Intraperitoneal Local Anesthetic Improves Recovery after Colon Resection: A Double-Blinded Randomized Controlled Trial by Arman Kahokehr, et al.
The randomized double blinded controlled trial (RCT) of intraperitoneal (IP) local anesthesia after colectomy by Kahokehr, et al., from the University of Auckland is a good example of clinical trial construction and analysis.
This article can (and should) be used to teach clinical trial methodology. The RCT mechanism requires a focus on a specific question in a homogeneous group of patients, treated identically in all ways with only one variation in the form of the study intervention. Definition of the primary outcome and secondary objectives must be defined a priori to avoid bias or violation of equipoise. A sample size calculation at a given desired power and presumed clinically significant difference between the control and study group guarantees a result that can be believed.
The hypothesis (in this instance that blocking visceral afferents carried in the vagus nerve using intraperitoneal infusion of local anesthetic after colectomy will improve recovery) must be clearly stated and the study team blinded to the intervention (both during the operation and the data analysis) to provide consistent, unbiased data. The statistical analysis must accommodate any variability between the randomized groups to provide an answer regarding the intervention without potential interference.
I believe the authors have accomplished their goals with this trial in an ethical and scientific way. The simple question of whether IP infusion of ropivacaine can enhance recovery after colectomy rapidly becomes complex as one considers the methodology of this study. Randomization of 60 subjects undergoing colectomy for cancer, diverticulosis or inflammatory bowel disease revealed little difference between the groups on evaluation of 9 baseline characteristics. All subjects were enrolled into an established enhanced recovery after surgery (ERAS) system which included thoracic epidural analgesia postoperatively. Both groups received an IP infusion post-op (control-normal saline, study-8mg per hour ropivacaine) at 4ml per hour in the area of visceral excision. The primary endpoint at day 7 was the Surgical Recovery Score (SRS) consisting of 5 domains: Fatigue, Vigor, Mental Function, Activity, and Activities of Daily Living. Secondary outcomes included discharge readiness (pain relief, bowel function, mobilization, readmission, and sleep), cytokine and inflammatory response, 30 day complication rates, and anesthetic systemic levels.
The authors found a significant difference favoring the study group during the IP infusion phase (up to day 3) in SRS, opioid use, IL-6 levels and cortisol levels. Anesthetic levels were always higher systemically in the study group due to the IP infusion and even reached toxic levels without toxic effect in 2 patients. There were no complications attributed to the treatment.
Discussion Questions: The authors appropriately acknowledge that this study raised a number of questions.
My questions are:
1. Could injection of the vagus nerve alone during the operation have produced the same effect as IP infusion?
2. Could longer infusion (7 days) produce longer lasting and more profound recovery differences?
3. What is the impact of laparoscopy on the visceral afferents? Could CO2 pneumoperitoneum produce the same result as IP infusion?
4. Which component of the SRS was most important to improved recovery? Could more subjects show the domain with the most response to IP anesthetic?
5. Could IP delivery to the esophageal hiatus with less volume of local anesthetic produce similar results and lower systemic anesthetic levels?
6. Could elimination of fentanyl from the epidural improve bowel recovery and positively affect the SRS?
7. Does preop administration of Decadron truly improve recovery and how did this affect the outcome of this study?
8. How would you design the next study?
Please feel free to comment on any or all of the questions above. We look forward to hearing from you, the Annals readers.