Abdominal Wall Hernia, Pancreatic Diseases, Bowel Disease, Gastric Disease
Conditions
Keywords
Post-operative pain, Major abdominal surgery, Colorectal surgery, Gastric surgery
Brief summary
Number of patients with unsatisfactory pain relief defined as average visual analog scale (VAS) more than 5 with or without requirement of IVPCA for pain relief during the first 48 hours postoperative period will be compared between the two groups and form the primary outcome for the study. Postoperative pain intensity will be measured by Visual Analog Scale (VAS) with 0- being no pain and 10-being maximum pain and the analgesic efficacy in both groups will also be evaluated by the amount of total narcotic consumption (measured with IV morphine equivalent doses of analgesics used to provide pain relief).
Detailed description
In response to an increased focus on improving patient outcomes and satisfaction with surgical care, a growing body of clinical evidence has recently been dedicated to enhanced recovery after surgery (ERAS) protocols. These evidence-based perioperative pathways aim to optimize patients undergoing surgery in the preoperative, intraoperative, and postoperative periods. ERAS protocols have incorporated the use of multimodal analgesia to minimize the use of intra- and postoperative opioid analgesics. Lidocaine, ketamine, magnesium, gabapentin, acetaminophen and non-steroidal anti-inflammatory drugs are some of the adjuvant analgesics used in combination with regional blocks to optimize analgesia and recovery. Multimodal analgesia has dependably been shown to significantly reduce postoperative opioid requirements as well as opioid-related side effects such as postoperative nausea and vomiting. Both oral and intravenous acetaminophen preparations have been shown to be useful adjuvants in multimodal analgesia. Intravenous acetaminophen has been of interest for its utility in post-surgical patients, who have not yet been cleared for oral intake. Intravenous acetaminophen should also be preferred over oral acetaminophen in patients after major abdominal surgery where absorption of medications given through oral route is erratic. Although the efficacy of intravenous acetaminophen as a postoperative pain adjunct is known, its exact role in ERAS protocols and non-narcotic multimodal analgesic regimens for major abdominal surgery has not been studied in randomized clinical trials to define its efficacy. The primary goal of this study is to assess the utility of a postoperative intravenous acetaminophen dosing schedule in minimizing postoperative pain, opioid consumption and opioid-related side effects. We also aim to study overall patient satisfaction and cost-effectiveness (direct and indirect costs) of this regimen as part of ERAS protocol at a large tertiary medical center.
Interventions
The interventional group will receive 1 gram intravenous acetaminophen at the start of wound closure to be repeated every 6 hours for 48 hours postoperatively
DRUGSodium Chloride 0.9%, Intravenous
The placebo group will be given an intravenous placebo of saline solution at wound closure and repeated every 6 hours for 48 hours postoperatively.
Sponsors
Mallinckrodt
Kathirvel Subramaniam
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Participant, care provider, outcomes assessor and investigator are all blinded to the treatment allocation
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male or Female * 18 years of age or older * patients scheduled for elective colorectal, pancreatic, and other major abdominal procedure. * Patient consent will be obtained preoperatively for eligible study participants.
