Multi-dose Acetaminophen for Patients Undergoing General Anesthesia

NCT ID: NCT02832687

Last Updated: 2021-12-09

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE4

Total Enrollment

88 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-06-19

Study Completion Date

2020-12-31

Brief Summary

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Study Objective The aim of the proposed study is to examine the effect of Q4 hour multidose IV acetaminophen on patients' readiness for discharge. In doing so the investigators will also investigate the various factors that could potentially contribute to a patient's readiness for discharge such as overall opioid consumption, time to rescue medication, incidence of postoperative nausea and vomiting, pain scores, and perioperative stress markers and their overall correlation with IV acetaminophen intake.

Detailed Description

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This is a randomized, double-blind, placebo-controlled, two-arm parallel study.. Patients 50kg or more will receive either 1000mg IV acetaminophen or placebo with the first dose given preoperatively in the holding area followed by re-dosing every four hours from that point up to a maximum of 4 doses or 4000mg in 24 hours. Patients \<50 kg will receive 12.5mg/kg to a maximum of 75 mg /per kg/per day as per the label dose with repeat dosing Q4 hours.

After pre-oxygenation, general anesthesia will be induced with lidocaine (1 mg/kg Ideal Body Weight), propofol (1-2 mg/kg Actual Body Weight), and fentanyl (up to 5 mcg/kg Actual Body Weight). Additionally all subjects with receive 2 mg midazolam. Tracheal intubation will be facilitated with rocuronium (0.6 - 1.2 mg/kg Actual Body Weight). Anesthesia will be maintained with air/oxygen (60%/40%) and desflurane. A remifentanyl infusion (0.05-2mcg/kg/min Ideal Body Weight) will be continued throughout the entire case with no further analgesics being administered. All patients will receive ondansetron 4 mg prior to the end of operation as well as additional antiemetics in the PACU as judged by the attending anesthesiologist. Patients will be awakened and extubated in the OR meeting standard extubation criteria. Once extubated all patients will then be transferred to the PACU where they will be assessed via the SPEEDs criteria 5 minutes after arrival and then every 15 minutes for the duration of their PACU stay. While in the PACU, all patients will be assessed for pain using the Visual Analog Scale. Pain will be treated as per our protocol with 0.2mg IV hydromorphone for mild pain (VAS 1-3), 0.4 mg IV hydromorphone for moderate pain (VAS 4-6), and 0.6 mg IV hydromorphone (VAS 7-10). As soon as a patient meets all the SPEEDs criteria he/she will be transferred to phase II of the recovery. In phase II, if need be, pain will be managed according to the following orders: 0.2mg intravenous hydromorphone for mild pain (VAS 1-3), 0.4 mg intravenous hydromorphone for moderate pain (VAS 4-6) and 0.6mg intravenous hydromorphone for severe pain (VAS 7-10).

The patient's readiness for discharge will be our primary outcome. Each patient will be assessed within 5 minutes of arriving in the PACU and then every 15 minutes thereafter until subject reaches maximum score. The assessment will be done using the SPEEDs criteria, which has recently been shown to be as specific and more sensitive for phase 1 nursing interventions and therefore more accurate in predicting which patients are fast-track eligible as compared to the standard Modified Aldrete 2 and Fast-Track criteria (38).

The secondary outcomes will include:

1. Post-operative pain scores a. Assessed every 15 minutes during the recovery period using the Visual and Numerical Analog Scales for 2 hours and then every 4 hours thereafter until discharge.
2. Time to first rescue medication a. 0.2mg intravenous hydromorphone for mild pain (VAS 1-3) b. 0.4mg intravenous hydromorphone for moderate pain (VAS 4-6) c. 0.6 mg intravenous hydromorphone for severe pain (VAS 7-10)
3. Total dosage of post-operative opioids given.
4. Incidence of post operative nausea and vomiting and need for additional antiemetics.
5. Phase II satisfaction survey:

a. This will focus on three of the following factors rated on a scale of 1 to 5, with 1 being dissatisfied/unlikely while 5 being most satisfied/very likely.

