Preoperative Paravertebral Block in Cancer Surgery of the Lung

Study Overview
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Brief Summary
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The investigators aim to determine whether ultrasound-guided preemptive paravertebral blockade (PVB) local anaesthetic (pre-PVB LA), administered in addition to the post-operative PVB (post-PVB) local anaesthetic (LA) infusion, reduces acute postoperative pain, opioid requirement, chronic pain, and improves surgical recovery, in thoracoscopic surgery for lung cancer.

Detailed Description
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In the UK, there has been an increase in lung cancer operations, especially in high risk and elderly patients, improving survival from 10.6% in 2008 to 15.1% in 2013. Lung cancer surgery is associated with severe acute pain, a high incidence of respiratory complications and chronic post-surgical pain. Severe acute postoperative pain is a strong predictor of CPSP. The improvement of perioperative outcomes in elderly patients, the benefits of regional anaesthesia and reduction of chronic pain are investigative priorities of the Anaesthesia and Perioperative Care Setting Partnership. Enhanced recovery strategies include video-assisted thoracoscopic surgery (VATS), a minimally invasive alternative to open thoracotomy, which may be associated with less postoperative pain. Regional anaesthesia, by thoracic epidural analgesia (TEA) or PVB, is superior to systemic opioids in reducing acute pain after thoracotomy surgery. Preemptive analgesia describes the aim of minimizing central spinal pain transmission by noxious stimuli arising from events at surgery, by administering an analgesic technique prior to surgical incision. Regional blockade affects central sensitization, allowing analgesia to outlast the pharmacological sensory blockade. Compared to TEA initiated after surgery, acute pain severity is reduced by preemptive TEA. There are conflicting reports on the benefit of preemptive analgesia in other types of surgery, but TEA and PVB may prevent CPSP in thoracotomy and breast surgery. Some small studies have shown that pre-PVB reduces acute postoperative pain. Paravertebral blockade is known to be as effective as TEA for acute postoperative analgesia following thoracic surgery, whilst having a lower incidence of pulmonary complications, hypotension and nausea. It is conventional practice in many centres for the surgical administration and placement of a catheter at the end of surgery for postoperative LA infusion (post-PVB) as the sole method of regional analgesia. Preoperative PVB is less common: anaesthetists may use a landmark technique, single or multiple injections and different volumes/strengths of LA. Ultrasound guidance for pre-PVB injection increases accuracy. In an audit using this technique with post-PVB compared to post-PVB only, the investigators demonstrated reduced pain numerical rating scale (NRS) scores in elective VATS patients, (mean NRS at 24h 2.5 vs 4.5), and a reduction in the proportion of patients who experienced moderate-to-severe pain of NRS≥ 3 from 83% to 50% at 24h. The investigators therefore aim to evaluate the contribution of ultrasound-guided pre-PVB, administered in addition to the post-PVB LA infusion, in reducing the severity of acute postoperative pain, perioperative opioid requirement, development of CPSP, and improving patient outcome in lung cancer patients undergoing VATS.

Official Title
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Preoperative Paravertebral Block in Cancer Surgery of the Lung: ParaSOL a Prospective Randomized Controlled Clinical Trial

Conditions
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Thoracic Neoplasm, Chronic Pain Post-Procedural, Acute Post-thoracotomy Pain, Anesthesia, Local

Intervention / Treatment
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* Drug: Levo-Bupivacaine Hydrochloride (HCl) 0.5 % in 20mL Injection
* Drug: 0.9% Sodium Chloride 20mL Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Elective radical primary lung cancer VATS surgery for single lobectomy American Society of Anesthesiology (ASA) I-III Age ≥18 Exclusion Criteria: Planned open thoracotomy, wedge resection, bilobectomy, pneumonectomy, chest wall resection or total pleurectomy Local anaesthetic or opioid allergy Coagulation disorders Inability to comply with study questionnaire completion Pre-existing pain in chest area or pre-existing pain conditions Local infection/tumour at proposed PVB site Previous lung surgery Planned surgery within 3 months of the primary lung resection