Exclusion criteria
* Patients who refuse to participate in the study or part of any other enhanced recovery after surgery (ERAS) research protocol. * Patients with a documented allergy to acetaminophen. * Chronic alcoholism * Hypovolemia * Chronic malnutrition * Preoperative renal insufficiency (creatinine clearance less than or equal to 30ml/min) or hemodialysis * Patients with a history of hepatic impairment, history of hepatic impairment or active hepatic disease * severe chronic pain condition that required daily preoperative opioid dependence * Patients with pre-existing dementia and/or other neuropsychiatric conditions impeding accurate assessment of pain scores or other study measures will be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Postoperative Pain Intensity | PACU admission every thirty minutes until discharge to the floor and thereafter every four hours for first 24-hour, then every six hours until 48 hours and then every twelve hours until 72 hours postoperatively. | Number of patients with unsatisfactory pain relief defined as average numeric rating scale (NRS) more than 5 will be compared between the two groups. This may include patients using IVPCA for pain relief during the first 48 hours postoperative. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Readiness for Discharge From Post Anesthesia Care Unit (PACU) | From time of PACU admission until the time of discharge, assessed up to 24 hours postoperatively | The time from PACU admission to PACU discharge to the floor will be measured. |
| Time to Bowel Movement | From time patient left operating room until the time of first documented bowel movement, assessed up to hospital discharge | The time it takes for the first bowel movement postoperatively will be measured. |
| Time to Oral Intake | From date of randomization until the date of first documented oral intake, assessed up to 72 hours postoperatively | The time it takes for the patient to ingest orally post-surgery will be measured. |
| Time to Ambulation | From date of PACU admission until the date of first documented ambulation, assessed up to 72 hours postoperatively | The time it takes for the patient to successfully ambulate post-surgery will be measured. |
| Time to Hospital Discharge | From date of randomization until the date of hospital discharge or 30 days postoperatively, whichever comes first | The time it takes for the patient to be fully discharged from the hospital post-surgery will be measured. |
| Total Post-operative Narcotic Consumption | From time of PACU admission until the time of discharge and 72-hours postoperatively, whichever comes first | Rescue analgesia will be given according to institutional pain management protocol. Unit of Measure recorded as OME (Oral Morphine Equivalent) consumption in mg. |
| Patient Satisfaction | These measurements will be taken at time of discharge up to 30 days, whichever comes first | Overall patient satisfaction as well as satisfaction relating to pain management and cost analyses will be measured. These will be measured with a numerical rating scale (NRS) with 0- being worst satisfaction and 10 - best satisfaction. |
| Intensive Care Delirium Screening Checklist (ICDSC) | The delirium scores will first be measured every 12 hours for 72 hours after surgery. | Number of patients who score greater than a 4 on the 0-8 point ICDSC scale to assess delirium scores. 8 separate levels of signs for delirium assessed (1. altered level of consciousness, 2. inattention, 3. disorientation, 4. hallucination, delusion, or psychosis, 5. psychomotor agitation or retardation, 6. inappropriate speech or mood, 7. sleep-wake cycle disturbance, 8. symptom fluctuation), with 0 points awarded when patient does not exhibit above signs of delirium and 1 point awarded per confirmed sign of delirium. Score then totaled, 0 = normal, 1-3 = subsyndromal delirium, 4-8 = delirium. |
| Post-operative Nausea | These will be evaluated from the time of PACU admission until 72 hours postoperatively. | Nausea will be evaluated by nausea score from 0 to 10, with 0 equaling no nausea and 10 equaling the worst nausea imaginable. |
| Post-operative Emesis | These will be evaluated from the time of PACU admission until 72 hours postoperatively. | Frequency of emesis and rescue antiemetic requirement will be documented |
| SF-12 Health Survey | These measurements will take place at 30-days post hospital discharge | Survey to assess patient's overall health (via a combination of mental and physical health assessment) at 30 days post-discharge. Two summary scores are reported from the SF-12 - a mental component score (MCS-12) and a physical component score (PCS-12). The scores may be reported as Z-scores (difference compared to the population average, measured in standard deviations). The United States population average PCS-12 and MCS-12 are both 50 points. The United States population standard deviation is 10 points. So each 10 increment of 10 points above or below 50, corresponds to one standard deviation away from the average |
| Number of Participants With Readmission to the Hospital | From the time of consent until 30 days post-operatively | If the patient is readmitted to the hospital after being fully discharged, the event will be recorded. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Acetaminophen Injectable Product Acetaminophen group: Half of subjects enrolled will be randomized to the acetaminophen group
