April 2022

This randomized clinical trial found that starting parenteral nutrition at 3 days versus 8 days reduced the number of nosocomial infections in patients undergoing major abdominal surgery who are unable to maintain adequate enteral intake and are at high risk for complications related to malnutrition.

Summary: Malnutrition is a common after major abdominal surgery, affecting 20-70% of patients, and is associated with increased morbidity, including impaired wound healing and increased risk of infections and other post-operative complications.

Currently, the European Society for Parenteral and Enteral Nutrition (ESPEN) recommends that surgeons consider initiating parenteral nutrition (PN) if the energy requirements (<50% of energy requirement) of the patient have not been met by enteral nutrition (EN) for more than 7 days. Conversely, The American Society for Parenteral and Enteral Nutrition (ASPEN) guidelines recommend that PN should be initiated within 3 to 5 days for patients who are at nutritional risk and unlikely to achieve a desired oral intake or with insufficient EN (<60% of energy requirement).

The goal of this randomized clinical trial was to compare the effect of initiation early supplemental PN (SPN) on day 3 after surgery vs. late SPN (day 8 after surgery).

In total, 230 adult patients undergoing elective gastric, colorectal, hepatic, and pancreatic resections (both benign and malignant disease), at risk of malnutrition (as defined by Nutritional Risk Screening 2002 score) poor tolerance to EN (≤30% of energy targets from EN on post-operative day 2, calculated as 25 and 30 kcal/kg of ideal body weight daily for women and men, respectively) were randomized.

Overall, the mean (SD) age was 60.1 (11.2) years, 61.1% were men, mean BMI was 23.0 kg/m2 (3.0), mean Albumin 4.0 g/dl (0.5) and all were of Han race and Asian ethnicity. 80% of patients had an NRS-2002 score of 3 (the lowest at-risk category). Approximately 70% of patients underwent surgery for gastric or colorectal cancer. The primary outcome was the incidence of nosocomial infections between postoperative day 3 and hospital discharge.

The E-SPN group had significantly fewer nosocomial infections compared with the L-SPN group (8.7% vs 18.4%; risk difference, 9.7%; 95% CI 0.9%-18.5%; p = .04). No significant differences were found between the E-SPN group and the L-SPN group in the mean (SD) number of noninfectious complications (27.0% vs 33.3%; risk difference, 6.4%; 95% CI −5.5% to 18.2%; p=0.32). There were no differences in length of hospital stay, cost or mortality.

Take-Home Points:

• This is one of the first large, randomized trials to investigate the route and timing of nutritional support in a cohort of non-critically ill patients undergoing major abdominal surgery.
• The results of this study suggest a significant benefit, reduced nosocomial infections, when early supplemental parental nutrition is initiated in a nutritionally at-risk patient population that is unable to meet their nutrition requirements through enteral nutrition alone.
• Further research is needed to replicate these findings, particularly across different demographic cohorts and in patients with more severe nutritional risk factors.

This prospective randomized multicenter trial found that there is no difference in mortality or neurodevelopmental impairment in low weight infants with NEC or intestinal perforation treated either with initial laparotomy vs initial peritoneal drainage. However, the data does suggest a reduced mortality risk after initial laparotomy in patients with a preoperative diagnosis of NEC.

Summary: Necrotizing enterocolitis (NEC) and intestinal perforation (IP) are rare conditions that occur most often in low-birth-weight infants. Morbidity and mortality are significant, with only half of these patients surviving and > 60% of survivors suffering neurodevelopment impairment (NDI). Though the presentation of these two conditions is similar, the etiology and pathology are distinct, and the accuracy of preoperative diagnosis is unknown. General treatment preference among surgeons includes laparotomy for presumed NEC and peritoneal drain for presumed IP. However, optimal treatment is difficult to assess based both on rarity of the condition and difficulty in conducting randomized trials of emergency surgical therapies.

The Necrotizing Enterocolitis Surgery Trial was a prospective randomized trial conducted at 20 US centers from 2010-2017. The group hypothesized that laparotomy would result in 15% lower death/NDI compared to drainage, for which 150 infants per treatment group were required to achieve 80% power. Low birth weight infants < 8 weeks of age were included; patients with major congenital anomalies, prior NEC or IP, or prior laparotomy were excluded. Primary outcome was a composite of death or NDI at 18-22 months.

The study included 310 patients and noted that death or NDI was 69% after laparotomy and 70% after peritoneal drainage. Importantly, however, the group found that preoperative diagnosis based on surgeon assessment is an effect modifier: with a preoperative diagnosis of NEC, 69% of patients died or suffered NDI after initial laparotomy compared to 85% mortality/NDI after initial peritoneal drainage. Posterior probability analysis indicated 97% likelihood that laparotomy results in lower rates of death/NDI in patients with preoperative diagnosis of NEC. For patients with preoperative diagnosis of IP, there was no difference between mortality/NDI after laparotomy (69%) compared to drainage (63%). Interestingly, in all patients undergoing laparotomy, there was only 64% concordance with preop vs intraop diagnosis. Notable secondary outcomes included a subsequent laparotomy after initial drain placement in 50% of infants with a 31% mortality rate.

This study attempted to answer an important clinical question despite the challenge of conducting a randomized trial on rare and emergent surgical conditions, as demonstrated by the 10 years it took to achieve the required sample size among 20 institutions. While the p value was not met to demonstrate a benefit of initial laparotomy in patients with NEC, a strength of this study is the utilization of robust statistical analysis to augment the interpretation of the trial results. As such, the data suggests that initial laparotomy is likely to reduce death/NDI in patients with preoperative diagnosis of NEC. Importantly, given the low intraoperative correlation with preoperative diagnosis, the study infers that the preop diagnosis based on physician judgement may be more predictive of outcomes than the intraoperative findings.

Hybrid procedures combining open and endovascular approaches are recommended for patients with concomitant iliac and common femoral artery occlusive disease, but this had not been formally compared to open repair. This clinical trial found that hybrid approaches were non-inferior to open approaches in terms of safety and efficacy at 3 years with potential benefits including reduced length of stay and 30-day mortality.

Summary: Historically, high-grade iliofemoral occlusive disease has been treated with open vascular reconstructions (OR) such as aorto-femoral or axillary-femoral bypass. With recent advances in endovascular technology, many vascular surgeons have adopted a hybrid (open combined with endovascular) repair (HR) strategy in treating these complex lesions to avoid the perioperative complications associated with open iliofemoral procedures in this sick patient population. However, there have been no randomized trials comparing these two treatment modalities in patients with concomitant iliac and femoral disease.

“Hybrid vs. Open Surgical Reconstruction for Iliofemoral Occlusive Disease: A Prospective Randomized Trial”, recently published in the European Journal of Vascular and Endovascular Surgery by Starodubstev et. al is a randomized prospective study comparing these two approaches (OR and HR). Inclusion criteria were ages between 45 and 75, Rutherford class II-VI (moderate claudication to tissue loss) chronic limb ischemia, and Trans-Atlantic inter- Society Consensus (TASC) C or D aortoiliac lesions (highest grade and most extensive lesions) with concomitating common femoral artery (CFA) stenosis >70%. Exclusion criteria included concomitant aortoiliac aneurysms, aortic thrombosis, acute limb ischemia, circumferential iliac calcification prohibiting safe angioplasty, and other high-risk patient characteristics. The HR group underwent endovascular recanalization and stenting of their iliac arteries combined with CFA endarterectomy, while the OR group underwent aortofemoral (or bifemoral) bypass with simultaneous CFA endarterectomy. Short (30 day) and midterm (36 month) outcomes including morbidity, mortality, and patency rates were compared between groups.

Between 2015-2017, the single-center Russian study randomized 102 patients into HR and 100 patients into OR. In 2 patients, the hybrid repair was converted to aortoiliac bypass as a result of failure to cross the iliac occlusion (they were still analyzed under HR). The average length of stay was significantly shorter in the HR arm (8.2 vs 15.7 days, P<0.001). There were no mortalities or major cardiovascular events observed in either group within the 30-day perioperative period, and there was no significant difference between the 2 groups in the 36-months mortality rates, (3% in HR vs 7% in OR, P=0.2). The OR group had a significantly higher rate (21% vs 8.8%, P=0.03) of perioperative complications (including seroma, wound infection, bleeding, graft/stent thrombosis, etc). The primary patency at 1 year was 93% in both groups; and at 36 months, the primary patency was 91% in the HR group vs 89% in the OR group (P=0.43). Both groups had an average increase of 0.4 in ABI postoperatively. Five patients in the OR groups developed ventral hernias.

In summary, this randomized trial showed comparable 1- and 3-year patency rates between OR and HR, and a significantly lower peri-operative morbidity rate in the HR group; demonstrating the safety and efficacy of a hybrid approach for treating iliofemoral occlusive disease, at least over a 3-year period. Traditionally, aortofemoral bypass has been considered the most durable repair option for aortoiliac occlusive disease, and is frequently offered to ‘younger-healthier’ patients. Long-term data on the durability of this less-morbid hybrid approach is needed before it can be adopted as a first-line approach for the treatment of aorto-iliac occlusive disease.