- Title
- Understanding the role of prehospital intubation and advanced brain imaging in severe traumatic brain injury
- Creator
- Bendinelli, Cino
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2019
- Description
- Research Doctorate - Doctor of Philosophy (PhD)
- Description
- Introduction: Traumatic Brain Injury (TBI) is a leading cause of hospitalisation, disability, and death worldwide. Often labelled as the “silent global epidemic”, TBI can affect any humans and any stage of life but remains more prevalent in the young adults and increasingly in elderly on anticoagulants. Furthermore, in developed countries, TBI represents the number one cause of death among children. Among survivors, the disabling effects of TBI may persist for years with huge emotional, social and financial costs (1-3). It represents an enormous problem. This thesis will focus on severe TBI. Severe TBI is diagnosed on patients who are in comatose state and who show neither meaningful response, nor voluntary activities and therefore have a Glasgow Coma scale (GCS) between 3 and 8. Among severe TBI patients who reach hospital alive the overall mortality at 6 months reaches 35% and, among the survivors, a favourable neurologic outcome is observed at 6 and 12 months, in 55 and 59%, respectively (1,2). These overall quite poor results have been consistently observed worldwide and have not improved or have improved only marginally over the last 2 decades (3). Prehospital intubation: The Brain Trauma Foundation guidelines condense the available knowledge and clinical evidence to offer a systematic and consistent approach to manage patients with severe TBI (4-7). These guidelines have been ubiquitously implemented with well proven improved outcome. Nevertheless, some aspects of these guidelines are based on minimal or conflicting evidence and, consequently, some recommended interventions are not broadly implemented (6). Part of this thesis will focus on the one controversial prehospital guideline which states: “airways should be established by the most appropriate means available in all trauma patients with GCS below nine” (4,5). Following a traumatic event, the damaged cells of the central nervous system (CNS) become extremely vulnerable to reduced tissue concentration of oxygen and accumulation of free radicals and other toxins. Furthermore the primary injury to cerebral neurons and glia results in scattering of ionic imbalances, reactive species, inflammation and reactive gliosis, leading to further loss of vulnerable tissue (8).This potentially preventable insult takes the name of ‘secondary brain injury’ and in vivo is typically caused by circulatory failure (shock) and/or respiratory failure (obstructed airway, lung tissue damage or impeded ventilation). Because hypoxia, hypercarbia and hypotension occur frequently in trauma patients, when TBI is suspected, most interventions aim to prevent these deleterious complications (3-10). Both hypoxia and hypercarbia are best prevented and treated by prompt airway protection and adequate lung ventilation. As a matter of facts, airway protection and ventilation are the first priorities when managing a patient with severe TBI (3-10). Endotracheal intubation (ETI) is the most reliable mean for securing airway patency; hence ETI is the first intervention in any patient with GCS below nine on arrival into ED. Physicians in hospital routinely use a combination of sedative and neuromuscular blocking agents to paralyse temporarily the muscles around the oral cavity and in the pharynx and facilitate ETI. This protocol takes the name of RSI. Prehospital cold intubation: In the prehospital arena, paramedics dealing with trauma patients with GCS below nine are meant to secure the airway by the safest and most effective available means, which can be very different to the routine practice in hospital (4). Most ambulance service protocols do not include the use of RSI agents and therefore their paramedics can attempt to obtain definitive airway protection only by intubating the unparalysed patient, this challenging practice takes the name of “cold intubation”. Only patients with extremely low GCS and those who have lost the primordial gag reflex may tolerate cold intubation, and as such this intervention is successful only when attempted in the sickest patients with severe TBI. The success rate of cold intubation varies in large retrospective studies between 10 and 20% (11-15) and consequently during their journey to hospital approximately 30% of patients with severe TBI experience at least one episode of airway obstruction and another 10% has a documented hypoxic event (1,10,11). Because only patients in deepest coma can tolerate this procedure, prehospital cold intubation represents a predictor for extremely poor outcome, with some even questioning its futility (16). With such a selection bias, it becomes nearly impossible to prove or disproof any survival advantage of prehospital cold intubation. And in facts most studies have failed to demonstrate any survival improvement in severe TBI patients who were successfully intubated prehospitally by paramedics without access to RSI protocols (11-15). Prehospital intubation facilitated by rapid sequence induction protocol: Paramedic use of RSI protocols to facilitate ETI has been adopted by some with appealing results (17-20). Several studies have demonstrated that, after adequate training, paramedics can safely use RSI drugs to increase prehospital ETI success rate to 95% (17-20). The outcome of patients with severe TBI treated by paramedics with access to RSI drugs has been investigated by several retrospective studies that exploit logistic regression models or neuronal analysis to control for the multiple factors that may affect outcome in TBI patients. Contrary to expectation, such studies and subsequent meta-analysis did not show any survival advantage when paramedics could use RSI drugs to facilitate ETI and therefore had high success rate in securing the airway (19-23). Running randomized control trials on critically injured moribund patients is extremely challenging and the prehospital environment is even more difficult to explore this way. Only two randomized studies exist that have investigated RSI facilitated ETI versus non-invasive ventilation. One paper studied 830 paediatric patients (less than 13 years old). Only a minority of these (7%) had severe TBI, yet the group which received ETI showed a reduced survival, but possibly an improved functional outcome (24). More recently, Bernard et al. have published the first ever randomized control trial conducted in adults with severe TBI. This compared prehospital RSI facilitated ETI by paramedics versus oxygen and assisted bag/mask ventilation (till ETI with RSI by a physician in emergency department (ED)) (20). This landmark study on 312 adults with prehospital GCS below nine and signs of head injury confirmed that paramedics using RSI may successfully intubated up to 97% of patients. Interestingly this extremely relevant study failed to prove a survival advantage or reduced in length of stay among the groups. Again though, a statistically significant improvement in long term functional outcome was observed among patients who received prehospital ETI (20). In line with the findings of Bernard et al. (20), Victoria has adopted an aggressive prehospital strategy which allows the use of RSI for ETI to trained paramedics, whereas all other Australian States and Territories have not yet implemented this strategy and still rely on cold-intubation. We have utilized this crucial difference in prehospital protocols to perform a multicentre and semi-experimental study to further investigate the role of prehospital ETI and try to solve the discordance among the above mentioned studies. Glasgow Coma Scale below nine: The GCS was developed almost 50 years ago (25), only had minor modifications recently, and it is universally accepted as the most pragmatic scoring system to promptly evaluate brain functionality. It was not designed to be used prehospitally, nor before resuscitation, but has been shown to predict mortality better than other vital signs and anatomical injury severity scores (26,27). Today, prehospital “GCS below nine” is routinely used in both research settings and management guidelines to define, stratify, and manage patients with severe TBI (4-8,20). Although a simple and straightforward criterion, “GCS below nine” includes a wide spectrum of TBI severity and in itself might not be adequate to discern alone which patients should receive a specific and invasive treatment. In other words, an otherwise clinically sensible intervention might be allocated to patients who would not benefit (or potentially might be harmed) by it. This selection bias may potentially dilute or contaminate the results of any randomized trial that does not correct for GCS variation. The current literature on severe TBI does not seem to address this oversimplification and even randomized trials do not correct for the possible difference in GCS (20,28-30). Not accounting for the variability of patients with GCS below nine has crucial implications in both the management of the individual patient and during the recruitment of patients in clinical trials. To prove our point, we have explored our database of patients with severe TBI and compared the clinical differences between patients with higher (6 to 8) and lower (3 to 5) GCS. Early advanced brain imaging: The second part of this thesis will address the role of a relatively novel diagnostic tool called brain computer tomography-perfusion( CTP) in the early radiologic assessment of severe TBI patients. CTP of CNS is a basically a computer tomography that observes in cine-mode the arrival, diffusion and washout of intravenous contrast through the brain. Dedicated software produces colourful maps that disclose the presence of areas of ischemia, hypoperfusion or hyperperfusion in the CNS. This information is commonly utilized by stroke neurologists to guide interventional and medical management of patients with acute stroke (31,32). Severe TBI is a simplistic definition