No Association of Sirolimus with Wound Complications in Children with Vascular Anomalies

Published:November 23, 2022DOI:


      • The transplant literature has identified an association between sirolimus therapy and wound complications, but similar studies have not been performed in children with vascular anomalies.
      • Sirolimus may not significantly increase perioperative complication rates (including wound complications) in pediatric patients undergoing resection of their vascular anomaly.



      Sirolimus has demonstrated effectiveness as a treatment option for several types of vascular anomalies; however, it has a potential side effect of delayed surgical wound healing. The purpose of this study was to evaluate the association of sirolimus with postoperative complications in the pediatric vascular anomaly population.


      A retrospective cohort study was performed for children with a vascular anomaly who underwent excision or debulking of the anomaly from 2015 to 2020. Patient demographics, vascular anomaly characteristics, operative variables, sirolimus dosing information, and perioperative outcomes were collected. Univariate analysis was performed to compare outcomes based on the administration of sirolimus.


      Forty-seven patients with vascular anomalies underwent 57 surgical procedures (36 without perioperative sirolimus, 21 with perioperative sirolimus). The median age at the time of surgery was seven years (IQR 1.7 – 14.0). The most common anomalies were lymphatic and venolymphatic malformations. Of the patients administered perioperative sirolimus, the median preoperative and postoperative sirolimus levels were comparable (preoperative 6.9 ng/mL (IQR 4.9– 10.1), postoperative 6.5 ng/mL (IQR 4.7–9.4)). The rate of postoperative complications (sirolimus 19%, without sirolimus 11%; p=0.45) and wound complications (sirolimus 14%, without sirolimus 6%; p=0.26) were comparable between the cohorts.


      Our results suggest sirolimus may not significantly increase perioperative complication rates in pediatric patients undergoing resection of their vascular anomaly.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Pediatric Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


      1. ISSVA Classification of Vascular Anomalies. 2018. (Accessed Feb 16, 2022, at

        • Adams D.M.
        • Trenor III, C.G.
        • Hammill A.M.
        • et al.
        Efficacy and Safety of Sirolimus in the Treatment of Complicated Vascular Anomalies.
        Pediatrics. 2016; 137
        • Hammill A.M.
        • Wentzel M.
        • Gupta A.
        • et al.
        Sirolimus for the treatment of complicated vascular anomalies in children.
        Pediatr Blood Cancer. 2011; 57: 1018-1024
        • Vlahovic A.M.
        • Vlahovic N.S.
        • Haxhija E.Q.
        Sirolimus for the Treatment of a Massive Capillary-Lymphatico-Venous Malformation: A Case Report.
        Pediatrics (Evanston). 2015; 136: e513-e516
        • Lackner H.
        • Karastaneva A.
        • Schwinger W.
        • et al.
        Sirolimus for the treatment of children with various complicated vascular anomalies.
        European journal of pediatrics. 2015; 174: 1579-1584
        • Kim D.
        • Benjamin L.
        • Wysong A.
        • Hovsepian D.
        • Teng J.
        Treatment of complex periorbital venolymphatic malformation in a neonate with a combination therapy of sirolimus and prednisolone: Treatment of VLM with sirolimus and steroid.
        Dermatologic therapy. 2015; 28: 218-221
        • Iacobas I.
        • Simon M.L.
        • Amir T.
        • et al.
        Decreased vascularization of retroperitoneal kaposiform hemangioendothelioma induced by treatment with sirolimus explains relief of symptoms.
        Clinical imaging. 2015; 39: 529-532
        • Margolin J.F.
        • Soni H.M.
        • Pimpalwar S.
        Medical Therapy for Pediatric Vascular Anomalies.
        Seminars in plastic surgery. 2014; 28: 79-86
        • Ozeki M.
        • Nozawa A.
        • Yasue S.
        • et al.
        The impact of sirolimus therapy on lesion size, clinical symptoms, and quality of life of patients with lymphatic anomalies.
        Orphanet journal of rare diseases. 2019; 14: 141
        • Nashan B.
        • Citterio F.
        Wound healing complications and the use of mammalian target of rapamycin inhibitors in kidney transplantation: a critical review of the literature.
        Transplantation. 2012; 94: 547-561
        • Zakliczynski M.
        • Nozynski J.
        • Kocher A.
        • et al.
        Surgical wound-healing complications in heart transplant recipients treated with rapamycin.
        Wound Repair Regen. 2007; 15: 316-321
        • Troppmann C.
        • Pierce J.L.
        • Gandhi M.M.
        • Gallay B.J.
        • McVicar J.P.
        • Perez R.V.
        Higher surgical wound complication rates with sirolimus immunosuppression after kidney transplantation: a matched-pair pilot study.
        Transplantation. 2003; 76: 426-429
        • Valente J.F.
        • Hricik D.
        • Weigel K.
        • et al.
        Comparison of Sirolimus vs. Mycophenolate Mofetil on Surgical Complications and Wound Healing in Adult Kidney Transplantation.
        American journal of transplantation. 2003; 3: 1128-1134
        • Dean P.G.
        • Lund W.J.
        • Larson T.S.
        • et al.
        Wound-healing complications after kidney transplantation: a prospective, randomized comparison of sirolimus and tacrolimus.
        Transplantation. 2004; 77: 1555
        • Tiong H.Y.
        • Flechner S.M.
        • Zhou L.
        • et al.
        A systematic approach to minimizing wound problems for de novo sirolimus-treated kidney transplant recipients.
        Transplantation. 2009; 87: 296-302
        • Heble A.
        • Everitt M.D.
        • Gralla J.
        • Miyamoto S.D.
        • Lahart M.
        • Eshelman J.
        Safety of mTOR inhibitor continuation in pediatric heart transplant recipients undergoing surgical procedures.
        Pediatr Transplant. 2018; 22
        • Wojarski J.
        • Zeglen S.
        • Ochman M.
        • Karolak W.
        Early Sirolimus-Based Immunosuppression is Safe for Lung Transplantation Patients: Retrospective, Single Arm, Exploratory Study.
        Ann Transplant. 2018; 23: 598-607
        • Beck D.O.
        • Gosain A.K.
        The presentation and management of hemangiomas.
        Plast Reconstr Surg. 2009; 123 (91e): 181e
        • Chalya P.L.
        • Kayange N.M.
        • Rambau P.F.
        • Manyama M.
        • Gilyoma J.M.
        Surgical management of vascular anomalies in children at a tertiary care hospital in a resource-limited setting: a Tanzanian experience with 134 patients.
        BMC Res Notes. 2015; 8: 732
        • Finn M.C.
        • Glowacki J.
        • Mulliken J.B.
        Congenital vascular lesions: clinical application of a new classification.
        J Pediatr Surg. 1983; 18: 894-900
        • Ryu J.Y.
        • Eo P.S.
        • Lee J.S.
        • et al.
        Surgical approach for venous malformation in the head and neck.
        Arch Craniofac Surg. 2019; 20: 304-309
        • Cheng J.
        • Liu B.
        • Lee H.J.
        30-Day outcomes analysis of NSQIP-pediatric for surgical management of head and neck lymphatic malformations in children.
        Int J Pediatr Otorhinolaryngol. 2019; 118: 21-24
        • Khanwalkar A.
        • Carter J.
        • Bhushan B.
        • Rastatter J.
        • Maddalozzo J.
        Thirty-day perioperative outcomes in resection of cervical lymphatic malformations.
        Int J Pediatr Otorhinolaryngol. 2018; 106: 31-34
        • Mills R.E.
        • Taylor K.R.
        • Podshivalova K.
        • McKay D.B.
        • Jameson J.M.
        Defects in skin gamma delta T cell function contribute to delayed wound repair in rapamycin-treated mice.
        J Immunol. 2008; 181: 3974-3983