Clinical case
Drug related colonic perforation: Case report
Perforación colónica secundaria a polifarmacia: reporte de caso
Edgar Núñez-García
, Luis César Valencia-García, Ricardo Sordo-Mejía, Daniel Kajomovitz-Bialostozky, Alberto Chousleb-Kalach
Corresponding author
edgar.nunez.g@gmail.com
Corresponding author at: Centro Médico ABC, Observatorio Sur 136 No. 116, Col.: Las Américas, C.P. 01120, México D.F., Mexico. Tel.: +52 (55) 5230 8000; fax: +52 (55) 5230 8123.
Corresponding author at: Centro Médico ABC, Observatorio Sur 136 No. 116, Col.: Las Américas, C.P. 01120, México D.F., Mexico. Tel.: +52 (55) 5230 8000; fax: +52 (55) 5230 8123.
Servicio de Cirugía General, Centro Médico ABC, México, D.F., Mexico
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Tel.: +52 (55) 5230 8000; fax: +52 (55) 5230 8123." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Perforación colónica secundaria a polifarmacia: reporte de caso" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 710 "Ancho" => 952 "Tamanyo" => 142377 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Product of colonic resection, with extensive necrosis of the caecum, ascending and transverse colon.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">Acute pseudo-obstruction of the colon is a disorder characterised by massive dilatation of the colon, where there is no evidence of mechanical obstruction, and by definition is associated with a secondary or base disease. Pseudo-obstruction, also known as Ogilvie syndrome, often occurs in elderly, patients who are being treated with a great many drugs, and although rare, drug-induced colonic toxicity is a disorder which should be recognised in time.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">1,2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Colonic pseudo-obstruction is always secondary to underlying disease such as: infectious, cardiac, neurological or drug-induced processes. Spontaneous perforation presents in 3–15% of cases with 40% mortality.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The pathophysiology of drug-related colon toxicity starts as a pseudo-obstruction of the colon where the ileus or colonic paresis which results in massive dilatation, is secondary to the use of drugs which act on colonic innervation or motility. The drugs which are most usually associated with this disease include: narcotics, phenothiazines, antidepressants, and calcium channel-blockers. Despite the fact that the association of drugs with this disease is based on case reports, an obvious causal relationship has been established with some drugs such as loperamide, narcotics, phenothiazines and vincristine. Probable association with: atropine, nifedipine, procainamide, tricyclic antidepressants, amphetamines, barbiturates, chlonidine, dicumarol and verapamil.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The clinical spectrum of drug-related colonic toxicity varies between: constipation, pseudo-obstruction, ischaemia and necrosis. Clinical suspicion of this disorder is important, as timely discontinuation of the drugs can prevent complications which result in a high morbimortality rate.<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">1,2</span></a> Initially the treatment guideline is conservative, colonic decompression can be effective although it carries with it a risk of perforation. Surgical treatment is reserved to cases presenting possible complications such as necrosis or perforation.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Objective</span><p id="par0025" class="elsevierStylePara elsevierViewall">To present a review of the subject and the case of a female patient with polypharmacy, who presented with colonic pseudo-obstruction and evolved torpidly, until she presented perforation with peritonitis. She was managed surgically, and after medical management due to sepsis the patient responded favourably with no complications.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Clinical case</span><p id="par0030" class="elsevierStylePara elsevierViewall">A 67-year old female patient who was admitted with distension and progressive diffuse abdominal pain of 8/10 intensity, with no signs of peritoneal irritation, accompanied by a difficulty in passing wind, and her last bowel movement was 2 days prior to admission. It was decided to hospitalise the patient with a diagnosis of colonic pseudo-obstruction. The patient's medical history included, arterial hypertension treated with nifedipine 20<span class="elsevierStyleHsp" style=""></span>mg/tid, dyslipidaemia treated with atorvastatin 10<span class="elsevierStyleHsp" style=""></span>mg/daily. In addition, the patient was taking quetiapine 300<span class="elsevierStyleHsp" style=""></span>mg/daily, levetiracetam 500<span class="elsevierStyleHsp" style=""></span>mg/bid, desvenlafaxine 50<span class="elsevierStyleHsp" style=""></span>mg/day, piracetam and raloxifene 60<span class="elsevierStyleHsp" style=""></span>mg/day for depression. She had no history of abdominal surgery; she only reported resection of a melanoma on her buttock, reduction mammoplasty, rhytidectomy and resection of an unspecified retro-orbital tumour.</p><p id="par0035" class="elsevierStylePara elsevierViewall">On admission the patient was, dehydrated, tachycardic with a heart rate of 100<span class="elsevierStyleHsp" style=""></span>bpm, low-grade fever, distended, tympanic abdomen, tender on palpation, no peristalsis, no rebound or muscle stiffness. The laboratory tests on admission showed: leucopoenia 4000, creatinine 1.5<span class="elsevierStyleHsp" style=""></span>mg/dl, procalcitonin 60.25<span class="elsevierStyleHsp" style=""></span>ng/ml and C-reactive protein 41<span class="elsevierStyleHsp" style=""></span>mg/l. Abdominal X-rays were requested which showed an increase in the calibre of the ascending and transverse colon, and areas of pneumatosis were observed in the ascending colon, and free intraabdominal fluid (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>), and therefore tomography of the abdomen and pelvis were requested, which corroborated distension of the ascending and transverse colon with images compatible with pneumatosis, associated with free air bubbles in close proximity to the colon (<a class="elsevierStyleCrossRef" href="#fig0010">Figs. 2 and 3</a>). Due to these findings it was decided to undertake an exploratory laparotomy, where purulent free fluid was found, dilated colon loops and necrosis of the caecum, ascending and transverse colon with micro perforation of the transverse colon (<a class="elsevierStyleCrossRefs" href="#fig0015">Figs. 4 and 5</a>). A resection was performed of the terminal ileum, ascending, transverse and descending colon with mechanical ileo-sigmoid anastomosis, with thorough lavage of the cavity. There were no surgical complications in the transoperative period, and the patient went to intensive care due to haemodynamic instability. In the postoperative period the patient had signs of systemic inflammatory response, and was prescribed meropenem and ketoconazol, as well as mechanical ventilation and hydric resuscitation. Mechanical ventilation was withdrawn on the fifth post-operative day, and the patient's haemodynamic status remained stable without the need for vasopressors. The patient remained in intermediate therapy and evolved well. On the eighth post-operative day she had a bowel movement, and started an oral diet, which she tolerated well. The patient was discharged without complications 11 days after surgery, tolerating an oral diet, and presenting adequate gastro-intestinal function.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0040" class="elsevierStylePara elsevierViewall">Acute colonic pseudo-obstruction is a clinical syndrome which, by definition, implies massive dilatation of the large intestine, with no mechanical obstruction; the disorder is also known as Ogilvie syndrome.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a> It is always secondary to underlying diseases such as infectious, cardiac, neurological or drug-related processes,<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">3</span></a> as in the case we present in this article, in whom the only identified factor was the use of drugs which reduced colonic motility such as nifedipine, which relaxes smooth muscle by blocking the calcium channels, antidepressants with anticolinergic effect which also inhibit intestinal motility, and which resulted in pseudo-obstruction with massive dilatation of the transverse colon with increased intraluminal pressure, ischaemia and necrosis of the wall and subsequent perforation.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">1</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">In cases of colonic pseudo-obstruction with no perforation or haemodynamic instability, treatment is conservative, effective in 53–96% of cases, with a risk of perforation of the colon of less than 2.5%, and mortality from 0% to 14%.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">4</span></a> Conservative treatment includes treating underlying disease, discontinuing the drugs causing colonic hypomotility, and correcting hydro-electrolyte abnormalities.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">2</span></a> Neostigmine is used for decompression of the colon; this is an acetylcholinesterase inhibitor<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">5</span></a> with efficacy of 64–91% on the first dose, and in cases of recurrence (30% of cases) a second dose is recommended to increase its effectiveness from 40% to 100%.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">4</span></a> If decompression of the colon is achieved, a transrectal tube or decompressive colonoscopy is used to decrease parietal tension, and thus increase blood flow in the wall and promote peristalsis, which is effective in 61–100% of cases. However, this is not a harmless procedure, as it carries a risk of perforation in 5% and increased mortality.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">4</span></a> Percutaneous or endoscopic caecostomy is used for cases where decompression has not been effective, providing the patient has no signs of perforation or necrosis; this procedure increases the morbidity carried by caecostomy, such as fistula and intestinal leakage.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">6,7</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Surgery is reserved for cases with clinical signs suggestive of peritonitis or perforation and laparotomy is recommended, as in the case of our patient who had signs of free air in the cavity without diagnostic confirmation. The procedure to be carried out will depend on intraoperative findings, as well as the haemodynamic status of the patient, and can go from resection with primary anastomosis to defunctionalisation and bypass of the ileum or colon. Laparoscopy is not recommended, as dilatation of the colon reduces the potential space to create a pneumoperitoneum and manoeuvre inside the abdominal cavity.</p><p id="par0055" class="elsevierStylePara elsevierViewall">Surgery, although it is the definitive treatment in many cases, carries with it a 6% morbidity and mortality of up to 30%; these figures depend on the disease causing the colonic ischaemia.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">7,8</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusion</span><p id="par0060" class="elsevierStylePara elsevierViewall">It is important to take drug interactions into account in patients with multiple diseases, especially in the geriatric population, as they can result in complications with high morbimortality, which can cause intestinal pseudo-obstruction and require surgical treatment which, if detected in time, can be avoided.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflict of interests</span><p id="par0065" class="elsevierStylePara elsevierViewall">The authors have no conflict of interests to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres611317" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objetive" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Clinical case" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec625346" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres611318" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Caso clínico" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec625345" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Background" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Objective" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Clinical case" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conclusion" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflict of interests" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-03-24" "fechaAceptado" => "2014-11-19" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec625346" "palabras" => array:4 [ 0 => "Intestinal perforation" 1 => "Drugs" 2 => "Colonic pseudo-obstruction" 3 => "Multiple medications" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec625345" "palabras" => array:4 [ 0 => "Perforación intestinal" 1 => "Fármacos" 2 => "Pseudo-obstrucción colónica" 3 => "Polifarmacia" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Acute pseudo-obstruction of the colon is a disorder characterised by an increase in intra-luminal pressure that leads to ischaemia and necrosis of the intestinal wall. The mechanism that produces the lesion is unknown, although it has been associated with: trauma, anaesthesia, or drugs that alter the autonomic nervous system. The pathophysiology of medication induced colon toxicity can progress to a perforated colon and potentially death.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objetive</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Present a case of a colonic pseudo-obstruction in a patient with polyfarmacy as the only risk factor and to review the medical literature related to the treatment of this pathology.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Clinical case</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The case is presented of a 67 year old woman with colonic pseudo-obstruction who presented with diffuse abdominal pain and distension. The pain progressed and reached an intensity of 8/10, and was accompanied by fever and tachycardia. There was evidence of free intraperitoneal air in the radiological studies. The only risk factor was the use of multiple drugs. The colonic pseudo-obstruction progressed to intestinal perforation, requiring surgical treatment, which resolved the problem successfully.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">It is important to consider drug interaction in patients with multiple diseases, as it may develop complications that can be avoided if detected on time.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objetive" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Clinical case" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La pseudo-obstrucción colónica aguda se caracteriza por la dilatación masiva del colon, con aumento de la presión intraluminal que condiciona isquemia y necrosis de la pared intestinal. No se conoce el mecanismo que produce la lesión, aunque se ha asociado con: traumatismo, anestesia o agentes farmacológicos que alteran el sistema nervioso autónomo. La patofisiología de la toxicidad colónica por fármacos puede progresar hasta la perforación colónica y potencialmente a la muerte.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Objetivo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Comunicar el caso de una paciente con polifarmacia como único factor de riesgo para la pseudo-obstrucción colónica, y presentar la revisión de la bibliografía médica relacionada con el tratamiento.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Caso clínico</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Presentamos el caso de una mujer de 67 años con distensión y dolor abdominal difuso, progresivo de intensidad 8/10 por pseudo-obstrucción colónica, acompañado de febrícula y, taquicardia. En los estudios de gabinete se observó aire libre en cavidad. El único factor de riesgo que tenía la paciente fue el uso de múltiples fármacos. El cuadro de pseudo-obstrucción evolucionó hasta la perforación intestinal, que requirió tratamiento quirúrgico, con resultado exitoso.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusión</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Es importante tener en cuenta las interacciones farmacológicas en los pacientes con múltiples enfermedades, ya que pueden condicionar complicaciones como la perforación colónica, que de ser detectadas a tiempo se podrían evitar.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Antecedentes" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Caso clínico" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Núñez-García E, Valencia-García LC, Sordo-Mejía R, Kajomovitz-Bialostozky D, Chousleb-Kalach A. Perforación colónica secundaria a polifarmacia: reporte de caso. Cirugía y Cirujanos. 2016;84:65–68.</p>" ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 839 "Ancho" => 700 "Tamanyo" => 45221 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Simple X-ray of the abdomen with dilatation of ascending and transverse colon (blue arrow).</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figures 2 and 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2v3.jpeg" "Alto" => 787 "Ancho" => 1700 "Tamanyo" => 96277 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Abdominal tomography with intravenous contrast. Massive dilatation of the ascending and transverse (left) colon can be seen. Intestinal pneumatosis and free air bubbles in close proximity to the colon (right) can be observed.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 709 "Ancho" => 952 "Tamanyo" => 99280 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Transverse colon with necrosis and punctiform perforation.</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 710 "Ancho" => 952 "Tamanyo" => 142377 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Product of colonic resection, with extensive necrosis of the caecum, ascending and transverse colon.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:8 [ 0 => array:3 [ "identificador" => "bib0045" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Colonic toxicity of administered drugs and chemicals" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M.S. 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Beyrouti" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Tunis Med" "fecha" => "2013" "volumen" => "91" "paginaInicial" => "565" "paginaFinal" => "572" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24281995" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0065" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ogilvie's syndrome: a new approach to an old problem" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "B.M. Stephenson" 1 => "A.R. Morgan" 2 => "J.R. Salamn" 3 => "M.H. 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| Year/Month | Html | Total | |
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