Impact of an Optimised Monitored Anesthesia on the Patients' Recovery After Cytoreduction Surgery Plus HIPEC
キーワード
概要
説明
Title: Evaluation of the combined intraoperative monitoring of depth of analgesia (NOL), depth of anesthesia (BIS) and continuous hemodynamic data (Flotrac EV1000 system) on the patients' recovery after cytoreduction surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). A pilot study.
Hypothesis: Investigators hypothesize that the intraoperative combination of new monitors, NOL index for depth of analgesia, BIS index for depth of anesthesia and Flotrac EV1000 system as continuous hemodynamic monitoring, to guide the delivery of opioids, hypnotics, fluids and inotropes, respectively, will improve the quality of recovery as well as the safety after anesthesia in patients undergoing HIPEC (Hyperthermic Intraperitoneal Chemotherapy) surgery.
Background: so far, only vital signs (mostly, blood pressure and heart rate) helped the anesthesiologist to administer hypnotics agents, analgesics, fluids and inotrope. Many devices have offered pain monitoring for anesthetized patients. The NOL index, a nociception monitor using a multiparametric approach, has shown an excellent sensitivity and specificity in detecting noxious stimuli under general anesthesia. More recently, it has been shown a strong inverse correlation between NOL index response to nociceptive stimulus and the increasing doses of opioid analgesia during surgery. Studies on post-operative outcomes when using intraoperative NOL monitoring to adapt nociception/anti-nociception balance during general anesthesia (GA) also reported in our center an improvement of the time to extubation and of the postoperative recovery criteria in PACU after colorectal surgery in the monitored group, leading to a quicker discharge from PACU (presented as an abstract at ASA 2018; manuscript in preparation). Recent studies also showed that avoiding too deep anesthesia by using the BIS index would improve patients' outcome in terms of morbi-mortality. It is also accepted that intra-venous fluid and inotropic/vasopressor drugs have an important effect on intra and postoperative patients' outcomes, in particular following major gastrointestinal surgery. The use of hemodynamic therapy management algorithms has been recommended in a report commissioned by the Centers for Medicare and Medicaid Services in the USA, and by the National Institute for Health and Care Excellence (NICE) in the UK as well as many groups working in ERAS protocols in Canada (and especially Montreal, McGill University) and worldwide.
Based on our recent systematic review (in preparation) and out of the 69 selected published articles, there is no study so far evaluating precisely the impact of anesthesia on postoperative outcomes, and no study combining the NOL, the BIS indexes and the Flotrac EV1000 system to evaluate the impact of a more precise anesthesia management on the postoperative outcomes after cytoreduction and HIPEC for peritoneal carcinomatosis of colorectal origin. Thus, the idea to propose the present study.
Specific Objectives: primary objective: to compare the time to reach the readiness for discharge from hospital and the total postoperative in-hospital length of stay between the Monitored group "M" (optimized, personalized and controlled anesthesia) versus the control group "C" (standard of care anesthesia). Secondary objectives: to evaluate the quality of recovery from anesthesia in the PACU and on the wards and all the adverse events every day and until patient's discharge from hospital. The emergence and extubation time of patients after anesthesia, time spent in PACU (Aldrete score), intra- and postoperative opioid requirements, pain scores (NRS) for several postoperative days, patients' postoperative recovery and satisfaction (the Quality of Recovery: QOR-15, 6min walking test, MOCA, etc.) will be also compared between the 2 groups. Finally, biological outcomes such as blood gas analysis, serum electrolytes, creatinine, DFG, hemoglobin, white blood cell and platelet counts, CRP, serum albumin, INR, PTT will be evaluated on a standard basis in both the groups.
Methods: 80 patients scheduled for HIPEC surgery with oxaliplatin for bowel adenocarcinoma surgery (without digestive resection) will be included. Randomisation will occur after the participant has provided informed consent and shortly before the surgical procedure is due to start. Patients in the Control group "C" will be managed by clinical staff according to usual practice, desflurane will be administered to keep MAC at 1, and remifentanil infusion rate will be adapted to the mean arterial blood pressure to keep it between 65 and 100. In the Monitored group "M", the NOL index will guide the administration of remifentanil to keep the index between 5-25, and the desflurane will be titrated to keep a BIS index between 45 and 55. Cardiac output and stroke volume variation will be measured by the Flotrac EV1000 system. Patients will receive 250ml fluid challenges with a recommended solution as required, in order to achieve a maximal value of stroke volume. Intraoperative epidural analgesia will be the same for all. Postoperative analgesia will be based on PCEA and hydromorphone for all. All anesthesia related side effects and quality of analgesia and rehabilitation will be evaluated daily and until patient's discharge from hospital.
