A randomized study to compare sugammadex with neostigmine for recovery of muscle function by ultrasonographic assessment in patients undergoing laparoscopic cholecystectomy

Study will be conducted after approval from the institutional ethical committee (IEC) and will be registered with clinical trial registry - India (CTRI). A detailed pre-anaesthetic check up including detailed history,  physical examination baseline investigations as per clinical requirements will be performed. A written and informed voluntary consent will be obtained from the patient.

An investigator with no further involvement in the study will generate a list of random numbers by using computer randomization and patients will be randomized to one of the two study groups: Group (I) and Group (II) in the operating room prior to surgery and a code will be allotted with no restrictions or bias.

Group (I)****: Patients will receive sugammadex for reversal of neuromuscular block in dose 2mg/kg

Group (II)****: Patients will receive neostigmine for reversal of neuromuscular block in dose 0.05mg/kg + glycopyrrolate 0.01mg/kg

The results of the allocation will be concealed in sequentially numbered sealed opaque envelopes mentioning the code and the group number. The independent observer will be unaware of the drug being administered.  Drugs as mentioned in the randomized envelope will be prepared in a 10ml syringe by a resident not  involved in the study and will be labelled with the code allotted to that particular patient.

Patients will be kept nil per oral (NPO) for at least 8 hours prior to surgery as per standard     guidelines. Patients will be pre-medicated with tablet alprazolam 0.25mg HS and tablet pantoprazole 40mg HS and 6AM on morning of surgery with sips of water. Baseline diaphragm thickening fraction (DTF), diaphragmatic excursion (DE) and internal oblique muscle thickening fraction (IO TF) will be measured pre-operatively.

Ultrasonography will be performed during spontaneous breathing to help identify the moving  diaphragm using  SonositeTM Edge II Total ultrasound machine.

The diaphragm thickening fraction (DTF) will be measured using curvilinear  transducer (2 to 5 MHz) in two-dimensional B-mode ultrasound at the zone of apposition during inspiration and expiration using intercostal approach (8th - 9th intercostal space) at the level of mid axillary line. The thickening fraction will be calculated as (thickness at end inspiration-thickness at end expiration)/thickness at end expiration.

The diaphragmatic excursion (DE) will be measured with anterior subcostal view at midclavicular line in M- mode.  The same transducer will be used, directed medially, cranially, and dorsally, so that the ultrasound beam reaches the posterior third of the right diaphragm. Either dome of diaphragm will be measured using liver and spleen window, whichever is clearly visible.

The internal oblique muscle thickening fraction(IO TF) will be measured using a linear probe (6 to 13 MHz) positioned on the right anterior axillary line, midway between the inferior border of the rib cage and the iliac crest, perpendicular to the abdominal wall. The thickness of the internal oblique muscle will be first measured at end inspiratory and at maximum contraction when the patient is told to cough with maximum strength. IO TF = (end coughing thickness-end inspiratory thickness)/end inspiratory thickness.

Patients will be wheeled in to the operation theatre and all routine monitors will be attached including neuromuscular monitor (NMT) and bispectral index (BIS).  Intravenous access will be obtained. Patients will be pre-medicated with intravenous fentanyl 2 µg/ kg.  Anaesthesia will be induced intravenously with slow administration of propofol 1.5-2 mg/kg to achieve a BIS of < 60 . Rocuronium 0.6mg/kg will be administered intravenously to facilitate endotracheal intubation under direct vision with an appropriately sized endotracheal tube.

Anaesthesia will be maintained with sevoflurane in oxygen (40%) + air. Age adjusted  minimum alveolar concentration (aaMAC) will be adjusted to maintain a BIS of 40-60. Electrocardiograph, heart rate, blood pressure,  SpO2,  EtCO2, aaMAC, NMT and temperature will be monitored throughout.

Injection fentanyl will be repeated hourly at a dose of 1 µg/ kg. Injection paracetamol 1 gram will be administered during the surgery and inj. Ondansetron 0.08mg/kg at the end of pneumoperitoneum. After the end of surgery, the residual neuromuscular block will be reversed with  sugammadex 2mg/kg or neostigmine 0.05mg/kg with glycopyrrolate 0.01mg/kg according to the group allocated when  when the train-of-four (TOF) count is 4. Inhalational anaesthetic agents will be stopped after administration of reversal agent and trachea will be extubated once the patient is awake.

Diaphragm thickening fraction, diaphragmatic excursion and internal oblique muscle thickening fraction will be measured post extubation, at 30 minutes and 1 hour after extubation.  If the patient complains of pain post-operatively, or the numeric pain rating scale (NRS) >3,  fentanyl will be repeated at 0.5 µg/ kg. All the above measurements will be made only when the NRS < 3. Post extubation, the patient will be monitored for any side effects such increased glandular secretions, bradycardia, vomiting, diarrhoea, chest discomfort, blurred or loss of vision, anaphylaxis, laryngospasm etc.