Comparison of multimodal analgesia with thoracic epidural after transthoracic oesophagectomy.

BACKGROUND: Thoracic epidural analgesia (TEA) has been regarded as the standard of care after oesophagectomy for pain control, but has several side-effects. Multimodal (intrathecal diamorphine, paravertebral and rectus sheath catheters) analgesia (MA) may facilitate postoperative mobilization by reducing hypotensive episodes and the need for vasopressors, but uncertainty exists about whether it provides comparable analgesia. This study aimed to determine whether MA provides comparable analgesia to TEA following transthoracic oesophagectomy. METHODS: Consecutive patients undergoing oesophagectomy for cancer between January 2015 and December 2018 were grouped according to postoperative analgesia regimen. Propensity score matching (PSM) was used to account for treatment selection bias. Pain scores at rest and on movement, graded from 0 to 10, were used. The incidence of hypotensive episodes and the requirement for vasopressors were evaluated. RESULTS: The study included 293 patients; 142 (48.5 per cent) received TEA and 151 (51.5 per cent) MA. After PSM, 100 patients remained in each group. Mean pain scores were significantly higher at rest in the MA group (day 1: 1.5 versus 0.8 in the TEA group, P = 0.017; day 2: 1.7 versus 0.9 respectively, P = 0.014; day 3: 1.2 versus 0.6, P = 0.047). Fewer patients receiving MA had a hypotensive episode (25 per cent versus 45 per cent in the TEA group; P = 0.003) and fewer required vasopressors (36 versus 53 per cent respectively; P = 0.016). There was no significant difference in the overall complication rate (71.0 versus 61.0 per cent; P = 0.136). CONCLUSION: MA is less effective than TEA at controlling pain, but this difference may not be clinically significant. However, fewer patients experienced hypotension or required vasopressor support with MA; this may be beneficial within an enhanced recovery programme.

Cardiopulmonary fitness before and after neoadjuvant chemotherapy in patients with oesophagogastric cancer.

BACKGROUND: Neoadjuvant chemotherapy may have a detrimental impact on cardiorespiratory reserve. Determination of oxygen uptake at the anaerobic threshold by cardiopulmonary exercise testing (CPET) provides an objective measure of cardiorespiratory reserve. Anaerobic threshold can be used to predict perioperative risk. A low anaerobic threshold is associated with increased morbidity after oesophagogastrectomy. The aim of this study was to establish whether neoadjuvant chemotherapy has an adverse effect on fitness, and whether there is recovery of fitness before surgery for oesophageal and gastric adenocarcinoma. METHODS: CPET was completed before, immediately after (week 0), and at 2 and 4 weeks after neoadjuvant chemotherapy. The ventilatory anaerobic threshold and peak oxygen uptake (Vo2 peak) were used as objective, reproducible measures of cardiorespiratory reserve. Anaerobic threshold and Vo2 peak were compared before and after neoadjuvant chemotherapy, and at the three time intervals. RESULTS: Some 31 patients were recruited. The mean anaerobic threshold was lower following neoadjuvant treatment: 15·3 ml per kg per min before chemotherapy versus 11·8, 12·1 and 12·6 ml per kg per min at week 0, 2 and 4 respectively (P < 0·010). Measurements were also significantly different at each time point (P < 0·010). The same pattern was noted for Vo2 peak between values before chemotherapy (21·7 ml per kg per min) and at weeks 0, 2 and 4 (17·5, 18·6 and 19·3 ml per kg per min respectively) (P < 0·010). The reduction in anaerobic threshold and Vo2 peak did not improve during the time between completion of neoadjuvant chemotherapy and surgery. CONCLUSION: There was a decrease in cardiorespiratory reserve immediately after neoadjuvant chemotherapy that was sustained up to the point of surgery at 4 weeks after chemotherapy.

Multimodal analgesia using intrathecal diamorphine, and paravertebral and rectus sheath catheters are as effective as thoracic epidural for analgesia post-open two-phase esophagectomy within an enhanced recovery program.

Thoracic epidural (TE) analgesia has been the standard of care for transthoracic esophagectomy patients since the 1990s. Multimodal anesthesia using intrathecal diamorphine, local anesthetic infusion catheters (LAC) into the paravertebral space and rectus sheaths and intravenous opioid postoperatively represent an alternative option for postoperative analgesia. While TE can provide excellent pain control, it may inhibit early postoperative recovery by causing hypotension and reducing mobilization. The aim of this study is to determine whether multimodal analgesia with LAC was effective with respect to adequate pain management, and compare its impact on hypotension and mobility. Patients receiving multimodal LAC analgesia were matched using propensity score matching to patients undergoing two-phase trans-thoracic esophagectomy with a TE over a two-year period (from January 2015 to December 2016). Postoperative endpoints that had been evaluated prospectively, including pain scores on movement and at rest, inotrope or vasoconstrictor requirements, and hypotension (systolic BP < 90 mmHg), were compared between cohorts. Out of 14 patients (13 male) that received LAC were matched to a cohort of 14 patients on age, sex, and comorbidity. Mean and maximum pain scores at rest and movement on postoperative days 0 to 3 were equivalent between the groups. In both cohorts, 50% of patients had a pain score of more than 7 on at least one occasion. Fewer patients in the LAC group required vasoconstrictor infusion (LAC: 36% vs. TE: 57%, P = 0.256) to maintain blood pressure or had episodes of hypotension (LAC: 43% vs. TE: 79%, P = 0.05). The LAC group was more able to ambulate on the first postoperative day (LAC: 64% vs. TE: 43%, P = 0.14) but these differences were not statistically significant. Within the epidural cohort, three patients had interruption of epidural due to dislodgement or failure of block compared to no disruption in the multimodal local anesthesia catheters group (P = 0.05). Therefore, multimodal anesthesia using spinal diamorphine with combined paravertebral and rectus sheath local anesthetic catheters appears to provide comparable pain relief post two-phase esophagectomy and may provide more reliable and safe analgesia than the current standard of care.

Pre-operative variables including fitness associated with complications after oesophagectomy.

Oesophagectomy is a technically-demanding operation associated with a high level of morbidity. We analysed the association of pre-operative variables, including those from cardiopulmonary exercise testing, with complications (logistic regression) and survival and length of stay (Cox regression) after scheduled transthoracic oesophagectomy in 273 adults, in isolation and on multivariate testing (maximum Akaike information criterion). On multivariate analysis, any postoperative complication was associated with ventilatory equivalents for carbon dioxide, odds ratio (95%CI) 1.088 (1.02-1.17), p = 0.018. Cardiorespiratory complications were associated with FEV1 and pre-operative background survival (in an analogous group without cancer), odds ratios (95%CI) 0.55 (0.37-0.80), p = 0.002 and 0.89 (0.82-0.96), p = 0.004, respectively. Survival was associated with the ratio of expected-to-observed ventilatory equivalents for carbon dioxide and predicted postoperative survival, hazard ratios (95%CI) 0.17 (0.03-0.91), p = 0.039 and 0.96 (0.90-1.01), p = 0.076. Length of hospital stay was associated with FVC, hazard ratio (95%CI) 1.38 (1.17-1.63), p < 0.0001.

Validity of the 6 min walk test in prediction of the anaerobic threshold before major non-cardiac surgery.

BACKGROUND: For perioperative risk stratification, a robust, practical test could be used where cardiopulmonary exercise testing (CPET) is unavailable. The aim of this study was to assess the utility of the 6 min walk test (6MWT) distance to discriminate between low and high anaerobic threshold (AT) in patients awaiting major non-cardiac surgery. METHODS: In 110 participants, we obtained oxygen consumption at the AT from CPET and recorded the distance walked (in m) during a 6MWT. Receiver operating characteristic (ROC) curve analysis was used to derive two different cut-points for 6MWT distance in predicting an AT of <11 ml O(2) kg(-1) min(-1); one using the highest sum of sensitivity and specificity (conventional method) and the other adopting a 2:1 weighting in favour of sensitivity. In addition, using a novel linear regression-based technique, we obtained lower and upper cut-points for 6MWT distance that are predictive of an AT that is likely to be (P≥0.75) <11 or >11 ml O(2) kg(-1) min(-1). RESULTS: The ROC curve analysis revealed an area under the curve of 0.85 (95% confidence interval, 0.77-0.91). The optimum cut-points were <440 m (conventional method) and <502 m (sensitivity-weighted approach). The regression-based lower and upper 6MWT distance cut-points were <427 and >563 m, respectively. CONCLUSIONS: Patients walking >563 m in the 6MWT do not routinely require CPET; those walking <427 m should be referred for further evaluation. In situations of 'clinical uncertainty' (≥427 but ≤563 m), the number of clinical risk factors and magnitude of surgery should be incorporated into the decision-making process. The 6MWT is a useful clinical tool to screen and risk stratify patients in departments where CPET is unavailable.

Emergency Laparotomy Follow-Up Study (ELFUS): prospective feasibility investigation into postoperative complications and quality of life using patient-reported outcome measures up to a year after emergency laparotomy.

BACKGROUND: Emergency laparotomy carries a significant risk profile around the time of surgery. This research aimed to establish the feasibility of recruitment to a study using validated scoring tools to assess complications after surgery; and patient-reported outcome measures (PROMs) to assess quality of life and quality of recovery up to a year following emergency laparotomy (EL). METHODS: We used our local National Emergency Laparotomy Audit (NELA) register to identify potential participants at a single NHS centre in England. Complications were assessed at 5, 10 and 30 days after EL. Patient-reported outcome measures were collected at 1, 3, 6 and 12 months after surgery using EQ5D and WHODAS 2.0 questionnaires. RESULTS: Seventy of 129 consecutive patients (54%) agreed to take part in the study. Post-operative morbidity survey data was recorded from 63 and 37 patients at postoperative day 5 and day 10. Accordion Complication Severity Grading data was obtained from 70 patients. Patient-reported outcome measures were obtained from patients at baseline and 1, 3, 6 and 12 months after surgery from 70, 59, 51, 48, to 42 patients (100%, 87%, 77%, 75% and 69% of survivors), respectively. CONCLUSIONS: This study affirms the feasibility of collecting PROMs and morbidity data successfully at various time points following emergency laparotomy, and is the first longitudinal study to describe quality of life up to a year after surgery. This finding is important in the design of a larger observational study into quality of life and recovery after EL.

A feasibility study to investigate the utility of a home-based exercise intervention during and after neo-adjuvant chemotherapy for oesophago-gastric cancer-the ChemoFit study protocol.

BACKGROUND: Treatment of locally advanced oesophago-gastric adenocarcinoma usually entails neo-adjuvant chemotherapy (NAC) and surgery. Surgery is associated with high morbidity and mortality. Cardiopulmonary reserve of patients having major surgery is related to postoperative outcomes. Complications are associated with poorer quality of life and may affect prognosis. Preventing complications may be beneficial to both of these and have cost implications. Prehabilitation may improve recovery from surgery by increasing a patients' fitness before surgery. Designing a potentially cost and resource effective regimen which improves cardiopulmonary reserve may have a beneficial impact on patient outcomes after surgery. METHODS: The ChemoFit study is a non-randomised, single-arm and single-centre pilot study designed to investigate the feasibility of a home-based prehabilitation exercise intervention for patients receiving neoadjuvant treatment prior to oesophago-gastric surgery. Forty patients will be recruited at a single high-volume centre. The simple, home-based exercise intervention involves patients increasing their daily step-count during and after NAC and in the weeks leading up to surgical resection of the cancer. Additionally, quality of life assessments (QLQ-C30 and QLQ-OG25), oncological treatment delivery and participant perceptions of the study assessed by focus groups and questionnaires will be performed. The primary outcomes are to assess feasibility of the exercise intervention. The secondary outcomes will evaluate changes in cardiopulmonary reserve, sarcopenia and fat composition. DISCUSSION: It is anticipated that during an important teachable moment, the diagnosis and treatment of cancer, our patients will be open to the possibility of improving their fitness during chemotherapy and before major cancer surgery. It is possible that the negative impact of NAC on cardiopulmonary fitness could be prevented by implementing a home-based prehabilitation programme during and after NAC, prior to surgery for oesophago-gastric adenocarcinoma. TRIAL REGISTRATION: This study has been approved by the Health Research Authority (REC 18/WA/0427). Newcastle upon Tyne Hospitals NHS Foundation Trust (NUTH) will act as the study sponsor and the work is funded by a grant awarded by The Jon Moulton Charitable Foundation, supported by a research post funded by the Sir Bobby Robson Foundation. Trial registration: Clinicaltrials.gov, NCT04194463. Registered 11th December 2019-retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04194463.

Determination of the anaerobic threshold in the pre-operative assessment clinic: inter-observer measurement error.

The variability between observers in the interpretation of cardiopulmonary exercise tests may impact upon clinical decision making and affect the risk stratification and peri-operative management of a patient. The purpose of this study was to quantify the inter-reader variability in the determination of the anaerobic threshold (V-slope method). A series of 21 cardiopulmonary exercise tests from patients attending a surgical pre-operative assessment clinic were read independently by nine experienced clinicians regularly involved in clinical decision making. The grand mean for the anaerobic threshold was 10.5 ml O(2).kg body mass(-1).min(-1). The technical error of measurement was 8.1% (circa 0.9 ml.kg(-1).min(-1); 90% confidence interval, 7.4-8.9%). The mean absolute difference between readers was 4.5% with a typical random error of 6.5% (6.0-7.2%). We conclude that the inter-observer variability for experienced clinicians determining the anaerobic threshold from cardiopulmonary exercise tests is acceptable.