Acetaminophen Injectable Product: The interventional group will receive 1 gram intravenous acetaminophen at the start of wound closure to be repeated every 6 hours for 48 hours postoperatively | 76 |
| Sodium Chloride 0.9%, Intravenous Sodium Chloride 0.9% group: Half of subjects enrolled will be randomized to the acetaminophen group
Sodium Chloride 0.9%, Intravenous: The placebo group will be given an intravenous placebo of saline solution at wound closure and repeated every 6 hours for 48 hours postoperatively. | 78 |
| Total | 154 |
Baseline characteristics
| Characteristic | Acetaminophen Injectable Product | Sodium Chloride 0.9%, Intravenous | Total |
|---|---|---|---|
| Age, Continuous | 62 years | 64 years | 63 years |
| American Society of Anesthesiologists Classification II | 17 Participants | 18 Participants | 35 Participants |
| American Society of Anesthesiologists Classification III | 57 Participants | 55 Participants | 112 Participants |
| American Society of Anesthesiologists Classification IV | 2 Participants | 5 Participants | 7 Participants |
| Atrial fibrillation | 2 Participants | 2 Participants | 4 Participants |
| Basal Metabolic Index | 27.7 kg/m^2 | 28.25 kg/m^2 | 28.15 kg/m^2 |
| Charlson Comorbidity Index 0 | 44 Participants | 41 Participants | 85 Participants |
| Charlson Comorbidity Index 1 | 4 Participants | 10 Participants | 14 Participants |
| Charlson Comorbidity Index 2 | 23 Participants | 24 Participants | 47 Participants |
| Charlson Comorbidity Index >2 | 5 Participants | 3 Participants | 8 Participants |
| Congestive failure | 1 Participants | 3 Participants | 4 Participants |
| Coronary artery disease | 2 Participants | 4 Participants | 6 Participants |
| Diabetes | 4 Participants | 3 Participants | 7 Participants |
| Hypertension | 10 Participants | 16 Participants | 26 Participants |
| Malignancy | 28 Participants | 23 Participants | 51 Participants |
| Number of participants taking medications for mental health | 15 Participants | 27 Participants | 42 Participants |
| Preoperative serum creatinine | 0.8 (mg/dL) | 0.82 (mg/dL) | 0.81 (mg/dL) |
| Pulmonary disease | 3 Participants | 6 Participants | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) White | 70 Participants | 73 Participants | 143 Participants |
| Region of Enrollment United States | 76 participants | 78 participants | 154 participants |
| Sex: Female, Male Female | 40 Participants | 44 Participants | 84 Participants |
| Sex: Female, Male Male | 36 Participants | 34 Participants | 70 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 76 | 0 / 78 |
| other Total, other adverse events | 8 / 76 | 8 / 78 |
| serious Total, serious adverse events | 3 / 76 | 3 / 78 |
Outcome results
Primary
Postoperative Pain Intensity
Number of patients with unsatisfactory pain relief defined as average numeric rating scale (NRS) more than 5 will be compared between the two groups. This may include patients using IVPCA for pain relief during the first 48 hours postoperative.
Time frame: PACU admission every thirty minutes until discharge to the floor and thereafter every four hours for first 24-hour, then every six hours until 48 hours and then every twelve hours until 72 hours postoperatively.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acetaminophen Injectable Product | Postoperative Pain Intensity | 33 Participants |
| Sodium Chloride 0.9%, Intravenous | Postoperative Pain Intensity | 42 Participants |
Secondary
Intensive Care Delirium Screening Checklist (ICDSC)
Number of patients who score greater than a 4 on the 0-8 point ICDSC scale to assess delirium scores. 8 separate levels of signs for delirium assessed (1. altered level of consciousness, 2. inattention, 3. disorientation, 4. hallucination, delusion, or psychosis, 5. psychomotor agitation or retardation, 6. inappropriate speech or mood, 7. sleep-wake cycle disturbance, 8. symptom fluctuation), with 0 points awarded when patient does not exhibit above signs of delirium and 1 point awarded per confirmed sign of delirium. Score then totaled, 0 = normal, 1-3 = subsyndromal delirium, 4-8 = delirium.
Time frame: The delirium scores will first be measured every 12 hours for 72 hours after surgery.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acetaminophen Injectable Product | Intensive Care Delirium Screening Checklist (ICDSC) | 0 Participants |
| Sodium Chloride 0.9%, Intravenous | Intensive Care Delirium Screening Checklist (ICDSC) | 0 Participants |
Secondary
Number of Participants With Readmission to the Hospital
If the patient is readmitted to the hospital after being fully discharged, the event will be recorded.
Time frame: From the time of consent until 30 days post-operatively
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Acetaminophen Injectable Product | Number of Participants With Readmission to the Hospital | 9 Participants |
| Sodium Chloride 0.9%, Intravenous | Number of Participants With Readmission to the Hospital | 10 Participants |
Secondary
Patient Satisfaction
Overall patient satisfaction as well as satisfaction relating to pain management and cost analyses will be measured. These will be measured with a numerical rating scale (NRS) with 0- being worst satisfaction and 10 - best satisfaction.
