By Louise de la Motte
Endovascular repair has substantially contributed towards making aortic aneurysm repair minimally invasive, achieving minimal skin incisions, no manipulation of the intestine and minimal blood loss. However, a post-implantation syndrome characterised by fever, flu-like symptoms, neutrophil leukocytosis and coagulation disturbances, has been observed in terms of the systemic inflammatory response syndrome in 13–60% of patients within the first five days after EVAR.
Apart from the immediate discomfort to the patient, a concern, at least theoretically, could be that post-implantation syndrome may increase the risk of late complications such as endoleak, stent graft migration or aneurysm rupture. The importance of a transient systemic inflammatory response to the sustained biological activity after EVAR is unclear, but it seems relevant to speculate that a rise in plasma neutrophils and interleukin 6 in relation to the procedure, could have an effect on the high levels of interleukin 6 and matrix metalloproteinase 9 reported to be present long after the procedure.
Although this inflammatory response often remains at subclinical levels, it can also lead to major organ dysfunction, especially in the elderly and patients with severe comorbidities. Moreover, post-implantation syndrome may be interpreted as an infectious complication mandating prolonged antibiotic management. A technically successful EVAR should lead to a length of stay of about 1–2 days, even in high-risk patients if the increased organ demands due to the systemic inflammatory response could be eliminated. In this context, the literature is inconclusive, since some centres have reported a short length of stay and even an outpatient procedure in selected EVAR patients in contrast to other reports of length of stay of more than four days. This indicates room for optimisation of patient recovery.
The administration of perioperative glucocorticoids has been shown to reduce the inflammatory response after various types of surgery, resulting in improved recovery. The ability of glucocorticoids to preserve the endothelial glycocalyx and thereby the vascular barrier is of particular interest in vascular surgery, where injury-induced disruption of the endothelial glycocalyx results in impairment of the vascular barrier, promotion of interstitial oedema and inflammation. High dose methylprednisolone may exert its effect up to a couple of weeks after administration and could have the potential to halt the inflammation reported after EVAR. Some might argue that post-implantation syndrome reduces endoleaks by enhancing the development of scar tissue; however, it can also be argued that post-implantation syndrome enhances continued modulation of the aneurysm wall and thereby endoleaks and migration of the stent graft. So far no reports of negative effects on tissue healing after a single preoperative dose of steroids have been published.
Perioperative glucocorticoids are used routinely in EVAR in some centres, primarily to attenuate the post-implantation syndrome. The outpatient report by Lachat et al (2013) described the administration of prolonged (five days) low dose prednisone therapy starting some hours after the EVAR procedure to reduce post-implantation syndrome. Gerasimidis et al (2005) reported the use of 500mg of hydrocortisone during EVAR and finally Nano et al (2014) described the administration of 1g of hydrocortisone intravenously on the third postoperative day in case of post-implantation syndrome. In all three non-randomised reports the timing of glucocorticoid is suboptimal considering the physiological functions of steroids. Steroids generally exert their effect via regulation of protein synthesis the optimal timing of administration would therefore be 1–2 hours before surgery in order to obtain full biological effect of the steroid at the time of incision. The effects of preoperative glucocorticoids in EVAR have only been tested in a recent randomised controlled trial (de la Motte et al 2014). The POMEVAR trial, which studied the effect of high-dose methylprednisolone (30mg/kg) two hours prior to EVAR, showed a pronounced reduction of the postoperative components of the systemic inflammatory response syndrome response from 92% to 27%. In addition, the reduction in the inflammatory responses and pro-inflammatory biomarkers was associated with an enhancement of the anti-inflammatory response. These physiological effects of methylprednisolone resulted in a reduction in time to meet discharge criteria without any apparent safety issues.
Post-implantation syndrome is more than just a theoretical concern especially in the elderly patients. The use of perioperative steroids in EVAR seems relevant and is supported by the findings of the POMEVAR trial. However, given the pharmacokinetics of glucocorticoids and the side effects related to their prolonged administration, the use of a single preoperative high dose of glucocorticoid during EVAR is, in our opinion, recommendable. Further dose-response and safety studies are warranted.
Louise de la Motte is a vascular surgeon, Department of Vascular Surgery, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark