Sender Liberman

Intravenous lidocaine versus thoracic epidural analgesia: a randomized controlled trial in patients undergoing laparoscopic colorectal surgery using an enhanced recovery program.

Background and Objective: Laparoscopy, thoracic epidural analgesia, and enhanced recovery program (ERP) have been shown to be the major elements to facilitate the postoperative recovery strategy in open colorectal surgery. This study compared the effect of intraoperative and postoperative intravenous (IV) lidocaine infusion with thoracic epidural analgesia on postoperative restoration of bowel function in patients undergoing laparoscopic colorectal resection using an ERP. Methods: Sixty patients scheduled for elective laparoscopic colorectal surgery were prospectively randomized to receive either thoracic epidural analgesia (TEA group) or IV lidocaine infusion (IL group) (1 mg/kg per hour) with patient-controlled analgesia morphine for the first 48 hours after surgery. All patients received a similar ERP. The primary outcome was time to return of bowel function. Postoperative pain intensity, time out of bed, dietary intake, duration of hospital stay, and postoperative complications were also recorded. Results: Mean times and SD (95% confidence interval) to first flatus (TEA, 24 [SD, 11] [19-29] hrs vs IL, 27 [SD, 12] [22-32] hrs) and to bowel movements (TEA, 44 ±19 [35-52] hrs vs IL, 43 [SD, 20] [34-51] hrs) were similar in both groups (P = 0.887). Thoracic epidural analgesia provided better analgesia in patients undergoing rectal surgery. Time out of bed and dietary intake were similar. Patients in the TEA and IL groups were discharged on median day 3 (interquartile range, 3-4 days), P = 0.744. Sixty percent of patients in both groups left the hospital on day 3. Conclusions: Intraoperative and postoperative IV infusion of lidocaine in patients undergoing laparoscopic colorectal resection using an ERP had a similar impact on bowel function compared with thoracic epidural analgesia.

Spinal analgesia for laparoscopic colonic resection using an enhanced recovery after surgery programme: better analgesia, but no benefits on postoperative recovery: a randomized controlled trial

BACKGROUND This study was undertaken to determine the impact of an intrathecal mixture of bupivacaine and morphine, when compared with systemic morphine, on the quality of postoperative analgesia and other outcomes in the context of the enhanced recovery after surgery (ERAS) programme for laparoscopic colonic resection. METHODS Fifty patients undergoing general anaesthesia were randomly allocated to receive either a spinal mixture of bupivacaine and morphine followed by oral oxycodone (spinal group) or patient-controlled analgesia (PCA group). The primary outcome was consumption of opioids during the first three postoperative days. Secondary outcomes were pain scores, return of bowel function and dietary intake, readiness to hospital discharge, and length of hospital stay. RESULTS Postoperative opioid consumption in the spinal group was significantly less over the first three postoperative days (P<0.001). The quality of analgesia at rest in the first 24 h was better in the spinal group (P<0.005). Excessive sedation and respiratory depression were reported in two elderly patients with spinal analgesia. There were no differences between the two groups in other outcomes (return of bowel function and dietary intake, readiness to hospital discharge, and length of hospital stay). CONCLUSIONS When ERAS programme is used for laparoscopic colonic resection, an intrathecal mixture of bupivacaine and morphine was associated with less postoperative opioid consumption, but has no other advantages over systemic opioids.

Goal-directed Fluid Therapy Does Not Reduce Primary Postoperative Ileus after Elective Laparoscopic Colorectal Surgery: A Randomized Controlled Trial.

Background: Inadequate perioperative fluid therapy impairs gastrointestinal function. Studies primarily evaluating the impact of goal-directed fluid therapy on primary postoperative ileus are missing. The objective of this study was to determine whether goal-directed fluid therapy reduces the incidence of primary postoperative ileus after laparoscopic colorectal surgery within an Enhanced Recovery After Surgery program. Methods: Randomized patient and assessor-blind controlled trial conducted in adult patients undergoing laparoscopic colorectal surgery within an Enhanced Recovery After Surgery program. Patients were assigned randomly to receive intraoperative goal-directed fluid therapy (goal-directed fluid therapy group) or fluid therapy based on traditional principles (control group). Primary postoperative ileus was the primary outcome. Results: One hundred twenty-eight patients were included and analyzed (goal-directed fluid therapy group: n = 64; control group: n = 64). The incidence of primary postoperative ileus was 22% in the goal-directed fluid therapy and 22% in the control group (relative risk, 1; 95% CI, 0.5 to 1.9; P = 1.00). Intraoperatively, patients in the goal-directed fluid therapy group received less intravenous fluids (mainly less crystalloids) but a greater volume of colloids. The increase of stroke volume and cardiac output was more pronounced and sustained in the goal-directed fluid therapy group. Length of hospital stay, 30-day postoperative morbidity, and mortality were not different. Conclusions: Intraoperative goal-directed fluid therapy compared with fluid therapy based on traditional principles does not reduce primary postoperative ileus in patients undergoing laparoscopic colorectal surgery in the context of an Enhanced Recovery After Surgery program. Its previously demonstrated benefits might have been offset by advancements in perioperative care.

Ensuring Early Mobilization Within an Enhanced Recovery Program for Colorectal Surgery: A Randomized Controlled Trial.

Objective: To estimate the extent to which the addition of staff-directed facilitation of early mobilization to an Enhanced Recovery Program (ERP) impacts recovery after colorectal surgery, compared with usual care. Summary Background Data: Early mobilization is considered an important component of ERPs but, despite guidelines recommendations, adherence remains quite low. The value of dedicating specific resources (eg, staff time) to increase early mobilization is unknown. Methods: This randomized trial involved 99 colorectal surgery patients in an established ERP (median age 63, 57% male, 80% laparoscopic) randomized 1:1 to usual care (including preoperative education about early mobilization with postoperative daily targets) or facilitated mobilization [staff dedicated to assist transfers and walking from postoperative days (PODs) 0–3]. Primary outcome was the proportion of patients returning to preoperative functional walking capacity (6-min walk test) at 4 weeks after surgery. We also explored the association of the intervention with in-hospital mobilization, time to achieve discharge criteria, time to recover gastrointestinal function, 30-day comprehensive complication index, and patient-reported outcome measures. Results: In the facilitated mobilization group, adherence to mobilization targets was greater on POD0 [OR 4.7 (95% CI 1.8–11.9)], POD1 [OR 6.5 (95% CI 2.3–18.3)], and POD2 [OR 3.7 (95% CI 1.2–11.3)]. Step count was at least 2-fold greater on POD1 [mean difference 843.3 steps (95% CI 219.5–1467.1)] and POD2 [mean difference 1099.4 steps (95% CI 282.7–1916.1)] There was no between-group difference in recovery of walking capacity at 4 weeks after surgery [OR 0.77 (95% CI 0.30–1.97)]. Other outcome measures were also not different between groups. Conclusions: In an ERP for colorectal surgery, staff-directed facilitation of early mobilization increased out-of-bed activities during hospital stay but did not improve outcomes. This study does not support the value of allocating additional resources to ensure early mobilization in ERPs. Trial Registration: ClinicalTrials.gov Identifier: NCT02131844

Clinical and Economic Impact of an Enhanced Recovery Pathway for Open and Laparoscopic Rectal Surgery

BACKGROUND The short-term benefits of laparoscopy for rectal surgery are equivocal. The objective of this study was to determine the clinical and economic impact of an enhanced recovery pathway (ERP) for laparoscopic and open rectal surgery. MATERIALS AND METHODS All patients who underwent elective rectal resection with primary anastomosis between January 2009 and March 2012 at two tertiary-care, university-affiliated institutions were identified. Patients who met inclusion criteria were divided into four groups, according to surgical approach (laparoscopic [lap] or open) and perioperative management (ERP or conventional care [CC]). Length of stay (LOS), postoperative complications, and hospital costs were compared. RESULTS A total of 381 patients were included in the analysis (201 open-CC, 34 lap-CC, 38 open-ERP, and 108 lap-ERP). Patients were mostly similar at baseline. ERPs significantly reduced median LOS after both open cases (open-CC 10 days versus open-ERP 7.5 days, P = .003) and laparoscopic cases (lap-CC 5 days versus lap-ERP 4.5 days, P = .046). ERPs also reduced variability in LOS compared with CC. There was no difference in postoperative complications with the use of ERPs (open-CC 51% versus open-ERP 50%, P = .419; lap-CC 32% versus lap-ERP 36%, P = .689). On multivariate analysis, both ERP (-3.6 days [95% confidence interval, CI -6.0 to -1.3]) and laparoscopy (-3.6 days [95% CI -5.9 to -1.0]) were independently associated with decreased LOS. Overall costs were only lower when lap-ERP was compared with open-CC (mean difference -2420 CAN

Reply to Drs. Cummings and Mascha

[95% CI -5628 to -786]). CONCLUSIONS ERPs reduced LOS after rectal resections, and the combination of laparoscopy and ERPs significantly reduced overall costs compared to when neither strategy was used.

Diagnosis and Treatment of Rectal Cancer

To the Editor: W e read with great interest the recent article by Wongyingsinn et al describing a comparison between the effects of intravenous lidocaine and thoracic epidural anesthesia on the return of bowel function after surgery. They are to be congratulated on an elegant and relevant clinical trial. We believe, however, that their statistical analysis is not congruent with their hypothesis. In the introduction, they state ‘‘It is hypothesized that intraoperative and postoperative lidocaine would result in postoperative restoration of bowel function similar to TEA in patients undergoing laparoscopic colorectal resection when an ERP was implemented.’’ Their hypothesis is thus one of equivalence, namely that 2 regimens are similar. Their sample size estimates and comparisons between groups are based on testing for superiority. They designed the study to have 80% power at the 0.05 significance level to detect a difference of 16 hours (with SD of 19 and 20 per group) in time to return of bowel function between regimens, for which 50 total patients were required. In their analysis, they failed to find a statistically significant difference and therefore concluded that the regimens lead to a similar outcome. Based on their methods, however, the authors can only assert that no difference in outcome was detected, not that no difference exists. As one of us has previously noted, a more correct approach would be to use an equivalence or noninferiority design. An equivalence trial depends on an a priori definition of ‘‘equivalence,’’ that is, the range of differences within which the groups are considered to be clinically the same. Study design and statistical testing thus aim to determine whether the true difference actually falls within this ‘‘equivalence’’ region. If the investigator wanted to determine that a new regimen is ‘‘better or not much worse than’’ the current, a noninferiority design should be used with a range of values ‘‘worse’’ than the reference group that are not clinically significantly worse. An appropriate equivalence delta should typically be smaller than the difference used to plan a superiority trial, given the goal of claiming 2 interventions are clinically the same. For the study by Wongyingsinn et al, we think a difference of more than 8 hours in time to return of bowel function would be clinically important. An appropriate equivalence design sample size for 80% power at the 0.05 significance level would require 206 total patients, much larger than planned. Furthermore, because 2 primary outcomes were analyzed (time to flatus and bowel function), and each within anastomosis and ileostomy patients, an appropriate significance level for each of the 4 tests would be 0.0125, requiring many more patients (150 per group) for each test! Applying an equivalence delta of 8 hours to the summary data in Wongyingsinn et al, 95% confidence intervals for the group differences in anastomosis patients arej10 to 4 andj11 to 13 for time to flatus and bowel function, respectively, and j18 to 12 and j16 to 22 for ileostomy patients. Thus, using a delta of 8 hours, equivalence cannot be claimed for any of the comparisons because all intervals go beyond T8 hours. If the a priori delta were 12 hours instead, equivalence would only be claimed for time to flatus in anastomosis patients. And although we think an unreasonably wide equivalence region, both anastomosis comparisons would be deemed equivalent using 16 hours, but for neither of the ileostomy comparisons. In summary, when the goal is to claim that 2 interventions are the same, as in Wongyingsinn et al, or that one is at least not worse than the other, traditional superiority designs and tests cannot be used. An appropriate equivalence or noninferiority design requires a priori specification of the equivalence region, which is used in design and analysis. In such studies, a statistically significant result is required to claim equivalence or noninferiority, thus avoiding claims of ‘‘equivalence’’ in negative and perhaps underpowered tests for superiority.

Impact of an enhanced recovery program on short-term outcomes after scheduled laparoscopic colon resection

Carcinoma of the rectum, a common malignancy in developed countries, accounts for approximately one third of colorectal cancers. Although majority of the localized rectal cancers are potentially curable, local recurrence remains a serious problem with severe disability and impaired quality of life. Rectal cancer, which was a surgically-managed tumour, now requires the coordinated efforts of multidisciplinary team, colorectal surgery, radiation oncology, medical oncology, radiology and others. In addition to the staging workup, pre-treatment evaluation of the local disease, by endorectal ultrasound (EUS) and multislice computer tomography (CT) and magnetic resonance imaging (MRI), is utmost important to determine the surgical approach and the need for the various other treatment modalities: radiation and chemotherapy (ChT). The introduction of Total Mesorectal Excision (TME) and neoadjuvant Radiation Therapy (RT) have led to significant improvement in the loco-regional control of the rectal cancer, 90–94%. TME is now widely accepted as the standard surgical technique for rectal cancer. Local recurrence rates have been shown to decrease significantly with TME alone. However, the addition of radiation therapy has furthered this improvement, especially in patients having a circumferential resection margin (CRM) that is involved with tumour on pre-operative imaging. There are two radiation modalities used in the treatment of patients with solid tumours, external beam radiation (EBRT) and brachytherapy (BT). In rectal cancer EBRT is primarily used to optimize the rate of local control achieved by surgery. Numerous clinical trials have confirmed its benefit, with or without chemotherapy, in improving local control. However, the survival advantage and the impact on distant metastasis are controversial. In view of normal organ toxicity associated with EBRT, newer radiation delivery techniques have been explored. High dose rate brachytherapy (HDRB) delivers radiation by an endoluminal approach, avoiding the delivery through other organs, and as such, decreases normal organ toxicity. The emerging prospective data are very promising and an international phase III study is being conducted. Despite significant improvement in local control, over the last decade, one third of the patients continue to fail at distance, with metastases. The role of chemotherapy in conjunction with radiation therapy as a neo-adjuvant modality to TME has been, mostly, accepted as routine in North America. However, to date, evidence from Phase III-randomized studies in rectal cancer fails to demonstrate any benefit from additional post-operative adjuvant 5-fluorouracil (FU)-based chemotherapy in terms of disease-free or overall survival in locally advanced rectal cancer. There have been significant achievements in the treatment of rectal cancer over the past decade with multidisciplinary approach becoming the standard of care. Such approach allows for the selection of those patients who are cured with surgery alone, as well as those at risk for failing locally, thus achieving a balance between treatment toxicity risks and tumour control gains.