Scientific Letter
Usefulness of interleukin 1 receptor antagonist (anakinra) in refractory post-pericardiotomy syndrome
Utilidad del bloqueo de interleucina 1 con anakinra en el síndrome pospericardiotomía refractario
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"nombre" => "Marta" "apellidos" => "Flores Fernández" "email" => array:1 [ 0 => "martafloresfdez@outlook.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Ana" "apellidos" => "Caro Barri" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Elena" "apellidos" => "Montañés Delmás" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Belén" "apellidos" => "Toral Vázquez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Jaime" "apellidos" => "de Inocencio Arocena" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Instituto Pediátrico del Corazón, Hospital Universitario 12 de Octubre, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Unidad de Reumatología Pediátrica, Hospital Universitario 12 de Octubre, Departamento de Salud Pública y Materno-Infantil, Universidad Complutense de Madrid, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Utilidad del bloqueo de interleucina 1 con anakinra en el síndrome pospericardiotomía refractario" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Postpericardiotomy syndrome (PPS) is an inflammation of the pericardium or pleura following a pericardial lesion, which may result from, among others, heart surgery, acute myocardial infarction or chest trauma. It is defined based on the presence of at least 2 of the following criteria: a) fever with no alternative explanation; b) pleuritic/pericardial chest pain; c) pericardial friction rub; d) pericardial effusion and e) pleural effusion with elevation of C-reactive protein.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> It is considered persistent or refractory when the symptoms last longer than 4 weeks. The incidence of pericarditis post pericardiotomy is of 10%–25%.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Its development entails a prolonged stay, need of additional medication and the risk of recurrence and severe complications, such as cardiac tamponade.</p><p id="par0010" class="elsevierStylePara elsevierViewall">This complication is treated with colchicine, nonsteroidal anti-inflammatory drugs and steroids, reserving intravenous immunoglobulin (IVIG) therapy for refractory cases. A growing body of evidence in patients with recurrent idiopathic pericarditis demonstrates the usefulness of anakinra, an antagonist of the receptor of interleukin-1β,<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3–5</span></a> a proinflammatory cytokine involved in innate immunity. However, this drug has not been used for treatment of severe refractory PPS to date.</p><p id="par0015" class="elsevierStylePara elsevierViewall">We present two cases of refractory postoperative PPS that required pericardiocentesis or drainage on account of the favourable outcomes associated with treatment with anakinra.</p><p id="par0020" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patient 1</span>: boy aged 9 years with congenitally corrected transposition of the great arteries and complete heart block. The patient underwent an initial surgery at age 4 years (pulmonary artery banding and epicardial pacing) and developed PPS, which was treated with 2 cycles of prednisone (2 mg/kg/day). At 8 years he underwent a second surgery (hemi-Mustard procedure, band removal, arterial switch and Glenn procedure), and once again developed PPS. The patient received ibuprofen and colchicine, and on day 20 required addition of prednisone (2 mg/kg/day). The effusion progressed, requiring performance of pericardiocentesis (day 35 post surgery) and leading to administration of IVIG (2 g/kg), with no improvement after 3 doses. On day 65 post surgery, anakinra was added, delivered by the subcutaneous route (100 mg/24 h = 2 mg/kg/day), which achieved a significant reduction in the effusion. Tapering off of anakinra started after 2 months of treatment, with addition of prednisone at a low dose (0.1 mg/kg/day). At 3 months, anakinra and prednisone were discontinued, followed by discontinuation of colchicine 4 months after. The patient has attended follow-up visits at regular intervals and has not experienced a recurrence in 3 years.