for a heterogeneous and multifaceted neurological disorder that involves diverse pathophysiological pathways and mechanisms. Despite this complexity, during the early hours/days following admission to a trauma centre, the brain is assessed and treated only as a simple end perfusion organ. All efforts are directed at achieving an adequate blood flow (by manipulating systolic and intracerebral pressures) and appropriate oxygenation (by reducing oxygen demand and optimizing oxygen delivery) in order to prevent secondary brain injury (9). The role of surgery in patients with severe TBI is limited to the insertion of pressure monitor or intraventricular drain, the evacuation of larger hematomas, the decompression of the cranial compartment with a decompressive craniectomy. As a matter of facts during the first crucial days the injured brain is evaluated only with serial non-contrast CT, so to diagnose and follow up any of these surgically treatable conditions (33-35). Advanced brain imaging aims to provide more information (such as viability, perfusion status, function). This information could be instrumental to forecast complications such as subsequent bleeding and intracerebral hypertension, but also for predicting functional outcome. The importance of prompt and accurate functional outcome prediction cannot be overemphasized for both health care providers and patient’s families. Today, functional outcome is predicted mainly based on the evolution of the neurologic status (it might take days to weeks to be able to prognosticate), and the presence and evolution of radiological findings on serial non-contrast CT (which has relatively poor sensitivity in detecting diffuse axonal injury and ischemic brain) (33, 35-36). The experience with CTP in severe TBI is extremely limited, with only few studies published on this topic (37-39). Wintermark et al. (37) first reported on the use of CTP in severe TBI patients. They demonstrated in 130 patients with severe TBI that CTP findings, specifically the number of arterial territories with low cerebral blood volume (CBV), predicted poor functional outcome, while a normal brain perfusion and high CBV were associated with favourable outcome. The correlation between invasive cerebral perfusion pressure and CTP findings was also investigated. About 60% of patients had a weak dependence of cerebral blood flow and cerebral perfusion pressure (most likely due to preserved autoregulation), while the rest of the patients showed a strong dependence between cerebral blood flow and cerebral perfusion pressure. This latest group of patients, hypothesised to have lost the cerebral vascular autoregulation, did worse in terms of functional recovery (38). CTP also provided better evaluation of hypodense areas surrounding the haematomas and contusions. The CTP maps showed congruence with the follow up non-contrast CT at seven days in 30 patients with severe TBI and cerebral contusions. Basically, CTP predicted the final extent of the CNS damage better than non-contrast CT (39). These studies, if extremely novel, were limited by broad patient inclusion criteria, dated, single slice technology of the CT scanner, and limited outcome measures. Based on these preliminary, but promising, studies and taking advantage of the availability of the technology and the vast experience of the local stroke neurologists, we have explored the role of acute brain CTP in patients with severe TBI. Aim of this thesis: Having identified areas of clinical care where optimal management remains uncertain, the primary aims for this research on severe TBI patients were as follows: 1. Understand whether paramedics with access to RSI protocols are more successful in prehospital ETI on patients with severe TBI, when compared with paramedics who can rely only on cold intubation, and if this leads to better outcomes. 2. Assess if patients with presumed severe TBI based on prehospital GCS below nine are homogenous enough to be treated all in the same way. 3. Investigate the findings of CTP performed within 48 hours from injury in selected severe TBI patients. 4. Determine if the findings of early CTP may play a role in functional outcome prognostication after severe TBI. 5. Compare two different CTP technologies: older (single slice) and newer (whole brain). 6. Assess whether CTP can predict the need for aggressive cerebral hypertension treatment. Six clinical studies were carried out to achieve these aims. And one book chapter summarize current knowledge on the role of CTP in TBI patients.
- Subject
- traumatic brain injury; perfusion CT; endotracheal intubation; functional outcome; thesis by publication
- Identifier
- http://hdl.handle.net/1959.13/1408433
- Identifier
- uon:35840
- Rights
- Copyright 2019 Cino Bendinelli
- Language
- eng
- Full Text
- Hits: 742
- Visitors: 1193
- Downloads: 522
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT01 | Thesis | 2 MB | Adobe Acrobat PDF | View Details Download | ||
| View Details Download | ATTACHMENT02 | Abstract | 885 KB | Adobe Acrobat PDF | View Details Download |