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Change in surgical practice and chemotherapy treatment by the surgery team
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Monitored group "M" (optimized controlled anesthesia) | Active Comparator | 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. |
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| Control group "C" (standard of care anesthesia) | Active Comparator | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Remifentanil infusion, desflurane titration and fluid infusion will be guided by NOL index, BIS index and Flotrac EV1000 system respectively | Drug | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| The hospital length of stay in days | The length of hospital stay in group "M" versus group "C" will be evaluated with the readiness for discharge from hospital criteria. These criteria for hospital discharge will be precisely and daily evaluated based on the previous published literature from experts who reached a consensus (J.F. Fiore et al. Disease of the Colon and Rectum, volume 55: 4, 2012). After these criteria are achieved, discharge may take place. | Evaluated 24 hours postoperative and everyday until hospital discharge, up to 21 days |
| Tolerance of oral intake | The length of hospital stay in group "M" versus group "C" will be evaluated with the readiness for discharge from hospital criteria. These criteria for hospital discharge will be precisely and daily evaluated based on the previous published literature from experts who reached a consensus (J.F. Fiore et al. Disease of the Colon and Rectum, volume 55: 4, 2012) and this will include: - Tolerance of oral intake. After these criteria are achieved, discharge may take place. | Evaluated 24 hours postoperative and everyday until hospital discharge, up to 21 days |
| Recovery of lower gastrointestinal function | The length of hospital stay in group "M" versus group "C" will be evaluated with the readiness for discharge from hospital criteria. These criteria for hospital discharge will be precisely and daily evaluated based on the previous published literature from experts who reached a consensus (J.F. Fiore et al. Disease of the Colon and Rectum, volume 55: 4, 2012) and this will include: - Recovery of lower gastrointestinal function. After these criteria are achieved, discharge may take place. | Evaluated 24 hours postoperative and everyday until hospital discharge, up to 21 days |
| Adequate pain control with oral analgesia | The length of hospital stay in group "M" versus group "C" will be evaluated with the readiness for discharge from hospital criteria. These criteria for hospital discharge will be precisely and daily evaluated based on the previous published literature from experts who reached a consensus (J.F. Fiore et al. Disease of the Colon and Rectum, volume 55: 4, 2012) and this will include: - Adequate pain control with oral analgesia. After these criteria are achieved, discharge may take place. |
| Measure | Description | Time Frame |
|---|---|---|
| Intraoperative anesthetic gas' consumption in ml/kg/h | Total consumption and absorption of desflurane in ml/kg/h during surgery and for each hour of surgery | Intraoperative |
| Intraoperative remifentanil consumption in mcg/kg/min |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Philippe PR Richebé, MD PhD | CIUSSS Est de l'île de Montréal | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hopital Maisonneuve Rosemont, CIUSSS de l'Est de l'Ile de Montréal | Montreal East | Quebec | H1T 2M4 | Canada |
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2 groups of patients. Randomization into Monitored group "M" (BIS + NOL + Flotrac EV1000) vs control group "C" (standard of care anesthesia) according to randomization list for a total number of 80 patients.
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Randomization into Monitored group "M" (BIS + NOL + Flotrac EV1000) vs control group "C" (standard of care anesthesia) will be done prior to the entrance in the OR, the day of the surgery.
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| Remifentanil infusion and desflurane titration will be guided by anesthesia usual practices | Drug | 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 |
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| Evaluated 24 hours postoperative and everyday until hospital discharge, up to 21 days |
| Ability to mobilize and self-care | The length of hospital stay in group "M" versus group "C" will be evaluated with the readiness for discharge from hospital criteria. These criteria for hospital discharge will be precisely and daily evaluated based on the previous published literature from experts who reached a consensus (J.F. Fiore et al. Disease of the Colon and Rectum, volume 55: 4, 2012) and this will include: - Ability to mobilize and self-care. After these criteria are achieved, discharge may take place. | Evaluated 24 hours postoperative and everyday until hospital discharge, up to 21 days |
| Clinical examination and laboratory tests show no evidence of complications or untreated medical problems | The length of hospital stay in group "M" versus group "C" will be evaluated with the readiness for discharge from hospital criteria. These criteria for hospital discharge will be precisely and daily evaluated based on the previous published literature from experts who reached a consensus (J.F. Fiore et al. Disease of the Colon and Rectum, volume 55: 4, 2012) and this will include: - Clinical examination and laboratory tests show no evidence of complications or untreated medical problems. After these criteria are achieved, discharge may take place. | Evaluated 24 hours postoperative and everyday until hospital discharge, up to 21 days |
Total consumption of i.v. remifentanil during surgery and for each hour of surgery
| Intraoperative |
| Intraoperative fluid's consumption in ml/h | Total of fluid perfused during surgery and for each hour of surgery | Intraoperative |
| Intraoperative number of hypotensive events | Total number of hypotensive events during surgery (defined as mean blood pressure below 60) | Intraoperative |
| Intraoperative phenylephrine consumption in mcg/kg/min | Total doses of intraoperative infused i.v. phenylephrine and doses per hour | Intraoperative |
| Intraoperative epidural consumption in 3 ml/h | Total doses of intraoperative Epidural infusion (lidocaine 2%+epinephrine) and doses per hour | Intraoperative |
| Time for awakening in seconds | Time for awakening (eyes opening) at the end of the surgery. Elapsed time in seconds between stopping the gas and opening the eyes of the patient | Intraoperative |
| Time for extubation in seconds | Time for extubation in seconds. Elapsed time in seconds between stopping the gas and patient's extubation | Intraoperative |
| Time for transfert to the PACU in seconds | Time for transfert to the PACU (Post Anesthesia Care Unit) in seconds, after extubatiuon | Intraoperative |
| First NRS pain score (0-10 scale) at times of awakening | NRS (Numeric Rating Scale) Pain Score evaluated at times of awakening, evaluation from 0 (no pain) to 10 (worst imaginable pain) scale | Intraoperative |
| First NRS pain score (0-10 scale) at arrival in PACU | First NRS Pain Score evaluated at arrival in PACU, evaluation from 0 (no pain) to 10 (worst imaginable pain) | Postoperative, evaluated at arrival in PACU |
| NRS pain score (0-10 scale) at rest, in PACU | NRS Pain Score at rest, evaluated every 15 minutes until time for readiness for PACU discharge, evaluation from 0 (no pain) to 10 (worst imaginable pain) | Postoperative, evaluated every 15 minutes until time for PACU discharge |
| NRS pain score (0-10 scale) with cough, in PACU | NRS Pain Score with cough, evaluated every 15 minutes until time for readiness for PACU discharge, evaluation from 0 (no pain) to 10 (worst imaginable pain) | Postoperative, evaluated every 15 minutes until time for PACU discharge |
| NRS pain score (0-10 scale) on the Shoulder, in PACU | NRS Pain Score on the Shoulder, evaluated every 15 minutes until time for readiness for PACU discharge, evaluation from 0 (no pain) to 10 (worst imaginable pain) | Postoperative, evaluated every 15 minutes until time for PACU discharge |
| Hydromorphone consumption (mg) in PACU | Total cumulative dose of titration of intravenous hydromorphone (mg), evaluated every 15 minutes until time for readiness for PACU discharge | Postoperative, evaluated every 15 minutes until time for PACU discharge |
| PONV score (0-3 scale) in PACU | PONV (PostOperative Nausea and Vomiting) score, evaluated every 15 minutes until time for readiness for PACU discharge, evaluation from 0 (no nausea) to 3 (nausea and vomiting) | Postoperative, evaluated every 15 minutes until time for PACU discharge |
| POSS score (1-4 scale) in PACU | POSS (Pasero Opioid-induced Sedation Scale) score evaluated every 15 minutes until time for readiness for PACU discharge, evaluation from 1 (awake and alert) to 5 (asleep deeply) | Postoperative, evaluated every 15 minutes until time for PACU discharge |
| Respiratory depression number in PACU | Respiratory depression number evaluated every 15 minutes until time for readiness for PACU discharge | Postoperative, evaluated every 15 minutes until time for PACU discharge |
| Blood pressure (mmHg) in PACU | Blood pressure (TAS/TAD/TAM) in mmHg evaluated every 15 minutes until time for readiness for PACU discharge | Postoperative, evaluated every 15 minutes until time for PACU discharge |
| Time for PACU discharge based on Aldrete scores (0-10 scale), in PACU | Time for readiness for PACU discharge based on Aldrete scores (0-10), Aldrete score must be ≥ 9 for PACU discharge | Postoperative, evaluated every 15 minutes until time for PACU discharge |
| NRS pain score (0-10 scale) at rest, evaluated everyday from 24 hours postoperative to hospital discharge | NRS Pain Score at rest, evaluated every day, from 24 hours postoperative until time for readiness for hospital discharge, evaluation from 0 (no pain) to 10 (worst imaginable pain) | Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days |
| NRS pain score (0-10 scale) with cough, evaluated everyday from 24 hours postoperative to hospital discharge | NRS Pain Score with cough, evaluated every day, from 24 hours postoperative until time for readiness for hospital discharge, evaluation from 0 (no pain) to 10 (worst imaginable pain) | Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days |
| NRS pain score (0-10 scale) on the Shoulder, evaluated everyday from 24 hours postoperative to hospital discharge | NRS Pain Score on the Shoulder, evaluated every day, from 24 hours postoperative until time for readiness for hospital discharge, evaluation from 0 (no pain) to 10 (worst imaginable pain) | Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days |
| Hydromorphone consumption (mg), evaluated everyday from 24 hours postoperative to hospital discharge | Total cumulative dose of titration of intravenous hydromorphone (mg), evaluated every day, from 24 hours postoperative until time for readiness for hospital discharge | Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days |
| Epidural consumption (mg), evaluated everyday from 24 hours postoperative to hospital discharge | Total cumulative dose of titration of epidural (mg), evaluated every day, from 24 hours postoperative until the cessation of the PCEA (Patient Controlled Epidural Analgesia) | Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days |
| PONV score (0-3 scale), evaluated everyday from 24 hours postoperative to hospital discharge | PONV (PostOperative Nausea and Vomiting) score, evaluated every day, from 24 hours postoperative until time for readiness for hospital discharge, evaluation from 0 (no nausea) to 3 (nausea and vomiting) | Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days |
| POSS score (1-4 scale), evaluated everyday from 24 hours postoperative to hospital discharge | POSS (Pasero Opioid-induced Sedation Scale) score evaluated every day, from 24 hours postoperative until time for readiness for hospital discharge, evaluation from 1 (awake and alert) to 5 (asleep deeply) | Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days |
| Respiratory depression number, evaluated everyday from 24 hours postoperative to hospital discharge | Respiratory depression number evaluated every day, from 24 hours postoperative until time for readiness for hospital discharge | Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days |
| Blood pressure (mmHg), evaluated everyday from 24 hours postoperative to hospital discharge | Blood pressure (TAS/TAD/TAM) in mmHg evaluated every day, from 24 hours postoperative until time for readiness for hospital discharge | Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days |
| Heart rate (bpm), evaluated everyday from 24 hours postoperative to hospital discharge | Heart rate (HR) in bpm (beats per minute), evaluated every day from 24 hours postoperative until time for readiness for hospital discharge | Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days |
| Oxygen saturation (%), evaluated everyday from 24 hours postoperative to hospital discharge | Oxygen saturation (SPO2) in %, evaluated every day from 24 hours postoperative until time for readiness for hospital discharge | Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days |
| Respiratory rate (bpm), evaluated everyday from 24 hours postoperative to hospital discharge | Respiratory rate (RR) in bpm (breaths per minute), evaluated every day from 24 hours postoperative until time for readiness for hospital discharge | Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days |
| Temperature (°C), evaluated everyday from 24 hours postoperative to hospital discharge | Temperature (T°C), evaluated every day from 24 hours postoperative until time for readiness for hospital discharge | Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days |
| Overall patient's satisfaction (0-100%), evaluated everyday from 24 hours postoperative to hospital discharge | Overall patient's satisfaction, evaluated every day from 24 hours postoperative until time for readiness for hospital discharge, evaluation from 0 (unsatisfied) to 100% (fully satisfied) | Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days |
| Quality of recovery (QoR-15), evaluated every day from 24 hours postoperative to hospital discharge | Patients' perceived quality of recovery (QoR-15). This questionnaire includes 15 questions that are divided into 2 parts, part A contains the first 10 questions that are scored between 0 (never) and 10 (constantly), and part B contains the last 5 questions scored between 0 (constantly) and 10 (never). Evaluation test every day from 24 hours postoperative until time for readiness for hospital discharge | Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days |
| 6-minutes walking score, evaluated every day from 24 hours postoperative to hospital discharge | 6-minutes walking score. The object of this test is to walk as far as possible for 6 minutes in the hospital hallway. Six minutes is a long time to walk after this surgery type, so it's important to practise 6 Minute Walk every day on a flat hard surface. Evaluation test every day from 24 hours postoperative until time for readiness for hospital discharge | Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days |
| MOCA scores, evaluated every day from 24 hours postoperative to hospital discharge | MOCA (Montreal Cognitive Assessment) scores test for Dementia, range from zero to 30, with a score of 26 and higher generally considered normal. In the initial study data establishing the MoCA, normal controls had an average score of 27.4, compared with 22.1 in people with mild cognitive impairment (MCI) and 16.2 in people with Alzheimer's disease. Evaluation test every day from 24 hours postoperative until time for readiness for hospital discharge | Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days |
| Time for first walking/mobilization, evaluated every day from 24 hours postoperative to hospital discharge | The time for first walking/mobilization, consist to determine the precise moment when the patient is able to get up from his bed, and sit on a chair, with and without help | Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days |
| Time for first flatus, evaluated every day from 24 hours postoperative to hospital discharge | Determine the time of first flatus which are a sign of recovery of lower GI function | Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days |
| Time for return to food oral intake, evaluated every day from 24 hours postoperative to hospital | Patient is able to tolerate at least one solid meal without nausea, vomiting, bloating or worsening abdominal pain. Patient drinks liquids actively (ideally > 800-1000 ml/day) and do not require intravenous fluids infusion to maintain hydration | Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days |
| Biological analysis, evaluated every day from 24 hours postoperative to hospital discharge | Biological analysis, intraoperative and daily during the 21 postoperative days: serum electrolytes (Na+ Cl- Ca2+ Ca total Phophore, glycemia) creatinine, DFG, CRP, hemoglobin, white blood cell and platelet counts, serum albumin, INR, PTT | Evaluated 24 hours postoperative, then everyday until hospital discharge, an average of 21 days |
| Rate of hospital readmission and mortality postoperative | Rate of hospital readmission and mortality postoperative up to 30 days following surgery | Postoperative evaluation, up to 30 days following surgery |
| ID | Term |
|---|---|
| D000084462 | Hyperthermia |
| D015179 | Colorectal Neoplasms |
| D002277 | Carcinoma |
| ID | Term |
|---|---|
| D001832 | Body Temperature Changes |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D018882 | Heat Stress Disorders |
| D014947 | Wounds and Injuries |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| D035061 | Control Groups |
| ID | Term |
|---|---|
| D015340 | Epidemiologic Research Design |
| D004812 | Epidemiologic Methods |
| D008919 | Investigative Techniques |
| D012107 | Research Design |
| D008722 | Methods |
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