When parents make up diseases in their children, the consequences can be dire. What happens when doctors find out that a disease that they have been treating probably doesn’t exist?
- Cotton PD et al. “Effect of endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction on pain-related disability following cholecystectomy: the EPISOD randomized clinical trial” JAMA 2014; 311: 2101-2109.
A detailed analysis of this study (Gastroenterol 2015; 148: 440-44) and the author’s reply provides some insight into that questions and helps place this study and its results into context.
Key points from the Gastroenterology Selected Summary:
- “Sphincter of Oddi dysfunction (SOD) is the term used to describe an episodic abdominal pain syndrome, typically occurring in young to middle-aged women in the setting of prior cholecystectomy…SOD remains a diagnosis of exclusion.”
- “The investigators conducted a double-blind, sham-controlled, randomized trial at 7 US tertiary centers, enrolling 214 adult post-cholecystectomy patients with debilitating abdominal pain due to suspected biliary SOD (predominantly type III).” Sham patients underwent ERCP, manometry, and pancreatic duct stenting.
- Patients were randomized 2:1 to sphincterotomy or sham; those randomized to sphincterotomy and subsequently shown to have a hypertensive pancreatic sphincter were then re-randomized (1:1) to have biliary or combined biliary/pancreatic sphincterotomies.
- “Most patients in both study groups experienced considerable reduction in their pain disability scores…the proportion meeting the trial’s 1-year primary endpoint was higher among those treated with sham compared with sphincter ablation (37% vs. 23%, P=.01)”
- “The manometry findings did not predict treatment success.” There were no other useful predictors of success identified (eg. elevated liver enzymes, prior stone at cholecystectomy)
- Adverse effects from procedures included 26 cases of acute pancreatitis (2 severe) and 2 perforations.
- “The results of this trial are fascinating…the authors, many of whom had dedicated entire careers to the management of these patients using the very procedure they have now conclusively shown to be futile, may be understandably disheartened by the results.”
- Numerous limitations of the study are noted. In particular, “the 1-year time frame of the trial is likely to have been too short to capture the deleterious impact of prophylactic pancreatic duct stenting, which…has been associated with interval induction of pancreatic ductal abnormalities mimicking chronic pancreatitis.”
- “It is our view that the authors’ data…provide an unambiguous mandate for imposing an immediate moratorium on subjecting this group of patients to ERCP.“
Dr. Cotton’s reply:
- “It may be premature to discard the whole concept of sphincter dysfunction as a cause of pain.”
- He indicates that “gallbladder dyskinesia” is another related question and was the reason for surgery in half of EPISOD subjects.
- The results of the study “clearly show the need for equally stringent studies to answer the many remaining questions.”
For those who read this much of this post: I wanted to let you know that yesterday’s online post on early peanut introduction was updated with recommendations from the associated editorial.
Related blog posts:
Another headline from Freaknomics Website follows. Of course I probably should think twice about poking fun at typos given the volume of them on this blog.
While there are pediatric patients who undergo endoscopic retrograde cholangiopancreatography (ERCP), this is a relatively infrequent occurrence. Nevertheless, a recent study has a couple useful clinical pearls that may have broader application.
- Clin Gastroenterol Hepatol 2014; 12: 303-07.
- Clin Gastroenterol Hepatol 2014; 12: 308-10 Associated editorial
- Gastroenterol 2014; 146: 581-82. Associated summary
- Aggressive hydration may prevent post-ERCP pancreatitis. In the study, the treatment group received an average of 3290 mL over the 9-hour period compared with 945 mL in the standard infusion group.
- Implication: The speculation from the study and the editorials is that improved pancreatic perfusion will result in better oxygenation and reduce the likelihood of pancreatitis. In the 2nd reference, the author states that his practice is to administer “at least 3 L of crystalloid in recovery to young, healthy patients who have undergone high-risk ERCP and an additional 3 to 5 L within the first 12 hospital hours to those admitted with postprocedure pain”
- The best fluid (for post-ERCP and acute pancreatitis) may be lactated Ringer’s (LR).
- Implication: The lactate in LR may help reduce pancreatitis by avoiding acidosis which could promote zymogen activation and pancreatic inflammation. A previous small trial (n=40) of acute pancreatitits from any cause showed lesser degrees of systemic inflammatory response with LR in compared with normal saline (Clin Gastroenterol Hepatol 2011; 9: 710-17e1).
- This study adds aggressive IVFs as another intervention to prevent ERCP. Rectal indomethacin and prophylactic stent placement (in high-risk patients) are other accepted treatments.
This pilot study randomly assigned 39 patients to aggressive hydration and 23 to standard hydration; all patients were inpatients who were not at risk for fluid overload. The aggressive group received 3 mL/kg/h during the procedure, a 20 mL/kg bolus after the procedure, and then continued on 3 mL/kg/hr for 8 hours. In contrast, the standard group received LR at 1.5 mL/kg/h during and for 8 hours afterwards.
Demographics: The average age was 43 years in the aggressive hydration group and 45 years in the standard group. 78% were hispanic. The ERCP procedures were mostly “average risk.” 74% had ERCP for choledocholithiasis. Only 2 subjects needed precut sphinterotomy (3%).
- No patients in the aggressive hydration group developed acute pancreatitis compared with 4 (17%) in the standard hydration group
- Elevated amylase (23% vs. 39%) and epigastric pain (8% vs 22%) were also less frequent in the aggressive hydration group.
Numerous Limitations: This was a small pilot study with an atypical population; thus, the findings are difficult to generalize. A false-positive (type 1 error) can easily occur due to the small numbers, especially as the standard hydration group had a rate of acute pancreatitis that was about double from previous studies. In addition, this study was not blinded and could have been susceptible to bias. Furthermore, the authors defined acute pancreatitis differently than in previous studies. In this study, the authors required enzyme increases 2 or 8 hours after ERCP with new abdominal pain; in previous studies, the definition of acute pancreatitis relied on enzyme increases for at least 24 hours after the ERCP.
Take-home message for those not doing ERCPs: Think about using lactated ringer’s and aggressive hydration in otherwise-well patients who present with acute pancreatitis.
Related blog entries:
A recent case vignette highlights several key points regarding use and timing of ERCP (endoscopic retrograde cholangiopancreatography) for gallstone pancreatitis (NEJM 2014; 370: 150-7). Figure 1 provides a nice illustration of ERCP.
Indications: Suspected bile-duct stones as the cause of pancreatitis AND one of the following:
- cholangitis (fever, jaundice, sepsis)
- persistent biliary obstruction (conjugated bilirubine level >5 mg/dL)
- clinical deterioration (worsening pain, increasing white cell count, worsening vital signs)
- stone evident in the common bile duct on imaging
AGA position paper (2007):
- Urgent ERCP (within 24 hours of admission) was recommended in those with cholangitis
- Early ERCP (within 72 hours of admission) was recommended if suspicion of persistent bile-duct stones remained high
Patient information/animated videos for pancreatic diseases from the National Pancreas Foundation: http://ow.ly/sF9vb
Indomethacin to prevent post-ERCP pancreatitis | gutsandgrowth