Comparing outcomes after incorporating a Multimodal analgesia protocol in a Tier 2 hospital for patients undergoing Lumbar spine surgeries

Aims & objectives (hypotheses if applicable):

Spinal surgeries often cause severe postoperative pain, delaying recovery and increasing hospital stays and costs.Lumbar fusion and complex spinal reconstruction are among the most painful procedures. Incorporating Multimodal Analgesia (MMA) techniques have become a mainstay therapy followed by many institutes for all spine surgeries.But its efficacy in Indian population, especially in tier 2 cities, remains unclear. Further research is needed to optimize pain management strategies, to pander to the Indian demography.

 Hypotheses- Patients receiving MMA have better postoperative pain scores, lesser analgesic consumption, stable intraoperative haemodynamics lesser hospital stay and better patient satisfaction.

4. Justification for study (whether of national significance with rationale):

Spine surgery is considered to be one of the most painful surgeries, due to its complexity and extent of surgery. Multimodal Analgesia (MMA) form the cornerstone of patient care. MMA involves the combined use of various non-opioid agents and regional techniques to target different pain pathways. These agents are administered in lower doses at regular intervals to maximize efficacy while minimizing side effects.These protocols typically include adding acetaminophen, NSAIDs, gabapentinoids, alpha-2 agonists, ketamine, and local anaesthetics via infiltration, regional block, or IV routes along with other routine analgesics agents.

Despite improvements in the understanding of perioperative pain and incorporation of an MMA protocol across several hospitals in other countries, the management of postoperative pain in hospitals in tier 2 cities, in India, still remain suboptimal. Conceptualisation and institutional implementation of evidence-based MMA regimens into clinical pathways, aim to incorporate best practice and improve measurable clinical outcomes- including pain, mortality, hospital length of stay, patient satisfaction and costs.

Moreover, the recent consensus statement for perioperative care in lumbar spinal fusion from the Enhanced Recovery After Surgery (ERAS) Society along with the Guidelines From the Society for Neuroscience in Anaesthesiology and Critical Care (SNACC) recommends use of – Multimodal analgesic strategies such as- intravenous ketamine, lignocaine and magnesium infusions, along with neuraxial techniques such as epidural analgesia/intrathecal morphine/ locoregional blocks. This has been proven to reduce opioid consumption, improve pain control and also reduce duration of hospitalization.

We aim to study whether the same result translates to the Indian population in a tier 2 city.

5. Departments involved: Department of Orthopaedics. Department of Anaesthesia.

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 c) Statistical methods:

Data will be analysed using IBM SPSS ver. 21.0 (IBM Corp., Armonk, NY, USA). Categorical data will be represented as frequencies and percentages. Continuous data will be shown as mean and standard deviation values. Unpaired t-test (parametric test) will be used as test of significance for continuous, normal data. Mann-Whitney test (non-parametric test) will be used as test of significance for continuous, non-normal data. Chi-square test will be used for testing the significance of difference in categorical data. Bar diagrams and line diagrams will be made wherever needed. Time trend graph will be utilized to visualize the rate of change in the VAS score. Inferential analysis will be performed for numerical data using repeated measures analysis of variance or other appropriate technique. The p-value will be determined to finally evaluate the levels of significance. A p-value of LESS THAN 0.05 will be considered as statistically significant

9. Detailed description of procedure / processes:

Following institutional ethics committee clearance, this randomised controlled trial will be conducted after obtaining CTRI number, over the course of 2 years.

After obtaining a written informed consent, all patients will be randomly allocated to either the MMA protocol group or the routine analgesic protocol group-by block randomisation with a block size of 4, using computer-generated random sequence table. The statistician doing the randomisation will be blinded to study and will inform the group allocation to the Co-Investigator, the day prior surgery via telephonic communication. The patients will be unaware of the group allocation and the interventions used, as they will be under anaesthesia. PI will also be blinded to group allocation . Preoperative NRS score and QoR 15 item score will be assessed by PI.

Preoperatively routine analgesic IV Paracetamol and Tab Gabapetin will be given 3 hours prior to shifting to OT.

All procedures will be managed by the same anaesthesiologist (Co- Investigator).

The two groups will be- Multimodal analgesia protocol group (Group A) and the routine analgesic group (Group B). The consultant surgeon (Principal Investigator) - who will be doing the case will be collecting postoperative data, and study subjects, will have no idea regarding the group allocation.

