Intrathecal Levobupivacaine With Opioids for Caesarean Section
Condition: Elective Caesarean Section Surgeries
Study type: Interventional
Phase: Phase 3

Summary: 
      In this prospective, randomized, double-blind, controlled study, the aim was to compare the
      effect of adding fentanyl (10 µg) or sufentanil (2.5 µg) to levobupivacaine (2.2±0.2 ml 0.5%)
      on the intraoperative anesthesia quality, block characteristics, the side effects on the
      newborn and mother, the duration of postoperative analgesia, and surgeon satisfaction score.
    

Detailed description: 
      Following the approval of the Baskent University Ethics Committee (KA08/48) and the written
      informed consents of the patients, 93 pregnant women above 18 years of age without fetal
      distress/anomaly (gestational pregnancy age ≥ 36 weeks, height ≥ 155 cm, weight ≤110 kg, and
      fetal weight ≥ 2500 g) and planned American Society of Anesthesiologists (ASA) Physical
      Status of I to II elective caesarean section surgeries were enrolled. Patients with allergies
      to any local anesthetic, with a history of hypersensitivity and anaphylactic reactions, who
      were taken to emergency surgery, and who had preeclampsia were excluded.

      Patients were randomized into three groups (Fentanyl Group F, Sufentanil Group S, Control
      Group C) by a computer, and the demographic data and gestational age of the patients were
      recorded. No premedications were administered. Following monitoring in all patients (with
      non-invasive blood pressure, electrocardiogram and pulse oxymeter), Ringer's Lactate solution
      (15 ml/kg) was administered for 10-15 minutes. Spinal anesthesia was administered with
      midline approach at the L3-4 interval while the patients assumed a seated position. Spinal
      blocks were performed by an anesthesiologist blinded to the drug injected, and the drug
      syringes were prepared immediately before injection by another anesthesiologist who otherwise
      was not involved in the study. Intraoperative and postoperative assessments were performed by
      an anesthesiologist blinded to patient allocations and study drugs. 2.2 ml (11 mg)
      levobupivacaine (Chirocaine®, Abbott Laboratories, Ireland) was administered to patients with
      heights <163 cm, while 2.4 ml (12 mg) levobupivacaine was administered to patients with
      heights ≥163 cm (Control Group). 2.2±0.2 ml 0.5% levobupivacaine + 10 µg fentanil (Fentanyl®,
      Johnson&Johnson, USA) was administered to Group F and 2.2±0.2 ml levobupivacaine + 2.5 µg
      sufentanil (Sufenta®, Johnson&Johnson, USA) was administered to Group S at rate of 3ml/30
      sec. Following intrathecal administration, patients were placed in the supine position, and
      their heads were slightly elevated. Patients were then brought to a 15-20° left lateral
      position to prevent aortocaval compression, and oxygen (at 2-4 L/min) was provided with a
      face mask.

      Sensory block was evaluated every two minutes with a pin prick test, while motor block was
      evaluated with the Bromage scale (0=no motor loss; 1= inability to flex the hip; 2= inability
      to flex the knee; 3= inability to flex the ankle). Onset times for sensory and motor blocks
      were recorded. Surgical intervention was initiated when block reached the T5 level. In case
      sensory block did not attain the T5 level within 20 minutes, general anesthesia was
      administered.

      Duration of sensory block, highest level of sensory block, time to L1-T10 level, time for
      two-segment and T10 sensory block regression, and the onset and end time of motor block were
      recorded.

      Systolic and diastolic blood pressures (SBP and DBP), heart rate (HR) and oxygen saturations
      (SpO2) were evaluated every three minutes during the first 15 minutes, and every five minutes
      afterwards. If systolic blood pressure values decreased more than 20% with respect to the
      baseline values, or decreased to <100 mmHg, fluid loading and ephedrine (5 mg) were
      administered. A decrease in heart rate to less than 55 beats/min was considered as
      bradycardia, and atropine (0.5 mg) was administered. A decrease in the respiratory rate to
      less than 10/min, and a decrease in oxygen saturation to less than 90%, was considered as
      indications of respiratory depression. In such cases, support was provided with face mask
      ventilation.

      APGAR scores were evaluated (at minutes 1 and 5) by a pediatrician with no information
      regarding the groups. For blood gas measurements, samples were obtained from the umbilical
      cord of newborns.