Time frame: These measurements will be taken at time of discharge up to 30 days, whichever comes first
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Acetaminophen Injectable Product | Patient Satisfaction | Patient satisfaction score, overall | 10 score on a scale |
| Acetaminophen Injectable Product | Patient Satisfaction | Patient Satisfaction score, pain management | 10 score on a scale |
| Sodium Chloride 0.9%, Intravenous | Patient Satisfaction | Patient satisfaction score, overall | 10 score on a scale |
| Sodium Chloride 0.9%, Intravenous | Patient Satisfaction | Patient Satisfaction score, pain management | 10 score on a scale |
Secondary
Post-operative Emesis
Frequency of emesis and rescue antiemetic requirement will be documented
Time frame: These will be evaluated from the time of PACU admission until 72 hours postoperatively.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Acetaminophen Injectable Product | Post-operative Emesis | Emesis incidence 0-72 hours | 12 Participants |
| Acetaminophen Injectable Product | Post-operative Emesis | Antiemetic use | 31 Participants |
| Sodium Chloride 0.9%, Intravenous | Post-operative Emesis | Emesis incidence 0-72 hours | 14 Participants |
| Sodium Chloride 0.9%, Intravenous | Post-operative Emesis | Antiemetic use | 45 Participants |
Secondary
Post-operative Nausea
Nausea will be evaluated by nausea score from 0 to 10, with 0 equaling no nausea and 10 equaling the worst nausea imaginable.
Time frame: These will be evaluated from the time of PACU admission until 72 hours postoperatively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Acetaminophen Injectable Product | Post-operative Nausea | Nausea score POD 1 (am visit) | 1.13 score on a scale | Standard Deviation 2.82 |
| Acetaminophen Injectable Product | Post-operative Nausea | Nausea score POD 1 (pm visit) | 0.49 score on a scale | Standard Deviation 1.54 |
| Acetaminophen Injectable Product | Post-operative Nausea | Nausea score POD 2 (am visit) | 0.71 score on a scale | Standard Deviation 1.97 |
| Acetaminophen Injectable Product | Post-operative Nausea | Nausea score POD 2 (pm visit) | 0.55 score on a scale | Standard Deviation 1.7 |
| Acetaminophen Injectable Product | Post-operative Nausea | Nausea score POD 3 (am visit) | 0.32 score on a scale | Standard Deviation 1.37 |
| Acetaminophen Injectable Product | Post-operative Nausea | Nausea score POD 3 (pm visit) | 0.56 score on a scale | Standard Deviation 1.77 |
| Sodium Chloride 0.9%, Intravenous | Post-operative Nausea | Nausea score POD 3 (am visit) | 0.66 score on a scale | Standard Deviation 2.18 |
| Sodium Chloride 0.9%, Intravenous | Post-operative Nausea | Nausea score POD 1 (am visit) | 0.60 score on a scale | Standard Deviation 1.76 |
| Sodium Chloride 0.9%, Intravenous | Post-operative Nausea | Nausea score POD 2 (pm visit) | 0.69 score on a scale | Standard Deviation 2.36 |
| Sodium Chloride 0.9%, Intravenous | Post-operative Nausea | Nausea score POD 1 (pm visit) | 0.92 score on a scale | Standard Deviation 2.53 |
| Sodium Chloride 0.9%, Intravenous | Post-operative Nausea | Nausea score POD 3 (pm visit) | 0.78 score on a scale | Standard Deviation 2.42 |
| Sodium Chloride 0.9%, Intravenous | Post-operative Nausea | Nausea score POD 2 (am visit) | 0.75 score on a scale | Standard Deviation 2.39 |
Secondary
SF-12 Health Survey
Survey to assess patient's overall health (via a combination of mental and physical health assessment) at 30 days post-discharge. Two summary scores are reported from the SF-12 - a mental component score (MCS-12) and a physical component score (PCS-12). The scores may be reported as Z-scores (difference compared to the population average, measured in standard deviations). The United States population average PCS-12 and MCS-12 are both 50 points. The United States population standard deviation is 10 points. So each 10 increment of 10 points above or below 50, corresponds to one standard deviation away from the average
Time frame: These measurements will take place at 30-days post hospital discharge
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Acetaminophen Injectable Product | SF-12 Health Survey | SF 12 Physical score | 38.72 Z-scores (difference compared to the pop |
| Acetaminophen Injectable Product | SF-12 Health Survey | SF 12 Mental score | 54.02 Z-scores (difference compared to the pop |
| Sodium Chloride 0.9%, Intravenous | SF-12 Health Survey | SF 12 Physical score | 38.07 Z-scores (difference compared to the pop |
| Sodium Chloride 0.9%, Intravenous | SF-12 Health Survey | SF 12 Mental score | 52.08 Z-scores (difference compared to the pop |
Secondary
Time to Ambulation
The time it takes for the patient to successfully ambulate post-surgery will be measured.
