Endoscopic retrograde cholangiopancreatography (ERCP) is now almost exclusively a therapeutic modality for pancreatic as well as biliary disorders. ERCP alone or with associated pancreatic and biliary therapy can cause a spectrum of mild and severe complications, including pancreatitis, hemorrhage, perforation, and cardiopulmonary events. Understanding of complications of ERCP has progressed substantially in the past decade, including widespread adoption of standardized consensus-based definitions of complications, large multicenter multivariate studies that have permitted clearer understanding of patient and technique-related risk factors for complications, and introduction of new technical approaches to minimize risks of ERCP.
- •
Complications occur after 5% to 10% of endoscopic retrograde cholangiopancreatography (ERCP).
- •
Risk factors for post-ERCP pancreatitis include patient-related as well as procedure-related variables.
- •
Placement of prophylactic pancreatic stents is effective, reducing risk of pancreatitis after ERCP.
- •
Hemorrhage after sphincterotomy is primarily related to coagulation defects, but can be treated by endoscopic hemostasis techniques.
- •
Perforation can involve bowel wall, sphincterotomy, or guidewire; early recognition and management are key to satisfactory outcomes.
- •
Endoscopist experience is reflected in complication rates.
Overview
Endoscopic retrograde cholangiopancreatography (ERCP) is now almost exclusively a therapeutic modality for pancreatic as well as biliary disorders. ERCP alone or with associated pancreatic and biliary therapy can cause a spectrum of complications, including pancreatitis, hemorrhage, perforation, and cardiopulmonary events ( Box 1 ). These complications can range from mild (defined as requiring 3 or fewer nights’ hospitalization), to severe (resulting in extended hospitalization, requiring surgical intervention, and resulting in permanent disability or even death). Understanding of complications of ERCP has progressed substantially in the past decade, including widespread adoption of standardized consensus-based definitions of complications, large multicenter multivariate studies that have permitted clearer understanding of patient and technique-related risk factors for complications, and introduction of new technical approaches to minimize risks of ERCP.
- •
Pancreatitis
- •
Hemorrhage
- •
Perforation
- •
Cholangitis
- •
Cholecystitis
- •
Stent-related
- •
Cardiopulmonary
- •
Miscellaneous
Consensus-based definitions of complications and other negative outcomes
Standardized definitions for complications of sphincterotomy were introduced in 1991 and are still widely used for therapeutic ERCP in general ( Table 1 ). Severity is assessed primarily by length of hospital stay, and intervention required to treat the complications. Universal consensus-based definitions have allowed valid comparisons of outcomes of therapeutic ERCP in various settings. There is an increasing awareness of the entire spectrum of outcomes, including technical failures, ineffectiveness of the procedure in resolving the presenting clinical problem, long-term sequelae, costs, extended hospitalization, and patient (dis)satisfaction. The term complications has to some degree been supplanted by the terms adverse events and unplanned events. A successful procedure with a minor or even a moderate complication may sometimes be a preferable outcome to a failed procedure attempt without any obvious complication: the kinds of advanced procedures discussed elsewhere in this issue show the complexity of therapeutics now performed at ERCP, often substituting for major surgery or interventional radiologic procedures, all with their own risk of morbidity and mortality, as well as resource use.
| Mild | Moderate | Severe | |
|---|---|---|---|
| Pancreatitis | Clinical pancreatitis, amylase at least 3 times normal at more that 24 h after the procedure, requiring admission or prolongation of planned admission to 2–3 d | Pancreatitis requiring hospitalization of 4–10 d | Hospitalization for more than 10 d, pseudocyst, or intervention (percutaneous drainage or surgery) |
| Bleeding | Clinical (ie, not just endoscopic) evidence of bleeding, hemoglobin drop <3 g, no transfusion | Transfusion (4 units or less), no angiographic intervention or surgery | Transfusion 5 units or more, or intervention (angiographic or surgical) |
| Perforation | Possible, or only slight leak of fluid or contrast, treatable by fluids and suction for ≤3 d | Any definite perforation treated medically 4–10 d | Medical treatment of more than 10 d, or intervention (percutaneous or surgical) |
| Infection (cholangitis) | >38°C for 24–48 h | Febrile or septic illness requiring more than 3 d of hospital treatment or percutaneous intervention | Septic shock or surgery |
Consensus-based definitions of complications and other negative outcomes
Standardized definitions for complications of sphincterotomy were introduced in 1991 and are still widely used for therapeutic ERCP in general ( Table 1 ). Severity is assessed primarily by length of hospital stay, and intervention required to treat the complications. Universal consensus-based definitions have allowed valid comparisons of outcomes of therapeutic ERCP in various settings. There is an increasing awareness of the entire spectrum of outcomes, including technical failures, ineffectiveness of the procedure in resolving the presenting clinical problem, long-term sequelae, costs, extended hospitalization, and patient (dis)satisfaction. The term complications has to some degree been supplanted by the terms adverse events and unplanned events. A successful procedure with a minor or even a moderate complication may sometimes be a preferable outcome to a failed procedure attempt without any obvious complication: the kinds of advanced procedures discussed elsewhere in this issue show the complexity of therapeutics now performed at ERCP, often substituting for major surgery or interventional radiologic procedures, all with their own risk of morbidity and mortality, as well as resource use.
| Mild | Moderate | Severe | |
|---|---|---|---|
| Pancreatitis | Clinical pancreatitis, amylase at least 3 times normal at more that 24 h after the procedure, requiring admission or prolongation of planned admission to 2–3 d | Pancreatitis requiring hospitalization of 4–10 d | Hospitalization for more than 10 d, pseudocyst, or intervention (percutaneous drainage or surgery) |
| Bleeding | Clinical (ie, not just endoscopic) evidence of bleeding, hemoglobin drop <3 g, no transfusion | Transfusion (4 units or less), no angiographic intervention or surgery | Transfusion 5 units or more, or intervention (angiographic or surgical) |
| Perforation | Possible, or only slight leak of fluid or contrast, treatable by fluids and suction for ≤3 d | Any definite perforation treated medically 4–10 d | Medical treatment of more than 10 d, or intervention (percutaneous or surgical) |
| Infection (cholangitis) | >38°C for 24–48 h | Febrile or septic illness requiring more than 3 d of hospital treatment or percutaneous intervention | Septic shock or surgery |
Variations in complication rates between studies
Complication rates of ERCP vary widely, even between apparently similar prospective studies. Variation is substantial. For example, in 1 large prospective study, post-ERCP pancreatitis rates were reported at 0.74% for diagnostic ERCP, and 1.4% for therapeutic ERCP, respectively ; in another similar study, postprocedure pancreatitis rates were 5.1% (7-fold higher) for diagnostic ERCP and 6.9% (5-fold higher) for therapeutic ERCP. Possible reasons for such wide variation in reported complication rates include variation in (1) definitions; (2) thoroughness of protocol for detection of complications; (3) patient population with attendant risk factors; and (4) differences in spectrum of technical approach such as use of pancreatic stents, or different end points of therapy.
Multivariable analysis is a useful statistical method to identify and quantify the effect of multiple potentially confounding risk factors. However, such analysis is not absolute because potentially key risk factors may or may not have been analyzed. In addition, sample size must be large for valid multivariable analysis, to avoid overfitting of the model and thus suggesting spurious associations. Only a few multicenter studies have included more than 1000 patients. Tables 2–4 present summaries of risk factors for complications of therapeutic and diagnostic ERCP based on published multivariate analyses.
| Definite a | Maybe b | No c |
|---|---|---|
| Suspected sphincter of Oddi dysfunction | Young age | Comorbid illness |
| Cirrhosis | Pancreatic contrast injection | Small common bile duct diameter |
| Difficult cannulation | Failed biliary drainage | Female sex |
| Precut sphincterotomy | Trainee involvement | Billroth II |
| Percutaneous biliary access | Periampullary diverticulum | |
| Lower ERCP case volume |
a Significant by multivariate analysis in most studies.
b Significant by univariate analysis only in most studies.
| Definite a | Maybe b | No c |
|---|---|---|
| Suspected sphincter of Oddi dysfunction | Female sex | Small common bile duct diameter |
| Young age | Acinarization | Sphincter of Oddi manometry |
| Normal bilirubin | Absence of common bile duct stone | Biliary sphincterotomy |
| History of post-ERCP pancreatitis | Lower ERCP case volume | |
| Difficult or failed cannulation | Trainee involvement | |
| Pancreatic duct injection | ||
| Pancreatic guidewire placement | ||
| Pancreatic tissue sampling by any means | ||
| Pancreatic sphincterotomy (especially minor papilla) | ||
| Balloon dilation of intact biliary sphincter | ||
| Precut sphincterotomy |
a Significant by multivariate analysis in most studies.
b Significant by univariate analysis only in most studies.
| Definite a | Maybe b | No c |
|---|---|---|
| Coagulopathy | Cirrhosis | Aspirin or nonsteroidal antiinflammatory drug |
| Anticoagulation <3 d after ERCP | Dilated common bile duct | Ampullary tumor |
| Cholangitis before ERCP | Common bile duct stone | Longer sphincterotomy |
| Bleeding during sphincterotomy | Periampullary diverticulum | Extension of previous sphincterotomy |
| Lower ERCP case volume | Precut sphincterotomy |
a Significant by multivariate analysis in most studies.
b Significant by univariate analysis only in most studies.
Complications of diagnostic and therapeutic ERCP
Prospective series of ERCP generally report an overall short-term complication rate of approximately 5% to 10%. Certain patterns emerge from most studies. There is a particularly high rate of complications (up to 20% or more, primarily pancreatitis, with up to 5% severe complications) for ERCP and sphincterotomy for suspected sphincter of Oddi dysfunction. In contrast, there is a consistently low complication rate for routine bile duct stone extraction (<5% in most series). Hemorrhage occurs primarily after sphincterotomy, and primarily in patients with bile duct stones, coagulopathy, and acute cholangitis. Cholangitis occurs mostly after ERCP in patients with malignant biliary obstruction or failed drainage, or after stent malfunction or occlusion. Perforation occurs primarily after sphincterotomy, or is endoscope-related, but risk factors are more difficult to determine.
Risk factors for overall complications of ERCP and sphincterotomy by multivariable analyses are shown in Table 2 . Although relevant studies are heterogeneous and sometimes omit potentially key risk factors, several patterns are apparent. Indication of suspected sphincter of Oddi dysfunction is a significant risk factor; technical factors, likely related to specific expertise or approach of the endoscopist and center, are also significant risk factors for overall complications. These technical factors include difficult cannulation, use of precut or access papillotomy to gain bile duct entry, failure to achieve biliary drainage, and use of simultaneous or subsequent percutaneous biliary drainage for otherwise failed endoscopic cannulation. In turn, the ERCP case volume of the endoscopists or medical centers, when examined, has almost always been a significant factor in complications by both univariate or multivariable analysis. Death from ERCP is rare (<0.5%), but is most often caused by cardiopulmonary complications. It is unclear whether the increasing use of anesthesia services for monitored anesthesia care or general anesthesia during ERCP has affected the cardiopulmonary complication rate.
Contrary to intuition and commonly held beliefs, risk factors found not to be significant for overall complications include older age or increased number of coexisting medical conditions; on the contrary, younger age generally increases the risk both by univariate and multivariate analysis, smaller bile duct diameter, and anatomic variants such as periampullary diverticulum or Billroth II gastrectomy, although they do increase technical difficulty for the endoscopist.
Post-ERCP pancreatitis
Pancreatitis is the most common complication of ERCP, with reported rates varying from 1% to 40%, with a rate of about 5% being most typical. In the Cotton consensus classification, post-ERCP pancreatitis is defined as clinical syndrome consistent with pancreatitis (ie, new or worsened abdominal pain) with an amylase level at least 3 times normal at more than 24 hours after the procedure, and requiring more than 1 night of hospitalization (see Table 1 ). More difficult to classify according to consensus definitions are patients with postprocedural abdominal pain and increase of serum lipase level to more than 3 times normal simultaneous with amylase level increase to less than 3 times upper limit of normal, or those with dramatic lipase increases but minimal symptoms that are not clearly suggestive of clinical pancreatitis. This situation is particularly true of patients with chronic pain in whom postprocedural pain can be difficult to assess and may persist despite normal pancreatic enzymes, or may persist long after pancreatic enzymes have normalized, and without imaging evidence of acute pancreatitis.