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study will be conducted at Guy's Hospital, London, United Kingdom (UK), a large tertiary thoracic centre for London, Sussex, Kent and Berkshire. In 2015, 459 lung cancer resection operations were performed; 8% of all lung cancer resections in England. Criteria for discontinuation/withdrawal or modifying allocated treatment: Participant request to withdraw from the study. Intraoperative identification of infection/tumour in paravertebral space Patient recruitment Eligible patients will be identified in the catchment outpatient clinics 4-6 weeks before surgery. The participant information sheet (PIS) will be introduced in the standard surgical booklet given by the surgeon. At the preoperative assessment clinic 2-3 weeks before surgery, a face-to-face discussion with the research nurse will support the PIS; the opportunity to ask any questions and contact a PPI (Patient and Public Involvement) representative and will be given. Written informed consent will be obtained.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Pre-PVB with saline<br>Placebo (20ml Saline) pre-PVB performed post-induction and pre-incision. | Drug: 0.9% Sodium Chloride 20mL Injection<br>* As per arm description<br>|
| Experimental: Pre-PVB with 0.5% Levo-bupivacaine<br>20ml 0.5% Levo-bupivacaine pre-PVB performed post-induction and pre-incision. | Drug: Levo-Bupivacaine Hydrochloride (HCl) 0.5 % in 20mL Injection<br>* As per arm description<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Moderate-to-severe pain Numerical Rating Scale (NRS) >/=3 | The proportion of patients with clinical relevant moderate-to-severe pain (NRS>/=3) related to the surgical site at rest at 24 hours. | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute postoperative pain related to the surgical site as measured by a numerical rating scale (NRS) at rest and on coughing. | Acute postoperative pain related to the surgical site as measured by a numerical rating scale (NRS) at rest and on coughing, preoperatively, and after arrival in recovery at 1, 6, 24 and 48 hours | 1 hour | 
| Acute postoperative pain related to the surgical site as measured by a numerical rating scale (NRS) at rest and on coughing. | Acute postoperative pain related to the surgical site as measured by a numerical rating scale (NRS) at rest and on coughing, preoperatively, and after arrival in recovery at 1, 6, 24 and 48 hours | 6 hours | 
| Acute postoperative pain related to the surgical site as measured by a numerical rating scale (NRS) at rest and on coughing. | Acute postoperative pain related to the surgical site as measured by a numerical rating scale (NRS) at rest and on coughing, preoperatively, and after arrival in recovery at 1, 6, 24 and 48 hours | 24 hours | 
| Acute postoperative pain related to the surgical site as measured by a numerical rating scale (NRS) at rest and on coughing. | Acute postoperative pain related to the surgical site as measured by a numerical rating scale (NRS) at rest and on coughing, preoperatively, and after arrival in recovery at 1, 6, 24 and 48 hours | 48 hours | 
| Cumulative morphine requirement | Cumulative morphine requirement over 48 hours post arrival in recovery | 48 hours | 
| Time to first mobilization | Time to first mobilization (walking 50 metres without the aid of another person), measured at baseline pre-operatively and postoperatively on daily assessment. | 3 days | 
| Incidence of in-hospital complications | Incidence of in-hospital complications (Atrial Fibrillation (AF), Myocardial Infarction (MI), unplanned ICU admission) and respiratory complications, as defined by the Melbourne Group Scale. | 3 days | 
| Length of hospital stay | Length of hospital stay (in days) | 3 days | 
| Quality of Life (QoL) score | Quality of Life (QoL) score as measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) version 3 | Pre-operative and at 3 and 6 months post-operatively | 
| Presence of chronic post-surgical pain | Presence of chronic post-surgical pain (CPSP) (binary yes/no) fulfilling CPSP criteria | Measured at 3 and 6 months post-operatively | 
| Presence of chronic post-surgical pain | Presence of chronic post-surgical pain assessed by the Brief Pain Inventory Short Form (BPI-SF) | Measured at 3 and 6 months post-operatively | 
| Presence of chronic post-surgical pain | Presence of chronic post-surgical pain assessed by as defined by the Melbourne Group Scale | Measured at 3 and 6 months post-operatively |