MedPath

Multi-dose Acetaminophen for Patients Undergoing General Anesthesia

Phase 4
Terminated
Conditions
Recovery Following Cholecystectomy
Interventions
Drug: normal saline
Registration Number
NCT02832687
Lead Sponsor
Rutgers, The State University of New Jersey
Brief Summary

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

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

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
88
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
Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
normal salinenormal salinePatients 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.
acetaminophenAcetaminophenPatients 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
Primary Outcome Measures
NameTimeMethod
Readiness for Discharge2 hours following surgery

Number (percentage) of Participants with Readiness for Discharge (achieving discharge-readiness status at end of 2- hours post-surgery evaluated using the SPEEDs criteria: oxygen saturation, pain control, emesis control, extremity movement, dialogue, and stable vital signs.

Secondary Outcome Measures
NameTimeMethod
Number of Participants Requiring Additional Anti-emeticsFrom arrival in PACU for 2 hours or until achieving discharge-readiness, whatever comes first, an average of 1 hour

Number of Participants Requiring Additional Anti-emetics (anti-vomiting)

Total Dosage of Post Operative OpioidsFrom arrival in PACU for 2 hours or until achieving discharge-readiness, whatever comes first, an average of 1 hour.

Total dosage of post operative opioids (hydromorphone)

Number of Participants With Post Operative Nausea and VomitingFrom arrival in PACU for 2 hours or until achieving discharge-readiness, whatever comes first, an average of 1 hour

Number of Participants with Post Operative Nausea and Vomiting

Plasma Stress MarkersBefore administration of any drug (after placement of intravenous (IV) line), before surgical incision (in operating room (OR)), and 1 h after arrival in post-anesthesia care unit (PACU)

Concentration of the plasma stress markers including epinephrine, norepinephrine, cortisol, interleukins (IL) 6, 8 and 10.

The Level of C-reactive ProteinBefore administration of any drug (after placement of intravenous (IV) line), before surgical incision (in operating room (OR)), and 1 h after arrival in post-anesthesia care unit (PACU)

Concentration of the plasma C-reactive protein (CRP)

Time to Rescue Pain MedicationFrom arrival in PACU to the first dose of pain medication is given during 2 hours or until achieving discharge-readiness, whatever comes first, an average of 1 hour.

Time to the first dose of pain medication

Post Operative Pain ScoresEvery 15 min for 2 hours or until achieving discharge-readiness, whatever comes first, an average of 1 hour

Pain scores every 15 min for 2 hours or until achieving discharge-readiness, whatever comes first, an average of 1 hour.

Visual Analogue Scale (VAS) for pain was used: score on a scale from 0 (no pain) to 10 (worst pain) were recorded.

Patient Satisfaction SurveyFor patients going home the day of surgery the survey is given prior to departing the hospital (approx 5 hours post surgery). For those being admitted, the survey is given once discharge criteria are met in the PACU (approx 3 hours post surgery).

Survey asking patients about their satisfaction with the experience, pain control, and anesthetic rated on a 5 point Likert scale, with 1 being dissatisfied/unlikely and 5 being most satisfied/very likely. Subscales were summed to receive total score.

Trial Locations

Locations (3)

New Jersey Medical School

🇺🇸

Newark, New Jersey, United States

University Hospital

🇺🇸

Newark, New Jersey, United States

New York Methodist Hospital

🇺🇸

Brooklyn, New York, United States

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