SUPER-ERAS: Suboxone User Perioperative Early Referral and Enhanced Recovery After Surgery- Orthopaedic Trauma Surgery Population
Study Details
Study Description
Brief Summary
Suboxone treated patients present a unique challenge to providers during the perioperative period in terms of pain control. If the patient is taken off their prescribed suboxone 48 hours prior to the procedure, the opioid pain medication will function but the patient is exposed to the very medications originally responsible for their substance addiction. The discontinuation of suboxone can potentially lead to opioid addiction relapse in this situation (Anderson et al., 2017). If the patient remains on their suboxone, opioid pain medications can be ineffective or require very large dosages to control pain but the patient's risk of relapse may be lower (Anderson et al., 2017). Classic opioid pain medications prescribed by providers for post-operative pain control such as hydromorphone, morphine and fentanyl have lower affinity for the Mu 1 and 2 receptors when compared to buprenorphine. These medications are less effective or ineffective when given to a patient treated with Suboxone due to their inability to bind to the Mu receptor in the presence of buprenorphine. The only clinically used full agonist opioid with stronger affinity for the MU 1 and 2 receptors is sufentanil. In theory, sufentanil would be able to displace buprenorphine from the receptor and stimulate the receptor as a full agonist leading to predictable pain control. Through the Kappa receptor antagonism, buprenorphine may improve the treatment of opioid-induced hyperalgesia (Koppert W et al., 2005). Additional benefits may include buprenorphine's Kappa receptor antagonism may help in treating forms of depression and depression (Lalanne et al., 2014). At our institution, orthopedic trauma patients have a high incidence of suboxone use and make an ideal study population as they are often otherwise healthy. Our study compares opioid consumption in the perioperative period in patients taking suboxone on presentation to the operating room. The patients will randomized to receive conventional opioid based regimen versus buprenorphine and sufentanil based opioid regimen. The goal of the study is to determine if the combination of buprenorphine and sufentanil based pain control is superior to classic opioid treatment strategies in patients taking suboxone while presenting for orthopedic trauma surgery.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Detailed Description
Primary Null Hypothesis A combination sufentanil and buprenorphine based pain control regimen will not result in lower morphine equivalent requirements for pain control when compared to a classic fentanyl and hydromorphone based regimen.
Secondary Working Hypothesis Patient satisfaction survey mean satisfaction scores will be higher in the buprenorphine and sufentanil treated group when compared to the classic fentanyl and hydropmorphone treated group.
Secondary Null Hypothesis Patient satisfaction surveys mean scores will not be significantly different in the buprenorphine and sufentanil treated group when compared to the classic fentanyl and hydropmorphone treated group.
Tertiary Working Hypothesis Patients will have significantly lower rates of relapse as defined by follow up with their home suboxone clinic at 2 and 4 weeks.
Tertiary Null Hypothesis Patients have equivalent rates of relapse as defined by follow up with their home suboxone cliic at 2 and 4 weeks.
Trauma Protocol Arm Inclusion Criteria
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Orthopaedic trauma patient with history of suboxone use for greater than 30 days. Trauma must involve major long bone fracture(s) (femur, tibia, fibula, humerus, radius, ulna)
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Must have taken suboxone in the last 24 hours and have participated in addiction treatment for greater than one month.
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Age 18-65
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ASA I-III
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Willing to participate in post-operative psychiatric care
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Glascow Coma Scale 15 Exclusion Criteria
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Severe renal disease (Creatinine clearance < 30) 2. Severe liver disease (AST/ALT greater than 3 times normal, bilirubin and INR WNL) 3. Acute Ethanol Intoxication (serum ethanol > 0.080) 4. Severe distracting injury that is close to pain levels expected from the orthopedic trauma (Ex surgical abdominal process, neurosurgical process, massive soft tissue trauma) 5. Pregnancy Design- After determining the patient qualifies for the study using the inclusion and exclusion criteria outlined above, the patient would then be taken through the informed consent process by one of the co-investigators. The orthopedics group at West Virginia University will be responsible for the informed consent process. The co-investigator would then use a block randomization table to assign the patient to standard (control) treatment versus IV buprenorphine plus IV sufentanil treatment group. The appropriate order set would then be selected in EPIC by the anesthesia department depending on the results of the randomization. Induction of anesthesia, anxiolysis and hypnosis would be at the discretion of the assigned anesthesiologist. Ketamine would be excluded as an option for maintenance of general anesthesia due to its profound analgesic properties. The control group would receive fentanyl 0.5mcg/kg q10 minute PRN, ketorolac 0.5mg/kg up to 30mg max IV, and acetaminophen 1000mg IV for pain control intraoperatively. The patient would then be treated with hydromorphone 0.005mg/kg q10 minutes (max single dose 1mg) in the post-anesthesia recovery unit (PACU) until their pain was described as manageable or the patient reported they were comfortable. The patient would then receive hydromorphone 0.005 mg/kg (max single dose 1mg) q1hr PRN, 1 gram acetaminophen IV scheduled q6hr, and methocarbamol 750mg QID following discharge from the PACU and transfer to the hospital floor. The patient would then be converted to oxymorphone 10mg (Roxicodone) q4hr PRN and 975 mg PO APAP scheduled for pain control on hospital day number 2. The patients would receive their home dose of suboxone on hospital day number 2. On hospital day number 3, patients would be transitioned to an increased dose of their Suboxone for pain control in preparation for discharge. At any time during admission the patient feels as if their pain is uncontrolled and comfort could not be achieved, the anesthesia pain service would evaluate the patient and order sufentanil PCA while discontinuing other opioid therapy. This treatment would be considered a rescue therapy and the patient would be removed from the study arm. The buprenorphine-sufentanil group would receive sufentanil 0.01 mcg/kg q10 min PRN, IV ketorolac 0.5mg/kg up to 30mg max and IV acetaminophen 15mg/kg up to 1000mg for pain control intraoperatively. In the PACU, IV buprenorphine 0.3mg IV q30 minutes would be given as the first line choice for pain control for 3 doses. IV PCA sufentanil would be used as a second line therapy if patient comfort is not achieved by IV buprenorphine alone. The patient would then receive 0.3 mg buprenorphine IV Q6hr PRN, scheduled IV acetaminophen 1 gram for 24 hours and methocarbamol 750mg QID after discharge from the PACU and transfer to the hospital floor on hospital day 1. The patient would then be converted to buprenorphine 2mg q6hr PRN and 975 gram PO APAP scheduled for pain control on hospital day number 2. The patient would receive their home dose of suboxone starting on hospital day number 2. On hospital day number 3, patients would be transitioned to an increased dose of their suboxone for pain control as determined by psychiatry in preparation for discharge.
Post-operatively both groups would receive psychiatric consult and PT/OT consult. Data on opioid consumption for the intra-operative period and post-operative period as well as post-operative pain scores will be recorded and analyzed for comparison. Morphine equivalents used per hour and per 24 hours would be analyzed as a primary endpoint. A patient pain satisfaction survey would be distributed and collected from both groups on hospital day #3. A copy of the survey is attached. Data on length of stay, pain scores, and ED readmission for pain control would also be recorded and analyzed. Patients would be discharged on increased dose suboxone for 2 weeks for post-operative pain control. The patients would then transition back to their normal suboxone maintenance dose. A follow up phone call would be made at 2 and 4 weeks to the home clinic to assess patient follow up and potential relapse.
Statistical Plan This is a randomized controlled trial. Patients will be randomly assigned to either the control or treatment group, with equal allocation using block randomization.
We will use univariate statistics (e.g. mean, median, standard deviation, interquartile range) to summarize the collected data. Balance between the two groups for key patient variables will be assessed using a two-sided two-sample t-test using unequal variances and the Welch modification to the degrees of freedom. For categorical variables, the Chi-square test will be used. If non-parametric tests or exact methods are required, we will use the Mann-Whitney U test and the Fisher exact test as appropriate.
The primary comparison of total opioid consumption between the two groups will be assessed using Student's t-test. Statistical significance will be assessed using a two-sided test with an alpha-level of 0.05. All statistical analysis will be performed using the R software environment for statistical computing and graphics.(1).
Sample Size:
We are planning a study of a continuous response variable from independent control and experimental subjects with 1 control per experimental subject. In a previous study the response within each subject group was normally distributed with standard deviation 135.5. (2) If the true difference in the experimental and control means is 90.3, we will need to study 48 experimental subjects and 48 control subjects (total = 96) to be able to reject the null hypothesis that the population means of the experimental and control groups are equal with probability (power) 0.9.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| No Intervention: Standard (control) treatment The control group receives 1mcg/kg fentanyl followed by fentanyl 0.5-1mcg/kg q10 minute PRN, ketorolac 0.5mg/kg up to 30mg max IV, and acetaminophen 1000mg IV for pain control intraoperatively. The patient is then treated with hydromorphone 0.005mg/kg q10minutes the post-anesthesia recovery. The patient would then receive hydromorphone 0.005 mg/kg q1hr PRN, 1 gram acetaminophen IV scheduled q6hr, and methocarbamol 750mg QID following discharge from the PACU and transfer to the hospital floor. The patient is converted to oxycodone 10mg (Roxicodone) q4hr PRN and 975 mg PO APAP scheduled for pain control on postoperative day number 1 or when appropriate for PO intake. The patients receives their home dose of suboxone onpostoperative day number 1 or when appropriate for PO intake. On postoperative day number 2 number 3, patients are transitioned to an increased dose of their Suboxone for pain control in preparation for discharge. |
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| Active Comparator: Treatment Group Buprenorphine-sufentanil group receives sufentanil 0.03mcg/kg followed by sufentanil 0.01-0.03 mcg/kg q10 min PRN, IV ketorolac 0.5mg/kg up to 30mg max and IV acetaminophen 15mg/kg up to 1000mg for pain control intraoperatively. In the PACU, IV buprenorphine 0.3mg IV q30 minutes would be given as the first line choice for pain control for 3 doses. IV PCA sufentanil is used as a second line therapy if patient comfort is not achieved by IV buprenorphine alone. The patient receives 0.3 mg buprenorphine IV Q6hr PRN, scheduled IV acetaminophen 1 gram for 24 hrs and methocarbamol 750mg QID after discharge from the PACU and transfer to the floor. The patient is converted to buprenorphine2mg q6hr PRN and 975 gram PO APAP scheduled for pain control on postoperative day 1. The patient receives their home dose of Suboxone starting on postoperative day 1 if tolerating PO intake. On postoperative day 2, patients would be transitioned to an increased dose of their Suboxone. |
Drug: Sufentanil
IV buprenorphine plus IV sufentanil treatment group.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Amount of Pain Medication Used [Dosing 72 hours (medication is administered) to 4 weeks]
Secondary Outcome Measures
- Patient Satisfaction Survey Results [Post operative day number 2]
Patient will complete a satisfaction survey on day 2
Eligibility Criteria
Criteria
Inclusion Criteria:
- 1.Orthopaedic trauma patient with history of suboxone use for greater than 30 days. Trauma must involve major long bone fracture(s) (femur, tibia, fibula, humerus, radius, ulna) 2.Must have taken suboxone in the last 24 hours and have participated in addiction treatment for greater than one month.
3.Age 18-65 4.ASA I-III 5.Willing to participate in post-operative psychiatric care 6.Glascow Coma Scale 15
Exclusion Criteria:
- Severe renal disease (Creatinine clearance < 40) 2.History of chronicSevere liver disease or an (AST/ALT greater than 2 times normal, direct/indirect bilirubin outside normal limits and INR> 1.4 if drawn as standard of care) or evidence of acute liver failure? 3.Acute Ethanol Intoxication (serum ethanol > 0.080 at time of informed consent) 4.Severe distracting injury that is close to pain levels expected from the orthopedic trauma (Ex surgical abdominal process, neurosurgical process, massive soft tissue trauma, severe spinal injury, multiple rib fractures) 5.Pregnancy 6.Polysubstance abuse on urine or serum drug screen (excluding marijuana due to its new legality in multiple states)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | West Viriginia University Hospital | Morgantown | West Virginia | United States | 26506 |
Sponsors and Collaborators
- West Virginia University
- West Virginia Clinical and Translational Science Institute
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 1802003669