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