Data Analysis: all data collected will be analyzed using an intent-to-treat approach. Summary statistics for each group, treatment effects, 95% confidence intervals, and p-values will be presented for primary and secondary outcomes, and process measures. Intraoperative data in the "M" and "C" groups will be compared using parametric (e.g. Student t-test) or non-parametric tests (e.g. Mann-Withney U test, Chi-squared test) depending on type of variables and distribution. General linear models will be used to carry out group comparisons on data on length of hospital stay. Potential pitfalls: analyses for secondary objectives may not be sufficiently powered but will nevertheless provide useful information for designing and conducting a future multicentric study. Bonferroni corrections will be used to protect against type I error.
Significance/Importance: Adding the NOL, the BIS and continuous hemodynamic monitoring will very likely reduce the total length of stay, and improve the postoperative speed and quality of recovery as well as will likely reduce the incidence of complications after cytoreduction + HIPEC procedures.
Study Design: Prospective, randomized controlled study.
Subject Population: Adult patients scheduled to undergo laparotomy for cytoreduction surgery + HIPEC for peritoneal carcinomatosis of colorectal origin and under general anesthesia with an active intraoperative epidural analgesia.
Sample Size: 80 patients will be evaluated in this study.
Study Duration: 2 year(s)
Study Center: Maisonneuve-Rosemont Hospital, Departments of Anesthesiology and Pain Medicine and Department of General Oncologic Surgery, CIUSSS de l'Est-de-l'Île-de-Montreal, Montreal, Quebec, Canada
Adverse Events: None expected.
Subvention/support: Department of Anesthesiology and Pain Medicine of HMR/CEMTL.
日付
| 最終確認済み: | 08/31/2019 |
| 最初に提出された: | 07/15/2019 |
| 提出された推定登録数: | 09/20/2019 |
| 最初の投稿: | 09/25/2019 |
| 最終更新が送信されました: | 09/20/2019 |
| 最終更新日: | 09/25/2019 |
| 実際の研究開始日: | 05/14/2019 |
| 一次完了予定日: | 04/14/2021 |
| 研究完了予定日: | 07/14/2021 |
状態または病気
介入/治療
Drug: Monitored group "M" (optimized controlled anesthesia)
Drug: Control group "C" (standard of care anesthesia)
段階
アームグループ
| 腕 | 介入/治療 |
|---|---|
| Active Comparator: Monitored group "M" (optimized controlled anesthesia) Patients in the Monitored group "M", the NOL index will guide the administration of remifentanil to keep the index between 5-25, and the desflurane will be titrated to keep a BIS index between 45 and 55. Cardiac output and stroke volume variation will be measured by the Flotrac EV1000 system. Patients will receive 250ml fluid challenges with a recommended solution as required, in order to achieve a maximal value of stroke volume. | Drug: Monitored group "M" (optimized controlled anesthesia) NOL index will guide the administration of remifentanil to keep the index between 5-25, and the desflurane will be titrated to keep a BIS index between 45 and 55. Cardiac output and stroke volume variation will be measured by the Flotrac EV1000 system. Patients will receive 250ml fluid challenges with a recommended solution as required, in order to achieve a maximal value of stroke volume |
| Active Comparator: Control group "C" (standard of care anesthesia) Patients in the Control group "C" will be managed by clinical staff according to usual practice, desflurane will be administered to keep MAC at 1, and remifentanil infusion rate will be adapted to the mean arterial blood pressure to keep it between 65 and 100. | Drug: Control group "C" (standard of care anesthesia) Desflurane will be administered to keep MAC at 1, and remifentanil infusion rate will be adapted to the mean arterial blood pressure to keep it between 65 and 100, according to anesthesia usual practices |
適格基準
| 研究の対象となる年齢 | 18 Years に 18 Years |
| 研究に適格な性別 | All |
| 健康なボランティアを受け入れる | はい |
| 基準 | Inclusion Criteria: - ASA status I, II or III - Patients older than 18 years - HIPEC for bowel surgery with oxaliplatin + dextrose 5% for a duration of 30 min - Duration and type of surgery requiring an epidural analgesia via an epidural catheter placed and tunnelled prior the general anesthesia induction and an arterial line placed after induction of general anesthesia. Exclusion Criteria: - Any allergy to one drug used in our anesthesia or HIPEC protocol - Any contra-indication or patient's refusal for epidural placement - Chronic arrhythmic cardiac conditions - Chronic pain with use of opioids more than 3 times per week for 4 weeks - Bowel occlusion - Physical/mental incapacities - Unexpected difficult airway requesting excessive, possibly painful airway manipulations. - Epidural failure |
結果
主な結果の測定
1. The hospital length of stay in days [Evaluated 24 hours postoperative and everyday until hospital discharge, up to 21 days]
2. Tolerance of oral intake [Evaluated 24 hours postoperative and everyday until hospital discharge, up to 21 days]
3. Recovery of lower gastrointestinal function [Evaluated 24 hours postoperative and everyday until hospital discharge, up to 21 days]
4. Adequate pain control with oral analgesia [Evaluated 24 hours postoperative and everyday until hospital discharge, up to 21 days]
5. Ability to mobilize and self-care [Evaluated 24 hours postoperative and everyday until hospital discharge, up to 21 days]
6. Clinical examination and laboratory tests show no evidence of complications or untreated medical problems [Evaluated 24 hours postoperative and everyday until hospital discharge, up to 21 days]