Risk Factors for Post-ERCP Pancreatitis Related to the Patient
Mechanical, chemical, hydrostatic, enzymatic, microbiologic, and thermal injury have all been postulated as potential mechanisms of injury to the pancreas during ERCP and endoscopic sphincterotomy. Although the relative contribution of these factors is not known, recent multivariate analyses have helped to identify the clinical patient-related and procedure-related factors that are independently associated with pancreatitis. The risk of post-ERCP pancreatitis is determined at least as much by the characteristics of the patient as by endoscopic techniques or maneuvers (see Table 3 ). Factors found to be significant in 1 or more major studies include younger age, indication of suspected sphincter of Oddi dysfunction, history of previous post-ERCP pancreatitis, and normal serum bilirubin level. Women may be at increased risk, but it is difficult to determine the confounding effect of sphincter of Oddi dysfunction, a condition that occurs almost exclusively in women. In 1 meta-analysis, female gender was clearly a risk, and women account for most cases of severe or fatal post-ERCP pancreatitis.
Sphincter of Oddi dysfunction, a controversial syndrome that is primarily suspected in women with postcholecystectomy abdominal pain, poses a formidable risk for pancreatitis after any kind of ERCP, whether diagnostic, manometric, or therapeutic. The risk of post-ERCP pancreatitis triples to 10% to 30% in patients with suspected sphincter of Oddi dysfunction. The reason for heightened susceptibility in these patients remains unknown. Contrary to widely held opinion, sphincter of Oddi manometry is not the culprit. Multivariable analyses all show that empiric biliary sphincterotomy or even diagnostic ERCP has similarly high risk. With the widespread use of aspiration instead of conventional perfusion manometry catheters, the risk of manometry has probably been reduced to that of cannulation with any other ERCP accessory. Most previous studies linking manometry with risk have been from tertiary centers in which manometry is always performed in patients with suspected sphincter of Oddi dysfunction, thus suggesting guilt by association rather than cause and effect. Two studies specifically compared risk of post-ERCP pancreatitis in patients having ERCP for suspected sphincter of Oddi dysfunction with and without sphincter of Oddi manometry and found no detectable independent effect of manometry on risk. Patients with suspected choledocholithiasis who are found not to have stone disease are at similarly high risk for post-ERCP pancreatitis, which points out the danger of performing diagnostic ERCP to look for bile duct stones in women with recurrent postcholecystectomy pain, because there is generally a low probability of finding stones in such patients, and a high risk of causing pancreatitis. It is an erroneous and potentially dangerous assumption that merely avoiding sphincter of Oddi manometry significantly reduces risk. Increased use of endoscopic ultrasonography and magnetic resonance cholangiopancreatography (MRCP) determines in advance that such patients do not harbor bile duct stones, and either eliminates the need for conventional ERCP, or allows triage of the patients to ERCP performed with maximal therapeutic benefit (dual sphincter manometry and therapy) and protective measures (pancreatic stents).
A history of previous post-ERCP pancreatitis increases risk substantially (up to 4-fold), On the other hand, advanced chronic pancreatitis confers some immunity against ERCP pancreatitis, perhaps because of atrophy and decreased enzymatic activity. Pancreas divisum is a risk factor only if minor papilla cannulation is attempted. Despite many early studies suggesting small bile duct diameter to be a risk factor for pancreatitis, most recent studies have shown no independent influence of duct size on risk; small duct diameter may have been a surrogate marker for sphincter of Oddi dysfunction or patients without true obstructive biliary disease in older studies suggesting higher risk. ERCP for removal of bile duct stones has been found to be relatively safe with respect to pancreatitis rates (usually <3%–4%) in multicenter studies regardless of bile duct diameter. Periampullary diverticula or Billroth II gastrectomy do not seem to influence risk of post-ERCP pancreatitis.
