title: Antioxidant drugs to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis: What does evidence suggest?
abstract: OBJECTIVE
  To determine whether or not the use of antioxidant supplementation aids in the prevention of post- endoscopic retrograde cholangiopancreatography pancreatitis.
  
  
  METHODS
  A systematic review of randomized controlled trials (RCTs) was made to evaluate the preventive effect of prophylactic antioxidant supplementation in post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). The inclusion criteria included: acute post-endoscopic retrograde cholangiopancreatography pancreatitis in adults; randomized clinical trials with the use of any antioxidant as an intervention compared with placebo, to reduce PEP. The outcome measure was the incidence and severity of PEP. Twelve RCTs involving 3110 patients since 1999 were included. The antioxidants used were selenite, β-carotene, and pentoxifylline (each one in one trial), N-acetylcysteine (NAC) in three trials, and allopurinol in six trials. The group of patients treated with NAC received different doses; either oral or intravenous, and allopurinol-treated patients received five different oral doses in two different administration periods. The results are expressed with raw numbers, proportions, as well as mean and standard deviations. The incidence of pancreatitis between groups was analyzed with Pearson's χ(2) test or Fisher's exact test (F). The main outcome is expressed as relative risks and 95%CI.
  
  
  RESULTS
  The incidence of pancreatitis in all antioxidant treatment groups was 8.6%, whereas it was 9.7% in the control group. The antioxidants used were selenite, β-carotene, and pentoxifylline (each one in one trial), NAC in three trials, and allopurinol in six trials. In allopurinol trials, three different dosifications were used; two trials reported a low dosage (of less than 400 mg), two trials reported a moderate dose (600 mg) and the remaining two employed higher doses (more than 900 mg). Supplementation was not associated with a significant reduction in the incidence of PEP [relative risk (RR) = 0.93; 95%CI: 0.82-1.06; P = 0.28]. In addition, the incidences of PEP in patients treated with allopurinol and those treated with other antioxidants were similar to that observed in patients who received the placebo (RR for trials with allopurinol, 0.92; 95%CI: 0.78-1.08; P = 0.31) and, with the use of other antioxidants, the incidence of PEP was 8.9%, whereas it was 9.7% in the control group (RR = 0.95; 95%CI: 0.77-1.18; P = 0.19).
  
  
  CONCLUSIONS
  Antioxidant supplementation shows no beneficial effect on the incidence of PEP. There is a lack of robust trials to support the use of antioxidants for prevention.
authors.affiliation: Clotilde Fuentes-Orozco, Michel Dassaejv Macías-Amezcua, Jesús García-Rentería, Jorge Rendón-Félix, Mariana Chávez-Tostado, Lizbeth Araceli Cuesta-Márquez, Ana Olivia Cortés-Flores, Alejandro González-Ojeda, Research Unit in Clinical Epidemiology, Specialties Hospital of the Western Medical Center, Medical Unit of High Specialty, Mexican Institute of Social Security, Guadalajara, Jalisco 44340, México.
authors.forename: Clotilde
authors.initials: C
authors.lastname: Fuentes-Orozco
authors.affiliation: Clotilde Fuentes-Orozco, Michel Dassaejv Macías-Amezcua, Jesús García-Rentería, Jorge Rendón-Félix, Mariana Chávez-Tostado, Lizbeth Araceli Cuesta-Márquez, Ana Olivia Cortés-Flores, Alejandro González-Ojeda, Research Unit in Clinical Epidemiology, Specialties Hospital of the Western Medical Center, Medical Unit of High Specialty, Mexican Institute of Social Security, Guadalajara, Jalisco 44340, México.
authors.forename: Carlos
authors.initials: C
authors.lastname: Dávalos-Cobián
authors.affiliation: Clotilde Fuentes-Orozco, Michel Dassaejv Macías-Amezcua, Jesús García-Rentería, Jorge Rendón-Félix, Mariana Chávez-Tostado, Lizbeth Araceli Cuesta-Márquez, Ana Olivia Cortés-Flores, Alejandro González-Ojeda, Research Unit in Clinical Epidemiology, Specialties Hospital of the Western Medical Center, Medical Unit of High Specialty, Mexican Institute of Social Security, Guadalajara, Jalisco 44340, México.
authors.forename: Jesús
authors.initials: J
authors.lastname: García-Correa
authors.affiliation: Clotilde Fuentes-Orozco, Michel Dassaejv Macías-Amezcua, Jesús García-Rentería, Jorge Rendón-Félix, Mariana Chávez-Tostado, Lizbeth Araceli Cuesta-Márquez, Ana Olivia Cortés-Flores, Alejandro González-Ojeda, Research Unit in Clinical Epidemiology, Specialties Hospital of the Western Medical Center, Medical Unit of High Specialty, Mexican Institute of Social Security, Guadalajara, Jalisco 44340, México.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Ambriz-González
authors.affiliation: Clotilde Fuentes-Orozco, Michel Dassaejv Macías-Amezcua, Jesús García-Rentería, Jorge Rendón-Félix, Mariana Chávez-Tostado, Lizbeth Araceli Cuesta-Márquez, Ana Olivia Cortés-Flores, Alejandro González-Ojeda, Research Unit in Clinical Epidemiology, Specialties Hospital of the Western Medical Center, Medical Unit of High Specialty, Mexican Institute of Social Security, Guadalajara, Jalisco 44340, México.
authors.forename: Michel Dassaejv
authors.initials: MD
authors.lastname: Macías-Amezcua
authors.affiliation: Clotilde Fuentes-Orozco, Michel Dassaejv Macías-Amezcua, Jesús García-Rentería, Jorge Rendón-Félix, Mariana Chávez-Tostado, Lizbeth Araceli Cuesta-Márquez, Ana Olivia Cortés-Flores, Alejandro González-Ojeda, Research Unit in Clinical Epidemiology, Specialties Hospital of the Western Medical Center, Medical Unit of High Specialty, Mexican Institute of Social Security, Guadalajara, Jalisco 44340, México.
authors.forename: Jesús
authors.initials: J
authors.lastname: García-Rentería
authors.affiliation: Clotilde Fuentes-Orozco, Michel Dassaejv Macías-Amezcua, Jesús García-Rentería, Jorge Rendón-Félix, Mariana Chávez-Tostado, Lizbeth Araceli Cuesta-Márquez, Ana Olivia Cortés-Flores, Alejandro González-Ojeda, Research Unit in Clinical Epidemiology, Specialties Hospital of the Western Medical Center, Medical Unit of High Specialty, Mexican Institute of Social Security, Guadalajara, Jalisco 44340, México.
authors.forename: Jorge
authors.initials: J
authors.lastname: Rendón-Félix
authors.affiliation: Clotilde Fuentes-Orozco, Michel Dassaejv Macías-Amezcua, Jesús García-Rentería, Jorge Rendón-Félix, Mariana Chávez-Tostado, Lizbeth Araceli Cuesta-Márquez, Ana Olivia Cortés-Flores, Alejandro González-Ojeda, Research Unit in Clinical Epidemiology, Specialties Hospital of the Western Medical Center, Medical Unit of High Specialty, Mexican Institute of Social Security, Guadalajara, Jalisco 44340, México.
authors.forename: Mariana
authors.initials: M
authors.lastname: Chávez-Tostado
authors.affiliation: Clotilde Fuentes-Orozco, Michel Dassaejv Macías-Amezcua, Jesús García-Rentería, Jorge Rendón-Félix, Mariana Chávez-Tostado, Lizbeth Araceli Cuesta-Márquez, Ana Olivia Cortés-Flores, Alejandro González-Ojeda, Research Unit in Clinical Epidemiology, Specialties Hospital of the Western Medical Center, Medical Unit of High Specialty, Mexican Institute of Social Security, Guadalajara, Jalisco 44340, México.
authors.forename: Lizbeth Araceli
authors.initials: LA
authors.lastname: Cuesta-Márquez
authors.affiliation: Clotilde Fuentes-Orozco, Michel Dassaejv Macías-Amezcua, Jesús García-Rentería, Jorge Rendón-Félix, Mariana Chávez-Tostado, Lizbeth Araceli Cuesta-Márquez, Ana Olivia Cortés-Flores, Alejandro González-Ojeda, Research Unit in Clinical Epidemiology, Specialties Hospital of the Western Medical Center, Medical Unit of High Specialty, Mexican Institute of Social Security, Guadalajara, Jalisco 44340, México.
authors.forename: Andrea Socorro
authors.initials: AS
authors.lastname: Alvarez-Villaseñor
authors.affiliation: Clotilde Fuentes-Orozco, Michel Dassaejv Macías-Amezcua, Jesús García-Rentería, Jorge Rendón-Félix, Mariana Chávez-Tostado, Lizbeth Araceli Cuesta-Márquez, Ana Olivia Cortés-Flores, Alejandro González-Ojeda, Research Unit in Clinical Epidemiology, Specialties Hospital of the Western Medical Center, Medical Unit of High Specialty, Mexican Institute of Social Security, Guadalajara, Jalisco 44340, México.
authors.forename: Ana Olivia
authors.initials: AO
authors.lastname: Cortés-Flores
authors.affiliation: Clotilde Fuentes-Orozco, Michel Dassaejv Macías-Amezcua, Jesús García-Rentería, Jorge Rendón-Félix, Mariana Chávez-Tostado, Lizbeth Araceli Cuesta-Márquez, Ana Olivia Cortés-Flores, Alejandro González-Ojeda, Research Unit in Clinical Epidemiology, Specialties Hospital of the Western Medical Center, Medical Unit of High Specialty, Mexican Institute of Social Security, Guadalajara, Jalisco 44340, México.
authors.forename: Alejandro
authors.initials: A
authors.lastname: González-Ojeda
mesh_terms: D000975:Antioxidants / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D002760:Cholangiopancreatography, Endoscopic Retrograde / Q000009:adverse effects*; D019317:Evidence-Based Medicine; D006801:Humans; D015994:Incidence; D010195:Pancreatitis / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants
keywords: Antioxidant drugs; Endoscopic retrograde cholangiopancreatography; Pancreatitis; Prophylaxis