i. How satisfied are you with the overall experience? ii. How likely are you to recommend this anesthetic and analgesic to others? iii. How likely would you ask for a similar anesthetic and analgesic in the future if need be? f) Concentration of the plasma stress markers including cortisol, norepinephrine, epinephrine, and C Reactive Protein (CRP).

a. Changes in mediator levels in the IV acetaminophen versus placebo groups will be compared. Plasma samples will be collected before administration of any drug (after placement of IV lines), before incision, and 60 minutes after arrival in PACU. Blood \[15millLiters\] will be collected at the time points described above from an additional intravenous catheter placed in the patient's arm. These specimens will be placed in vacutainer tubes with no anti-coagulant. Blood will be drawn with a syringe attached directly to the angiocatheter which has been placed intravenously. To prevent hemolysis, blood will be transferred without a needle, to a vacutainer whose top has been removed. The vacutainer top will be replaced and specimens labeled with study name, subject's study IDentification number, sample number (1, 2, 3,), and dated. Bloods from the first two time points will be kept refrigerated until the final sample is obtained postoperatively. They will be centrifuged, serum removed, aliquoted and stored at -80 degrees C until analysis. All samples will be run in duplicate on with plates and reagents of the same lot. Any samples varying greater than 15% between duplicates

Conditions

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Recovery Following Cholecystectomy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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normal saline

Patients will receive 100 milliliters of normal saline with the first dose given preoperatively in the holding area followed by re-dosing every four hours from that point up to a maximum of 4 doses in 24 hours. Blinded medication will be prepared by research pharmacist.

Group Type ACTIVE_COMPARATOR

normal saline

Intervention Type DRUG

100mL of normal saline every 4 hours to a maximum administration of 400mL

acetaminophen

Patients 50kg or more will receive either 1000mg IV acetaminophen with the first dose given preoperatively in the holding area followed by re-dosing every four hours from that point up to a maximum of 4 doses or 4000mg in 24 hours. Patients \<50 kg will receive 12.5mg/kg to a maximum of 75 mg /per kg/per day as per the label dose with repeat dosing Q4 hours. Blinded medication will be prepared by research pharmacist in 100mL of normal saline

Group Type EXPERIMENTAL

Acetaminophen

Intervention Type DRUG

patients 50kg or more receive1000mg in 100milliliters of normal saline every 4 hours to a maximum dose 4000mg/24 hours. \<50kg receive 12.5mg/kg to a maximum of 75mg/kg/24 hours.

Interventions

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Acetaminophen

patients 50kg or more receive1000mg in 100milliliters of normal saline every 4 hours to a maximum dose 4000mg/24 hours. \<50kg receive 12.5mg/kg to a maximum of 75mg/kg/24 hours.

Intervention Type DRUG

normal saline

100mL of normal saline every 4 hours to a maximum administration of 400mL

Intervention Type DRUG

Other Intervention Names

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Ofirmev placebo

Eligibility Criteria

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Inclusion Criteria

* Undergoing ambulatory laparoscopic cholecystectomy.
* American Society of Anesthesiologists physical status 1, 2 or 3.-

Exclusion Criteria

* Cognitively impaired (by history) and unable or unwilling to consent
* Chronic steroid or opioid user (as prescribed for a chronic systemic illness)
* Parturient or nursing mother. Patients who have been informed by a physician that they have liver or kidney disease
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mallinckrodt

INDUSTRY

Sponsor Role collaborator

Rutgers, The State University of New Jersey

OTHER

Sponsor Role lead

Responsible Party

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Michal Gajewski

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Michal Gajewski, Do

Role: PRINCIPAL_INVESTIGATOR

Rutgers, State University of New Jersey

Locations

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New Jersey Medical School

Newark, New Jersey, United States

Site Status

University Hospital

Newark, New Jersey, United States

Site Status

New York Methodist Hospital

Brooklyn, New York, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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20150002613

Identifier Type: -

Identifier Source: org_study_id