Risk Factors for Post-ERCP Pancreatitis Related to Technique
Technique-related issues have long been recognized to be important in causing post-ERCP pancreatitis. Papillary trauma induced by difficult cannulation has a negative effect that is independent of the number of pancreatic duct contrast injections. Importance of contrast injection alone in causing post-ERCP pancreatitis has probably been overemphasized. Pancreatitis occurred after 2.5% of ERCP in 1 study involving no pancreatic duct contrast injection. Acinarization of the pancreas, although undesirable, is probably less important than generally believed and has not been found to be significant in 2 recent studies. Risk of pancreatitis is generally similar after diagnostic and therapeutic ERCP. Performance of biliary sphincterotomy does not seem to add significant independent risk of pancreatitis to ERCP. This observation does not reflect the safety of sphincterotomy, but rather the risk of diagnostic ERCP. Pancreatic sphincterotomy of any kind, including minor papilla sphincterotomy has been found to be a significant risk factor for pancreatitis, although the risk of severe pancreatitis has been low (<1%), perhaps because nearly all of these patients had pancreatic drainage via a pancreatic stent.
Risk related to use of precut or access papillotomy is controversial and difficult to sort out from other variables, including difficult cannulation. Use of precut to access bile duct varies widely among endoscopists, from less than 5% to as much as 30% of cases. There are many variations on precut technique: standard needle-knife inserted at the papillary orifice and cutting upwards; needle-knife fistulotomy starting the incision above the papillary orifice and then cutting either up or down; use of a pull-type sphincterotome wedged either in the papillary orifice or transpancreatic precut performed by cutting the pancreatic sphincter intentionally. Any of the access techniques has the potential to lacerate and injure the pancreatic sphincter. Precut techniques have been uniformly associated with a higher risk of pancreatitis by univariate and multivariate analysis in multicenter studies involving endoscopists with varied experience. In contrast, many series from tertiary referral centers have found complication rates no different than for standard sphincterotomy, suggesting that risk of precut sphincterotomy is highly operator-dependent. In 1 study, endoscopists performing more than 1 sphincterotomy a week averaged 90% immediate bile duct access after precutting, versus only 50% for lower-volume endoscopists, a success rate that hardly justifies the risk of complications. Comparative studies of precut with standard sphincterotomy are difficult to interpret because indications and settings may be different, with precut preferentially performed in lower-risk situations such as obstructive jaundice, and prominent papillae. In addition, increasing use of pancreatic stents in series from tertiary centers may have neutralized the otherwise higher risk of precut sphincterotomy. Complications of precut sphincterotomy vary with the indication for the procedure, occurring in as many as 30% of patients with sphincter of Oddi dysfunction in older studies without use of pancreatic stents. Paradoxically, in patients with sphincter of Oddi dysfunction, needle-knife sphincterotomy over a pancreatic stent placed early in the procedure has been shown to be substantially safer than conventional pull-type sphincterotomy without a pancreatic stent.
It has been unclear whether increased risk of access papillotomy is because of the technique itself or because of prolonged cannulation attempts, which often precede its use. A meta-analysis of 6 randomized trials comparing precut papillotomy with persistent cannulation provides some insight. These trials included 966 patients assigned to early precut implementation or persistent attempts at standard cannulation. Post-ERCP pancreatitis was significantly less common in patients undergoing precut compared with the group who underwent persistent attempts at cannulation (3% vs 5%). However, the overall rate of complications, including pancreatitis, bleeding, cholangitis, and perforation, did not significantly differ between the 2 groups (5% vs 6%). Limiting the relevance of these studies is the fact that few of these studies included patients with high-risk indications such as sphincter of Oddi dysfunction, or involved use of pancreatic stents, which is now considered fairly standard.
Presence of multiple risk factors for post-ERCP pancreatitis substantially escalates the probability that a patient will develop this complication. The interactive effect of multiple risk factors is reflected in the profile of patients developing severe post-ERCP pancreatitis. In 1 study predating widespread use of pancreatic stents, women with a normal serum bilirubin level had a 5% risk of pancreatitis; with addition of difficult cannulation risk increased to 16%; with further addition of suspected sphincter of Oddi dysfunction (ie, no stone found), the risk increased to 42%. In 2 different studies, nearly all of the patients who developed severe pancreatitis were young to middle-aged women with recurrent abdominal pain, a normal serum bilirubin level, and with no biliary obstructive disease. These observations emphasize the importance of tailoring the approach of ERCP to the individual patient.