二次的な結果の測定
1. Intraoperative anesthetic gas' consumption in ml/kg/h [Intraoperative]
2. Intraoperative remifentanil consumption in mcg/kg/min [Intraoperative]
3. Intraoperative fluid's consumption in ml/h [Intraoperative]
4. Intraoperative number of hypotensive events [Intraoperative]
5. Intraoperative phenylephrine consumption in mcg/kg/min [Intraoperative]
6. Intraoperative epidural consumption in 3 ml/h [Intraoperative]
7. Time for awakening in seconds [Intraoperative]
8. Time for extubation in seconds [Intraoperative]
9. Time for transfert to the PACU in seconds [Intraoperative]
10. First NRS pain score (0-10 scale) at times of awakening [Intraoperative]
11. First NRS pain score (0-10 scale) at arrival in PACU [Postoperative, evaluated at arrival in PACU]
12. NRS pain score (0-10 scale) at rest, in PACU [Postoperative, evaluated every 15 minutes until time for PACU discharge]
13. NRS pain score (0-10 scale) with cough, in PACU [Postoperative, evaluated every 15 minutes until time for PACU discharge]
14. NRS pain score (0-10 scale) on the Shoulder, in PACU [Postoperative, evaluated every 15 minutes until time for PACU discharge]
15. Hydromorphone consumption (mg) in PACU [Postoperative, evaluated every 15 minutes until time for PACU discharge]
16. PONV score (0-3 scale) in PACU [Postoperative, evaluated every 15 minutes until time for PACU discharge]
17. POSS score (1-4 scale) in PACU [Postoperative, evaluated every 15 minutes until time for PACU discharge]
18. Respiratory depression number in PACU [Postoperative, evaluated every 15 minutes until time for PACU discharge]
19. Blood pressure (mmHg) in PACU [Postoperative, evaluated every 15 minutes until time for PACU discharge]
20. Time for PACU discharge based on Aldrete scores (0-10 scale), in PACU [Postoperative, evaluated every 15 minutes until time for PACU discharge]
21. NRS pain score (0-10 scale) at rest, evaluated everyday from 24 hours postoperative to hospital discharge [Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days]
22. NRS pain score (0-10 scale) with cough, evaluated everyday from 24 hours postoperative to hospital discharge [Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days]
23. NRS pain score (0-10 scale) on the Shoulder, evaluated everyday from 24 hours postoperative to hospital discharge [Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days]
24. Hydromorphone consumption (mg), evaluated everyday from 24 hours postoperative to hospital discharge [Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days]
25. Epidural consumption (mg), evaluated everyday from 24 hours postoperative to hospital discharge [Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days]
26. PONV score (0-3 scale), evaluated everyday from 24 hours postoperative to hospital discharge [Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days]
27. POSS score (1-4 scale), evaluated everyday from 24 hours postoperative to hospital discharge [Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days]
28. Respiratory depression number, evaluated everyday from 24 hours postoperative to hospital discharge [Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days]
29. Blood pressure (mmHg), evaluated everyday from 24 hours postoperative to hospital discharge [Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days]
30. Heart rate (bpm), evaluated everyday from 24 hours postoperative to hospital discharge [Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days]
31. Oxygen saturation (%), evaluated everyday from 24 hours postoperative to hospital discharge [Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days]
32. Respiratory rate (bpm), evaluated everyday from 24 hours postoperative to hospital discharge [Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days]
33. Temperature (°C), evaluated everyday from 24 hours postoperative to hospital discharge [Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days]
34. Overall patient's satisfaction (0-100%), evaluated everyday from 24 hours postoperative to hospital discharge [Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days]
35. Quality of recovery (QoR-15), evaluated every day from 24 hours postoperative to hospital discharge [Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days]
36. 6-minutes walking score, evaluated every day from 24 hours postoperative to hospital discharge [Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days]
37. MOCA scores, evaluated every day from 24 hours postoperative to hospital discharge [Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days]
38. Time for first walking/mobilization, evaluated every day from 24 hours postoperative to hospital discharge [Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days]
39. Time for first flatus, evaluated every day from 24 hours postoperative to hospital discharge [Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days]
40. Time for return to food oral intake, evaluated every day from 24 hours postoperative to hospital [Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days]
41. Biological analysis, evaluated every day from 24 hours postoperative to hospital discharge [Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days]
42. Rate of hospital readmission and mortality postoperative [Postoperative evaluation, up to 30 days following surgery]
