To assess the feasibility and inform the design and conduct of a pragmatically conducted, interventional, multi-centre RCT in adult patients admitted to UK major trauma centres with rib fractures examining ESP block as an analgesic adjunct to existing multimodal analgesia in the early management of rib fracture pain.

TRIAL PROTOCOL

Erector Spinae Plane blocks for the Early Analgesia of Rib fractures in trauma: a multicentre pilot randomised controlled trial with feasibility and embedded qualitative assessment.

1. BACKGROUND

   Trauma is one of the commonest causes of death and disability worldwide [Murray 2012]. There are 20,000 cases of major trauma annually in England with 5,400 deaths. In 2016, 13,000 patients in England presented with chest injuries due to moderate or severe trauma. Traumatic rib fractures (broken ribs) are common and cause severe acute pain [Peek 2019]. An increased number of fractures, older age and pre-existing respiratory disease are associated with increased rates of prolonged hospital stay and death following rib fracture [Battle 2012]. Patients with rib fractures can present to NHS emergency departments in non-specialised hospitals as well as designated Major Trauma Centres and subsequently require admission to acute surgical wards, trauma units or critical care units. Care of patients with rib fractures is therefore a major financial and clinical responsibility of the NHS. The pain from rib fractures is often described by patients as the worst pain they have ever experienced. The major complication of this pain is that patients are unable to cough and breathe deeply, causing small airways collapse (atelectasis), retained secretions, low oxygen levels (hypoxaemia), pneumonia and progressive respiratory failure. Deterioration may require mechanical ventilation on an intensive care unit and lead to death [Ahn 2013; Sirmali 2003]. This morbidity and mortality is a direct result of severe pain (patients are unable to breathe deeply and cough) and impaired gas exchange from underlying contused lung parenchyma and altered ventilatory mechanics from the bone injury [May 2016]. The presence of rib fractures in trauma is associated with a significantly increased risk of death, regardless of other injuries, with an odds ratio of 1.4 (95% CI 1.3-1.6) for adults 18-45 years old and 2.5 (95% CI 2.3-2.8) for adults older than 64 years [Kent 2008]. This injury is therefore particularly devastating for older adults [Holcolmb 2003] who not only have a higher risk of death but are also likely to sustain rib fractures from less traumatic accidents (due to bone fragility), for example falling from standing height.

   A key objective in the multidisciplinary care of people with rib fractures is the assessment and treatment of pain to provide patient comfort and allow normal respiration and cough to minimise the risk of respiratory failure [London Major Trauma System 2018; May 2016]. Alongside specialist physiotherapy and daily multidisciplinary review, good pain management is a vital element of early rib fracture care. Despite this, there is no agreement about the optimal pain relief to give patients. The literature on the use of the different analgesic techniques in rib fractures is inconclusive. Although national and international guidance recommends a multimodal approach in preference to opioid medications alone [Galvagno 2016], two recently performed meta-analyses concluded that the evidence to recommend any specific treatment modality is insufficient, and that there is no firm evidence for benefit or harm of one analgesic technique over another [Carrier 2009, Duch 2015]. This leaves clinicians unsure of which analgesic techniques to use. National Guidance [British Orthopaedic Association 2016] specified protocolised analgesic regimes as a standard of care for every patient with multiple rib fractures. However the paucity of evidence meant that this guidance could not recommend which analgesic modality (epidural, peripheral nerve blocks or opioid) should be used in which clinical circumstances. Although some patients need surgery to fix their broken ribs (especially if they have multiple fractures causing a floating (flail) segment), for the majority of people with rib fractures surgery is not a suitable treatment . Most patients with rib fractures are given a combination of analgesic drugs like paracetamol, non-steroidal anti-inflammatories, opioids and ketamine to help them cope with their severe pain; these are the cornerstones of multimodal analgesia in this setting. These medications come with side-effects (such as nausea, pruritus, hallucinations, constipation, renal failure and respiratory depression) which significantly limit their use. Some patients receive thoracic epidural analgesia (TEA) and some receive other forms of regional anaesthesia nerve blocks, but the delivery of these interventions by pain specialist anaesthetists is driven more by local expertise and experience and less by high quality evidence.

   Regional anaesthesia (nerve blocks) are clinically useful following rib fractures due to their opioid sparing effect (therefore reducing serious drug related side-effects) and the superior dynamic pain relief they provide (pain on movement is better treated). Traditional techniques to block the thoracic nerve supply to the ribs include thoracic epidural analgesia (TEA), paravertebral blockade and intercostal blockade. Systematic review and metaanalysis of these techniques suggested that TEA provides good pain relief, however this benefit does not translate into superior outcomes such as occurrence of pulmonary complications and length of time spent in hospital, intensive care or requiring mechanical ventilation [Peek 2019]. Unfortunately, TEA has a significant failure rate [Peek 2019] and is also associated with common and potentially catastrophic complications [Hewson 2018] leading to permanent paralysis, and is therefore contraindicated in approximately one fifth of people with significant injuries. TEA is a complex intervention to perform, practiced by a small and reducing number of anaesthetists nationally and is not available equitably to patients in the NHS. A patient in one hospital admitted on one day might receive TEA for pain relief, but another patient at the neighbouring hospital will not because the staff are not available to safely insert or monitor an epidural. Even within a single hospital the care delivered varies depending on the time of day and availability of staff to perform such a complex analgesic technique. We know this from work our group has already undertaken as part of our "Evaluation of chest wall stabilisation through operative rib fixation" (ORIF) study (HTA Programme: 16/61/10). Because none of these analgesic options are a 'golden bullet' [Galvagno 2016], patients in the NHS are subject to large variation in practice [Beard, Holt 2020]. This is why only an estimated 9.9-18.4% of patients receive TEA for rib fracture pain [Beard, Hillermann 2020]. Patients with rib fractures need a simple method of effective pain relief that can be safely administered and monitored by a wide number of NHS staff and is therefore available across all hospitals and at all times of day. Such an intervention should be immediately available on admission to hospital (at the 'front door' of care), when patients with rib fractures stand the most to gain from effective pain relief [Kourouche 2018]. For comparison, another group of seriously injured patients - those who have sustained hip fractures - have significantly benefited from the evidence-based implementation of early pain relief in the form of fascia iliaca nerve blocks [Foss 2007; Ritcey 2016; Dangle 2020]. This technique now forms part of the National Institute for Health and Care Excellence (NICE) recommendations for the care of patients with hip fractures [NICE 2017].

2. RATIONALE Our team would like to test if a regional anaesthetic block, the erector spinae plane block, can help patients with rib fractures across the NHS in the same way that fascia iliaca blocks help patients with hip fractures.

The erector spinae plane (ESP) block is a regional anaesthetic technique involving the infiltration and infusion of local anaesthetic along fascial planes containing dorsal and ventral rami of thoracic spinal nerves supplying the chest wall [Chin 2019]. The injection is performed away from the spinal cord (thereby avoiding the complications of TEA.

ESP blocks were first described in 2016 [Forero 2016] and have demonstrated analgesic efficacy for patients on enhanced recovery after surgery protocols (ERAS) following spinal [Singh 2020], breast [Gurkan 2018], thoracic [Ciftci 2020] and cardiac surgery [Macaire 2020]. In these post-operative acute pain settings, ESP blocks have been shown to reduce patient-reported pain scores and opioid consumption significantly in the early postoperative period compared to multimodal analgesia regimes alone. However, the role of ESP blocks in the management of acute rib fracture pain is currently uncertain [El-Boghdadly 2017]. There are no experimental pragmatic multi- centre trials published in this setting, however single-centre cohort data demonstrates ESP blocks provide effective pain relief and improve respiratory function when added to multimodal analgesia in patients with rib fractures [Hamilton 2017; Adhikary 2019]. Higher quality clinical evidence is urgently needed to guide NHS clinicians on whether the ESP block is a suitable addition to current multimodal analgesia in patients with rib fractures. A definitive trial on this topic would promote evidence-based practice in rib fracture management and reduce unnecessary variation in clinical practice across UK trauma centres. However there is currently not enough evidence on the effectiveness and acceptability of ESP blocks for rib fractures to undertake a definitive randomised controlled trial (RCT).

There are anatomical, safety and practical reasons to justify investigating the early use of ESP blocks over other analgesic techniques for patients with rib fractures. Anatomical studies of the ESP block demonstrate unilateral sensory block over 6 dermatomes following a 30 ml thoracic ESP injection of local anaesthetic and gadolinium with subsequent spread of contrast (shown on MRI) to the paravertebral and epidural spaces via the intervertebral foraminae in addition to some intercostal spread of local anaesthetic along fascial planes to block sensory nerves supplying the posterior, lateral and anterior chest walls [Schwartzmann 2020]. ESP blockade is therefore plausibly effective for all locations of rib fractures, unlike serratus plane blocks which are effective for anterior but not posterior rib fractures [Mayes 2016]. From a safety and practical perspective, ESP blocks are much easier to perform than TEA or paravertebral blocks. The ESP needle insertion technique (away from pleural and spinal cord) intuitively carries much less risk of pneumothorax, epidural haematoma or inadvertent intrathecal injection - all well recognised complications of TEA and paravertebral blockade. A significant minority of patients with rib fractures have medical contraindication to TEA or paravertebral analgesia such as spinal or head injuries, coagulopathy or haemodynamic instability. We believe that if shown to be effective, ESP blocks would therefore be a suitable technique in a greater number of patients than TEA or paravertebral blockade and could therefore potentially be offered quickly as a 'lower skill' first line technique, reserving TEA and/or paravertebral for selected complex patients when appropriate skilled personnel are available. This means that ESP block could benefit a larger number of patients at an earlier stage of their hospital admission.

Inclusion Criteria:

Age ≥ 18 Mechanism of injury blunt thoracic trauma Radiographic evidence of 1 or more new traumatic rib fractures Moderate or severe unilateral acute pain (defined as 11-point numerical rating scale (NRS) pain >4 when patient performing vital capacity breath or effective cough) at time of enrolment. Patients may have bilateral fractures, but pain must be unilateral.

Exclusion Criteria:

Patient refusal or inability to give informed written consent for any reason Thoracic injury requiring emergent operative or interventional radiology management Allergy to local anaesthetic Infection at site of ESP block Actual or estimated

Only anesthetist will be un blinded. Research nurse and participant will be blinded to treatment arm.