This is Amalia Cochran, I'm the web and social media editor for JAMA Surgery. For our listeners, we have a few abbreviations you're likely to hear throughout this interview. These include EN or Enteral Nutrition, PN or Parenteral Nutrition, and SPN, which is Supplemental Parenteral Nutrition. You will also hear the author refer to ERAS, which is early recovery after surgery. And you'll hear reference to IC, which is indirect calorimetry and REE, or resting energy expenditure. Today I am speaking with Xinying Wang, on a randomized clinical trial of early versus late supplemental parenteral nutrition in patients undergoing abdominal surgery. Welcome, Professor Wang. We are glad that you're here with us.
Thanks very much. I really appreciate the honor of being here.
I always start our interviews by asking why a question was of particular interest to the researchers. Will you share with our listeners why you wanted to learn more about the effects of different timing schemes for parenteral nutrition following major abdominal surgery?
Our early inspiration came from clinical practice and the previous supplemental parenteral nutrition study. This study reported that early optimization of energy provision by SPN, studying four days after ICU admission reduced the nosocomial infection in critical ill patients who failed to achieve energy goals with EN alone. This suggests that early SPN can benefit critical AEO patients and reduce infectious complications. However, only some abdominal surgery patients need SPN treatment in clinical practice, but not all patients need it. That being said, we need to use SPN for patients who can benefit, not all patients undergoing major surgery. Therefore, we did a preliminary survey and retrospective analysis to identify patients who could really benefit. Also in clinical practice. It has found that early SPN can help abdominal surgery patients with nutritional risk, but how early, it is uncertain. The latest guidelines also recommend initiation of SPN within seven days post the GI surgery. If energy and nutrient requirements have not been made by enteral feeding, the optimal timing remains unclear. We have been thinking about these questions. Is it too late to consider PN seven days after surgery for patients at preoperative nutritional risk? Is it possible to start SPN earlier to benefit their postoperative recovery? Moreover, guideline recommendations are the opinions of experts, which lack high-quality evidence-based medical evidence. All these questions motivated us to come up with this study.
The specific primary outcome that you selected was nosocomial infections. You also have quite a few secondary outcomes that you examined. How did you decide to use nosocomial infection as your primary outcome? And why did you choose to perform an intention to treat analysis?
Surgery is an area with high incidence of nosocomial infections. Nosocomial infection is an important factor limiting the rapid recovery of postoperative patients. This results with ESPN and ERAS recommendation for enteral nutrition as the first choice for postoperative patients nutritional support. Preventing this complication, enteral nutrition has unique advantages compared to parenteral nutrition, EN, is associated with lower postoperative infections and the mortality in patients undergoing major abdominal surgery. However, in many cases, energy delivery in post surgical patients using EN alone is less than the estimated requirements for various reasons. To supplement insufficient EN, SPN is a strategy that can increase energy delivery more closely to estimated energy requirements. However, PN-related infectious risk has been a concern. Many surgeons are very concerned about initiating SPN that it may increase postoperative complications. At the same time, many clinical studies related to PN have also used the nosocomial infection as the primary outcome. Our study listed several observation indicators to demonstrate that early SPN in patients ongoing abdominal surgery may be beneficial. However, nosocomial infection was one of the most critical indicators. Therefore, we also choose nosocomial infection as a primary outcome in this study. Our intention to treat analysis was based on the full analysis stage under the intention to treat principle. The principle asserts that a factor of a treatment policy can be best assessed by evaluating based on the intention to treat a subject rather than the actual treatment given. It has a consequence that subjects allocated to a treatment group should be followed up, assessed, and analyzed as members of that group, irrespective of their compliance with the plain treatment cause. Our trial was designed to test the superiority. In superiority trials, the full analysis set tends to avoid over-optimistic efficacy estimates since the non-compliers included in the full analysis set will generally diminish the estimated treatment effect. We have excellent medical statistics team, together with us, to provide effective support and communication.
You had to screen a huge number of patients in order to achieve your enrollment targets. Can you tell me more about why you had such strict exclusion criteria?
The inclusion and exclusion criteria are the most critical points in randomized clinical trials and decisive in whether subjects can be enrolled. We know that the inclusion criteria as a target population determined according to the research purpose. We know that parenteral nutrition support therapy is an in dispensable treatment method for surgical patients and is by no means the optional It is beneficial for patients with nutritional risk and poor enteral nutrition tolerance, but it may be harmful to patients without nutritional risk. Postoperative gastrointestinal disfunction, POGD, often occurs in patients after abdominal surgery, mainly due to gut injury, bowel edema, and dysmotility leading to gastro to intestinal intolerance and increase the risk of malnutrition. The patients who experience POGD and cannot be nourished adequately while enteral feeding could benefit from additional nutrition to bridge the nutritional gap without the symptoms of digestive intolerance. When enteral nutrition is intolerant for surgical patients with clinical nutritional risk, can the time of SPN be moved forward? External parenteral support or the disease itself may significantly affect clinical outcomes. Therefore, this study had strict exclusion criteria mainly to reduce confounding factors to identify patient who can benefit from postoperative SPN.
Do you have any concerns about having used formulas, which generally over predict requirements, rather than indirect calorimetry at centers where calorimetry was not available? How many centers was this the case for?
Ideally indirect calorimetry, I think, should be used to provide measurements instead of predictive equations, making for a more exact energy balance. However, a survey showed that as indirect calorimetry was unavailable to 80% of nutrition staff members only estimated values were used. IC came to China very early and our center was one of the first units in China to use IC to measure energy expenditure to guide the patient's energy supply. Most medical centers in China lack IC instruments. There are four of our participating centers that can conduct IC inspections.
In the absence of available IC, the equations are generally preferred in surgical or trauma patients, but estimates of 25 to 30 kilo calorie per kilogram per day may be used to begin with and then changes according to nutritional parameters. A recent study found that the resting energy expenditure did not vary greatly in the first few days following major abdominal surgery. Only a third of the patients had a greater than 10% elevation in their REE, and it seems that energy requirements generally do not go up during the first few days after surgery. Therefore, this study uniformly uses the formula method to guide energy requirements. Estimations are generally considered accurate if they fall within an error range of 10%, compared with IC. ERAS will minimize the stress and the patient's energy expenditure after major surgery. And the predicted value of the formula will be as close as possible to actual expenditure of the patient. Meanwhile, a unified clinical pathway and SOP training can reduce the bias in each center in the perioperative period.
What was most surprising about your findings?
We were thrilled to finally be able to pull through the first multicenter randomized control trial that evaluated this particular issue. Our studies finding that the earlier initial of the SPN in combination with EN reduces incidence of nosocomial infection and improves nutritional status at discharge, which is consistent with our initial research hypothesis. We were the first to propose that earlier initiation of SPN might be beneficial in abdominal surgery patients. It is an enormous encouragement for us, because to every clinical study can get the same results as what was initially expected. Early SPN in patients undergoing major abdominal surgery is not as detrimental as many surgeons' clinical experience suggests. Thus, we were able to provide solid evidence that early initiation of SPN can be of clinical benefit in post abdominal surgery patients.
How have your findings from this study impacted your clinical practice?
This study will undoubtedly improve our patient care. Moreover, throughout this process, I personally have learned how to pull a multi-center study and find out how essential collaborations between centers can solve problems that we all face in our day-to-day clinical practice. Hopefully as our work in clinical settings has been the initial inspiration, it will continue to encourage us more to study and make more discoveries.
Do you have plans for future studies in this area? And what thoughts do you have about where do we still have gaps in our knowledge?
Yes, we are going to continue to explore the application of rational nutrition therapy in surgical patients in the future. We also plan to continue to follow up on the long term prognosis of such patients. This study mainly focuses on the timing of SPN in abdominal surgery patients, which solves the early initiation of SPN in patients with high nutritional risk to make up for the poorer prognosis caused by insufficient energy in enteral nutrition.
Current comprehensive nutritional support programs are not suitable for all clinical patients. Therefore, individualized nutritional therapy, including energy and protein should be pursued. In particular, the content of protein in parenteral nutrition formulation is of great interest. For example, the latest research found that high protein intake can help improve clinical outcomes in critically ill patients, and there was a significant difference in protein intake between the early SPN and late SPN group in our study. Therefore, we should continue to study the role of protein content in parenteral nutrition on clinical outcomes in the future.
Professor Wang, thank you so very much for your time today. It was a pleasure to get to talk with you.
I want to thank JAMA Surgery for having me in this interview. I hope that what we have studied can be beneficial and provide some solid ground in improving our patient care, especially in nutrition therapy. Thank you.
This episode of JAMA Surgery was produced by Shelly Steffens at the JAMA Network. The audio team here also includes Jesse McQuarters, Daniel Marrow, Lisa Harden, Audrey foreman, and Mary Lynn Ferkaluk. Dr. Robert Golub is the JAMA executive deputy editor. To follow this other JAMA Network podcasts, please visit us online at jamanetworkaudio.com. I'm Dr. Amalia Cochran. Thanks for listening.