Fentanyl Versus Morphine in Spinal Anesthesia for Caesarian Section - Study on Analgesia, Side Effects and Patient 's Satisfaction
Condition: Anesthesia
Study type: Observational

Summary: 
      Intrathecal morphine and fentanyl are used for anesthesia and perioperative pain management
      in caesarian section. Despite the fact that spinal Fentanyl is better tolerated, might not be
      enough for postoperative pain control. Morphine offers an improved analgesia but might be not
      tolerated due to a higher incidence of side effects, especially nausea and vomiting.

      This is a prospective, randomized, double-blind, parallel study including 80 parturients
      scheduled for elective CS. Spinal anesthesia is consisting in bupivacaine (7.5 - 10 mg in
      relation to height) and either fentanyl 25 mcg (F group) either morphine 100 mcg (m group).
      It will be assessed intraoperative and postoperative pain scores, the incidence of sides
      effects, patient's satisfaction and systemic opioids consumption.
    

Detailed description: 
      The patients were randomly allocated into one of the two groups M (morphine) or F (fentanyl)
      with a sample size calculation at 1:1 ratio, using the envelope technique.

      Group F (fentanyl) was administered hyperbaric bupivacaine 0.5% along with a standard dose of
      25 mcg fentanyl, while group M (morphine) received hyperbaric bupivacaine 0.5% with a
      standard dose of 100 mcg morphine. The dose of hyperbaric bupivacaine 0.5% to be injected,
      was based on the patient's height and here were used a range of doses between 7.5 mg and 11
      mg.

      The study required two anesthetists. The first anesthetist was "in charge" and performed the
      spinal anesthesia and he was blind to the solution used. The second anesthetist randomly
      assigned the patient, drew up the intrathecal solution and provided the anesthetic mixture.
      By this method, the first anesthetist was totally blinded to the opioid used. All drugs were
      from the same manufacturer.

      During the pre-anesthetic visit, the patient received information about the aims of the
      study, the method of anesthesia, and details about the pain management and about the pain
      assessment with the numeric pain scale (NPS). Patient's demographics data were obtained:
      height, term weight and age. Also, full medical past and drugs history, previous allergies
      and other important medical data were documented.

      Pre-operatively a venous access was obtained with an 18 G. cannula and 500 ml of Ringer
      lactate solution was infused prior to anesthesia. Participants were fasting and received
      pantoprazol 40 mg and metoclopramide 10 mg as pre-anesthetic medication. The spinal
      anesthesia was performed in an aseptic technique with the patient in a sitting position, in
      the L3 - L4 interspace, using a midline approach, with a Whitacre 27 G. needle and the
      anesthetic mixture manually injected at a rate of 1 ml.15s-1, with a barbotage effect. A
      previous skin local anesthetic infiltration was performed with 2 ml of 1% lidocaine. After
      the block, the patient was placed in a supine position with a roll wedge placed under the
      right hip to displace the uterus to the left until fetal extraction. Volemic supply was
      assured with warm Ringer lactate (10-20 ml.kg-1hr-1). All patients than had anti-embolic
      socks on lower limbs.

      Surgery started when sensory block, as assessed by the cold test, reached the T4 dermatome
      level.

      Non-invasive blood pressure (BP) was measured every minute until the baby was delivered and
      every 3-5 minutes afterwards. Any decrease in systolic blood pressure below the background
      level resulted in intravenous ephedrine and doses of 5-15 mg being given, repeated every
      minute until the systolic blood pressure had been restored. At delivery, oxytocin 5 I.U. was
      given intravenously (normal practice when the study was conducted) and afterwards as
      required.

      We took a proactive action to prevent the perianesthetic emetic syndrome. So, our patients
      received from the time of surgery a nausea prophylaxis with granisetron 1 mg and a dose o
      dexamethasone 4 mg. A second dose of granisetron 1 mg was given at 12 hours apart. Afterwards
      only as required anti-emetic medication was given.

