Clinical trial NCT04495374: Oral Pregabalin as Preemptive Analgesia in Abdominal Hysterectomy
Official title: Use of Oral Pregabalin as Preemptive Analgesia in Abdominal Hysterectomy: Evaluation of Postoperative Pain and Opioid Consumption
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Pain, Postoperative
Analgesia
Gabapentin Adverse Reaction
Opioid Abuse
Keywords: postoperative pain
multimodal analgesia
pregabalin
preemptive analgesia
abdominal hysterectomy
gabapentins
Lead sponsor: Universidade Federal de Alfenas
Sponsor class: OTHER
First posted: 2020-07-31
Enrollment: 58
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Postoperative pain affects 80% of surgical patients and is one of the main negative symptoms resulting from surgery. It impairs the recovery of patient since it is related to chronic pain, nausea and vomiting and longer hospital stay, generating higher cost to the health system. Thus, the use of new methods to control postoperative pain is recommended and multimodal analgesia, an opioid-sparing strategies, has been widely used by several researchers. Studies show that gabapentins have beneficial effects on postoperative pain control when used as pre-anesthetic medication, also showing a reduction in opioid consumption, with few adverse effects. Among gynecological surgeries, abdominal hysterectomy is one of the procedures that generates the highest degree of acute postoperative pain. Thus, the aim of the present study is to investigate the effect of oral pregabalin (300 mg) two hours before abdominal hysterectomy procedures on postoperative pain. This study is a randomized, double-blind, placebo controlled clinical trial. Patients submitted to abdominal hysterectomy for benign pathologies will be selected and divided into two groups: the placebo controlled group (P0) and the pregabalin 300 mg group (P1). Group P0 will receive a placebo tablet one hour before the procedure, while group P1 will receive a 300 mg tablet of pregabalin identical to the placebo tablet. The reduction of postoperative pain and the best quality of patient recovery will be evaluated using the Visual Analogue Pain Scale (VAS) and the McGill Pain Questionnaire. Also, it will be evaluated the consumption of opioids as a rescue analgesic medication and the presence of adverse effects such as nausea and vomiting.

Detailed description: The sample population of this study is 102 female patients (50 already included in the study), who have undergone abdominal hysterectomy surgery for benign conditions, with or without joint oophorectomy / salpingectomy. The patients received spinal anesthesia, at hospital "Santa Casa de Alfenas" - Minas Gerais / Brazil ("Casa de Caridade Nossa Senhora do Perpétuo Socorro"). All surgeries were performed by the same team of surgeons.

All patients were evaluated and followed from the preoperative period, up to 24 hours postoperatively, passing through the intraoperative period. During all stages, patients were assisted by a properly trained multi-professional team, consisting of a doctor, nurse and nursing technician.

For the patient to be included in the study, she must have understood and agreed with the informed consent form that was explained in detail to all possible candidates in the preoperative period.

This is a double blind randomized study. The patients were randomly allocated to 02 groups, in which Group 1 received medication A (designated in the study as medication 1), whereas Group 2 received medication B (designated in the study as medication 2).

Study participants and researchers were blinded as to the use of drug / placebo to avoid measurement bias. To carry out the blinding process, an external researcher was assigned to randomize the groups and prepare the pills in opaque and closed envelopes characterized only by a control identification (A or B), which is known only to this researcher. Patients in both groups received identical sealed envelopes, 02h before the start of the anesthetic procedure, only identified as medication A or B, which contained two pills in each envelope. A second researcher is responsible for collecting data and monitoring the patient from the intraoperative period up to 24 hours after discharge from the post-anesthetic recovery room (PARR).

In the operating room, venoclysis was performed with jelco No. 18 or No. 20, and an infusion of 08 ml.kg-1 of crystalloid solution (lactated ringer). The patients were properly monitored with pulse oximetry, cardioscope, and non-invasive blood pressure monitor. After monitoring, patients were premedicated with intravenous (IV) midazolam at a dosage of 0.03 mg.kg1.

To perform spinal anesthesia, the patients were seated on the surgical stretcher by the nursing team. Asepsis and antisepsis were performed at the puncture site with alcoholic chlorhexidine solution. After placement of sterile drapes, local anesthesia was performed with 2.0% lidocaine without vasoconstrictor. The first attempt at subarachnoid puncture was performed, using the median technique, between the intervertebral levels L3-L4 or L4-L5 or L5-S1, with a 25 gauge Quincke needle for subarachnoid anesthesia. If there was a technical difficulty in the puncture, the paramedian puncture technique was chosen. The confirmation of the correct puncture was based on the aspiration of cerebrospinal fluid. Anesthesia was performed with the local anesthetic 0.5% bupivacaine at a dosage of 0.3 mg.kg-1, injected from a 5 ml disposable syringe. After anesthesia, the patients were placed in the supine position, and the correct level of anesthesia was proven with thermal sensitivity tests using cotton soaked with alcoholic solution. After the anesthesia reached the sensory level of the T4 thoracic vertebra, the surgical team was allowed to start the procedure. Prior to the beginning of the surgical incision, a delayed bladder probe was performed in all patients according to the surgeon's indication.

Hemodynamic changes in blood pressure were controlled with the use of vasoactive medications such as ephedrine or metaraminol. For prophylaxis of postoperative nausea and vomiting (PONV) ondansetron was administered at a dosage of 4 mg intravenously (IV) 30 minutes before the end of surgery. Tenoxicam was prescribed for all patients at a dosage of 20 mg IV at regular intervals every 12 hours for the purpose of anti-inflammatory and analgesic action. For analgesic relief, dipyrone IV was also prescribed at a dosage of 50 mg.kg-1 at regular intervals every 6 hours. During the surgery, and also at the end of the surgery, the patients were evaluated for the degree of sedation using the Ramsay sedation scale as a basis.

At the end of the surgery, the patients were referred to the post-anaesthesia care unit, where they were monitored again, and went through the pain assessment process using the visual analog scale (VAS) in relation to pain at rest and "movement" (the patient was asked to perform the forced cough movement), through a direct question with scale demonstration. Pains characterized as mild (0 - 2 VAS) received no medication other than those already prescribed; pain characterized as moderate (3 - 7 EVA) received IV morphine at a dosage of 0.025 mg.kg-1; and severe pain (8 - 10 VAS) received IV morphine at a dose of 0.05 mg.kg-1 every 01 h until analgesic control.

To consider themselves able to be discharged from the post-anaesthesia care unit for clinical follow-up in wards, patients should reach a score ≥ 9 on the modified Aldrete Scale and have VAS pain scores ≤ 2.

In the infirmary, patients were tested at regular intervals for pain intensity, by of a team of nurses trained and qualified to do so. The patients had pain classified as moderate (VAS ≥ 2 \<8) or severe (VAS ≥ 8), receiving drugs with morphine IV in the dose of 1 mg and 2 mg respectively, according to the medical prescription.

24 h after discharge from the post-anaesthesia care unit, in the ward, all the patient was assessed by the same examiner who performed an assessment at the post-anaesthesia care unit, who stratified the patient again from the EVA and assessed using the McGill questionnaire.

During the entire hospitalization period, the use of central nervous system (CNS) depressant drugs (example: ketamine, droperidol, promethazine) and / or analgesic drugs that do not contain any study protocol was avoided. If some patients were medicated with these drugs, they were excluded from the study.

The data related to surgery (pre, trans and postoperative) were collected for statistical analysis, according to Annex II, in which a total duration of surgery in minutes; the total intravenous medication infused; the values of mean arterial pressure and heart rate in the pre, intra and postoperative period; a presence or not, as well as a quantity, of PONV in the post-anaesthesia care unit and after 24h; presence or not of dizziness as a possible side effect; among others.

All data selected through the study will be digitized and analyzed using the Statistic® 7.0 software. The data will be compared using repeated measures ANOVA, followed by Newman-Keuls post-hoc, being considered for p \<0.05.

Eligibility criteria: Inclusion Criteria:

1. Patients who will undergo elective abdominal hysterectomy surgery due to benign pathologies;
2. Be classified as physical status by the Society of Anesthesiologists (ASA) as ASA I (healthy individual) or ASA II (patient with mild and controlled systemic disease);

Exclusion Criteria:

1. Allergy or intolerance previously known to pregabalin or opioids;
2. Patients with chronic pain or fibromyalgia;
3. Patients on chronic opioid use;
4. Carriers of malignant neoplasms;
5. Pregnant women;
6. People with active uncontrolled cardiovascular disease;
7. Patients with kidney and / or liver disease;
8. Patients who have spinal deformities that make spinal anesthesia impossible;
9. Presence of coagulation disorders or anticoagulant therapy that cannot be suspended for surgery;
10. Presence of active sepsis.

Primary outcomes:
measure: Postoperative Pain in Rest Assessed 24 Hours After Abdominal Hysterectomy Surgery Using the Visual Analog Scale (VAS)
timeFrame: End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery)
measure: Postoperative Pain Assessed 24 Hours After Abdominal Hysterectomy Surgery, Using the McGill Pain Questionnaire
timeFrame: End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery)
measure: Postoperative Pain in Active Movement Assessed 24 Hours After Abdominal Hysterectomy Surgery Using the Visual Analog Scale (VAS)
timeFrame: End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery)
Secondary outcomes:
measure: Number of Doses of Opioids Used as Analgesic Rescue in the Postoperative Period
timeFrame: End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery)
measure: Time Required for the Use of the First Dose of Opioid as an Analgesic Rescue in the Postoperative Period
timeFrame: End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery)
measure: Number of Participants With Dizziness Between the Intervention and Control Groups
timeFrame: End of the first postoperative day of abdominal hysterectomy surgery (24 hours after the end of surgery) and also immediately in the post-anesthetic recovery room
Other outcomes:
Locations:
city: Alfenas
country: Brazil
facility: Universidade Federal de Alfenas
state: Minas Gerais
Study officials:
affiliation: Universidade Federal de Alfenas
name: Larissa H Torres, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Santa Casa de Alfenas
name: Fabrício G Silva, BSc
role: STUDY_CHAIR
affiliation: Universidade Federal de Alfenas
name: Carlos M de Barros, BSc
role: STUDY_CHAIR
affiliation: Universidade Federal de Alfenas
name: Marcia H Podestá, PhD
role: STUDY_CHAIR
affiliation: Universidade Federal de Alfenas
name: Carla S Ceron, PhD
role: STUDY_CHAIR
affiliation: Santa Casa de Alfenas
name: Thayná C Silva, BSc
role: STUDY_CHAIR
affiliation: Universidade Federal de Alfenas
name: Denismar A Nogueira, PhD
role: STUDY_CHAIR
affiliation: Universidade Federal de Alfenas
name: Tiago M Reis, PhD
role: STUDY_CHAIR
affiliation: Universidade Federal de Alfenas
name: Milena C Espósito, PhD
role: STUDY_CHAIR
affiliation: Universidade Federal de Alfenas
name: Danielle A Oliveira, BSc
role: STUDY_CHAIR
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