Suboxone User Perioperative Early Referral and Enhanced Recovery After Surgery- Orthopaedic Trauma Surgery Population
Suboxone User Perioperative Early Referral and Enhanced Recovery After Surgery- Orthopaedic Trauma Surgery Population
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.
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

 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

 1. 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.
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)