      Heart rate, BP, oxygen saturation as measured by pulse oximetry (SpO2), requirement for
      supplemental analgesics, need for conversion to general anesthesia were recorded
      intraoperatively. In addition to these parameters, the level of sensory block was assessed by
      the cold test, and the maximum motor block score was recorded using a 4-points Bromage scale
      as the complete motor recovery time.

      The postoperative pain control strategy was relaying on regular paracetamol 1 gr., every 6
      hrs. and ibuprophen 400 mg every 8 hrs., both drugs given in intravenous or oral
      administration. As required for breakthrough pain, were available doses of 50 to 100 mg. of
      iv. tramadol, 6 hourly to a maximum dose of 400 mg.

      Data collection We collected data regarding: demographics (age, weight, height, smoke
      consumption, gesta/para status and preoperative contractions); time from anesthesia to
      incision; time to sensory block; pain scores (at surgical incision, end of surgery, at 4 h, 6
      h, 12 h, 24 h, 48 h, 72 h - postoperative the pain scores were assessed at rest and on
      mobilizing); AUE72h (sum pain intensity differences area over 72 hours) and SPID72h
      (time-weighted sum pain intensity differences over 72 hours); side effects associated with
      anesthesia (pruritus with a grading scale, nausea, vomiting, over sedation, dizziness and
      respiratory depression).

      Contribution to pain intensity assessment metrics Besides assessing and understanding the
      level of pain, pain scales help healthcare practitioners to make a well-informed and accurate
      diagnoses as well as to formulate carefully-considered treatment plan for their patients.

      The Numeric Pain Rating Scale is a type of unidimensional pain scale which comes with
      numbers, from 0 to 10. A person simply needs to rate their pain based on written or verbal
      prompts, from 0 meaning no pain to 10 meaning worst pain imaginable.

      But for a more comprehensively comparison of the post-operative pain in the study groups, two
      additional assessment metrics were employed:

        1. time-weighted sum pain intensity differences over 72 hours

        2. sum pain intensity differences area over 72 hours Descriptive statistics included the
           observed frequency counts (percentage) for categorical variables; and mean ± standard
           deviation for numerical variables, irrespective of their distribution. Normality was
           tested with the Kolmogorov-Smirnov test. For comparing means in normally distributed
           values, the t-test for independent samples was applied, with Levene's test for equality
           of variances. For comparing distribution of non-normally distributed numerical values,
           the non-parametric Mann-Whitney U statistical tests was applied and median
           (Inter-Quartile Range) with Tukey's hinges was additionally provided as a descriptive
           statistic.

      The Chi-square statistical test (either asymptotic, Fisher's exact test, or Monte-Carlo
      simulation with 10,000 samples) was applied to check the statistical significance of the
      association between the categorical variables. The odds ratio (OR) values were calculated for
      the symptoms associated with the two anesthetics, such as nausea and dizziness.

      The statistical analysis was conducted at a 95% level of confidence and a 5% level of
      statistical significance. All reported probability values were two-tailed.

      Statistical analysis was performed with the statistical software IBM SPSS v. 20 and open
      source R v.4.0.5 packages.

      Ethics The study was conducted in accordance with the Declaration of Helsinki, and the
      protocol was approved by the Ethics Committees of Pelican Hospital from Oradea
      (no.2672/28.12.2021).
    

Intervention name(s): Fentanyl; Morphine
Intervention type(s): Drug; Drug
Intervention description(s): The trial aims to study the quality of anesthesia and perioperative analgesia and patient's satisfaction provided by fentanyl and bupivacaine versus morphine and bupivacaine.; The trial aims to study the quality of anesthesia, perioperative analgesia and patient's satisfaction provided by fentanyl and bupivacaine versus morphine and bupivacaine.
Other intervention name(s): plus Bupivacaine; plus Bupivacaine
Intervention MeSH terms: Fentanyl; Morphine; Bupivacaine
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        The study population will be selected from the pregnant patients of Oradea Pelican Clinic
        Hospital.
      
Keywords: spinal anesthesia, pain scores, spinal opioids side effects, patient's satisfaction