Comparison of Opioid-Free Anesthesia Versus Opioid-Containing Anesthesia for Elective Laparoscopic Surgery (COFA: LAP): A Protocol Measuring Recovery Outcomes
Abstract
:1. Introduction
2. Experimental Design
2.1. Aim
2.2. Objective
- Post-operative complications of medication administration including:
- ○
- Respiratory depression;
- ○
- Nausea and vomiting;
- ○
- Delirium/hallucinations;
- ○
- Pruritus;
- ○
- Participant pain scores;
- ○
- Functional activity scores;
- ○
- Sedation level;
- ○
- Local anesthetic toxicity.
- The use of analgesia:
- ○
- Time post-operatively to first analgesia;
- ○
- Type of analgesia;
- ○
- Oral Morphine Equivalent Daily Dose (OMEDD).
- Time until post-operative mobilization.
- Length-of-stay in PACU.
- Hospital length-of-stay.
- Peri-operative adverse events.
3. Procedure
3.1. Inclusion, Exclusion, Recruitment and Consent
3.2. Sample Size, Randomization and Blinding
3.2.1. Sample Size
3.2.2. Randomization
3.2.3. Blinding
3.3. Treatment Regimen
3.3.1. Intra-Operative Participant Medication
3.3.2. Post-Operative Participant Assessment
3.4. Data Collection
3.4.1. Participant Documentation
- QoR-15 questionnaire (baseline and 24-h post-operatively).
- Preoperative anesthetic clinic assessment form.
- AARK.
- Post-anesthetic care unit (PACU) documents.
- National In-patient Medication Charts (NIMC).
- Queensland Hospital Admitted Patient Data Collection.
- Intravenous Patient Controlled Analgesia Order—Adult.
- Analgesia monitoring forms, intravenous, PCA, epidural and regional analgesia.
- Queensland Adult Deterioration Detection System (Q-ADDS).
- Clinical notes.
3.4.2. Electronic Data Handling
3.5. Measures and Statistics
3.5.1. Measures
3.5.2. Statistical Methods
4. Expected Results
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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How Have you Been Feeling in the Last 24 h? (0 to 10, where 0 = none of the time [poor] and 10 = all of the time [excellent] | ||||||||||||||
1. | Able to breathe easily | None of the time | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | All of the time |
2. | Able to enjoy food | None of the time | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | All of the time |
3. | Feeling rested | None of the time | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | All of the time |
4. | Have had a good sleep | None of the time | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | All of the time |
5. | Able to look after personal toilet and hygiene unaided | None of the time | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | All of the time |
6. | Able to communicate with family or friends | None of the time | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | All of the time |
7. | Able to get support from hospital doctors and nurses | None of the time | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | All of the time |
8. | Able to do usual home activities | None of the time | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | All of the time |
9. | Feeling comfortable and in control | None of the time | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | All of the time |
10. | Having a feeling of general well-being | None of the time | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | All of the time |
How Have you Had Any of the Following in the Last 24 h? (0 to 10, where 0 = none of the time [excellent] and 10 = all of the time [poor] | ||||||||||||||
1. | Moderate pain | None of the time | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | All of the time |
2. | Severe pain | None of the time | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | All of the time |
3. | Nausea or vomiting | None of the time | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | All of the time |
4. | Feeling worried or anxious | None of the time | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | All of the time |
5. | Feeling sad or depressed | None of the time | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | All of the time |
Inclusion | Exclusion |
---|---|
Aged 18–65 years | Pregnant women |
Booked for elective laparoscopic cholecystectomy or tubal ligation (with or without oophorectomy | Body Mass Index > 35 |
Independent capacity to consent to participate in the trial | Allergy to opioids |
American Society of Anesthesiologists (ASA) physical health score of I-II | Allergy to adjuvant drugs |
Persistent opioid use. Patients with OMEDD greater than 0 during previous week pre-op and taken for seven successive days or more including recreational drug use. | |
Non-elective surgery | |
Non-English speaking |
Step 1 | The research nurse investigator will liaise with the theater booking team to identify potentially eligible patients scheduled on theater lists. |
Step 2 | At the patient’s pre-anesthetic appointment, the research nurse investigator will undertake an initial screening of those patient’s clinical records for inclusion and exclusion criteria. |
Step 3 | Potentially eligible patients will then be approached by the research nurse and the project outlined with them. Patients who initially indicate interest will be provided with an information sheet; the researcher nurse will talk about the project broadly and encourage the patient to ask questions. The research nurse will contact the principal investigator if response clarification is required. |
Step 4 | Those patients who have been provided with an information sheet will then see the anesthetist who will explain in detail the project, the mechanism by which OFA works, and the process of randomization. |
Step 5 | Patients will be assured that the treating doctors will follow all usual procedures to ensure the patient does not experience pain. That is, if it is evident that the patient is in pain, standard pain management protocols will be enacted during surgery and while the patient is in recovery. |
Step 6 | If the patient is comfortable with participation, the formal consent procedures will be undertaken. The random allocation as to whether the participant receives OFA or standard anesthesia will be explained to participants. It will also be explained that participants can choose to withdraw consent at any time and that the right of any participant to refuse to participate in the trial at any time without giving reasons will be respected and will not prejudice their further treatment. |
Standard Anesthetic Induction | Opioid-Free Anesthesia Induction |
---|---|
Anxiolytic agent: 1 min prior to induction Midazolam 1–3 mg IV | Anxiolytic agent: 1 min prior to induction Midazolam 1–3 mg IV |
Fentanyl 1–2 mcg/kg IV | Clonidine 1–3 mcg/kg IV in 3 divided doses (at induction, mid-surgery and end) |
Lidocaine as per Table 5 | Lidocaine as per Table 5 |
Propofol 1–2.5 mg/kg IV bolus or as per programmed Target Control Infusion (TCI) | Propofol 1–2.5 mg/kg IV bolus or as per programmed Target Control Infusion (TCI) |
Magnesium sulphate 40 mg/kg (ideal body weight IBW) | |
Dexamethasone 8 mg IV and Parecoxib 40 mg IV | Dexamethasone 8 mg IV and Parecoxib 40 mg IV |
Neuromuscular blocker (NMB): Choice of any NMB is at the anesthetist’s discretion with NMB monitoring | Neuromuscular blocker (NMB): Choice of any NMB is at the anesthetist’s discretion with NMB monitoring |
Beta-blocker: Esmolol 10–50 mg IV bolus 20 s prior to intubation | |
On standby IV bolus medications:
| On standby IV bolus medications:
|
Maintenance of Standard Anesthesia | Maintenance of Opioid-Free Anesthesia |
---|---|
Lidocaine 1.5–2.5 mg/kg/h IVI as per Table 5 | Lidocaine 1.5–2.5 mg/kg/h IVI as per Table 5 |
Opioids analgesics:
| Magnesium sulphate: 20 mg/kg/h IVI (IBW) |
Sevoflurane/desflurane 0.6–0.8 MAC (Minimal alveolar concentration) with BIS (Bispectral Index Score) target around 40 or Propofol TCI infusion (TCI 4-8 mcg/mL) | Sevoflurane/desflurane 0.6–0.8 MAC (Minimal alveolar concentration) with BIS (Bispectral Index Score) target around 40 or Propofol TCI infusion (TCI 4–8mcg/mL) |
Ketamine 0.25–0.5 mg/kg IV (bolus before end of surgery) | |
Paracetamol IV 1000 mg IV | Paracetamol IV 1000 mg |
Clonidine 1–3 mcg/kg IV in 3 divided doses (at induction, mid surgery and end) | |
Ondansetron 4 mg IV | Ondansetron 4 mg IV |
Criteria | Points Scored |
---|---|
Hypoalbuminaemia | 1 point |
Heart block (first degree) | 1 point |
Participant on Vaughan–Williams Type 1 medications; sodium channel blocker | 1 point |
Deranged liver function or hemihepatectomy | 1 point |
CKD stages 3–4 | 1 point |
Age ≥ 65 years | 2 points |
Risk category | Sum of points scored |
Low risk | <2 points |
Intermediate risk | 2–3 points |
High risk | >3 points |
Low risk Administer a loading dose of 1.5 mg/kg by intravenous injection over 2–5 min. Maximum loading dose of 150 mg. Followed by a maintenance intravenous infusion at 2.5 mg/kg/h until local anesthetic infiltration by surgeon after wound closure. Intermediate risk Administer a loading dose of 1.25 mg/kg by intravenous injection over 2–5 min. Maximum loading dose of 150 mg. Followed by a maintenance intravenous infusion at a rate of 2 mg/kg/h until local anesthetic infiltration by surgeon after wound closure. High risk Administer a loading dose of 1 mg/kg by intravenous injection over 2–5 min. Maximum loading dose of 100 mg. Followed by a maintenance intravenous infusion at a rate of 1.5 mg/kg/h until local anesthetic infiltration by surgeon after wound closure. |
Measure | Definition | Assessment | ||
---|---|---|---|---|
Pre-op | Intra-op | Post-op | ||
Administration of all peri-operative analgesia (theater/PACU and ward/unit)
| Time, type and dose of all analgesia peri-operatively | x | x | |
Adverse events (AE) and serious adverse event (SAE) | Adverse events are considered “serious” if they threaten life or function. Due to the significant information they provide, serious adverse events require expedited reporting. Serious adverse events (SAEs) are defined as any AE which:
SAEs will be reported, whether or not it is considered related to trial treatment. | x | x | |
American Society of Anesthesiologists (ASA) score | The ASA score is a subjective assessment of a participant’s overall health that is based on five classes (I to V) and will be completed at eligibility screening. Only participants scoring I or II are eligible for the study.
