Prophylactic Mirtazapine or Dexamethasone for Post-spinal Anesthesia Shivering
Condition: Shivering
Study type: Interventional
Phase: Phase 4

Summary: 
      This study was conducted to evaluate the effect of a prophylactic dose of oral mirtazapine on
      shivering compared with prophylactic intravenous infusion (IVI) dexamethasone in patients
      undergoing gynecological surgeries under spinal anesthesia.
    

Detailed description: 
      Enrollment After approval by the institute ethics committee, this study was conducted at
      Ain-Shams university hospitals, from the 1st of March 2018 till the 31st of August 2018, on
      300 patients aged 18-60 years of the American Society of Anesthesiologists (ASA) physical
      status I or II and underwent gynecological surgeries under spinal anesthesia. A written
      informed consent was obtained from all patients to participate in the study.

      Patient's refusal, duration of surgery more than 120 min, obesity with body mass index (BMI)
      >35 kg/m2, generalized infection or localized infection at level of blockade, neurologic
      disease, coagulation disorder, patients with hypo- or hyperthyroidism, cardiopulmonary
      disease, psychological disorders, a need for blood transfusion during surgery, an initial
      body temperature >38.0C or <36.0C, a known history of alcohol or substance abuse, or
      receiving vasodilators, or medications likely to alter thermoregulation excluded the patient
      from the study.

      Randomization and Blinding This study was designed to be a randomized, placebo-controlled,
      double-blinded parallel study. Following enrollment, patients were randomized into 3 equal
      groups;

        1. The M (Mirtazapine) (Merta) group:(n=100) each patient received 30 mg Mirta tablet
           orally with sips of water and 100 ml 0.9% sodium chloride (normal saline [NS]) (IVI)
           over 15 min as a placebo for Dex 2 h preoperatively.

        2. The D (Dexamethasone) (Dex) group: (n=100) each patient received a placebo tablet
           identical to Mirta tablet orally with sips of water and Dex 8 mg ampoule diluted in 100
           ml 0.9% NS IVI over 15 min, 2 h preoperatively.

        3. The C (Control) group: (n=100) each patient received the same placebo tablet identical
           to Mirta tablet orally with sips of water and 100 ml 0.9% NS IVI over 15 minas a placebo
           for Dex 2 h preoperatively.

      Randomization was done using computer-generated table of random numbers in a 1:1 ratio in
      opaque and sealed envelope (SNOSE). The assigned treatment was written on a card and sealed
      in opaque envelopes consecutively numbered. These envelopes were opened just immediately
      before infusing the medication in the patient's room. The study drugs were prepared by the
      hospital pharmacy and follow-up of patients were conducted by anesthesia residents not
      involved in any other part of the study.

      Study Protocol On arrival in the operating theatre, all patients had an inserted venous
      cannula. I.V. fluids were preheated to 37oC. No other warming device was used. Lactated
      Ringer's solution was warmed to 37 oC and was infused at 10 ml/kg over 30 min before spinal
      anesthesia. The infusion rate was reduced to 6 ml/ kg.

      Subarachnoid anesthesia was instituted at either L3/4 or L4/5 interspaces. Hyperbaric
      bupivacaine, 5 mg /ml, 15 mg was injected using a 25 G Quincke spinal needle.

      Supplemental oxygen (5 liter/ min) was delivered via a facemask during the operation. All
      patients were covered with one layer of surgical drapes over the chest, thighs, and calves
      during the operation and one cotton blanket over the entire body after operation. The
      operating and recovery rooms temperatures were maintained at 23-25°C with approximately 60%
      humidity.

      Assessment parameters Heart rate, mean arterial pressure (MAP), and peripheral oxygen
      saturation were recorded using standard noninvasive monitors before intrathecal injection and
      thereafter at 5, 10, 15, 20 minutes then every 10 minutes to complete 90 minutes from the
      intrathecal injection.

      Sensory levels were assessed by pinprick to determine the peak sensory level and time to two
      segment regression in minutes. Motor block were assessed by using Modified Bromage scale(16)
      (0 = no block 1 = hip block, 2 = hip and knee block, 3 = hip, knee, and ankle block) to
      determine the time to reach complete motor block and duration of motor blockade (minutes).

      Sedation score was assessed with a four-point scale as per Filos et al.(17): 1: Awake and
      alert. 2: Somnolent, but responsive to verbal stimuli. 3: Somnolent, arousable to physical
      stimuli. 4: Unarousable.

      Body temperature (axillary temperature) was recorded with an axillary thermometer. The
      ambient temperature was measured by a wall thermometer. The ambient temperature will be
      maintained at 25oC with constant humidity.

      Shivering severity was assessed with a four-point scale (Badjatia et al):

        1. None (Grade 0): no shivering noted on palpation of the masseter, neck, or chest wall

        2. Mild (Grade 1): shivering localized to the neck and/or thorax only

        3. Moderate (Grade 2): shivering involved gross movement of the upper extremities (in
           addition to neck and thorax)

        4. Severe (Grade 3): shivering involved gross movements of the trunk and upper and lower
           extremities.

      Shivering was assessed immediately before the block and every 10 minutes till the first 90
      min (end point of the study) after the completion of the subarachnoid drug injection (start
      point of the study). Grade 2 or 3 of shivering score was regarded failure of prophylaxis and
      meperidine 25 mg IV was administered.

      Side-effects, including hypotension (defined as a decrease in MAP of more than 20% from
      baseline or a decrease of arterial blood pressure below 90 mmHg and baseline MAP was
      calculated from three measurements taken on the ward before surgery) was treated by
      crystalloid infusion and if necessary ephedrine 5 mg IV was administered. The amount of
      ephedrine given in each group was recorded. Bradycardia was considered if the heart rate <50
      beats/min and was treated with IV atropine (0.01mg/kg). Respiratory depression (RR < 12 bpm),
      incidence of nausea and vomiting during early 2 hours postoperatively were recorded. IV
      granisetron (1 mg) was given in case of vomiting or after 2 successive episodes of nausea.

      Patients' satisfaction with shivering prophylaxis was done by asking the patient to answer
      the question, "How would you rate your experience after the surgery?" using a 7-point Likert
      verbal rating scale and acceptable satisfaction score of the patient being 5-7.

      3-Analysis of Data:

      The collected data were coded, tabulated, and statistically analyzed using IBM SPSS
      statistics (Statistical Package for Social Sciences) software version 22.0, IBM Corp.,
      Chicago, USA, 2013.
    

Intervention name(s): Mirtazapine; Dexamethasone phosphate; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Each patient received 30 mg Mirta tablet orally with sips of water and 100 ml 0.9% sodium chloride (normal saline [NS]) (IVI) over 15 minutes as a placebo for Dex solution 2 hours preoperatively.; Each patient received a placebo tablet identical to Mirta tablet orally with sips of water and Dex 8 mg ampoule diluted in 100 ml 0.9% NS IVI over 15 minutes, 2 hours preoperatively.; Each patient received a placebo tablet identical to Mirta tablet orally with sips of water and 100 ml 0.9% NS IVI over 15 minutes as a placebo for Dex solution 2 h preoperatively.preoperatively.
Other intervention name(s): Remeron
Intervention MeSH terms: Dexamethasone; Mirtazapine; Dexamethasone 21-phosphate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention