Penn Evidence-Based Literature Review (PEBLR)

Summarized highlights from contemporary literature in surgical and allied disciplines for general surgery residents.

September/October 2017

  1. Effect of Individualized vs Standard Blood Pressure Management Strategies on Postoperative Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery
  2. Futier et al. JAMA; September 2017 (PDF)
    Contributor: Charlie Vasquez
    Discipline: Surgical Critical Care

Synopsis: Intraoperative hypotension is associated with increased risk of post-operative injury to multiple organ systems, especially in high-risk surgical populations. Despite this, there is no consensus regarding appropriate blood pressure targets during surgery and it is not clear if a more individualized blood pressure management protocol will improve patient outcomes. Patients enrolled in the INPRESS trial were age >50 undergoing major abdominal or non-cardiac surgery expected to last >2 hours, were ASA class 2 or higher and had to have an Acute Kidney Injury (AKI) risk index >4. Important exclusions included severe, uncontrolled hypertension, chronic kidney disease requiring dialysis, ongoing acute cardiac event, and/or preoperative shock/sepsis.. All patients received a standardized regimen for intra-operative anesthesia and mechanical ventilation. Additionally, patients were maintained on a continuous maintenance fluid infusion of Ringer’s lactate at 4 ml/kg/hr with an additional protocol of fluid boluses with hydroxyethyl starch based on stroke volume index measured via radial artery catheter. Patients were then randomized to either standard therapy, requiring treatment of SBP <80 mmHg or <40% from patient’s baseline, or to an individualized therapy group in which SBP was targeted between +/- 10% of patient’s baseline using norepinephrine infusion. 292 patient completed the trial. The primary outcome was a composite of systemic inflammatory response syndrome (SIRS) and dysfunction of at least one organ system by day seven after surgery. This outcome occurred in significantly fewer patients in the intervention group (56 of 147 patients (38.1%) vs. 75 of 145 patients (51.7%), absolute risk difference 14%). Within the primary outcome, the only significant differences were in the incidence of renal dysfunction (32.7% intervention vs. 49% standard therapy) and altered mental status (5.4% intervention vs. 15.9% standard therapy). Both groups received similar volume of fluids and blood products during the surgeries. In conclusion, in high-risk patients undergoing predominantly major abdominal surgery, the INPRESS trial demonstrated that intra-operative management targeting an individualized systolic blood pressure goal reduced the risk of postoperative organ dysfunction.

  1. Early versus late surgical management of complicated appendicitis in children
  2. Saluja et al. Journal of Pediatric Study; September 2017 (PDF)
    Contributor: Avery Rossidis
    Discipline: Pediatric Surgery

Synopsis: While appendicitis is the most common surgical emergency in the pediatric patient, the treatment of complicated appendicitis (i.e. appendiceal rupture resulting in abscess or generalized peritonitis) is variable. Some advocate for immediate surgery, while others prefer initial treatment with antibiotics followed by “interval appendectomy” at least four weeks later. In this retrospective review of over 8000 children with complicated appendicitis, Saluja et al. analyze outcomes in early versus late appendectomy with one-year follow-up. Early appendectomy was defined as surgery within two days of admission, while late appendectomy included patients who underwent appendectomy greater than two days after admission during the index hospitalization or during a subsequent admission. The primary outcome was any complication within one year of follow-up. Overall, 87% of included patients underwent early appendectomy and these patients were more likely to be male, older, White, and have a non-Medicaid insurance carrier. Patients with a diagnosis of abscess were significantly more likely to undergo late appendectomy and late surgeries were more likely to be laparoscopic. With regard to the primary outcome, the late surgery group was significantly more likely to have at least one complication compared to the early group (26.1% vs. 22.9%, p<0.01). Furthermore, index admission length of stay and total one-year hospitalization times were longer, and readmission rates as well as costs of care were higher in the late surgery group. Patients undergoing early appendectomy, however, were more likely to have wound complications. Importantly, only about half of patients in the late surgery group had an elective operation and 25% required an urgent appendectomy during a subsequent admission. While this study is limited by its retrospective nature and its reliance on an administrative database, the investigators corroborate many of the findings reported in recent studies supporting early operative management of complicated appendicitis. Additionally, the authors highlight sociodemographic factors associated with differences in care that merit further study.

  1. Combination of Oral Antibiotics and Mechanical Bowel Preparation Reduces Surgical Site Infection in Colorectal Surgery
  2. Ohman et al. JACS; June 2017 (PDF)
    Contributor: Jenn Fieber
    Discipline: Quality Improvement

Synopsis: Surgical site infections (SSI) are especially high after colorectal surgery (15-30%). Interventions to decrease SSI, especially bowel prep and antibiotics, have been controversial. This study compared the rate of SSI in patients that underwent an “infection prevention bundle” to historic institutional ACS NSQIP SSI rates in patients undergoing elective colorectal surgery. SSI decreased impressively from 19.7% to 8.2% (p<0.0001) with implementation of the “bundle.” Univariate analysis found mechanical bowel prep, oral antibiotics (neomycin + flagyl) and preoperative chlorhexidine shower had a significant association with lower rates of SSI. Trends suggested that chlorhexidine skin prep and separate closing table may be associated with decreased SSI with a higher powered study but showed no similar trend with hair clipping or antibiotic irrigation. Compliance with each aspect of the bundle varied from 69 - 94%. A small subset of patients during the intervention period with no prep vs oral antibiotics and/or mechanical bowel prep were evaluated. Oral antibiotics + mechanical bowel preparation had only a 2.7% SSI rate (adjusted OR 0.2, CI: 0.1-0.9, p=0.006). Antibiotics or bowel prep alone did not improve SSI. Limitations include: single institution study, underpowered when assessing independent components of the bundle, unclear what portions of the bundle were performed in the historic cohort, and not randomized.

  1. Morphological suitability for endovascular repair, non-intervention rates, and operative mortality in women and men assessed for intact abdominal aortic aneurysm repair: systematic reviews with meta-analysis
  2. Ulug et al. Lancet; June 2017 (PDF)
    Contributor: Jon Quatromoni
    Discipline: Vascular Surgery

Synopsis: Sex-specific differences in the natural history of abdominal aortic aneurysms (AAAs) and outcomes after surgical intervention have only recently been investigated, as much of the early trials aimed at defining whento intervene (i.e., aneurysm size criteria) and how to best intervene (i.e., open surgery vs. endovascular repair [EVAR]) were comprised mostly of men. Accumulated data since then suggests that the prognosis of abdominal aortic aneurysms (AAAs) is worse for women than men. The aim of the present study, a systematic review and meta-analysis, was to quantify the differences in outcomes between men and women being assessed for the repair of intact AAAs using contemporary data. To accomplish this, they examined three sequential stages of the care pathway: 1) the determination of anatomic suitability for EVAR, 2) the decision to offer a repair, and 3) the thirty-day mortality after elective repair (either open surgical repair or EVAR). A thorough search of the literature between 2005-2016 yielded five studies that assessed the anatomic eligibility for EVAR (1,507 men, 400 women), four studies that reported non-intervention rates (1,365 men, 247 women), and nine studies that published 30-day mortality data (52,018 men, 11,076 women). To be selected, each study had to include men and women from the same population and time period in order to limit baseline variance between both groups. Meta-analysis of the pooled data found that the proportion of women eligible for EVAR was significantly lower than it was in men (34% vs. 54%; odds ratio [OR] 0.44, 95% CI 0.32-0.62), that non-intervention rates were significantly higher in women than in men (34% vs. 19%; OR 2.27, 1.21-4.23), and that 30-day mortality was higher in women than in men for both EVAR (2.3% vs. 1.4%, OR 1.67, 1.38-2.04) and open surgical repair (5.4% vs. 2.8%; OR 1.76, 1.35-2.30). One important limitation includes the relative paucity of data available regarding the first two stages, i.e., the number of women and men either eligible for EVAR or not considered for intervention. Another limitation concerns the incomplete adjustment for confounding variables. Most importantly, age may have partially confounded the relationship between female sex and operative mortality, as females appear to develop clinically relevant aneurysms at a later age (when operative mortality would be higher). Nevertheless, when adjusted data were available, the difference between sexes remained. Lastly, patients selected for EVAR and open repair across studies are likely different, which might account for some of the differences seen in thirty-day mortality. Despite these shortcomings, the data currently available clearly suggest that the prognosis of AAAs in women is worse than that in men. Thus, it is imperative that further research is conducted to improve our understanding of this disease process in women in order to optimize our treatment strategy, recognizing that it will likely differ from that in men.

  1. Transcatheter Versus Surgical Aortic Valve Replacement
  2. Brennan et al. Journal of the American College of Cardiology; May 2017. (PDF)
    Contributor: Jenn Chung
    Discipline: Cardiac Surgery

Synopsis: Aortic valve disease affects approximately 2.5 million adults, and severe symptomatic aortic stenosis is the most common valvular disease affecting elderly patients. Up to 30-40% of patients are deemed to be prohibitively high risk for surgical intervention secondary to significant co-morbidities. Transcatheter aortic valve replacement (TAVR) has been FDA approved as a less invasive alternative to conventional surgical aortic valve replacement (SAVR) in patients ineligible for surgery. Advancements in device technology as well as increased experience among clinicians performing TAVR have broadened the potential indications for TAVR in intermediate to high risk patients. This multicenter, retrospective study included patients deemed to be potential candidates for either TAVR or SAVR, without characteristics which would strongly favor one intervention over another. Data were extracted from the Society of Thoracic Surgeons (STS) National Database and STS/American College of Cardiology Transcatheter Valve Therapy (TVT) database for SAVR and TAVR patients, respectively. Using a propensity score matching algorithm, the authors found that TAVR patients experienced a significantly lower rate of in-hospital mortality compared to their surgical counterparts (3.0% vs. 5.0%, p<0.001). A notable improvement from earlier experience with TAVR was seen in the incidence of stroke, which was not significantly different between groups (2.5% in TAVR vs. 2.7% in SAVR, p=0.40). One-year mortality also demonstrated no significant difference between TAVR and SAVR (17.3% vs. 17.9%, p=0.40). Patients in both groups experienced an equal of proportion of days alive and out of hospital after discharge from the index hospitalization (rate ratio: 1.0; 95% CI: 0.98-1.02). . These results corroborate many of the findings from three randomized clinical trials in terms of one year mortality and stroke risk between intermediate- to high-risk TAVR and SAVR patients, and support the safety of TAVR in this population who would historically have been treated with surgical intervention, with the added benefits of shorter ICU and overall hospital length of stay, decreased blood transfusions and increased likelihood of discharge to home vs. to another facility. There was however, an increased risk of pacemaker/ICD placement as well as increased risk of major vascular complications associated with TAVR compared to SAVR. Although this was a robust study with 4,732 patients in each of the matched cohorts, it is notable that the median follow up time was only 169.5 days for the TAVR group as compared to 328 days for the SAVR cohort. The retrospective design of this study does subject it to the usual shortcomings of variations in data quality and bias due to missing data, and additional prospective studies with subjects reflective of the “real-world” patient presenting with severe aortic stenosis are necessary.