Non-opioid Analgesia for Fast-track Surgery

NCT ID: NCT01275911

Last Updated: 2013-03-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-01-31

Study Completion Date

2010-08-31

Brief Summary

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In this randomized observer-blinded trial the analgesic efficacy of intravenous esmolol, as alternative to intraoperative opioids, is tested in patients undergoing laparoscopic prostatectomy and upper gastrointestinal surgery (such as Nissen fundoplication). The purpose of this study is to determine whether intravenous esmolol improves postoperative analgesia and accelerate the surgical recovery. We hypothesize that patients receiving intravenous esmolol will consume less analgesic in the postoperative period, will have less opioid-related side effects and will recover their functional status faster then patients receiving intravenous esmolol.

Patients will be stratified according to the type of surgical procedure in 2 arms: 40 patients with prostate cancer and undergoing elective laparoscopic prostatectomy, and 40 patients with gastro-esophageal reflux undergoing upper gastrointestinal surgery (Nissen funduplication) will be enrolled.

Patients will receive total intravenous anesthesia with propofol and esmolol (Esmolol group, n=20 in each arm) or propofol and remifentanil (Remifentanil Group, n=20 in each arm).

Detailed Description

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Outcomes:

1. Primary: The amount of fentanyl needed in PACU and the amount of PCA morphine used during the first 24 postoperative hours.
2. Secondary: intensity of postoperative pain (visual analogue scale,VAS), opioids side effects, length of stay in PACU and in the hospital, short-term SF-36 questionnaire, CHAMPS questionnaire, and the 2 and 6 minutes walking tests.

Methodology:

In each arm patients will be assigned by computer generated random letters to two groups:

The Esmolol group: patients will receive no opioids but will receive esmolol at induction and as a continuous infusion during the surgery.

The Remifentanil group: patients will receive remifentanil as sole opioid during induction of anesthesia as a continuous infusion during the surgery.

During the preoperative assessment patients will be asked to fill out the CHAMPS and the Short-term SF-36 questionnaires. The 2 and 6 minutes walking tests will be also administered

On arrival in the operating room, routine monitors will be applied for recording heart rate, systolic blood pressure, and oxygen saturation. In addition, the electroencephalographic bispectral index (BIS) value was obtained using a single channel sensor in a frontal temporal area. The BIS is a standard monitor of depth of anesthesia and measures cortical activation. It has been found to be well correlated to electroencephalogram. After obtaining baseline values, midazolam 1-2mg IV will be administered for pre-medication. Anesthesia will be subsequently induced with Propofol 2-2.5 mg/kg, Rocuronium 0.45-0.9 mg/kg.

The Esmolol group will receive 1.0 mg/kg of esmolol and the Remifentanil group 1.0 mcg/kg of remifentanil for induction of anesthesia. After direct laryngoscopy and tracheal intubation will have been performed, anesthesia will be maintained with a continuous infusion of propofol 80-250 mcg/kg/min to maintain a "targeted" BIS value of 50 or less (BIS below 60 signifies the patient is asleep and unaware, 90 and over signifies intraoperative wakefulness). Patients will receive either esmolol infusion of 5-15 mcg/kg/min or remifentanil infusion of 0.025-0.25mcg/kg/min (in Esmolol group or in the Remifentanil group respectively) titrated to maintain HR within 25% of the pre-induction baseline value with targeted HR in between 55-90. Furthermore, the patients will also receive IV fluid at 6 ml/kg. All patients will be mechanically ventilated to maintain the end-tidal carbon dioxide (CO2) concentration in the range of 36-44 mm Hg and will receive toward the end of surgery Ketorolac 30mg IV, Droperidol 0.625mg IV and neuromuscular reversal if needed. Propofol will be discontinued after the last skin suture and the remifentanil or esmolol infusions will be stopped. After closure 10cc of bupivacaine 0.25% with epinephrine 1:200.000 will be infiltrated in the surgical ports. Nurses in the PACU will be informed that patients are taking part of the study but will not be aware of the hypothesis and will provide patients with standard care. Patients will have access in PACU to Fentanyl 25mcg IV q5min and to Ondansetron 2-8mg IV prn (standard medications used in this institution). Patients will receive PCA morphine for 24-48 h with tylenol 650mg PO q4h and naproxen 500mg or celebrex 200 mg PO bid.

Heart rate, blood pressure, BIS and oxygen saturation will be recorded at baseline, induction of anesthesia, tracheal intubation, skin incision, and subsequently at 5 min intervals until the end of surgery. Patients will be extubated in the operating room. They will then be transported to the post anesthesia care unit (PACU).

Assessment:

Recovery time will be assessed by a blinded observer (research fellow) unaware of the study hypothesis from the time the study drugs are discontinued. Times to awakening (opening eyes on verbal command), and orientation to person, date and place will be recorded, whereas the time to home readiness will be evaluated using standardized discharge criteria as described by White-Song17 at 30 min intervals. The score maximum of 12 out of 14 allows the patients to be discharged to the surgical ward from the PACU. Pain will be assessed every 15 minutes using (visual analog scale) (VAS)18 (0-10 cm) at rest, on movements and on coughing by the recovery nurse. Postoperative side effects (nausea, vomiting, pain), requirement for analgesics and antiemetics therapy (morphine and zofran respectively), as well as patient satisfaction will be assessed on discharge from PACU and 24-48 hrs after the procedure.

Conditions

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Pain

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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Esmolol

Group Type EXPERIMENTAL

Esmolol

Intervention Type DRUG

Induction of anesthesia: 1mg/Kg; Maintenance during surgery: 5-15 mcg/kg/min

Remifentanil

Group Type ACTIVE_COMPARATOR

Remifentanil

Intervention Type DRUG

At the induction of anesthesia: 1mcg/Kg; Maintenance during surgery: 0.025-0.25mcg/kg/min

Interventions

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Esmolol

Induction of anesthesia: 1mg/Kg; Maintenance during surgery: 5-15 mcg/kg/min

Intervention Type DRUG

Remifentanil

At the induction of anesthesia: 1mcg/Kg; Maintenance during surgery: 0.025-0.25mcg/kg/min

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Patients with prostate cancer undergoing laparoscopic prostatectomy
2. Patients with gastro-esophageal reflux undergoing upper abdominal surgery (Nissen funduplication)

Exclusion Criteria

1. Age \<18 yr or \> 85 yr
2. ASA physical status 3 and greater
3. History of hepatic failure (Child \& Pug A-C)
4. Renal failure (creatinine outside the normal range)
5. Cardiac failure (NYHA I-IV)
6. Organ transplant
7. Diabetes mellitus type 1 and 2
8. Morbid obesity (BMI \> 40)
9. Chronic use of opioids and beta-blockers
10. Severe mental impairment
11. History of allergic reactions to all the medications used in the study or inability to understand pain assessment.
12. Asthma or Reactive airway disease
13. Patient with known or suspected peritoneal adhesion
14. Pregnancy
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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McGill University Health Centre/Research Institute of the McGill University Health Centre

OTHER

Sponsor Role lead

Responsible Party

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Gabriele Baldini, MD, MSc, Assistant Professor

MD, MSc, Anesthesiologist, Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Gabriele Baldini, MD

Role: PRINCIPAL_INVESTIGATOR

McGill University Health Centre/Research Institute of the McGill University Health Centre

Locations

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Montreal General Hospital, McGill University Health Centre

Montreal, Quebec, Canada

Site Status

Countries

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Canada

References

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Collard V, Mistraletti G, Taqi A, Asenjo JF, Feldman LS, Fried GM, Carli F. Intraoperative esmolol infusion in the absence of opioids spares postoperative fentanyl in patients undergoing ambulatory laparoscopic cholecystectomy. Anesth Analg. 2007 Nov;105(5):1255-62, table of contents. doi: 10.1213/01.ane.0000282822.07437.02.

Reference Type RESULT
PMID: 17959952 (View on PubMed)

Coloma M, Chiu JW, White PF, Armbruster SC. The use of esmolol as an alternative to remifentanil during desflurane anesthesia for fast-track outpatient gynecologic laparoscopic surgery. Anesth Analg. 2001 Feb;92(2):352-7. doi: 10.1097/00000539-200102000-00014.

Reference Type RESULT
PMID: 11159231 (View on PubMed)

Johansen JW, Schneider G, Windsor AM, Sebel PS. Esmolol potentiates reduction of minimum alveolar isoflurane concentration by alfentanil. Anesth Analg. 1998 Sep;87(3):671-6. doi: 10.1097/00000539-199809000-00034.

Reference Type RESULT
PMID: 9728851 (View on PubMed)

White PF, Wang B, Tang J, Wender RH, Naruse R, Sloninsky A. The effect of intraoperative use of esmolol and nicardipine on recovery after ambulatory surgery. Anesth Analg. 2003 Dec;97(6):1633-1638. doi: 10.1213/01.ANE.0000085296.07006.BA.

Reference Type RESULT
PMID: 14633533 (View on PubMed)

Chia YY, Chan MH, Ko NH, Liu K. Role of beta-blockade in anaesthesia and postoperative pain management after hysterectomy. Br J Anaesth. 2004 Dec;93(6):799-805. doi: 10.1093/bja/aeh268. Epub 2004 Sep 17.

Reference Type RESULT
PMID: 15377583 (View on PubMed)

Erdil F, Demirbilek S, Begec Z, Ozturk E, But A, Ozcan Ersoy M. The effect of esmolol on the QTc interval during induction of anaesthesia in patients with coronary artery disease. Anaesthesia. 2009 Mar;64(3):246-50. doi: 10.1111/j.1365-2044.2008.05754.x.

Reference Type RESULT
PMID: 19302635 (View on PubMed)

Smith I, Van Hemelrijck J, White PF. Efficacy of esmolol versus alfentanil as a supplement to propofol-nitrous oxide anesthesia. Anesth Analg. 1991 Nov;73(5):540-6.

Reference Type RESULT
PMID: 1683182 (View on PubMed)

White PF. The role of non-opioid analgesic techniques in the management of pain after ambulatory surgery. Anesth Analg. 2002 Mar;94(3):577-85. doi: 10.1097/00000539-200203000-00019. No abstract available.

Reference Type RESULT
PMID: 11867379 (View on PubMed)

Other Identifiers

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GEN#08-22

Identifier Type: -

Identifier Source: org_study_id

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