      Intraoperative pain evaluation was performed with the visual analog scale (VAS score; 0= No
      pain, 10= worst pain possible) while performing surgical incision, uterine incision, and skin
      closure. In cases where VAS>3, IV fentanyl (50 µg) was administered. Sedation levels were
      monitored, and propofol (up to 0.5 mg/kg) was administered if patients had discomfort. When
      patients required more than 50 µg fentanyl and/or 0.5 mg/kg propofol, the block was
      considered as unsuccessful and general anesthesia was administered. Intraoperative and
      postoperative nausea, vomiting, pruritus, respiratory depression and other side effects were
      recorded at the first, second, sixth, and twelfth hours. Metoclopramide (10 mg IV) was
      administered for nausea, and diphenhydramine (25 mg) was administered for severe pruritus,
      Surgery procedures were performed by the same surgeon with no knowledge regarding the groups.
      Surgeon satisfaction score was evaluated according to the sufficiency of muscle relaxation
      and the provision of adequate surgical conditions (0= pair, 1= fair, 2= good, 3= excellent).

      The time of first analgesic requirement was recorded for the patients, and pethidine
      hydrochloride (50 mg IM) was administered as the first analgesic. Following this, analgesic
      treatment was continued with diclofenac sodium (75 mg IM) as additional analgesic among cases
      in which VAS>3. Diclofenac sodium requirement during the first 24 hours were recorded.

      Statistical Analysis Sensory block duration was used as main end-point for statistical
      analysis. Power analysis based on previous studies14,15 indicated that the minimum number of
      patients required for 80% power (α=0,05, β=0,20) was 24 per group for detecting 25%
      difference in sensory block duration. Statistical analysis was performed using SPSS version
      17.0 (SPSS Inc, Chicago, Illinois). Categorical measurements were recorded as numbers and
      percentages, continuous measurements with mean and standard deviation (Mean±SD), and also
      with the median (minimum-maximum) where necessary. In the comparison of categorical
      variables, the chi-square test or the Fischer's exact test were used. The ANOVA test was used
      for distributions, in the comparison of continuous measurements between the groups, while the
      Kruskal-Wallis test was used for parameters without normal distribution. Hemodynamic data
      were analyzed with repeated measure analyses. Values of p<0.05 were considered statistically
      significant.
    

Intervention name(s): Control Group Chirocaine; Group Fentanyl; Group sufentanil; Ephedrine; Atropine sulfate; Propofol; Metoclopramide; Diphenhydramine; pethidine hydrochloride; Diclofenac sodium
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Control group: Spinal anesthesia with levobupivacaine+Serum Physiologic %0.9 (Total volume 3 mL); If systolic blood pressure values decreased more than 20% with respect to the baseline values, or decreased to <100 mmHg, fluid loading and ephedrine (5 mg) were administered.; A decrease in heart rate to less than 55 beats/min was considered as bradycardia, and atropine (0.5 mg) was administered; Intravenous propofol (up to 0.5 mg/kg) was administered if patients had discomfort; Metoclopramide (10 mg IV) was administered for nausea; for severe pruritus; pethidine hydrochloride (50 mg IM) was administered as the first analgesic postoperatively; as additional analgesic among cases in which VAS>3(Postoperatively)
Other intervention name(s): Chirocaine; Chirocaine®, Abbott Laboratories, Ireland; 113/13; 16.12.2002; Serum Physiologic %0.9; Serum Fizyolojik %0.9 10 ml Ampul; Adeka İlac; 8699587751799; Fentanyl®, Johnson&Johnson, USA; 110/53; 01.08.2001; Sufenta®, Johnson&Johnson, USA; 108/26; 15.08.2000; EFEDRİN HİDROKLORÜR AMPUL 0.05 g, 1 ml; 30.06.1999 - 192/42; OSEL İlaç San. ve Tic. A.Ş. Beykoz/İSTANBUL; ATROPİN SÜLFAT AMPUL 1/4 mg, 1 ml; 30.06.1999 - 192/9; OSEL İlaç San. ve Tic. A.Ş. Beykoz/İSTANBUL; Propofol Ampul; Abbott Laboratories, USA; 23.12.1998 - 105/37; Metpamid Ampul; Üretici Firma:YENI ILAC VE HAMMADDELERI SANAYI VE TICARET A.S.; Esenyurt/ISTANBUL; 300188-1 BR; Etken Madde(ler):Metoklopramid HCI 10 mg/2 ml; Benison Ampul; Osel İlaç; 8699788750300; Aldolan ampul; Liba Laboratuarları A.Ş.; 20.12.1985 - 86/29; Gerot Pharmazeutika GmbH, Arnethgasse 3, 1171 Viyana, Avusturya; Diclomec Ampul 75 mg/ 3 ml; Mecom Saglik Urunleri San. ve Tic. A.S; 8699633759366
Intervention MeSH terms: Diphenhydramine; Promethazine; Diclofenac; Atropine; Ephedrine; Fentanyl; Sufentanil; Meperidine; Metoclopramide; Propofol; Levobupivacaine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: spinal anesthesia; caesarean section; local anesthetics; levobupivacaine; sufentanil; fentanyl; above 18 years of age; pregnant women; multiparous; nulliparous