Ringer’s Lactate Hydration and Incidence of Post ERCP Pancreatitis: A Descriptive Cross-sectional Study

ABSTRACT Introduction: Endoscopic retrograde cholangiopancreatography is one of the most frequently used treatment modality for various pancreatobiliary problems. Frequent complications of endoscopic retrograde cholangiopancreatography include pancreatitis, cholangitis, hemorrhage and perforation. This study was done to see the prevalence of post endoscopic retrograde cholangiopancreatography pancreatitis in patient aggressively hydrated with Ringer's Lactate solution. Methods: A descriptive cross sectional study was carried out on patient undergoing endoscopic retrograde cholangiopancreatography at Bharatpur Hospital from June 2018 to August 2020. Ethical clearance was taken from Institutional Review Committee Bharatpur Hospital (reference number 16/076/77). The convenient sampling method was applied. Data were collected and analyzed in statistical package for the social sciences version 16. Point estimate at 95% confidence interval was calculated along with frequency and proportion for binary data. Results: Pain abdomen was assessed using Visual Analogue Scale and it was found that 8.1% of patients (15 patients) complained of pain abdomen with visual analogue scale > 3. Serum amylase was sent only in those patients who complained of pain abdomen and only in three patients (1.6%) serum amylase was increased more than 3 times the upper limit of normal value suggestive of pancreatitis. All three patients who had pancreatitis had precut sphincterotomy. Conclusions: In this study we found that incidence of pancreatitis slumped after aggressive hydration with Ringer's lactate solution and adjunct use of other prophylactic measures for prevention of post endoscopic retrograde cholangiopancreatography pancreatitis might yield further better results.


INTRODUCTION
Post Endoscopic Retrograde Cholangiopancreatography Pancreatitis (PEP) is the most common complication of Endoscopic Retrograde Cholangiopancreatography (ERCP). It ranges from 2%-10% and upto 40% in high risk cases. 1 Various procedural techniques and pharmacological interventions have been investigated.
Aggressive hydration with Ringer's lactate (RL) fluid has been found to have promising result. Anti-inflammatory effect of RL has two possible explanations. First, lactate in RL gets metabolized to bicarbonate in liver which results in lowering metabolic acidosis whereas, normal saline (NS) when given in large volumes produces dilutional hyperchloremic acidosis due to high sodium and chloride content. Besides, plasma bicarbonate concentration decreases as chloride concentration increases. Studies show acidosis enhances inflammation and necrosis in acute pancreatitis.Second, RL may directly decrease inflammatory response in these patients by preventing activation of nuclear factor kappa B (NF-KB) transcription factor involved in the inflammatory process. 2,3 Therefore, this study was carried out to find out the incidence of PEP after aggressive hydration with RL in patients undergoing ERCP.

METHODS
A descriptive cross sectional study was conducted in the Department of Surgery, Bharatpur Hospital from June 2018 to August 2020. All the procedures were performed by same endoscopic surgeon in the same operative setting. Ethical approval was taken from the institutional review committee (IRC) Bharatpur Hospital (reference number 16/076/77).
The sample size was calculated using the following formula, Sample size (n)= z 2 p(1-p)/(e) 2  Patients were aggressively hydrated with ringer lactate solution (3 ml/kg/hr) during procedure, 20 ml/kg bolus immediately after procedure, and 3 ml/kg/hr for 8 hours post procedure. 4,5 Patient at risk of fluid overload were excluded from the study. Serum amylase>3 times the upper limit of normal was defined as PEP.
Serum amylase was only sent if patient complain of pain (visual analogue score>3) persisting more than 8 hours. 6 Injection diclofenac 75mg intramuscular was given during procedure. Only guidewire cannulation technique was used. Five French (Fr.) pancreatic duct (PD) stent was placed if PD cannulated >3 times.
Inclusion criteria: All patients undergoing ERCP with American Society of Anesthesiologist Physical Status (ASA-PS) I and II, with at least one risk factor for pancreatitis which may be procedure related or patient factor were included.

RESULTS
A total of 186 patients undergoing ERCP were enrolled in this study. Each patient had a minimum risk factor for pancreatitis. During the post operative period, pain abdomen was assessed using Visual analogue Scale (VAS) and it was found that 15 patients (8.1%, C.I 95% patients) complained of pain abdomen with VAS> 3. Serum amylase was sent only in those patients who complained of pain abdomen and only in three patients (1.6%, C.I 95%) serum amylase was increased more than 3 times the upper limit of normal value suggestive of pancreatitis.
During the procedure, ease of cannulation into ampulla of vater was assessed and it was found that in 123 patients (66.1%), cannulation was easy. However, 63 patients (33.9%) had difficult cannulation. Similarly, precut sphincterotomy, pancreatic duct cannulation, and continuous radial expansion were performed in these patients as shown (Table 1).

Mean Age
Similarly, post ERCP pain abdomen was significantly higher in patient with difficult cannulation compared to easy cannulation. Thirteen patients with difficult cannulation had pain abdomen compared to two patients with easy cannulation. All three patients who had pancreatitis (pain abdomen with increased serum amylase > 3 times) had difficult cannulation while none patient with easy cannulation had pancreatitis.

Figure 2. Ease of cannulation and post ERCP pain Abdomen
Incidence of post ERCP pain abdomen in patients who had precut sphincterotomy, pancreatic duct cannulation and continuous radial expansion was as follows ( Table  2). One of the methods for reducing incidence of pancreatitis is early vigorous hydration. The rationale behind vigorous hydration is to resolve hypovolemia so that perfusion is adequate. But now choice of fluid is shifted toward Ringer's lactate solution because of more suitable acid base balance and its anti-inflammatory  17 In our study also marked reduction in incidence of PEP was seen (1.6% on aggressive Ringer's Lactate hydration protocol. Besides for reduction of PEP rectal administration of NSAIDS is found to be effective in various study. 18,19,20 Mok SRS et al. randomized, double blinded, placebocontrolled trial showed reduced incidence of PEP in ringer lactate plus rectal indomethacin versus normal saline plus placebo. 21 In our study we have also included NSAIDs (diclofenac intramuscular) in all cases however, various studies support effectiveness of NSAIDs given only per rectal compared to other routes. But in our country rectal NSAIDS is not easily available so we don't practice giving prophylactic rectal NSAIDs for pancreatitis. In 2014, Ignasi Puigetal performed metaanalysis and also showed supporting evidence with rectal diclofenac or indomethacin given either before or after procedure but, there was no evidence to support oral or parenteral administration. [22][23][24]

CONCLUSIONS
Our study demonstrates that the introduction of selective and routine use of aggressive hydration with Ringer's lactate significantly reduces the incidence of pancreatitis. However, there are some confounding factors in our study like we had used guidewire cannulation technique, PD stents if PD cannulation >3 times and intramuscular diclofenac which might have also influenced in our result. Therefore, we conclude that aggressive hydration with RL reduces PEP and combining RL hydration with other methods for decreasing PEP may offer even better results.