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 one 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.

Review of Literature:

1.  IbrahimA et al, in their prospective, double-blinded, and randomized clinical study allocated Forty four patients randomly into 2 groups of equal size to receive either lidocaine infusion (Lidocaine group), or 0.9% sodium chloride infusion (Control group). Randomization was performed using lidocaine group, and control group registers, which were placed in sealed envelopes prior to study initiation, and opened prior to anaesthesia by a physician who prepared the IV solution, and identified it with the patient number, according to the envelope drawn. The solution was handed to another physician, blind to the prepared solutions’ content, who was responsible for the anaesthesia. The investigator was also blinded to the groups till the end of the study. General anaesthesia was induced by propofol 2.5mg/kg, and cisatracurium 0.15mg/kg to facilitate orotracheal intubation. Patients were then assigned to either the lidocaine, or control group by closed-envelope randomization. In both the groups, anaesthesia was maintained with isoflurane in oxygen/air mixture at sufficient concentration to maintain systolic blood pressure within the limit of 20% baseline value. All patients received 60 mg ketorolac IV infusion after induction of anaesthesia, and fentanyl 1.5mg/kg IV before skin incision. Acetaminophen (paracetamol) 1gm was given by IV infusion to all patients before extubation. Reversal of residual muscle relaxant was accomplished using neostigmine, and atropine at the end of the operation. The infusion in both groups was initiated at the time of anaesthesia induction, and continued until the end of the operation. In the first 24 hours postoperative; patients were given Ketorolac 30mg slowly IV (diluted to 10mL), and paracetamol 1 g injection for 8 hours. Morphine 0.1mg/kg slowly IV was given as rescue analgesia when VAS was ≥4, or if the patient requested additional analgesia. A maximum of 3 doses of IV morphine were prescribed, with a minimum 8 hours interval between the 2 consecutive injections. After 24 hours post-operation; paracetamol 1 g, and ketorolac 10mg for 8 hours were given orally for 2 weeks. They found that the mean values of hospital stay was significantly lower in the lidocaine group when compared to that of the control group. The mean values of postoperative VAS pain score were significantly lower in the lidocaine group in the first 48 hours post operation, and during the study period up to 3 months after the operation . The mean time to first analgesic request was significantly longer in lidocaine group compared to the control group .However the limitation of their study was the decreased number of patients enrolled in the study and they haven’t specified what were the type of surgeries or at what spinal level the surgeries were done for these patients undergoing spinal fusion surgeries. ⁷

2.  Batko I et al, in their prospective randomized double blind study, enrolled all children undergoing multilevel spine surgery from May 2015- June 2016 , wherein patients were randomly assigned to the lidocaine or the control group using a computer-generated random table and an allocation ratio of 1:1. The randomization sequence was generated by a hospital pharmacist who was not involved in the study and they then prepared a coded syringe which contained a blinded fluid (BF): lidocaine 20 mg/ml (Lignocainum hydrochloricum WZF 2%: Polfa S.A. Warsaw, Poland) or placebo -multi-electrolyte fluid (Fresenius Kabi, Warsaw, Poland). BF was administered intravenously as a half hour bolus before skin incision 0.075 ml/kg/30 min, and then continued intraoperatively for up to 6 h after surgery at a fow of 0.05 ml/kg/h. The medical personnel responsible for the perioperative patient care (anaesthesiologists, surgeons, nurses) and the patient himself were blind to what BF was. The protocol of perioperative management was identical for all patients. The first dose of oral gabapentin 15 mg/ kg (max. 600 mg)was given 4 h before surgery. For induction to the general anaesthesia: fentanyl 1 Î¼g/kg, propofol 2 mg/kg and rocuronium 0.6 mg/kg  were used. Anaesthesia was maintained with a mixture of sevofurane, oxygen and air . Thirty minutes before skin incision, acetaminophen 15 mg/kg, dexamethasone 0.1 mg/kg and a BF (lidocaine 1.5 mg/kg/30 min or placebo) were applied. During surgery, analgesia was provided with fractionated doses of fentanyl. After induction and before the end of anaesthesia, the first two doses of 0.1 mg/kg morphine were administered intravenously .Intravenous BF infusion (lidocaine 1 mg/kg/h or placebo) was continued during the entire procedure and for 6 h postoperatively. The severity of pain felt by the child was assessed immediately after surgery and at 2, 6, 9, 15, 24, 30, 40, 48 h postoperatively. In the same time intervals, the intensity of postoperative nausea (the NRS scale: 0=no nausea, 10=the worst imaginable form of nausea) and the required antiemetic and analgesic agents were evaluated. Intravenous morphine and non-opioid analgesics were used to treat postoperative pain. For two days after surgery, pain was treated as patient-controlled analgesia (PCA) with i.v. morphine sulfate at a concentration of 1 mg/ml, with a bolus of 1 mg, a lockout-interval—15 min and a maximum dose—0.3 mg/kg/4 h. During the first 16 h after surgery (night time), a background infusion of morphine was about 20 Î¼g/kg/h (0.5 mg/h—patients weighing less than 40 kg or 1 mg/h—patients weighing more than 40 kg). With pain reported above 3 NRS, an additional morphine bolus was administered by a blinded non-study nurse (1 mg/kg). After two days, morphine was administered as a single bolus of 0.1 mg/kg via subcutaneous route depending on demand. Postoperatively, morphine consumption was recorded once a day and converted to mg/kg/24 h. They found that the lidocaine group had significantly lower cumulative morphine consumption compared to the control, with a reduction of over 30% at 48 h. The cumulative morphine consumption for entire postoperative period was lower in the lidocaine group compared to control, with a reduction of approximately 35%.Patients from the lidocaine group had lower severity of pain at the rest up to 9 h postoperatively, and during coughing up to 6 h. The severity of nausea was higher up to 9 h postoperatively in the control group. The average time of the first intake of liquid diet and solid food in children from the lidocaine group was significantly shorter in comparison with the control group. But there was no statistical difference in hospital stay after surgery between both groups. ⁸

