November 2019

Synopsis: Multiple large randomized controlled trials have demonstrated that elective endovascular repair of abdominal aortic aneurysms (EVAR) has superior perioperative morbidity and mortality in comparison to traditional open repair (OR) (1-3). Interestingly, this advantage was lost in mid-term follow up (2-5 years) in all three trials. Furthermore, this trend continued in the long term follow-up for the two European trials, the Dutch Randomised Endovascular Aneurysm Management (DREAM) and the United Kingdom Endovascular Aneurysm Repair Trial 1 (EVAR 1), suggesting that survival was worse after EVAR than OR due to late mortality among patients who had undergone EVAR. Whether this long term trend held in the OVER trial was unknown. Thus, an updated series of long-term data was analyzed by the authors of the Standard Open Surgery Versus Endovascular Repair of Abdominal Aortic Aneurysm (OVER) trial to answer this question.

The OVER trial was funded by the United States Department of Veteran Affairs and conducted within the VA medical system. It randomly assigned patients with asymptomatic AAAs to either EVAR or OR for aneurysm treatment and followed them for up to 14 years (median follow-up 9.4 years). The study was composed of 881 patients who were candidates for either procedure, with 444 assigned to EVAR and 437 to OR. The primary outcome was all-cause mortality. Secondary outcomes included secondary therapeutic procedures that resulted from the initial procedure. 

The principal finding was that no significant difference in all-cause mortality was noted between patients who underwent EVAR and patients who underwent OR (hazard ratio EVAR vs. OR, 0.96; 95% confidence interval 0.82-1.13; P=0.61). Furthermore, there was also no significant difference in aneurysm-related mortality between both groups (2.7% EVAR vs. 3.7% open). Most of these deaths occurred in the perioperative period. However, not surprisingly, more patients in the EVAR group underwent a secondary procedure (26.7% EVAR vs. 19.8% OR, difference 6.9 percentage points, 95% CI 2.0-17.5). 

The two main critiques of this trial center around its generalizability: the first is in relation to its anatomic inclusion criteria, while the second is in regard to its lack of inclusion of women. In regards to the first issue, close to 52% of patients who were screened were excluded because they were ineligible to undergo both EVAR or OR. Furthermore, the trial lacks anatomic criteria or detail—it’s possible that the EVAR group was a highly selected patient population and not reflective of routine treatment of patients with challenging infrarenal anatomy. In regards to the second issue, the percentage of women in the OVER trial was much lower than the two European trials: 0.6% OVER vs. 6% EVAR1 and 9% DREAM. Long term data from the Vascular Quality Initiative has found that long term survival at 10 years is significantly lower in women relative to men after EVAR, but equivalent after OR4. When men and women were considered together in this analysis, these differences contributed to an overall survival advantage for OR over EVAR, a finding similar to that of DREAM and EVAR1. Thus, the concern is that the equivalent long term survival in the OVER trial between OR and EVAR for AAA may not be generalizable to women. 

References

1. Lederle FA, Kyriakides TC, Stroupe KT, Freischlag JA, Padberg FT,Jr, Matsumura JS, et al. Open versus Endovascular Repair of Abdominal Aortic Aneurysm. N Engl J Med 2019 May 30;380(22):2126-2135.
2. Patel R, Sweeting MJ, Powell JT, Greenhalgh RM, EVAR trial investigators. Endovascular versus open repair of abdominal aortic aneurysm in 15-years' follow-up of the UK endovascular aneurysm repair trial 1 (EVAR trial 1): a randomised controlled trial. Lancet 2016 Nov 12;388(10058):2366-2374.
3. van Schaik TG, Yeung KK, Verhagen HJ, de Bruin JL, van Sambeek MRHM, Balm R, et al. Long-term survival and secondary procedures after open or endovascular repair of abdominal aortic aneurysms. J Vasc Surg 2017 Nov;66(5):1379-1389.
4. Ramkumar N, Goodney PP, Cronenwett JL. Open versus Endovascular Repair of Abdominal Aortic Aneurysm. N Engl J Med 2019 Sep 12;381(11):e24. 

Synopsis: Several retrospective series have compared extracorporeal vs. intracorporeal anastomosis after laparoscopic right hemicolectomy, where the latter was associated with lower perioperative morbidity. Allaix et al. present the first RCT to address this surgical issue; 140 patients at a single Italian institution were randomized to either anastomotic technique after a standardized laparoscopic medial-to-lateral dissection of the right colon. There were no differences in median operative time or operative complications, although there was a nonsignificant increase in the rate of anastomotic leak in the intracorporeal anastomosis group (8.6% vs. 2.9%). An intracorporeal anastomosis led to a quicker recovery of bowel function [gas: 2 (IQR 2–3) vs. 3 (IQR 2–3) days, P=0.003; stool: 4 (IQR 3–5) vs. 4.5 (IQR 3–5) days, P=0.032]. However, the primary endpoint of median LOS was similar in the 2 groups [6 (IQR 5–7) vs. 6 (IQR 5–8) days; P=0.839]. At 6-month clinical evaluation, incisional hernia was detected in 1 (1.4%) intracorporeal patient and 2 (2.9%) extracorporeal patients. The authors conclude that intracorporeal anastomosis leads to earlier recovery of bowel function, although this difference is not clinically meaningful nor reflected in a shorter LOS. Some limitations include the low adherence to ERAS (with median LOS of 6 days in each study arm), the lack of ICG imaging (which may impart a higher rate of anastomotic leak for the intracorporeal anastomosis), and the underpowered analysis of the incisional hernia rate (which may be the most valuable contribution of this technique). 

Synopsis: Balanced resuscitation is essential for survival in trauma, however excess blood product and fluid administration are not without risk. Thus strategies are needed to decrease the need for transfusions and improve outcomes in traumatic hemorrhage. Studies suggest a role for arginine vasopressin (AVP). AVP is a neuroendocrine hormone secreted in response to increased hypotension or osmolarity that improves vascular tone and shunts blood away from non-vital structures. Early work from Sims et al found that trauma patients are frequently deficient in AVP, likely due to decreased endogenous secretion and increased dilution due to resuscitation (PMID: 28716309). AVP deficiency is associated with catecholamine resistant hypotension and increased venous capacitance suggesting supplementation may be of benefit in the bleeding trauma patient. AVP is already used as a vasopressor in the critically ill and has been shown to improve survival in animal models of hemorrhagic shock, however, no study had directly evaluated the benefit of AVP in early traumatic shock.

In the AVERT Shock Trial, Sims et al conducted a randomized control trial of 100 adult trauma patients in hemorrhagic shock to determine if AVP supplementation improves outcomes. Patients received a bolus of either AVP or placebo, followed by continued administration of their respective intervention over the following 48 hours to maintain a MAP>65 mmHg. Primary endpoint was the need for blood transfusions, while secondary endpoints included need for resuscitative support such as fluids or vasopressors, associated complications, and 30-day mortality. Dr. Sims and colleagues found that at 48 hours patients who received AVP required nearly half as many blood products compared to patients who received placebo without an increase in morbidity (median 1.4L vs 2.9L, P=0.01). Further, while 30-day mortality did not differ, patients who received AVP exhibited a decreased rate of deep venous thrombosis (P=0.02), potentially due to the decrease in blood products or downregulation of inflammation by AVP. Future studies hope to further explore these findings in a larger, multi-institutional trial that is better powered to detect the effect of AVP on clinically relevant outcomes and survival. 

JAMA Surgery Author Interview with Dr. Sims and Dr. Reilly: https://edhub.ama-assn.org/jn-learning/audio-player/17847411