B&O for TLH Post-operative Pain and Nausea
Condition: Hysterectomy; Pain, Postoperative
MeSH terms: Pain, Postoperative
Study type: Interventional
Phase: Phase 4

Summary: 
      A prospective, single-center, double-blind, randomized, placebo-controlled trial to assess
      the impact of immediate post-operative placement of a Belladonna and Opium (B&O) rectal
      suppository on postoperative pain and nausea following laparoscopic and robot-assisted
      hysterectomy.
    

Detailed description: 
      This study is a single-center, double-blind, randomized placebo-controlled trial to assess
      the impact of immediate postoperative Belladonna and Opium rectal suppository use on
      postoperative pain and nausea following total laparoscopic and robot-assisted hysterectomy.
      Study took place at Mercy Medical Center, involving both outpatient and inpatient surgical
      settings. The duration of the trial was 12 months, with 56 patients enrolled during this time
      period. Patients eligible for trial participation were women between ages 18 and 75
      undergoing level I total laparoscopic or robot-assisted hysterectomy with or without
      bilateral salpingo-oophorectomy, with or without cystoscopy performed post-procedure, with or
      without lysis of adhesions, and with or without surgical treatment of endometriosis, with no
      additional surgical procedures being performed (i.e. no lymph node dissection or
      urogynecologic suspension or sling procedures). Patients were excluded from the study if they
      had contraindications to the use of B&O suppositories: these contraindications are glaucoma,
      severe hepatic or renal disease, bronchial asthma, history of narcotic idiosyncracies,
      respiratory depression, convulsive disorders, acute alcoholism or delirium tremens, or
      regular use of an anticholinergic medication (twice per week or more frequently). Patients
      were withdrawn from the study if the original planned surgery was not performed. If the
      original planned surgery was not performed, a suppository was not placed following surgery.
      There were no financial incentives offered for trial participation.

      Only the patients of clinical investigators from this trial were considered for participation
      in this study. Clinical investigators posting patients for total laparoscopic or robotic
      hysterectomy at Mercy Medical Center informed patients of the presence of the clinical trial
      at the time of surgical posting, using an IRB-approved script. The chart number of patients
      posted for total laparoscopic or robot-assisted hysterectomy was be forwarded to the
      co-investigator by the clinic surgical coordinator at the time of surgical posting. The
      co-investigator reviewed each chart and conducted a telephone interview with each patient
      prior to surgery to verify trial eligibility and to answer any questions about the trial.
      Patients were made aware that study participation is voluntary, and that if they chose to not
      participate, they would receive standard postoperative pain and nausea pharmacologic
      management. On the day of surgery, a member of the research team met with the patient
      pre-operatively in a private pre-operative holding area to review and sign a written consent
      for participation in the trial. This member of the research team was familiar with the study
      protocol and risks of the pharmacologic intervention under investigation. These steps allowed
      patients to be fully informed, and ensured patient safety and support during the short
      interval of the study.

      On the day of surgery, patients were randomized to either B&O rectal suppository or to a
      placebo of glycerin rectal suppository. This study employed a glycerin rectal suppository as
      a placebo because this over-the-counter medication has limited effects, similar to those of a
      Belladonna & Opium Supprette, and is similar in size, physical appearance and mechanical
      properties to a Belladonna & Opium Supprette. A placebo-free comparison group was not used,
      as this would have changed the study design from a double-blind clinical trial to a
      single-blind clinical trial, with greater potential for investigator bias to influence study
      results. Additionally, it is not thought that results for a placebo-free comparison group
      would substantially differ from those of a glycerin suppository placebo group, and would
      require a larger study population and greater study resources to achieve findings of similar
      significance and power. Randomization was performed by a biostatistician, with a sealed
      envelope created for each patient containing information regarding randomization to either
      placebo or intervention group. In the operating room, this envelope was opened, and the
      circulating nurse would draw the indicated medication from the Pyxis system. Drug dictionary
      entries were created within the Pyxis system by the Mercy Medical Center Department of
      Pharmacy, so that the Belladonna & Opium Supprette #16A (16.2mg / 60mg), and the glycerin
      suppository were represented as "Protocol Drug A" and "Protocol Drug B". The patient's
      electronic medical record reflected that "Protocol Drug A" or "Protocol Drug B" was received
      by the patient, so that the nurses and physicians caring for the patient postoperatively were
      blinded as to which suppository the patient received.

      A suppository was placed rectally by a member of the surgical team at the conclusion of
      surgery, prior to departure from the OR and awakening from anesthesia. Post-operative
      placement was selected to minimize interaction with intraoperative anesthetic and analgesic
      medications, to maximize peak plasma concentrations and therapeutic efficacy of Belladonna
      alkaloids and Opium within the immediate postoperative period, and control for variation in
      procedure length between study participants. The nurses caring for the patient
      postoperatively were blinded to which suppository the patient did receive, but were made
      aware that the patient had received a suppository containing either glycerin or one
      containing belladonna 16.2mg and opium 60mg, equivalent to approximately 6mg of morphine. The
      nurses were be educated about potential side effects of Belladonna & Opium suppositories, and
      of potential drug interactions; they were asked to document and to inform the covering
      provider of the occurrence of any such adverse effects. Patients remaining in the hospital
      overnight following their surgery underwent a postoperative exam by a resident physician
      familiar with the study protocol and familiar with potential side effects of the B&O
      suppository. Standard of care at Mercy Medical Center is for nurses to assess patient's
      postoperative pain by visual analog scale at regular time intervals. Data regarding patients'
      visual analog pain scores for the first 12 hours following surgery were extracted from the
      electronic medical record and analyzed by the research team. PO and IV narcotic use in IV
      morphine equivalents, PO and IV NSAIDs, and PO and IV antiemetic use were also assessed over
      the first 12 following surgery, this data was extracted from the electronic medical record
      and analyzed by the research team. Study surveillance did not extend beyond the duration of
      the participant's postoperative hospitalization, usually less than 24 hours.
    

Intervention name(s): Belladonna Opium; Glycerin Suppository
Intervention type(s): Drug; Drug
Intervention description(s): Belladonna Opium 16.2-60mg rectal suppository; Glycerine rectal suppository
Intervention MeSH terms: Glycerol
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomization to one-time intervention A (medicated suppository) or intervention B (placebo), allocation was sealed in consecutively numbered opaque envelopes generated by biostatistician using blocked randomized technique.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment