Impact of an Optimised Monitored Anesthesia on the Patients' Recovery After Cytoreduction Surgery Plus HIPEC

Official Title

Evaluation of the Impact of Combined Intraoperative Monitoring of Depth of Analgesia, Depth of Anesthesia and Continuous Hemodynamic Data on the Patients Recovery After Cytoreduction Surgery and Hyperthermic Intraperitoneal Chemotherapy

Summary:

The objective of our PILOT study is to evaluate the impact of a controlled (monitored) randomized anesthesia during cytoreductive surgery with HIPEC to oxaliplatin in order to treat adenocarcinomas of colorectal origin. The combination of NOL monitoring, BIS monitoring and continuous hemodynamic monitoring (FloTrac EV1000 system) can improve patient safety by reducing the length of hospital stay by decreasing total hypnotic doses and intraoperative opioids and side effects following anesthesia.

Trial Description

Primary Outcome:

  • The hospital length of stay in days
  • Tolerance of oral intake
  • Recovery of lower gastrointestinal function
  • Adequate pain control with oral analgesia
  • Ability to mobilize and self-care
  • Clinical examination and laboratory tests show no evidence of complications or untreated medical problems
Secondary Outcome:
  • Intraoperative anesthetic gas' consumption in ml/kg/h
  • Intraoperative remifentanil consumption in mcg/kg/min
  • Intraoperative fluid's consumption in ml/h
  • Intraoperative number of hypotensive events
  • Intraoperative phenylephrine consumption in mcg/kg/min
  • Intraoperative epidural consumption in 3 ml/h
  • Time for awakening in seconds
  • Time for extubation in seconds
  • Time for transfert to the PACU in seconds
  • First NRS pain score (0-10 scale) at times of awakening
  • First NRS pain score (0-10 scale) at arrival in PACU
  • NRS pain score (0-10 scale) at rest, in PACU
  • NRS pain score (0-10 scale) with cough, in PACU
  • NRS pain score (0-10 scale) on the Shoulder, in PACU
  • Hydromorphone consumption (mg) in PACU
  • PONV score (0-3 scale) in PACU
  • POSS score (1-4 scale) in PACU
  • Respiratory depression number in PACU
  • Blood pressure (mmHg) in PACU
  • Time for PACU discharge based on Aldrete scores (0-10 scale), in PACU
  • NRS pain score (0-10 scale) at rest, evaluated everyday from 24 hours postoperative to hospital discharge
  • NRS pain score (0-10 scale) with cough, evaluated everyday from 24 hours postoperative to hospital discharge
  • NRS pain score (0-10 scale) on the Shoulder, evaluated everyday from 24 hours postoperative to hospital discharge
  • Hydromorphone consumption (mg), evaluated everyday from 24 hours postoperative to hospital discharge
  • Epidural consumption (mg), evaluated everyday from 24 hours postoperative to hospital discharge
  • PONV score (0-3 scale), evaluated everyday from 24 hours postoperative to hospital discharge
  • POSS score (1-4 scale), evaluated everyday from 24 hours postoperative to hospital discharge
  • Respiratory depression number, evaluated everyday from 24 hours postoperative to hospital discharge
  • Blood pressure (mmHg), evaluated everyday from 24 hours postoperative to hospital discharge
  • Heart rate (bpm), evaluated everyday from 24 hours postoperative to hospital discharge
  • Oxygen saturation (%), evaluated everyday from 24 hours postoperative to hospital discharge
  • Respiratory rate (bpm), evaluated everyday from 24 hours postoperative to hospital discharge
  • Temperature (°C), evaluated everyday from 24 hours postoperative to hospital discharge
  • Overall patient's satisfaction (0-100%), evaluated everyday from 24 hours postoperative to hospital discharge
  • Quality of recovery (QoR-15), evaluated every day from 24 hours postoperative to hospital discharge
  • 6-minutes walking score, evaluated every day from 24 hours postoperative to hospital discharge
  • MOCA scores, evaluated every day from 24 hours postoperative to hospital discharge
  • Time for first walking/mobilization, evaluated every day from 24 hours postoperative to hospital discharge
  • Time for first flatus, evaluated every day from 24 hours postoperative to hospital discharge
  • Time for return to food oral intake, evaluated every day from 24 hours postoperative to hospital
  • Biological analysis, evaluated every day from 24 hours postoperative to hospital discharge
  • Rate of hospital readmission and mortality postoperative
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 centre 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 Centres 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 Centre: 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.

View this trial on ClinicalTrials.gov

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