The Effect of Oral Pregabalin on Epidural-induced Shivering and Epidural Characteristics
Condition: Epidural Anesthesia; Shivering
Study type: Interventional

Summary: 
      -  Background: The previous reports tried to reduce shivering and improve neuroaxial
           anesthesia characteristics by the systemic use of different drugs. This study was
           directed to evaluate the effect of pregabalin premedication on both shivering and
           epidural outcome data following single shot loading.

        -  Patients and Methods: Eighty patients, ASA grade I and II, undergoing surgeries under
           epidural anesthesia were studied. The patients were divided into two groups: Pregabalin
           group and Control group in which the patients received 150 mg of pregabalin and placebo
           capsules respectively sixty minutes prior to surgery. Following epidural loading, the
           onset and degree of shivering were compared between the two groups. Also, the epidural
           outcome including onset, level and duration were traced and compared. The perioperative
           hemodynamics, sedation scores, patient satisfaction and side effects were followed up
           and registered.
    

Detailed description: 
      After obtaining the ethical committee approval of Beni Suef University hospital, in Egypt and
      an informed consent from the patients, Eighty female patients with an American society of
      Anesthegiologists physical status (ASA) I-II who were undergoing gynecological surgery
      (Posterior repair and transobturator transfixation) under epidural anesthesia, were enrolled
      in this randomized double -blind study in May 2018.

      The patients were excluded from the study if ASA class was more than II, anticipated
      difficult epidural insertion or there was any contraindication to epidural anesthesia, if any
      patient developed wet or bloody tab, or the patients were under psychotropic or antiepileptic
      therapy.

      The 80 Patients were randomly allocated into one of two groups (using sealed opaque numbered
      envelopes indicating the group of each patient, carried out by an independent
      anesthesiologist and given to the ward nurse) [40 patients in each group]:

        -  Pregabalin group (P), [n=40]: received pregabalin 150 mg capsules (Lyrica®,Pfizer) sixty
           minutes prior to the epidural insertion.

        -  Control group (C), [n=40]: received placebo capsules sixty minutes prior to epidural
           insertion.

      Prior to administration of study drugs, mean arterial blood pressure (MAP), heart rate (HR),
      oxygen saturation (SpO2), and tympanic temperature (T temp) were taken as [baseline reading].
      Upon reaching the operation theater, a second set of readings were taken [preoperative
      reading], together with sedation score using a 4 points "Modified Wilson" Sedation Scale
      [1=awake; 2=drowsy but arousable to command; 3= asleep but arousable to mild physical
      stimulation; and 4= asleep but not arousable to mild physical stimulation].

      On the operating table and after attaching the standard monitoring [5 lead ECG, pulse
      oximetry, non-invasive arterial blood pressure], the epidural anesthesia was standardized for
      all patients. After intravenous infusion of 500 ml of lactated Ringer's solution in a
      wide-bore canula, the epidural catheter was inserted in a lateral position. Following the
      exclusion of both subarachnoid and intravascular insertion of the catheter, a loading
      epidural dose of 10 ml levo-bupivacaine 0.5% and 50 mcg fentanyl were injected.

      The hemodynamic readings [MAP, HR and SpO2] were monitored and registered every 5 minutes (as
      routine practice) and tympanic temperature [T temp] was taken upon arrival to operating room,
      after activation of epidural, then every 15 minutes till the end of surgery.

      Intraoperatively, arterial blood pressure was maintained within 20 % of the baseline readings
      using intravenous boluses of Lactated Ringer's solution and 6 mg increments of ephedrine (if
      required). Bradycardia (HR less than 60 beats per minutes) was treated with intravenous
      atropine boluses 0.6 mg.

      Also, all patients were active warmed using a convection machine (hot air blower).

      Shivering (as a primary outcome) was graded by a blinded observer during the intraoperative
      and postoperative period using the scale validated by Crossley and Mahajan and Tsai and Chu:
      [0= no shivering, 1= piloerection or peripheral vasoconstriction but no visible shivering, 2=
      muscular activity in only one muscle group, 3= muscular activity in more than one muscle
      group but not generalized shivering, 4= shivering involving the whole body]. Grades 3, and 4
      shivering for at least 3 minutes were considered positive, and maximum shivering was
      considered if generalized shivering interfering with ECG monitoring. Positive shivering or
      lower grade shivering but described as distressful by the patient were treated with
      intravenous administration of meperidine 20 mg. If no improvement after this management, the
      patient was excluded from the study.

      For the selection of safe and effective anti-shivering treatment, the medications were
      revised and meperidine in this small dose was picked up due to its effectiveness in treatment
      and the epidural parameters will not be significantly affected when compared to ketanserine,
      doxapram, clonidine, magnesium, ketamine, orphenadrine, methylphenidate, pentazocin and
      nefopam.

      At the end of surgery, the patients were transferred to PACU (for one hour), where
      hemodynamics and tympanic temperature were taking (every 15 minutes). Shivering was also
      observed and scaled and treated the same way as intraoperatively. Patients were only
      discharged from PACU if modified Aldrete score was ≥ 9 after registering and treating any
      other complications.

      Postoperatively, when the patients started to experience pain at the surgical site and
      according to the acute pain management protocol by the anesthesia department in the hospital,
      a loading of levo-bupivacaine 0.125% 8 ml was given followed by infusion of levo-bupivacaine
      0.125% and fentanyl 2mcg/ ml at a rate of 6 ml/hour.

      Any perioperative complications (e.g. bradycardia, hypotension, desaturation or nausea and
      vomiting) were observed, registered and treated appropriately.

      The following were observed (by anaesthetist blinded to the studied drugs):

        -  Demographic data (age, weight and height), duration of surgery (in minutes).

        -  Tympanic temperature (T temp.) in Celsius degree as baseline (before drug intake),
           preoperative (on arrival to operating room), after epidural loading, then every 15
           minutes intraoperative.

        -  Shivering (as a primary outcome): incidence of positive shivering (at any time),
           incidence of maximum shivering (at any time) and median and range of shivering severity
           between the two studied groups.

        -  Sedation: assessed 60 minutes after studied drug in take (preoperatively).

        -  Epidural characteristics (as secondary outcome): onset of the block (the time from
           epidural loading until feeling of numbness in the lower extremities), duration of the
           block (the time from the onset till starting feeling of pain at the surgical site) and
           level of the block (assessed by the ice technique).

        -  Meperidine consumption: total consumed dose of meperidine in both groups.
    

Intervention name(s): Pregabalin 150mg; Placebo oral capsule
Intervention type(s): Drug; Drug
Intervention description(s): pregabalin 150 mg capsules (Lyrica®,Pfizer) given 60 minutes prior to epidural anesthesia; Placebo oral capsule given 60 minutes prior to epidural anesthesia
Other intervention name(s): Lyrica
Intervention MeSH terms: Pregabalin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment