydration, type of fluid, and methods for monitoring resuscitation efforts. See Table 5 for details of QIs in this domain.
ERCP domain—evidence summary
Cholangitis is an uncommon but potentially life-threatening complication of biliary pancreatitis. In most patients, intravenous antibiotics alone will be effective, and thus, ERCP for definitive endoscopic therapy can be deferred for at least 24 hours (75,76). However, for patients with severe disease manifested by hypotension and/or altered mental status, urgent ERCP is recommended following optimization of medical status (77).
Biliary pancreatitis is typically caused as a result of small stones or sludge passing through the ampulla spontaneously; therefore, persistent common bile duct stones are infrequent and routine ERCP not indicated (78,79). Elective ERCP in the setting of biliary pancreatitis may be indicated, however, based on the likelihood of common bile duct stones as assessed by liver test abnormalities, bile duct dilation, and the presence or absence of an intact gallbladder. ERCP should be performed for patients with biliary pancreatitis in whom common bile duct stones are identified on transabdominal ultrasound, cross-sectional imaging, and/or on intraoperative cholangiography. The need and timing for ERCP in patients with an intermediate probability of common bile duct stones as suggested by liver test abnormalities or by bile duct dilation alone depend on preoperative ancillary imaging and/or intraoperative cholangiography. If intraoperative cholangiography is unavailable or the diagnosis is still uncertain before surgery, preoperative endoscopic ultrasonography or magnetic resonance cholangiopancreatography is appropriate in centers with low ERCP expertise (80). Ancillary imaging is not required in patients with a low probability of bile duct stones (minimal liver test abnormalities and absence of bile duct dilation) before cholecystectomy.
Elective ERCP in the setting of biliary pancreatitis may also be required for the management of complications and/or to prevent further attacks (81). For patients with bile duct stones in whom laparoscopic cholecystectomy is contraindicated based on comorbidity, ERCP and biliary sphincterotomy should be performed preferably during the hospitalization to decrease the subsequent risks of symptomatic common bile duct stones. See Table 6 for details of QIs in this domain.
Nutrition domain—evidence summary
Nutrition support via oral or enteric (either with nasogastric [NG] or nasojejunal [NJ]) route is recommended as early as possible in patients with AP (19). Enteral nutritional within 48–72 hours is preferred over the parenteral route as long as there are no contraindications for oral feeding (tolerance, abdominal pain, and ileus) or tube placement (bowel obstruction or other complications). Total parenteral nutrition should be considered only if enteral feeding is not tolerated or cannot be administered. Both oral and enteral feeding have been shown to be more cost-effective and superior to total parenteral nutrition in preventing pancreatic infectious complications and sepsis-related sequelae in AP (82). Oral and enteral nutrition prevents intestinal mucosal atrophy and preserves the gut mucosal barrier, preventing bacterial translocation across the gut.
In mild AP, a diet should be started immediately once the patient's symptoms have improved to the point where they can tolerate oral intake. With initiation of a low fat, a solid diet is as safe and effective as starting clear liquids (83–86). Oral feeding with a low-fat solid diet may accelerate recovery without increased risk of adverse gastrointestinal events (e.g., pain with refeeding) and may result in shorter inpatient length of stay (87).
In severe AP, early (within 48 hours of admit) enteral nutrition has been associated with decreased rates of pancreatic infectious complications, organ failure, mortality, and length of stay (88–90). Contrast-enhanced CT in these patients may be helpful to confirm diagnosis, guide management of complications, and rule out contraindications for tube placement. Enteral feeding via NG route has been shown to be as safe and effective as NJ feeding in patients with AP. Meta-analyses suggest that there are no significant differences in mortality, infectious-related complications, diarrhea, and pain associated with feeding, or length of stay between the NG or NJ routes of enteral nutrition (91,92). See Table 7 for details of QIs in this domain.
Pharmacotherapy domain—evidence summary
Severe abdominal pain is the cardinal symptom of AP and pain relief should be a clinical priority. A critical step to providing adequate pain control is pain assessment (93). This may require focused training of medical personnel in pain assessment and implementation of an institutional policy on pain management. Parenteral analgesics are usually required for adequate pain control in patients with AP. Inadequate pain management can cause adverse physical and psychological effects on individual patients and their family members.
Extrapancreatic infections are a major cause of morbidity and mortality in patients with AP. If there is clinical evidence of cholangitis or an alternate source of infection, appropriate antibiotics should be promptly initiated. However, routine prophylactic use of antibiotics in severe AP is not recommended (94). There is concern that the use of prophylactic broad-spectrum antibiotics could lead to fungal superinfections. Prophylactic use of antibiotics failed to reduce risk of infection in 2 double-blind prospective controlled trials (95,96). Meta-analyses concluded that prophylactic antibiotics do not reduce infected necrosis and/or mortality (97,98). Prophylactic antibiotics should be considered, however, in the management of severe AP in specific patients, such as those with suspected infected necrosis and associated clinical deterioration.
Infection of pancreatic/peripancreatic necrosis is believed to occur from translocation of intestinal bacterial flora. In an effort to prevent the bacterial translocation, probiotics have been considered but are not recommended. A randomized double-blind placebo-controlled trial reported increased mortality associated with the use of probiotics in severe AP (99). A meta-analysis of 4 studies concluded that probiotics do not reduce the risk of infected necrosis (100). See Table 8 for details of QIs in this domain.
Management of Early Complications (72 hours–4 weeks) domain—evidence summary
Early complications of AP cause significant morbidity and potential mortality if not recognized quickly and managed appropriately. If patients are hospitalized for >72 hours, CT scan or MRI should be performed to evaluate for complications in those who fail to improve clinically (e.g., increased pain requirements, inability to tolerate oral intake, and persistence of SIRS) and/or in those who develop signs of worsening severity such as organ failure (19,101). Necrotizing pancreatitis, thrombosis, or pseudoaneurysms can be assessed with CT, and this modality is preferred over the use of MRI (102). In patients with contraindications to CT, such as contrast allergy or elevated creatinine, MRI should be performed.
For patients with AP and persistent severe abdominal distension, often in association with hypotension, abdominal compartment syndrome should be considered, and appropriate diagnostic evaluation and treatment should be initiated (103,104). Initial therapy for suspected abdominal compartment syndrome should be conservative. There are limited data suggesting benefit of continuous veno-venous hemofiltration (105,106).
Infected necrosis can be one of the most devastating early complications of AP and must be recognized and treated appropriately (94). Empiric broad-spectrum antibiotics should be initiated in febrile patients in whom infected necrosis is suspected (necrotizing pancreatitis documented on cross-sectional imaging without another source of infection). If a patient with suspected infected necrosis has been treated with appropriate antibiotics for 48–72 hours and has persistence of fever and/or sign of clinical deterioration, then minimally invasive drainage should be initiated (107,108). The choice of drainage modality (e.g., percutaneous, endoscopic and/or laparoscopic) should be guided by local expertise.
Vascular complications of AP such as pseudoaneurysm or thrombosis can lead to serious consequences including bleeding and intestinal ischemia (109). In patients who develop signs of hemorrhage, contrast-enhanced CT should be performed immediately to rule out vascular complications. Patients with evidence of bleeding should be considered for evaluation and therapy by interventional radiology. Anticoagulation for thrombosis (i.e., of the splenic or portal vein) is controversial; the general consensus is to consider anticoagulation for portal or mesenteric vein, but not splenic vein thrombosis, if acute (no collaterals), and there are clinically significant effects such as development of portal hypertension and/or intestinal ischemia. See Table 9 for details of QIs in this domain.
Surgery domain—evidence summary
Surgical interventions for AP and early complications include cholecystectomy, drainage of fluid collections/necrosectomy, and decompressive procedures for abdominal compartment syndrome. Decisions regarding timings for these interventions should take into account etiology and severity of AP and patient comorbidities. Other than elective cholecystectomy, surgical intervention should only be undertaken when all other measures have failed or the patient has a rapidly declining clinical course associated with abdominal compartment syndrome or overwhelming sepsis.
In patients with uncomplicated, mild to moderate acute gallstone pancreatitis, outcomes are improved when cholecystectomy is performed during the index admission (110–114). Readmissions are decreased when cholecystectomy is performed within 4 weeks from the index episode of acute gallstone pancreatitis (115). Delayed cholecystectomy should be reserved for patients with severe pancreatitis associated with fluid collections/necrosis (116). Cholecystectomy may also be considered in hopes of decreasing recurrent attacks in patients with idiopathic pancreatitis (117,118).
Asymptomatic pseudocysts and pancreatic collections can resolve spontaneously and should not undergo operative intervention due to potential complications. For management of complicated necrotizing pancreatitis, minimally invasive percutaneous, endoscopic, and/or laparoscopic procedures are preferred (108,119–121).
Patients with suspected abdominal compartment syndrome should be managed in a multidisciplinary fashion that includes nephrology, interventional radiology, and surgical consultation. Firm conclusions regarding the need and timing for interventional therapy remain unclear (104). When indicated, there are a variety of surgical approaches that can be implemented (122). See Table 10 for details of QIs in this domain.
Structure of Care domain—evidence summary
To objectively measure the quality of care of AP and to assist in accuracy of patient recruitment into clinical trials, a scheme for risk adjustment of outcomes is warranted (123). Early and persistent organ failure is a reliable predictor of poor outcome and mortality (26). Mortality differs significantly between patients classified as having moderately severe AP and severe AP (52). Even local or systemic complications without persistent organ failure can impact outcomes, so they should be routinely considered in classifying patients with AP into risk categories (19,26). Standard classification and documentation can assist in assessing expectations of outcomes and gaps in meeting expectations.
Patients admitted to medical centers with high-volume admissions for AP have better outcomes (e.g., length of stay) compared with low-volume centers (124,125). For those patients with severe AP, an experienced multidisciplinary team plays a role in development and execution of a therapeutic plan. For example, >90% of patients with severe AP will require intensive care stay and nutritional support (126). Patients with necrotizing pancreatitis may require all components of a team consisting of surgery, pancreaticobiliary endoscopy, interventional radiology, intensive care, and appropriate nutritional support (127).
Regarding specialized care, patients with AP should have readily available access to EUS and ERCP expertise. For example, a decrease in mortality of patients with biliary pancreatitis was associated with centers having higher volume ERCP, less diagnostic ERCP, and less unsuccessful ERCP (128). For this reason, hospitals treating AP should be able to provide these services without encountering delays in obtaining care from such specialists. See Table 11 for details of QIs in this domain.
Clinical practice guidelines are developed with the intention to summarize standards of care and inform treating providers in an effort to improve patient safety and quality of care (129). The notion of having too many guidelines for AP was raised 10 years ago (130). Since then, at least 10 additional AP consensus statements/guidelines have been published (19,29,43,94,131–136). Having multiple guidelines is likely to generate confusion and reduce adherence to guideline-based practice (137). There are also a number of limitations associated with guidelines (138) including variable quality according to endorsements and multidisciplinary influence (9), being derived without a clear grading of quality of evidence (139), and being subject to risk of expert bias (140).
A literature search in 2016 revealed that the groundwork for identification and development of QIs for AP management had been initiated (141), yet the formal evaluation and validation of indicators had not been performed. Validated QIs are developed with scientific rigor in a transparent process. A modified version of the RAM was used, a highly used and scientifically rigorous statistical methodology. This was a Delphi process designed to combine scientific evidence and expert opinion to achieve group consensus (convergence of opinion). In reiterative rounds, the proposed QIs were rephrased for clarity or eliminated from consideration. This resulted in a set of QIs with face, construct, and predictive validity (7), for which the panelists set adherence thresholds. Caregivers, patients, payors, regulators, and administrators can use QIs to provide trusted data for determining priorities, making judgments, and benchmarking for accountability and quality improvement (142). Validated QIs are not recommendations (i.e., Clinical Practice Guidelines); instead, they represent desired standards of care. To identify the potentially most impactful indicators, clinicians and organizations may find it useful to focus on QIs that have GRADE classifications with moderate to high quality of evidence corresponding with a strong strength of recommendation. Implementation and monitoring of clinical care pathways in patients with AP have been associated with improved clinical outcomes (143,144).
Quality medical care is difficult to define, particularly for complex conditions such as AP that has a variety of causes, variable course, and potential for devastating outcomes that may require a multidisciplinary approach. High-quality management has been defined as the degree to which health care services both (i) increase the likelihood of desired health outcomes and (ii) are consistent with current professional knowledge (145). A model for the integration of quality into the cycle of therapeutic development has been described to define the development of professional knowledge (146). It starts with concepts that evolve from clinical observations, then to clinical research, from which that with the highest-level evidence, clinical practice guidelines are developed. QIs are specific recommendations that are to be applied in defined clinical circumstances.
The work described herein is part of a project that builds on itself. The next step would involve identifying QIs, which are measurable, and developing those into “performance/quality measures.” Performance measures can be further specified (with inclusion/exclusion criteria) and evaluated using risk adjustment to understand their relationships to patient perspectives (e.g., satisfaction) and patient outcomes (e.g., mortality) (12). Linking measured performance with better outcomes closes the circle. A registry study would be required to retrospectively or prospectively obtain clinical data related to performance measures. After statistical analyses, those found to be significant with strong supporting evidence could be submitted to national benchmark organizations such as the National Quality Forum for endorsement. Organizations like the National Quality Forum require the information obtained in the first phase (i.e., expert panel ratings, performance thresholds, literature, and GRADE classifications) combined with statistical evidence to gauge the suitability of quality measures for endorsement (13). For more than 50 years, clinical outcomes have remained the principle validation of the effectiveness and quality of medical care (147).
The principle weakness of this initiative pertains to the fact that results of this study are time limited and lack firm recommendations in some clinical domains. It is important to recognize that validated QIs are based on currently available evidence, some of which is expert opinion only. There is potential for expert bias if experts are using their own opinions as the basis of their recommendations. We minimized this risk by grading expert opinion sources as weak recommendations (20). Furthermore, each indicator was evaluated using the GRADE classification (22).
Evaluation of clinical practice guidelines for AP has shown areas of clear agreement but also aspects that reflect knowledge gaps (148). Randomized controlled trials in AP have yielded a number of important answers to clinical questions (94). The process of validating QIs in AP has exposed the areas of pancreatitis care (e.g., fluid resuscitation) that need further high-quality studies.
The strengths of this quality initiative are several, mostly related to the rigorous methodology as outlined above. To minimize expert bias, a qualified library and research staff conducted the literature search and initial grading of strength of evidence. Furthermore, our multidisciplinary expert panel achieved group consensus. The Institute of Medicine declared that effective medical care is one of the 6 aims of quality. Requisites of effective medical care include (i) avoidance of overuse, underuse, and misuse; (ii) evidence-based practice; and (iii) required monitoring to assess performance (149). The development of the set of validated QIs from this study will enable hospitals and providers to monitor and achieve effective medical care for the management of AP.
CONFLICTS OF INTEREST
Guarantor of the article: Paul Tarnasky, MD, FACG, Chair, American College of Gastroenterology and ACG Institute's Acute Pancreatitis Task Force on Quality, accepts full responsibility for the conduct of the study.
Specific author contributions: E.V., P.K., H.O., and P.T. planned and conducted the study, collected and interpreted data, and drafted the manuscript. L.C., D.C., G.A.C., R.D., M.F., T.B.G., R.H.H., R.K., S.J.P., G.I.P., A.R., A.S., S.V., S.S.V., W.W., C.M.W., D.C.W., B.U.W., D.Y., A.E., S.H., S.R., R.R., T.Y., and M.R.B. participated in the study and/or drafted the manuscript. All authors have approved the final draft submitted.
Financial support: The ACG Institute for Clinical Research & Education provided funding for this study, but the work was conducted independently. No writing assistance was provided for this manuscript.
Potential competing interests: D.C.W. serves as a consultant for AbbVie, Regeneron, and Ariel Precision Medicine; received research support from Regeneron and Shire; cofounded and may have equity in Ariel Precision Medicine; is a board member of the National Pancreas Foundation and Ariel Precision Medicine; and is Editor-in-Chief, Clinical and Translational Gastroenterology and Pancreas Section Editor, UpToDate. All other authors disclosed no financial relationships relevant to this publication. This work was presented in abstract form (oral presentation) at the 2018 Annual ACG Meeting in Philadelphia, PA.
WHAT IS KNOWN
- ✓ Detailed recommendations and guidelines for AP management currently exist. However, QIs serve a different purpose: to measure performance in health care.
- ✓ Hospitals and providers managing patients with known or suspected AP should ensure that patients receive high-quality care and desired outcomes according to current evidence-based best practices.
- ✓ The burden of pancreatic disorders is expected to rise over time, and the future of health care requires tracking quality.
WHAT IS NEW HERE
- ✓ A multidisciplinary expert panel composed of physicians (gastroenterologists, hospitalists, and surgeons) who are acknowledged leaders in their specialty and who represent geographic and practice setting diversity was convened.
- ✓ This physician-led initiative formally developed 40 QIs and performance threshold targets for AP management across 10 different domains outlining the plan of care for a patient with typical AP from diagnosis to disposition.
- ✓ These domains included Diagnosis, Etiology, Initial Assessment and Risk Stratification, Initial Management (baseline–72 hours.), ERCP, Nutrition, Pharmacotherapy, Management of Early Complications (72 hours–4 weeks), Surgery, and Structure of Care. The Structure of Care domain reflected the resources, infrastructure, and policies that a hospital or organization would need to have in place to have a quality program.
- ✓ The development of the set of validated QIs from this study will enable hospitals and providers to monitor and achieve effective medical care for the management of AP.
The American College of Gastroenterology endorses this document and the quality indicators contained therein.
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