| x | ||
Analgesia monitoring form | Hospital analgesia monitoring form for intravenous, PCA, epidural and regional analgesia—adult | x | x | x |
Clinical assessment | Standard clinical observations, temperature, pulse, blood pressure, physical examination and cognitive assessment, height and weight—BMI | x | x | x |
Complications–anesthetic and surgical | Yes/no plus text description of complication | x | x | |
Date and time discharged from hospital | Participant notes, discharge summary | x | ||
Date of surgery | Participant clinical notes | x | ||
Day 1 observations | Assessment conducted at 24 h (± two-hours) post-discharge from theater (i.e., admission to PACU time) on Day 1 post-operatively | x | ||
Delirium/hallucinations | Any evidence/report of = Yes | x | ||
Documentation confirming participant eligibility | Trial eligibility and consent form in participant notes | x | x | |
Duration of surgery | AARK times. | x | x | |
Functional activity scores | Scored A = activity unlimited, B = activity mild to moderately limited by pain, C = activity severely limited by pain. | x | x | |
Local anesthetic toxicity | Any evidence of symptoms = Yes | x | x | |
Medical history/comorbidities | Participant clinical notes- text description | x | ||
Medication administered | Intra-operative, PACU and post-operative list of medications, dose, route | x | x | |
Oral morphine equivalent daily dose (OMEDD) | Oral morphine equivalent daily dose (OMEDD) allows for comparison of other opioids from all routes, oral, sublingual, transdermal, parental or rectal preparations to be summed and converted to an equivalent total oral morphine daily dose. Calculated with the Faculty of Pain Medicine (FPM), Australia and New Zealand College of Anesthetists (ANZCA) Opioid Calculator Participant self-report of prescription or recreational use of opioids pre-surgery. OMEDD scores will be calculated at baseline (for eligibility criteria) and at Day 1 to include surgery, PACU and ward/home | x | x | x |
Overall length of stay (LOS) | LOS from theater start time to discharge from hospital (hours: minutes) | x | x | x |
PACU | Post-anesthetic care unit | |||
PACU LOS | PACU LOS from automated anesthetic record keeping (AARK) admission time to PACU discharge time | x | ||
Pain | Severity of pain is measured using the numerical rating scale, a points scale from zero to ten. Pain is documented as stated by the participant. 0 = no pain, 1 to 3 = mild pain, 4 to 6 = moderate pain and 7 to 10 = severe pain. | x | x | |
Pain score on Day 1 | 0 = no pain, 1 to 3 = mild pain, 4 to 6 = moderate pain and 7 to 10 = severe pain. | x | ||
Pain score–highest pain score recorded while in PACU | 0 = no pain, 1 to 3 = mild pain, 4 to 6 = moderate pain and 7 to 10 = severe pain. | x | ||
Participant demographics and clinical characteristics | Collected at baseline including: Date of birth (age) Gender Smoking status Medical history/comorbiditiesCurrent weight and height (Body Surface Area/Body Mass Index) | x | ||
Quality of recovery form (QoR-15) | Evaluation of post-operative recovery from the participant’s perspective with total QoR-15 score ranging from 0 (extremely poor recovery) to 150 (excellent recovery). Assessment at baseline and at 24-h post-operatively. | x | x | |
Sedation levels | Sedation scored as 0 = awake, 1 = mild (easy to rouse), 2 = moderate (rousable but unable to keep eyes open more than 10 s) and 3 = severe (difficult or unable to rouse) | x | ||
Time until post-operative mobilization | Time from admission to PACU until the time first mobilized | x | ||
Time admitted to PACU | Arrival time in PACU | x | ||
Type of surgery | Tubal ligation/cholecystectomy | x | x | |
Urinary complications | Urinary system complications | x | ||
Vital signs | All vital signs from baseline until hospital discharge including: Respiratory rate Blood pressure Oxygen saturation Pulse rate Temperature | x | x | x |
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Eidan, A.; Ratsch, A.; Burmeister, E.A.; Griffiths, G. Comparison of Opioid-Free Anesthesia Versus Opioid-Containing Anesthesia for Elective Laparoscopic Surgery (COFA: LAP): A Protocol Measuring Recovery Outcomes. Methods Protoc. 2020, 3, 58. https://doi.org/10.3390/mps3030058
Eidan A, Ratsch A, Burmeister EA, Griffiths G. Comparison of Opioid-Free Anesthesia Versus Opioid-Containing Anesthesia for Elective Laparoscopic Surgery (COFA: LAP): A Protocol Measuring Recovery Outcomes. Methods and Protocols. 2020; 3(3):58. https://doi.org/10.3390/mps3030058
Chicago/Turabian StyleEidan, Anthony, Angela Ratsch, Elizabeth A. Burmeister, and Geraldine Griffiths. 2020. "Comparison of Opioid-Free Anesthesia Versus Opioid-Containing Anesthesia for Elective Laparoscopic Surgery (COFA: LAP): A Protocol Measuring Recovery Outcomes" Methods and Protocols 3, no. 3: 58. https://doi.org/10.3390/mps3030058