</p><p id="par0025" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patient 2</span>: boy aged 10 years with severe mitral valve stenosis and mixed aortic valve disease (moderate aortic valve and subaortic stenosis and mild regurgitation). After cardiac surgery (mitral and aortic valvuloplasty, subaortic membrane resection), the patient developed bilateral pleural effusion and pericardial effusion, with a prolonged need of pleural drainage with removal of up to 1900 mL/day. He was treated with ibuprofen and colchicine. During the postoperative period, he developed severe mitral insufficiency due to a suture tear that required reintervention on day 22 post surgery. Due to the persistence of pleural and pericardial effusion, prednisone (2 mg/kg/day) and IVIG were added, which were not effective. Due to the lack of improvement, anakinra was initiated on day 37 post surgery, delivered subcutaneously at a dose of 100 mg per 24 h (4 mg/kg/day), which achieved resolution of pericardial effusion and a significant reduction of pleural effusion, allowing removal of the drains and hospital discharge. On month 3 post surgery, prednisone was discontinued and tapering of anakinra started, which was followed by an increase in the left-sided pleural effusion that required readmission to hospital. We increased the dose of anakinra (100 mg/12 h), which achieved a favourable response. At present (11 months post surgery) mild pleural effusion persists in the left hemithorax, and the patient remains in treatment with colchicine and low-dose prednisone, tolerating the tapering of anakinra without complications (current dose, 100 mg/72 h).</p><p id="par0030" class="elsevierStylePara elsevierViewall">Both patients tolerated the drug well, as they only developed local reactions at the site of injection in the first doses.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Several hypotheses have been formulated to explain the pathogenesis of PPS, including a systemic inflammatory response triggered by exposure of pericardial/pleural structures to the immune system, the presence of blood in the pericardial–pleural space or perioperative tissue hypoxia. Tissue necrosis or mesothelial damage associated to traumatic injury or heart surgery may stimulate the release of autoantigens. Patients that develop PPS exhibit elevation of various cytokines, including interleukins 1, 8 and 6.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Since interleukin 1 plays a key role in the development of inflammation, blocking its activity could contribute to inhibiting the mechanisms involved in the pathogenesis of PPS.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Although anakinra has proven effective in the management of recurrent idiopathic pericarditis,<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3–5</span></a> our literature search did not yield any studies that assessed its role in the management of severe refractory PPS.</p><p id="par0045" class="elsevierStylePara elsevierViewall">In our experience, anakinra was effective and safe for treatment of patients with severe refractory PPS. In the future, performance of multicentre studies with larger samples will determine its efficacy for this indication.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Flores Fernández M, Caro Barri A, Montañés Delmás E, Toral Vázquez B, de Inocencio Arocena J. Utilidad del bloqueo de interleucina 1 con anakinra en el síndrome pospericardiotomía refractario. 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Wasik" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0108822" "Revista" => array:3 [ "tituloSerie" => "PLoS One" "fecha" => "2014" "volumen" => "21" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23412879/0000009500000003/v1_202109080620/S2341287921001290/v1_202109080620/en/main.assets" "Apartado" => array:4 [ "identificador" => "38181" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Scientific letters" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23412879/0000009500000003/v1_202109080620/S2341287921001290/v1_202109080620/en/main.pdf?idApp=UINPBA00005H&text.app=https://analesdepediatria.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287921001290?idApp=UINPBA00005H" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 13 | 6 | 19 |
| 2024 October | 286 | 48 | 334 |
| 2024 September | 67 | 50 | 117 |
| 2024 August | 70 | 60 | 130 |
| 2024 July | 51 | 37 | 88 |
| 2024 June | 47 | 24 | 71 |
| 2024 May | 55 | 36 | 91 |
| 2024 April | 48 | 40 | 88 |
| 2024 March | 36 | 16 | 52 |
| 2024 February | 27 | 25 | 52 |
| 2024 January | 48 | 28 | 76 |
| 2023 December | 45 | 20 | 65 |
| 2023 November | 45 | 29 | 74 |
| 2023 October | 29 | 32 | 61 |
| 2023 September | 46 | 30 | 76 |
| 2023 August | 29 | 17 | 46 |
| 2023 July | 45 | 28 | 73 |
| 2023 June | 40 | 32 | 72 |
| 2023 May | 33 | 26 | 59 |
| 2023 April | 21 | 12 | 33 |
| 2023 March | 39 | 23 | 62 |
| 2023 February | 22 | 22 | 44 |
| 2023 January | 25 | 23 | 48 |
| 2022 December | 44 | 30 | 74 |
| 2022 November | 48 | 36 | 84 |
| 2022 October | 45 | 37 | 82 |
| 2022 September | 33 | 27 | 60 |
| 2022 August | 41 | 50 | 91 |
| 2022 July | 43 | 45 | 88 |
| 2022 June | 38 | 35 | 73 |
| 2022 May | 46 | 44 | 90 |
| 2022 April | 43 | 49 | 92 |
| 2022 March | 50 | 49 | 99 |
| 2022 February | 37 | 18 | 55 |
| 2022 January | 39 | 63 | 102 |
| 2021 December | 41 | 38 | 79 |
| 2021 November | 33 | 44 | 77 |
| 2021 October | 97 | 97 | 194 |
| 2021 September | 106 | 70 | 176 |
| 2021 August | 79 | 64 | 143 |
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