3. Farag E et al , in their study enrolled 116 American Society of Anesthesiologists Physical Status I–III patients, between the ages of 18 and 75 yr, who were scheduled for elective multilevel spine surgery with or without instrumentation from September 2009 to October 2011 . Patients were assigned to one of two groups using a reproducible set of computer-generated random numbers just before induction of anaesthesia : (1) IV lidocaine (2 mg·kg−1·h−1) with maximum of 200mg/h starting at induction of anaesthesia and continuing until discharge from the post anaesthesia care unit (PACU) or a maximum of 8 h; or (2) an equal volume of saline placebo. Investigators, clinicians, and patients were all fully blinded to treatment allocation. General anesthesia was induced with propofol or etomidate and maintained with sevoflurane. Postoperatively, pain was treated with patient-controlled analgesia with morphine sulfate at a concentration of 1mg/ ml, with a demand dose of 1mg and a lockout interval of 10min. Comparable doses of fentanyl or hydromorphone were used on patients unable to tolerate morphine. Bolus doses of opioid were provided if additional analgesia was required. Patients were transitioned to oral opioids on the first postoperative day (POD) according to the pain management protocol at our institution. They found that the mean post op pain scores, total IV morphine dose was lesser in the lidocaine group. The lidocaine group also exhibited a significantly higher SF-12 physical composite score at 1 and 3 months, postoperatively. They also had fewer complications post operatively.⁹

4.  Sloan T B et al, in their retrospective analysis studied the effect of Lidocaine infusion as an adjunct to TIVA on the total dose of propofol given intraoperatively. They reviewed records of all spine surgeries between September 1 , 2012 and march 31, 2013. They found that out of 129 spine procedures, 50 used lidocaine infusion with propofol-opioid TIVA and the remainder 79 received propofol-opioid TIVA only. When used, a lidocaine infusion was started at induction using a rate of 1.5 milligrams per kilogram per hour (mg/kg/h) with a maximum infusion rate of 120 mg per hour. The infusion was stopped approximately 45 min prior to the estimated conclusion of the procedure. The rate of propofol infusion was adjusted clinically at the discretion of the anaesthesiologist as was the choice and infusion rate of the opioid. To estimate the potential savings of propofol, it was assumed that the amount of propofol used in the TIVA group would be reduced by the percentage reduction of the propofol infusion observed in the TIVA/Lido group. The average propofol infusion in the TIVA group was 115 and 99 mcg/kg/min in the TIVA/Lido group. The average savings of propofol was estimated to be 383 mg per case. Calculating the actual and estimated propofol used on a case-by-case basis, and considering the waste of partially used 50 ml bottles, 751 (50 ml) bottles of propofol were estimated to have been used if all cases were done with propofol-opioid TIVA and 647 (50 ml) bottles would have been used if lidocaine supplemented the TIVA, resulting in a savings of 104 (50 ml) bottles. Evaluation of the sufentanil used showed a reduction of the infusion rate from an average of 0.36–0.2 mcg/kg/h, which resulted in a net savings of 2–98 mcg per case with an average of 28 mcg per case. Along with these findings they also concluded that the recorded MEP, SSEP responses were not affected by the Lidocaine infusion.¹⁰
5. Herzog J et al,in their randomised controlled trial included 60 patients undergoing robot assisted laproscopic colorectal surgery in their study, wherein 30 patients received IV Lignocaine infusion at 1.5mg/kg/hour after a bolus dose of 1.5 mg /kg at the start of induction. This infusion was continued upto 2 hour in the Post Anaesthesia Care unit (PACU) after end of surgery. Intraoperative analgesia was maintained with Sufentanil(dose not specified in study). Upon arrival to the PACU, the patient was connected to a morphine intravenous pump without background infusion and patient-controlled bolus doses of 0.04 mg/ kg were possible every 7 min .They found that the median cumulative opioid consumption was 43.3 (range: 35- 70.6) mg in the lidocaine group versus 41.3 (25-63.8) mg in the control group. This difference was not significant. For NRS(Numerical Rating Scale) at 24 and 72 h, no significant difference was seen in outcomes between both the groups.¹¹

Objectives of study:

1. To study the role of Intraoperative IV lignocaine in reducing post operative Visual Analogue Scale(VAS) Scores in Robotic one level lumbar decompression and fusion Spine surgeries
2. To compare total analgesics used in the two groups.
3. To compare the patient mobilisation post surgery in the two groups
4. To compare the LOS in hospital in the two groups
5. To assess patient and surgeon satisfaction

Departments involved : Department of Spine Anaesthesiology, Manipal Hospital, Old airport Road.

Study Design: A prospective double blinded randomized control study.

Study period : Following ethics committee  approval study will be conducted for a duration of 12 months

Sample size : Assuming a medium effect size for the difference between the pain scores of the two groups(d=0.5), setting power at 80% and level of significance (alpha) at 5% , a sample size of at least 128 patients (64 per group) is required. After adjusting for 10% dropout rate , a sample size of at least 142 patients (71 per group) will be needed . R software has been used for calculating the sample size.

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.

2. 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 participant and researcher 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 who will prepare the drug and administer it to the patient as per the group to which they belong.

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 6^th hourly, IV Tramadol 50mg in 100 ml NS given 12^th 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

 Potential risks and benefits :

Risks- NIL

Benefits- Better patient outcomes and improving quality of care.

References

1. Bianconi M, Ferraro L, Ricci R, Zanoli G, Antonelli T, Giulia B, Guberti A, Massari L. The pharmacokinetics and efficacy of ropivacaine continuous wound instillation after spine fusion surgery. Anesthesia & Analgesia. 2004 Jan 1;98(1):166-72
2. Prabhakar H, Mahajan C, Kapoor I. Anesthesia for minimally invasive neurosurgery. Current Opinion in Anaesthesiology. 2017 Oct 1;30(5):546-50.
3. Gerbershagen HJ, Aduckathil S, van Wijck AJM, Peelen LM, Kalkman CJ, Meissner W: Pain intensity on the first day after surgery: a prospective cohort study comparing 179 surgical procedures. Anesthesiology 118:934–944, 2013
4. Farag E, Ghobrial M, Sessler DI, et al. Effect of perioperative intravenous lidocaine administration on pain, opioid consumption, and quality of life after complex spine surgery. Anesthesiology 2013;119:932–40.
5.  Beilin B, Shavit Y, Trabekin E, et al. The effects of postoperative pain management on immune response to surgery. Anesth Analg 2003; 97:822–7.
6.  De Oliveira CMB, Sakata RK, Slullitel A, et al. Effect of intraoperative intravenous lidocaine on pain and plasma interleukin-6 in patients undergoing hysterectomy. Braz J Anesthesiol 2015;65:92–8.
7. Ibrahim A, Aly M, Farrag W. Effect of intravenous lidocaine infusion on long-term postoperative pain after spinal fusion surgery. Medicine. 2018 Mar;97(13).
8. Batko I, Kościelniak-Merak B, Tomasik PJ, Kobylarz K, Wordliczek J. Lidocaine as an element of multimodal analgesic therapy in major spine surgical procedures in children: a prospective, randomized, double-blind study. Pharmacological Reports. 2020 Jun;72:744-55.
9. Farag E, Ghobrial M, Sessler DI, Dalton JE, Liu J, Lee JH, Zaky S, Benzel E, Bingaman W, Kurz A. Effect of perioperative intravenous lidocaine administration on pain, opioid consumption, and quality of life after complex spine surgery. Anesthesiology. 2013 Oct 1;119(4):932-40.
10. Sloan TB, Mongan P, Lyda C, Koht A. Lidocaine infusion adjunct to total intravenous anesthesia reduces the total dose of propofol during intraoperative neurophysiological monitoring. Journal of clinical monitoring and computing. 2014 Apr;28:139-47.
11. Herzog J, Schou M, Jensen KM, Lauridsen JT, Jensen AG. A randomised controlled trial of lidocaine infusion on post-operative opioid consumption in patients undergoing robotic colorectal surgery. Dan Med J. 2020 Jan 1;67(1):A06190342.