Time frame: From date of PACU admission until the date of first documented ambulation, assessed up to 72 hours postoperatively
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Acetaminophen Injectable Product | Time to Ambulation | 18.82 hours |
| Sodium Chloride 0.9%, Intravenous | Time to Ambulation | 17.38 hours |
Secondary
Time to Bowel Movement
The time it takes for the first bowel movement postoperatively will be measured.
Time frame: From time patient left operating room until the time of first documented bowel movement, assessed up to hospital discharge
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Acetaminophen Injectable Product | Time to Bowel Movement | 46.30 hours |
| Sodium Chloride 0.9%, Intravenous | Time to Bowel Movement | 64.66 hours |
Secondary
Time to Hospital Discharge
The time it takes for the patient to be fully discharged from the hospital post-surgery will be measured.
Time frame: From date of randomization until the date of hospital discharge or 30 days postoperatively, whichever comes first
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Acetaminophen Injectable Product | Time to Hospital Discharge | 4.08 days |
| Sodium Chloride 0.9%, Intravenous | Time to Hospital Discharge | 4.94 days |
Secondary
Time to Oral Intake
The time it takes for the patient to ingest orally post-surgery will be measured.
Time frame: From date of randomization until the date of first documented oral intake, assessed up to 72 hours postoperatively
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Acetaminophen Injectable Product | Time to Oral Intake | 12.15 hours |
| Sodium Chloride 0.9%, Intravenous | Time to Oral Intake | 9.40 hours |
Secondary
Time to Readiness for Discharge From Post Anesthesia Care Unit (PACU)
The time from PACU admission to PACU discharge to the floor will be measured.
Time frame: From time of PACU admission until the time of discharge, assessed up to 24 hours postoperatively
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Acetaminophen Injectable Product | Time to Readiness for Discharge From Post Anesthesia Care Unit (PACU) | 129.00 minutes |
| Sodium Chloride 0.9%, Intravenous | Time to Readiness for Discharge From Post Anesthesia Care Unit (PACU) | 152.50 minutes |
Secondary
Total Post-operative Narcotic Consumption
Rescue analgesia will be given according to institutional pain management protocol. Unit of Measure recorded as OME (Oral Morphine Equivalent) consumption in mg.
Time frame: From time of PACU admission until the time of discharge and 72-hours postoperatively, whichever comes first
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Acetaminophen Injectable Product | Total Post-operative Narcotic Consumption | 24-48 hours | 31.3 mg |
| Acetaminophen Injectable Product | Total Post-operative Narcotic Consumption | 0-48 hours | 74 mg |
| Acetaminophen Injectable Product | Total Post-operative Narcotic Consumption | 48-72 hours | 30 mg |
| Acetaminophen Injectable Product | Total Post-operative Narcotic Consumption | 0-72 hours | 105.00 mg |
| Acetaminophen Injectable Product | Total Post-operative Narcotic Consumption | 0-24 hours | 27.4 mg |
| Sodium Chloride 0.9%, Intravenous | Total Post-operative Narcotic Consumption | 0-72 hours | 127.1 mg |
| Sodium Chloride 0.9%, Intravenous | Total Post-operative Narcotic Consumption | 0-24 hours | 36 mg |
| Sodium Chloride 0.9%, Intravenous | Total Post-operative Narcotic Consumption | 24-48 hours | 45 mg |
| Sodium Chloride 0.9%, Intravenous | Total Post-operative Narcotic Consumption | 48-72 hours | 37.5 mg |
| Sodium Chloride 0.9%, Intravenous | Total Post-operative Narcotic Consumption | 0-48 hours | 88.8 mg |