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Revista de Gastroenterología del Perú

versión impresa ISSN 1022-5129

Rev. gastroenterol. Perú vol.34 no.2 Lima abr. 2014

 

Artículo original

Risk factors associated with the development of hyperamylasemia and post-ERCP pancreatitis in the Cuban National Institute

Factores de riesgo con el desarrollo de la hiperamilasemia y pancreatitis post PCRE en el Cuban National Institute

 

Héctor Ruben Hernández Garcés1,a, Alonso Almeida Linnet1,b, María del Rosario Abreu Vázquez1,c, Luis Calzadilla Bertot1,d, Kevin Peña1,b, Yudit Andrain Sierra1,e, Issoufo Moutary1,d, Nilmer Segura Fernández 1,d

1 Institute of Gastroenterology. La Habana, Cuba.

a Second degree specialist in Gastroenterology. Auxiliary professor in gastroenterology. Auxiliary Investigator. b Specialist in Family Medicine. Gastroenterology resident. c First degree specialist in Biostatistics. Assistant professor in biostatistics. d First degree specialist in Gastroenterology. e Nurse.


RESUMEN

Contexto: La pancreatitis aguda es la complicación más frecuente de la PCRE y algunos factores de riesgo son asociados con el desarrollo de hiperamilasemia y pancreatitis post PCRE. Objetivos: Identificar factores nuevos asociados con hiperamilasemia y pancreatitis post PCRE en pacientes que acudieron a nuestro centro. Material y métodos: Un estudio retrospectivo de cohorte se llevó a cabo en 170 pacientes en quienes se realizó una CPRE diagnóstico-terapéutica por enfermedad biliopancreática. 67 pacientes desarrollaron hiperamilasemia (39,4%) y 6 pancreatitis post PCRE (3,5%). Se aplicaron los siguientes criterios diagnósticos: Hiperamilasemia: elevación de la amilasa sérica por encima del valor normal (90IU).Pancreatitis aguda post PCRE: dolor abdominal continuo por más de 24 horas y elevación de la amilasa tres veces por encima del valor normal. Resultados: El número de canulaciones, más de 4 (19 pacientes), (p=0,006; RR= 3,00) se asoció significativamente con el desarrollo de la hiperamilasemia y la puesta de stents biliares (14 pacientes) se asoció como un factor protector (p=0,00; RR= 0,39). Los factores asociados con el desarrollo de la pancreatitis post PCRE se relacionaron con el paciente (localización peridiverticular de la papila (p=0,00; RR= 2,00) y disfunción del Esfinter de Oddi (p=0,000; RR=1,20). Conclusiones: Factores técnicos fueron asociados con el desarrollo de la hiperamilasemia, sin embargo, los relacionados con el desarrollo de la pancreatitis post PCRE fueron mayoritariamente relacionados al paciente.

Palabras clave: Pancreato-Colangiografía Retrógrada Endoscópica; hiperamilasemia; pancreatitis post PCRE (fuente: DeCS BIREME).


ABSTRACT

Context: Acute pancreatitis is the most common complication in ERCP, and some risk factors were associated with the development of hyperamylasemia and post-ERCP pancreatitis. Objectives: identifying new factors associated with the development of hyperamylasemia or post-ERCP pancreatitis in patients attended at our center. Material and methods: A (retrospective) cohort study was carried out in 170 patients on which a diagnostic-therapeutic ERCP was done due to biliopancreatic disease. 67 patients developed hyperamylasemia (39.4%) and 6 post-ERCP pancreatitis (3.5%). The following diagnostic criteria were applied: Hyperamylasemia: increase in the serum amylase level above the normal value (90I/U). Acute post-ERCP pancreatitis: clinical: continuous abdominal pain for over 24 hours and biochemical: elevation of amylase 3 times above normal value (90U/I). Results: The number of cannulations more than 4 (19 patients), (p=0.006; RR= 3.00) was associated significantly with the development of hyperamylasemia and the placing of biliary stent (14 patients), (p=0.00; RR= 0.39) was a protective factor. The factors associated with the development of post-ERCP pancreatitis were related with the patient (peridiverticular location of the papilla (p=0.00; RR= 2.00) and the sphincter of Oddi dysfunction (p=0.000; RR=1.20). Conclusion: Technical factors were associated with the development of hyperamylasemia, however, the factors associated with the development of post-ERCP pancreatitis in our universe of study were related mainly with the patient.

Key words: Endoscopic Retrograde Cholangiopancreatography; hyperamylasemia; post-ERCP pancreatitis (source: MeSH NLM).


INTRODUCTION

Endoscopic retrograde cholangiopancreatography (ERCP) reported for the first time in 1968 by McCune et al. had a fast acceptance as a direct and secure technique and has been converted into the therapeutic procedure of excellence in the biliopancreatic tract. Even though its technological advances, it remains as the technique with the highest morbimortality in digestive endoscopy (1-3).

Acute pancreatitis is the most common complication in ERCP, with a reported incidence between 1.8 and 7.2% in some prospective series. However, the incidence report can vary largely up to 40%, depending on the criteria used for the diagnosis of pancreatitis as well as the type and duration of follow up of the patient. The generally accepted criteria for post-ERCP pancreatitis were presented in a consensus in 1991. These criteria include the presentation of a new pancreatic type abdominal pain, associated with at least an increase of serum amylase or lipase three times its value between the 24 hours after the ERCP (4-8).

The risk factors for the development of post-ERCP complications have been classified in three types and it includes the patient’s own factors (young patients, female sex, sphincter of Oddi dysfunction, recurrent pancreatitis, personal history of previous post-ERCP pancreatitis and patients with normal serum bilirubin), the procedures risk factors (sphincterotomy, papillary precut, difficult cannulation of the pancreatic duct, multiple injections of the pancreatic duct, acinarization of the pancreas, extraction of stones, diameter of common bile duct, size of the common bile duct stones, anticoagulation) and factors related to the endoscopist and the technique used (low experience and the carrying out by trainees) (9-11).

The best strategy to prevent post-ERCP pancreatitis consists of: avoiding unnecessary procedures, the use of guides for cannulation and the wise judgment in the usage of stents in the pancreatic duct as well as classifying the patients in high or low risk (12,13).

All this motivated us to carry out the following study with the objective of identifying factors associated with the development of hyperamylasemia or post-ERCP pancreatitis in patients attending at our center.

MATERIAL AND METHODS

A (retrospective) cohort study was carried out to identify the factors associated with the development of hyperamylasemia and post-ERCP pancreatitis, at the Institute of Gastroenterology between May 2011 and January 2012.

The universe of study consisted of 170 patients on which a diagnostic-therapeutic ERCP was done due to bilio-pancreatic disease.

  • The calculation of the size of the sample was done based on the following suppositions:
  • Prevalence of factors in the non exposed: 0.05
  • Level of significance: 0.05
  • Potency: 0.90
  • Prevalence of the factors in the exposed: 0.10
  • Relative risk: 2.00
  • Ratio exposed/not exposed: 1:1
  • Size of minimum sample: 134 patients
  • Considering a loss of 6%: 142 patients
  • Size of sample: 142 patients
Inclusion criteria:
  1. Patients on whom an ERCP was performed for any reason.
  2. Patients older than 18 years.
  3. Patients on which a clinical and biochemical follow up was carried out at 4, 24 and 72 hours depending on the evolution.

ERCP procedure

All patients once received at the endoscopy department at the Institute of Gastroenterology and their clinical history being analyzed, detailing their motives or indications for ERCP, complementary tests, etc., an endoscopic retrograde cholangiopancreatography was carried out by four endoscopists, (two under formation and two experts) using an Olympus EVIS LUCERA TJF 240 videoduodenoscope with lateral vision, previous evaluation of the patient by the anesthesiologist for sedation during the procedure.

Initially we proceed to the cannulation of the desired duct using a sphincterotome (Olympus KD-411Q-Q720) by the ERCP fellows, if it was satisfactory, the endoscopic-radiologic diagnosis was made followed by the adequate endoscopic therapy by the expert endosocpists. If after 4 attempts, the cannulation of the desired duct wasn’t achieved, another attempt of cannulation was tried by one of the expert endoscopists. If the cannulation was satisfactory, the diagnosis and adequate therapy were carried out, if it wasn’t achieved, a papillary precut was carried out using a needle knife (Olympus KD10Q-1) for a successful cannulation followed by the endoscopic therapy.

After the procedure was finished, the patient was admitted in a hospitalization room at our institution for a clinical evaluation every 4 hours and the determination of serum amylase at 4 and 24 hours after the procedure and it was repeated at 48 and 72 hours if the amylase values maintained elevated with clinical symptoms of acute pancreatitis.

Patients with an adequate clinical and biochemical evolution after 24 hours of the procedure were discharged and followed up on external consultation at our institution.

Exclusion criteria:
  1. Patients with acute pancreatitis or chronic pancreatitis with symptoms of acute exacerbation.
  2. Patients with tumor infiltration of the second portion of the duodenum or an abnormal position of the papilla.
  3. Patients with immediate ERCP complications that require surgical or urgent medical attention (perforation, bleeding that cannot be controlled endoscopically, cardiopulmonary etc.)
  4. Patients of other institutions or provinces who cannot be followed up clinically nor biochemically.
  5. Patients with an incomplete data collecting form.