The effect of endoscopist case volumes and experience on post-ERCP pancreatitis seems to be intuitively obvious, but has been difficult to show. A recent study showed that trainee participation adds independent risk of pancreatitis. In contrast, most multicenter studies have failed to show a significant correlation between endoscopists’ ERCP case volumes and pancreatitis rates. It is possible that none of the participating endoscopists in those studies reached the threshold volume of ERCP above which pancreatitis rates would diminish (perhaps >250–500 cases per year). However, most American endoscopists average fewer than 2 ERCPs per week, and the reported rates of pancreatitis from the highest-volume tertiary referral centers in the United States are often higher than those in private practices. All of these observations suggest that case mix is at least as important as expertise in determining risk of post-ERCP pancreatitis.
Specific Techniques to Reduce Risk of Post-ERCP Pancreatitis
In general, the most atraumatic and efficient method of cannulation is associated with the fewest complications, but the importance of cannulation difficulty in causing pancreatitis has probably been exaggerated. Use of a papillotome or steerable catheter for biliary cannulation has been prospectively compared with a standard catheter in randomized trials. All of these studies showed significantly higher success rates with the sphincterotome or steerable cannula; however, there was no difference in rates of pancreatitis or other complications. Another randomized trial did show significant reduction of pancreatitis risk when a guidewire was used in conjunction with a papillotome, as opposed to a papillotome and conventional contrast injection alone; the relevance of this study is questionable because few use only a cannula and contrast to access ducts any more.
Using the guidewire as a primary cannulation device is an increasingly used technique, either by leading with the guidewire, or by inserting the cannula or papillotome into the papillary orifice then advancing the guidewire without contrast injection. Guidewire cannulation has been shown to decrease post-ERCP pancreatitis rates in several prospective randomized trials, with rates of 0% to 3% using wire cannulation compared with rates of 4% to 12% using contrast injection. In practice, many advanced endoscopists now use a hybrid of the 2 techniques, using minimal contrast to outline the course of the distal ducts in combination with wire probes. Such a hybrid technique may avoid dissections or passage of the guidewire out a side branch of the pancreatic duct, but has not been formally evaluated.
Thermal injury is believed to play some role in causing pancreatitis after biliary and pancreatic sphincterotomy. Several randomized trials have compared the impact of pure cutting versus blended current, with mixed results but generally lower rates of pancreatitis using the pure cut current. Automated current delivery systems programmed to deliver a specific tissue effect are now widely used. None of the available studies suggests a significant difference in rates of pancreatitis between these units compared with blended current, and it is not yet clear whether automated current delivery systems provide the same benefit for prevention of pancreatitis as do those using pure cutting current.
Pancreatic Stents for Prevention of Post-ERCP Pancreatitis
Pancreatic stent placement is increasingly used as a method to reduce risk of post-ERCP pancreatitis. Such use of pancreatic stents now extends into routine practice, and is increasingly becoming considered standard of care in high-risk circumstances ( Figs. 1 and 2 ). Specific situations in which placement of a pancreatic stent has been shown to reduce risk include biliary sphincterotomy for sphincter of Oddi dysfunction, suspected sphincter of Oddi dysfunction with normal manometry, pancreatic sphincterotomy, precut sphincterotomy, balloon dilation of the biliary sphincter, and endoscopic ampullectomy, after pancreatic wire-assisted biliary cannulation, probably after difficult cannulation in general, and even after unselected ERCP in patients with virgin papilla, excluding those with pancreas divisum or cancer ( Table 5 ).
Related posts:
Therapeutic and Advanced ERCP Is Rapidly Progressing
Endoscopic Retrograde Cholangiopancreatography for Stone Burden in the Bile and Pancreatic Ducts
Sampling at ERCP for Cyto- and Histopathologicical Examination
Endoscopic Retrograde Cholangiopancreatography for Distal Malignant Biliary Stricture
Metal Stents for Hilar Lesions
Endoscopic Retrograde Cholangiopancreatography
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