 Anaesthesia technique and perioperative care:

Patient will be connected to standard ASA monitors like pulse oximetry, continuous electrocardiogram observation, and non-invasive arterial blood pressure measurement. For induction of patients received intravenous fentanyl (2 micro g per kg), fixed dose propofol (1.5-2 mg per kg), and for intubation, vecuronium (0.1 mg per kg). Temperature monitoring will be established in all patients. Maintenance will be as per the preference of the anaesthesiologist doing the case. Muscle relaxation will be with intravenous vecuronium (0.02 mgper kg). Mechanical ventilation will be achieved with a 50 is to 50 mixture of oxygen and air (fractional inspired oxygen – 60percent) with adequate tidal volume and respiratory rate titrated to an end-tidal carbon dioxide between 30 and 35 mmHg. Fluid therapy will be provided according to goal directed fluid therapy using dynamic monitors. Vasoactive drugs will be administered when necessary to maintain mean arterial pressure and heart rate within 20percent from baseline. Intravenous dexamethasone 0.1mg per kg and Intravenous Ondansetron 0.12mg per kg will be given to counter post-operative nausea and vomiting. If mean arterial pressure and heart rate is more than 20percent from baseline Intravenous bolus 0.5mcg per kg of fentanyl will be administered. Patients will be placed in prone position under general anaesthesia.

 MMA protocol (Group A):

Analgesic interventions utilised:

Intraoperatively-

A)      Intravenous Ketamine infusion (bolus 0.5 mg per kg) followed by infusion (0.2-0.3) intraoperatively. This will be stopped after spinal instrumentation is completed.

B)      After intubation patient will be made lateral, under Aseptic precautions, the interspinous space above the uppermost level of site of fusion will be chosen and a 16-gauge Touhy’s needle is advanced till the loss of resistance (LOR) is felt at the epidural space using LOR technique. Based on number of levels being fused in lumbar spine surgery, dose of 1.5ml per segment of 0.25 Levobupivacaine, local anaesthetic solution will be used, will be administered slowly with regular aspiration after each 2 ml of the solution. It will be given as a single shot epidural injection. The epidural will be given by anaesthesiologist in lateral position after intubation, before surgeon comes for case. In the group B only a pin prick will be made at the required level, to blind the surgeon.

(Group B).

The above regimen will not be followed. Instead, a Diclofenac transdermal patch will be placed by anaesthesiologist after induction of anaesthesia.

At any time during surgery bolus doses of “rescue dose” Fentanyl 0.5 mcg per kg will be administered. The total number of bolus doses of rescue fentanyl will be noted.

In both the groups, anaesthetic agents used- will be tapered and stopped before extubation. Post surgery, once patient is made supine, residual neuromuscular blockade will be reversed with Intravenous Neostigmine 50 mcg per kg, Glycopyrrolate 10 mcg per kg. MAC(Minimum Alveolar Concentration) maintained intraoperatively will be noted. Time to awakening after switching off all anaesthetic agents, will be recorded in both the groups. Intraoperative incidence of hypotension and bradycardia will also be recorded.

All surgeries were conducted by the same spine surgeon. To avoid possible bias, the Co-PI will be blinded to the postoperative NRS scores and total analgesic usage. These will be recorded by the principal investigator (PI).

10. Outcome measures:

Primary outcomes to be measured:

To Determine and compare the postoperative pain scores.

Secondary outcomes measured:

Determine and compare the intraoperative and postoperative analgesic consumption. intraoperative haemodynamics, incidence of postoperative nausea and vomiting, time to awakening from anaesthesia, time to postoperative patient mobilization, length of hospital stay, quality of recovery score and patient satisfaction score.

 11. Potential risks and benefits:

RISKS-

With MMA:

·       Accidental dural puncture during epidural injection- If occurs, procedure will be abandoned. Bed rest is usually adequate if this complication were to arise.

·       Postoperative delirium / disorientation due to ketamine effects. - Unlikely to occur since this study is using subanaesthetic doses of ketamine. These side effects occur only if infusion is given more than 0.5 mg/kg/hour

With Routine procedure: NIL. Since no new intervention is being applied.

If any complications were to occur, which would lead to ICU admission / additional treatments directly related to above complications- Cost will be covered via applying to the group insurance.

BENEFITS- The validation of the efficacy of MMA techniques enables the integration of non-opioid medication, regional techniques and other minimally invasive modalities into the analgesic framework for complex spine surgeries. This advancement facilitates the acceptance and incorporation of multimodal analgesic protocols, especially in the Indian scenario, in tier 2 hospitals. Consequently, these refinements contribute to optimizing patient recovery and expediting postoperative rehabilitation. This will be systematically incorporated into the Enhanced Recovery After Surgery (ERAS) framework for spine surgeries.

12. Ethical considerations and methods to address issues:

Written informed consent, Participant Information sheet will be discussed and shared with participants. The identity of patients will be confidentia