Diagnostic criteria

The following diagnostic criteria were applied:

Hyperamylasemia: increase in the serum amylase level above the normal value (90I/U).

Acute post-ERCP pancreatitis: continuous abdominal pain for over 24 hours and elevation of amylase 3 times above normal value (90U/I).

Severity of pancreatitis

The grades of severity of acute post-ERCP pancreatitis were defined as:

a) Mild: If a prolongation of hospitalization 1 to 3 days ws required

b) Moderate: required prolongation of hospitalization 4 to 10 days.

c) Severe: more than 10 days of hospitalization or acute hemorrhagic pancreatitis, abscess, pseudocyst or surgery.

Ethics

Patients were asked for verbal and written informed consent to document their clinical data and endoscopic procedures. The study was approved by the local ethics committees of the National Institute of Gastroenterology.

Statistical analysis

For the descriptive analysis of the data, summary measurements were used for qualitative variables (absolute and relative frequencies).

To evaluate the factors associated with hyperamylasemia and post-ERCP pancreatitis, the association between dependent variables (hyperamylasemia and post-ERCP pancreatitis) and independent variables (epidemiologic, toxic habits, personal medical history, appearance of the major papilla, localization of the major papilla, diameter of the distal common bile duct, cannulation of the main pancreatic duct, sphincter of Oddi dysfunction, endoscopic-therapeutic procedure carried out) was investigated.

Univariate analysis was carried out using chi squared and multivariate by means of logistic regression with binary response. The adjusted risks were estimated for each independent variable. The model that best estimates the (Y) effect was estimated in a more precise way (with less standard error or a more narrow CI 95%) and that best adjusts; evaluating the adjustment by means of verisimilitude (-2LL).

RESULTS

Table 1, shows the relation of patients according to groups of ages and sex, on whom an ERCP was performed, observing predominance in the age group of 60 and 69 years (22.4%) and 70 to 79 years (23.5%) for both sexes with a female predominance of 102 patients (60.0%). The mean age in the study group was of 57.3 and 59.4 years for male and female sex respectively.

Figure 1, shows the frequency of patients that presented hyperamylasemia and acute post-ERCP pancreatitis. Of a total of 170 patients, 67 developed hyperamylasemia (39.4%) and 6 patients post-ERCP pancreatitis (3.5%).

Figure 2, shows the distribution of patients according to the presence of post-ERCP pancreatitis and its severity. Six patients developed post-ERCP pancreatitis, in 2 (67%) the intensity was mild and in 1 (33%) moderate, no patient developed severe post-ERCP pancreatitis.

Table 2, analyses factors associated with the development of hyperamylasemia, related to the patient. It was observed that none of these were related with the development of hyperamylasemia. No statistically significant differences existed in the factors being analyzed.

Table 3, shows factors associated with the development of hyperamylasemia related to the procedure. It was observed that the number of cannulations more than 4 (19 patients), (p=0.006, RR=3.00, IC=1.54-6.69) was associated significantly with the development of hyperamylasemia, and the placing of biliary stent (14 patients), (p=0,00, RR=0.39, IC=0.19-0.81) was a protective factors for the development of hyperamylasemia.

Factors associated with the development of post ERCP pancreatitis related with the patient are illustrated in Table 4. It is observed that the peridiverticular location of the papilla (p=0,00, RR= 2.00, IC= 2.80-142), and the sphincter of Oddi dysfunction (p=0,00, RR=1.20, IC=0.83-1.21), were associated significantly with the development of this complication.

Table 5, shows the factors associated with the development of post-ERCP pancreatitis related to the procedure. It was observed that none of these were related with the development of post-ERCP pancreatitis. No statistically significant differences existed in the factors being analyzed.

DISCUSSION

For many years, endoscopists have studied the problem of post-ERCP pancreatitis, a recent review of prospective series found the mean frequency to be 5.2% after diagnostic procedures and 4.1% after therapeutic ERCP. In prospective trials, post-ERCP pancreatitis was recorded in 1% to 7% of cases. The variation in frequency among studies could be related to differences in the definition of pancreatitis, study populations, and/or techniques (14,15).


In a retrospective study carried out at the Institute of military medicine “Dr. Luis Díaz Soto” and in the Center for Endoscopic Surgery in Havana, in the period between May 1997 until December 1998, 230 (39.25%) procedures on the male sex and 356 (60.75%) on the female sex were carried out, distributed in different age groups: younger than 40 years, 125 patients (21.3%), between 40 and 79 years, 410 patients (70%) and more than 80 years, 51 patients (8.7%) (16).

However in another study carried out at the General University Hospital “Dr. Gustavo Aldereguía Lima” in the city of Cienfuegos, the age was at an interval of 31 to 90 years with an average of 60.8 ±16 years while the male sex showed an evident predominance (17).

In our investigation, patients on whom an ERCP was performed had predominance in the age group above 60 years and in the female sex, the findings previously referred to could be related to biliopancreatic diseases that appear and increase their frequency with age. Also the presence of biliary stones and its complications are more frequent in female than in male in all adult age groups.

In a multicentre study in China, in 14 centers, of a total of 3178 procedures, 116 patients (4.31%) developed post-ERCP pancreatitis and 396 patients (14.72%) asymptomatic hyperamylasemia. In another study carried out in Germany, out of a total of 2364 ERCP’s carried out in 1275 patients, 54 (2.3%) developed post-ERCP pancreatitis, 50 of these (92.6%) presented a mild pancreatitis and 54 (7.4%) severe pancreatitis, 613 patients (25.6%) developed hyperamylasemia , 24 hours after the procedure was done (18).

In the multivariate analysis, female gender (adjusted odds ratios (ORs): 1.52, 95% confidence interval (CI): 1.14 – 2.02, p= 0.004), periampullary diverticulum (OR: 2.02, 95% CI: 1.49–2.73, p< 0.001), cannulation time >10 min (OR: 1.51, 95% CI: 1.08–2.10, p= 0.016), ≥ 1 pancreatic deep wire pass (OR: 1.80, 95% CI: 1.33–2.42, p< 0.001), and needle-knife precut (OR: 2.70, 95% CI: 1.42–5.14, p= 0.002) were risk factors for overall complications. Female gender (OR:1.84, 95% CI: 1.25–2.70, p=0.002), age ≤ 60 years (OR: 1.59, 95% CI: 1.06–2.39, p= 0.025), cannulation time >10 min (OR: 1.76, 95% CI: 1.13–2.74, p= 0.012), ≥ 1 pancreatic deep wire pass (OR: 2.77, 95%
CI: 1.79–4.30, p< 0.001), and needle-knife precut (OR: 4.34, 95% CI: 1.92–9.79, p< 0.001) were risk factors 95% CI: 1.52–2.54, p< 0.001), ≥ 1 pancreatic deep wire pass (OR: 2.24, 95% CI: 1.74–2.89, p< 0.001), needle-knife precut (OR: 2.34, 95% CI: 1.32–4.14, p= 0.004), and major papilla pancreatic sphincterotomy (OR: 1.71, 95% CI: 1.23–2.37, p= 0.001) were risk factors for asymptomatic hyperamylasemia (19).

Masci et al. in a meta-analysis of 15 studies identified three patient-related and two procedure related factors associated with a definite risk of post-ERCP pancreatitis. The patient-related factors included suspected sphincter of Oddi dysfunction (relative risk (RR) 4.09, 95% CI: 3.37–4.96; p< 0.001), female gender (RR: 2.23, 95% CI: 1.75–2.84; p< 0.001), and previous pancreatitis (RR: 2.46, 95% CI: 1.93–3.12; p< 0.001). The procedurerelated factors included precut sphincterotomy (RR: 2.71, 95% CI: 2.02–3.63; p< 0.001) and pancreatic injection (RR: 2.2, 95% CI: 1.6–3.01; p< 0.001) (20).

The mechanism by which contrast injection can cause pancreatitis remains controversial. The osmolality of the contrast media used has been proposed as a possible contributing factor. Low osmolality is thought to be safer than high osmolality contrast media as it is associated with less osmotically driven fluid shifts and subsequent lower increases in intraductal pressure. While the results from a number of randomized trials have been contradictory, a meta analysis by George et al. showed that there was no significant difference between high- and low-osmolality contrast media with respect to the development of pancreatitis. (21).

Factors associated with the development of post-ERCP pancreatitis in our universe of study were related mainly with the patient, which could be related with the procedure’s indication criteria, (only with a therapeutic end), the endoscopists experience, in a terciary level center with more than 200 procedures a year and to technical factors like the selective cannulation, the use of the guide wire and the early precut. We consider that the presence of transitory and asymptomatic hyperamylasemia is in relation with the pancreatic sphincter response and by the own gland due to manipulation of the papilla, obligatory and necessary for the procedure.

Conclusions

Technical factors such as more than four cannulations of the papilla and the placement of biliary stent were associated with the development of hyperamylasemia, however, the factors associated with the development of post-ERCP pancreatitis in our universe of study were related mainly with the patient (peridiverticular papilla and sphincter of Oddi dysfunction).

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Correspondence:

Dr. Hernández Garcés Héctor Ruben Av. San Martin 931. Ica, Peru E-mail: hectorhdez67@yahoo.es

 

Recibido: 20/08/2013

Aprobado: 14/04/2014

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