Comparative study of intraoperative Intravenous lignocaine infusion as a part of the multimodal analgesic therapy in Robotic multilevel (2-3) lumbar fusion surgery- A Prospective Randomized Double Blinded Controlled trial

Introduction

Spine surgeries are known to cause severe postoperative pain , which may last for at least 3 days.1 In the current scenario with continuous innovations in surgical instruments and computer-assisted technology, minimally invasive surgical approach and robot assisted surgeries is becoming more of a norm. The ultimate aim is to improve the patient’s overall outcome and satisfaction. These new surgical advancements allow for minimal dissection, less blood loss, pain, scarring, short surgical time and faster recovery time to name a few.2Inadequate analgesia often delays recovery and discharge of patients, and increases the man power and cost burden on the hospital .Even with the introduction of the robot and minimally invasive techniques, Lumbar fusion and complex spinal reconstruction are still among the six most painful procedures in the Gerbershagen et al study on pain intensity across 179 different surgical procedures.3 A common mechanism for many adverse outcomes in patients with spinal fusion surgery is the systemic inflammatory response to surgical tissue injury.4 In addition, the activation of glial cells in the surgical wound stimulates the production of cytokines in the central nervous system, which can induce peripheral, and central sensitization through generation of nitric oxide, free radicals, and excitatory amino acids, possibly also causing chronic, and neuropathic pain.5 Lidocaine has been shown to have analgesic and anti-inflammatory effects that are induced by reduction of cytokines production through inhibition of neutrophil activation, and the analgesia may persist even after plasma concentration reduction.6

Therefore the use of  intravenous (IV) Lidocaine infusion as part of the intraoperative total intravenous anaesthetic (TIVA) regimen makes it a viable option for post operative pain control in patients undergoing robotic lumbar decompression and fusion surgery arising from various spine pathologies. Most of the current literature in Spine surgery have used Intraoperative Lignocaine infusion for open spine surgeries and presently there is no consensus on its usage in Robotic Spine surgeries. Our aim is to study the effects of IV lignocaine on Intraoperative hemodynamics, postoperative Visual Analogue Scale(VAS) pain scores, total analgesic consumption ,time to mobilization , hospital Length Of Stay(LOS), satisfaction scores and Quality of recovery scores especially in patients undergoing Robotic Spine surgeries.

Type of Study –Randomised controlled trial

 Aims & objectives: To assess the role of Intraoperative intravenous (IV) lidocaine on postoperative pain, analgesic consumption and its effect on recovery in adults undergoing Robotic 2- 3 level lumbar decompression and fusion Spine surgeries  Justification for study: The efficacy of Intraoperative IV lignocaine to decrease post operative pain scores and opioid consumption in patients undergoing Robotic lumbar spine surgery requires further exploration to facilitate and develop future opioid sparing multimodal analgesia regimens.  We hope such regimens can be further applied to other types of robotic spine surgeries also.

INCLUSION CRITERIA:

1. Adult patients aged between 18 and 65 years of either sex.

2. ASA I and ASA II undergoing general anesthesia for elective Robotic Spine surgery.

3. Mallampati class I and II.

EXCLUSION CRITERIA:

1. Patient refusal.

Body mass index ≥ 35 kg/ m2

3. Patients with cardiac, coronary, renal, hepatic, cerebral diseases and peripheral vascular diseases.

4. Patients coming for emergency surgeries.

5. Pregnancy.

6. Neuromuscular disorder.

7. Anticipated difficult intubation.

8. Inability to use VAS (Visual Analogue Scale).

9. History of allergy to Local Anaesthetics

 BLINDING: It will be a double blinded study, both researcher and observer will be unaware of drug being administered.

Study subjects allocation –

Patients fulfilling the inclusion criteria will be divided randomly into two groups using the random table generator. On the day of surgery, the drug to be administered will be picked randomly from a sealed envelope by an anesthesiologist unrelated to study.

Group A- will receive IV lignocaine infusion 2 mg per kg per hour along with the standard TIVA regimen.

Group B- will receive IV placebo infusion (saline) along with the standard TIVA regimen.

c) Statistical methods :

Statistical analysis will be performed on SPSS software Version 20.0 (IBM Corp., Armonk, New York, USA). The distribution of variables will be evaluated for normality using the Kolmogorov-Smirnov and histogram tests. Descriptive data will be expressed as mean standard deviation. Categorical variables will be analyzed using the chi square test. Normally, distributed data comprising continuous variables will be analyzed using the Student t test. Otherwise, the Mann Whitney U test will be used. P < 0.05 will be considered statistically significant

Methodology:

After obtaining approval by the Institutional  scientific and ethics  Committee patients will be enrolled to the study. Written informed consent will be obtained from every patient. During the preoperative interview, in addition to the detailed pre anaesthetic check up and relevant work up, patient’s pain score will be assessed by the Visual Analogue Scale . Detailed Consent for the study will be taken.

The study will have two groups.

Group A : Will receive IV Lidocaine 2 mg/kg/hour infusion along with TIVA

Group B : Those will receive IV saline infusion along with TIVA.

On arrival to the operating room, standard ASA monitors will be applied (electrocardiography, non invasive blood pressure monitor, and pulse oximetry). A balanced intravenous crystalloid solution (lactated Ringer’s solution) will be  administered (2ml/kg/hr). Before induction, IV Ondansetron 4mg, IV Pantoprazole 40 mg will given. Anaesthetic induction will be performed while providing 100% oxygen (10 L/min). IV Lidocaine bolus of 1.5 mg/kg will be administered followed by which Infusion of study drug(based on the group randomisation) will be started . All patients will receive pre emptive analgesia with fentanyl (2mcg/kg), followed by hypnotic dose of IV Propofol (1.5–2 mg/kg) and Rocuronium (0.6-1.2mg/kg) for intubation. After endotracheal intubation,  patient will be positioned prone with optimal padding of pressure points .

Group A

• Patients will receive the following TIVA regimen:1) propofol (50–150 μg/kg/hr), titrated to maintain entropy 40-60 

2. lidocaine (2 mg/kg/hr) and 3) Fentanyl (0.5mcg/kg/hr)

Group B- Patients will receive the following TIVA regimen 1) propofol (50–150 μg/kg/hr titarted to maintain entropy 40-60 2)Placebo infusion containing physiological saline and 3) Fentanyl (0.5mcg/kg/hr) .

IV dexamethasone (4 or 8 mg) and IV Paracetamol 1g will be given intra operatively .

In both the groups Infusions will be stopped once skin suturing commences. Inhaled halogenated agents (sevoflurane) will be permitted, up to 0.5 minimum alveolar concentration (MAC), as needed and will also be tapered and stopped before extubation. Mechanical ventilation will be achieved with 1:1 mixture of oxygen:air (FiO2 50%) with a tidal volume of 6–8 ml/kg and respiratory rate of 12- 14 titrated to an end-tidal carbon dioxide between 30–35 mm Hg. Convective warming devices will be used to maintain normothermia . Need based fluid management will be carried out using dynamic indicators such as systolic pressure variability(SPV).  Invasive Hemodynamic monitoring will be done as per patient requirements. Entropy and Neuromuscular monitoring with Train of Four (TOF) and Post Tetanic Count( PTC) will be done throughout the surgery. In all patients, more than 20% elevation in mean arterial pressure and/or heart rate 15% above baseline (or higher) will be treated with additional bolus doses of Fentanyl(0.5 mcg/kg) and/or propofol (up to a 50-mg) boluses, and/ or by increasing the MAC of inhaled anaesthetics. These will be recorded. Post surgery, once patient is made supine, residual neuromuscular blockade will be reversed with IV Sugammadex 2mg/kg as per TOF count. Time to awakening after switching off propofol will be recorded in both the groups. Intraoperative incidence of hypotension and bradycardia will be recorded.

All procedures will be performed by a single surgeon and his team . All procedures will be provided anaesthesia by the same two anaesthesiologists .

In the PACU (Post Anaesthesia Care Unit) our analgesic regimen will be IV Ketorolac 0.5mg/kg in 100 ml NS and IV Paracetamol 1 g (15mg/kg) given 6th hourly, IV Tramadol 50mg in 100 ml NS given 12th hourly/ SOS and IV Pentazocine 10mg SOS(Upto 3 doses) . Rescue analgesic will be IV Fentanyl 0.5mcg/kg (given only in PACU for the first 4 hours) .

All patients will be assessed for pain scores( VAS)  at following time intervals- 30 minutes,  2 hr,4 hrs,8 hrs, 12 hrs and 16 hours, from the time of arrival to the PACU.

Their Hemodynamics will also be continuously monitored.

Incidence of PONV(Post Op Nausea and Vomiting) will be recorded in both groups.

Post operatively , NPO(Nil per oral) will be maintained  for 6 hours, following which patient will be restarted gradually on oral feeds with sips of water/juice.

Time to first mobilisation soon after surgery under guidance of a physical therapist will be recorded and patients will be discharged home early, as soon as the following conditions are true: 1) pain optimally controlled by oral analgesics, 2) no complication (e.g., incidental durotomy) that would require prolonged hospital stay, and 3) ability to climb stairs. Post discharge, patients will have a dedicated support line provided by the Spine care team; Surgical consultation will be routinely undertaken at 7th day Post operatively, during which Satisfaction Scores and Quality of Recovery will be recorded. The above two parameters will also be assessed at 1 month post operatively.

Outcome measures :

Primary outcome will be to assess –

●       Visual Analog Scale (VAS) ranging from 0 to 10 (0=no pain, 10=worst imaginable pain) to score the postoperative pain. The VAS scores will be recorded immediately in the recovery room at 30 minutes, 2 hr,4hr, 8hr, 12hr , and 24 hours postoperatively during bed rest and at 8, 12, and 24 hours during movement. Movement state defined as “moving from supine to semi sitting position”

Secondary outcomes will be :

●       Time to request of 1st rescue analgesic

●       Total Rescue analgesic used .

●       Total analgesics used in both groups

●       Total intraoperative Fentanyl use

●       Total Intraoperative Propofol use

●       Time to awakening( TA) after shutting anaesthetic agents in both groups

●       Richmond Agitation Sedation Score(RASS) at 1st, 2nd, 4th hour in PACU.

●       Hemodynamics recorded at the following time points: before induction, post intubation, before incision, at 1,2,4 hrs, at extubation,and at 1, 2 and 4 hrs post-operatively.

●       Time to feeding(Tf), Time to ambulation(Ta),

●       Adverse effects such as hypotension, Bradycardia(> 20% decline from baseline)/pruritus/ nausea and vomiting post operatively.

●       Length of Stay(LOS) in hospital(post surgery)

●       Incidence of Major/Minor complications will be recorded

●       Incidence of readmission will be recorded

●       Quality of recovery [15-item QoR questionnaire (QoR-15)15: scores ranging from 0 (poorest quality of recovery) to 150 (best quality of recovery)  will be assessed at 24 h, 7 days and 1month after surgery (APPENDIX)

●       Satisfaction scores of patients and surgeon 24 h , 7th day, 1 month following surgery (APPENDIX) using Five-point Likert scales (from 5 = very satisfied to 1 = very unsatisfied) will be used to assess patient satisfaction, including satisfaction with 1) overall participation of various specialities, 2) organization of preparation, 3)Pain control and 4) organization of discharge