Efficacy of Esmolol Versus Magnesium Sulphate on Quality of Recovery in Patients Undergoing Laparoscopic Cholecystectomy: Randomized Controlled Study
Condition: Esmolol Adverse Reaction
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      sixty patients, of both sexes, of ASA I or II planned for ambulatory laparoscopic
      cholecystectomy under general anaesthesia were engaged into 2 groups. Esmolol group were
      given 1 mg/kg loading dose followed by 30 μg/kg/min throughout the surgery, whereas magnesium
      sulphate (MgSo4) group were given loading dose 40 mg/kg over 15 mins then maintenance dose 15
      mg/kg/h till end of surgery. General anaesthesia was standardized and postoperative analgesia
      included fentanyl. Variables denoting immediate recovery from anaesthesia, pain score and
      time of stay in PACU were recorded. White-Song score ≥ 12 along with pain score < 4 were the
      cut off levels for patients' discharge from PACU.
    

Detailed description: 
      The primary end point of this study are variables concerning immediate postoperative recovery
      like times needed for spontaneous eye opening, tongue protrusion, extubation and ability of
      the patient to mention name. Secondary outcomes includes pain assessment using pain numerical
      scale, time for first call to analgesia, total amount of intraoperative fentanyl consumption,
      total dose of rescue antiemetics and time of discharge from PACU.

      Following attaining Ethical committee approval and patient's written consent- after broad
      explanation of the entire procedure- 60 patients aged 20-65 years of both sexes, of American
      society of Anesthesiologists (ASA) physical status I and II planned for ambulatory
      laparoscopic cholecystectomy under general anaesthesia were engaged to this study.

      Exclusion criteria were: patients on chronic use or known allergic to the study drugs, body
      mass index >35 kg/m2, significant organ dysfunction, cardiac dysrhythmias, neuromuscular
      diseases, liver or renal disease, known asthma or reactive airway diseases.

      Preoperatively all participants were carefully evaluated via detailed history taking,
      thorough physical examination and routine investigations (complete blood picture, renal
      function tests and liver functions). Also, they were instructed in the utilization of the
      verbal rating scale (VRS).

      For blinding purpose, both the study drugs were prepared by an anaesthesiologist not enrolled
      in data assumption. Accordingly, for every case 2 prefilled syringes; one 10-ml for loading
      dose and the other 20-ml for maintenance infusion were given unidentified to the operating
      theater containing either Esmolol (Esmolol hydrochloride; Baxter Healthcare Corp., Deerfield,
      USA) or MgSo4 ( Egyptian international pharmaceutical indust., EYGPT).

      Randomization was achieved prior to the study by means of randomization table prepared by
      computer software to assign the number of cases among the studied groups. Patients were
      randomly allocated using closed envelopes method into 2 equal groups (n=30 each):

        -  Group (E): (Esmolol group) received loading dose 1 mg/kg followed by maintenance dose of
           30 μg/kg/min throughout the surgery.

        -  Group (M): (Magnesium sulphate group) received loading dose 40 mg/kg over a period of 15
           mins and maintenance 15 mg/kg/h throughout the surgery.

      Loading dose was given after fentanyl injection and before propofol induction. Maintenance
      dose was continued until the end of the procedure.

      No premedication was offered. On arrival to the operating room, an intravenous cannula was
      placed and secured before induction of anaesthesia and all patients were attached to standard
      monitors including pulse oximetry, ECG, non- invasive blood pressure and end tidal carbon
      dioxide (ETCO2) monitor (Datex ohmeda S/5).

      Anaesthesia was induced with 1 μg/kg fentanyl and 1.5 - 2 mg/kg propofol till cessation of
      verbal contact. Cisatracurium 0.15 mg/kg was used for neuromuscular relaxation and
      endotracheal intubation (via 8 or 8.5 mm for males, 7 or 7.5 mm for female patients,
      high-volume/low pressure portex endotracheal tubes). Soon after induction, in both groups IV
      dexamethasone 8 mg was given and 1 g paracetamol IV was infused over 15 mins. Anaesthesia was
      maintained with sevoflurane 1-2 % with 50 % oxygen in air. Increments of IV fentanyl 0.5
      µg/kg was given for analgesia if systolic blood pressure or heart rate was increased by more
      than 20 % of baseline level, also incremental dose of cisatracurium 0.03 mg/kg was used to
      maintain muscle relaxation according to nerve stimulation. Patients were mechanically
      ventilated to maintain ETCO2 between 33-35 mmHg and an oxygen saturation of 98 %. The port
      sites were infiltrated by the surgical team with 3ml of 0.25% bupivacaine. Pneumoperitoneum
      with carbon dioxide was achieved, maintaining the intraabdominal pressure at 12 mm Hg
      throughout surgery. Patients were positioned in 30 degrees anti-Trendelenburg position and
      rotated toward the left side to facilitate exposure of the gall bladder. IV warmed 0.9 % NaCL
      was given during surgery at a rate 6 ml/kg/hr. If required, intraoperative hypotension (mean
      arterial blood pressure lower than 50 mm Hg) and bradycardia (heart rate < 40 bpm) were
      managed in both groups with i.v ephedrine and atropine respectively. At the end of surgery,
      patients were returned to the supine position and the Co2 left in the peritoneal cavity was
      expelled by abdominal compression slowly. 0.25 % bupivacaine was injected again at the
      surgical incisions. Esmolol and Mgso4 infusions were stopped and discarded at end of the
      procedure, which was marked at the end of skin closure and wound coverage. Anaesthesia was
      discontinued and 100 % oxygen was administrated. Reversal of muscle relaxants by i.v
      neostigmine 0.04-0.08 mg/kg and atropine 0.02 mg/kg, and then oral secretion was suctioned
      and the patients were extubated fully awake after return of the protective airway reflexes
      with full muscle power. Times passed from end of procedure till spontaneous eye opening (from
      cessation of infusions till spontaneous eye opening), extubation, tongue protrusion, and
      patient's ability to mention name were recorded. Duration of surgery (time from skin incision
      till end of procedure) and duration of anaesthesia (time from induction till shifting the
      patients from operating table to the PACU) were also recorded.

      Patients were transferred to the postanesthesia care unit (PACU) where heart rate, arterial
      blood pressure, respiration, and temperature were continuously monitored by a nurse blind to
      the study deign to avoid bias. Postoperative pain management included 1 g of paracetamol IV
      at 8 hr. Assessed of postoperative pain was done using pain numerical rating scale (NRS) on
      immediate arrival to PACU and every 30 mins for the first 2 hours afterwards. NRS is a (0-10)
      scale, where (0) denotes no pain, whereas (10) refers to maximal pain imagined. Fentanyl (25
      μg) IV was used when NRS exceeded 4. Times to first rescue analgesia and total amount of
      fentanyl consumed were recorded. Recue antiemetic ondansetron (4 mg) IV was given for nausea
      lasting > 5 min (persistent) or vomiting and repeated as required. Total dose of ondansetron
      was noted.

      The White-song scoring system a more up to date quick track scoring framework incorporating
      fundamental fast track variables like physical steadiness, vitals and consciousness level has
      been proposed to evaluate the recovery profile. Furthermore it involved assessment of adverse
      events like postoperative pain and vomiting, which were unfortunately missed by the modified
      Aldrete score. A minimum score (12 / 14) should be established prior to patient safe
      fast-tracked. It was evaluated on immediate arrival to PACU and every 30 mins for the first 2
      hours afterwards. Patients reached White-Song score 12 + NRS < 4 were discharged from PACU.
      Length of stay in PACU till discharge were also recorded
    

Intervention name(s): Esmolol; Magnesium sulfate
Intervention type(s): Drug; Drug
Intervention description(s): loading dose 1 mg/kg followed by maintenance dose of 30 μg/kg/min throughout the surgery.; loading dose 40 mg/kg over a period of 15 mins and maintenance 15 mg/kg/h throughout the surgery.
Intervention MeSH terms: Magnesium Sulfate; Esmolol
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: 60 patients aged 20-65 years of both sexes, of American society of Anesthesiologists (ASA) physical status I and II planned for ambulatory laparoscopic cholecystectomy under general anaesthesia were engaged to this study.
Group (E): (Esmolol group) received loading dose 1 mg/kg followed by maintenance dose of 30 μg/kg/min throughout the surgery.
Group (M): (Magnesium sulphate group) received loading dose 40 mg/kg over a period of 15 mins and maintenance 15 mg/kg/h throughout the surgery.
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: cholecystectomy; recovery profile; opioid sparing