Implementing smart materials and technologies for medical emergency airway access devices

Airway management and intubation procedures continue to challenge anaesthetists daily. Failure to secure the airway with an endotracheal tube in a timely manner upon induction of anaesthesia can lead to serious complications, including death or disability. Most anaesthetists consider endotracheal tube introducers (bougies) as essential equipment; however, there are many different types with relatively little performance data to help anaesthetists make an informed choice. Standard bougies have a requirement to be reshaped multiple times in an attempt to create the desired navigation path of the endotracheal tube. Manoeuvring within the trachea presents significant navigation and control challenges whilst attempting to minimise trauma. Improvements in airway management care is often facilitated by the introduction of new or improved airway management equipment, however understanding their physical properties is imperative for the development of an improved device. This research addresses the development of a new emergency airway access device; the steerable bougie has been designed to enhance device control and improve the speed and the safety of bougie guided endotracheal intubation. Initial work focussed on assessing the case of need for the development of an improved bougie, in addition to identifying design criteria and specifications. A number of anaesthetists were surveyed and identified increased manoeuvrability in-situ, improved shape retention and steerable control as desirable device attributes. Initial design, development and testing explored the feasibility of actuators and smart materials capable of replicating a steerable movement. Initial prototyping and testing demonstrated that flexible steerable tips controlled by Flexinol® actuator wires could effectively control the navigation of the tip. Understanding the physical properties of bougies is fundamental to patient safety, device operation and ultimately equipment procurement decisions. Accurate and reliable bougie safety performance data, including perforation forces, bougie tip pressures and shape retention is not available. Equipment evaluations often fail to consider key testing criteria including testing equipment specifications. Tip pressure studies conducted identified current equipment weaknesses with airway trauma, including significant mucosa damage and perforation easily achieved by low tip pressure forces. The steerable bougie demonstrated significantly lower tip pressure forces compared to commercially available bougies. Repeatability testing conducted assessing tip pressure performance identified variable degradation over time for all commercially available bougies; the developed steerable bougie presented limited degradation over time. Anaesthetists define shape retention as a critical performance characteristic for a bougie. To match the curvature of a patient's airway multiple bougie shaping iterations are usually required, however bougies often return to their original shape within seconds of being manipulated. All bougies present initial snap back and shape loss. To identify bougies with optimal shape retention, an innovative Shape Retention Testing System (SRTS) was designed and built to test shape retention characteristics. Testing demonstrated that bougies with dual or multi-lumened structures provided the highest level of shape retention hold. The steerable bougie outperformed the commercially available bougies at most shaping distances, demonstrating limited shape loss. Utilising the accumulated bougie performance data, a steerable bougie with improved shape retention, reduced tip pressures and reduced likelihood of causing airway trauma has been developed. The steerable bougie is connected to an ergonomically designed controller attached to a laryngoscope that can also be easily attached/detached and sterilised. This research has demonstrated that a steerable bougie with augmented physical properties can be developed that not only provides medical professionals with a device that has increased steerability and usability for time critical procedures but will also reduce the likelihood of patient airway trauma

Process–Structure–Properties in Polymer Additive Manufacturing II

Additive manufacturing (AM) methods have grown and evolved rapidly in recent years. AM for polymers is particularly exciting and has great potential in transformative and translational research in many fields, such as biomedicine, aerospace, and even electronics. The current methods for polymer AM include material extrusion, material jetting, vat polymerization, and powder bed fusion. In this Special Issue, state-of-the-art reviews and current research results, which focus on the process–structure–properties relationships in polymer additive manufacturing, are reported. These include, but are not limited to, assessing the effect of process parameters, post-processing, and characterization techniques

Laser-assisted processing of multilayer films for inexpensive and flexible biomedical microsystems

Flexible/stretchable electronics offer ideal properties for emerging health monitoring devices that can seamlessly integrate with the soft, curvilinear, and dynamic surfaces of the human body. The resulting capabilities have allowed novel devices for monitoring physiological parameters, improving surgical procedures, and human-machine interfaces. While the attractiveness of these devices are indubitable, their fabrication by conventional cleanroom techniques makes them expensive and incompatible with rapid large-scale (e.g., roll-to-roll) production. The purpose of this research is to develop inexpensive fabrication technologies using low-cost commercial films such as polyimide, paper, and metalized paper that can be utilized for developing various flexible/stretchable physical and chemical sensors for wearable and lab-on-chip applications. The demonstrated techniques focus on an array of laser assisted surfaces modification and micromachining strategies with the two commonly used CO2 and Nd: YAG laser systems. The first section of this dissertation demonstrates the use of localized pulsed CO2 laser irradiation to selectively convert thermoset polymer films (e.g., polyimide) into electrically conductive highly porous carbon micro/nanostructures.Thisprocessprovidesauniqueandfacileapproachfordirect writing of carbonized conductive patterns on flexible polyimide sheets in ambient conditions, eliminating complexities of current methods such as expensive CVD processes and complicated formulation/preparation of conductive carbon based inks used in ink jet printing. The highly porous laser carbonized layer can be transferred to stretchable elastomer or further functionalized with various chemical substances such as ionic solutions, nanoparticles, and chemically conductive polymers to create different mechanical and chemical sensors. The second section of this dissertation describes the use of laser ablation for selective removal of material from multilayer films such as ITO-coated PET, parchment paper, and metalized paper to create disposable diagnostic platforms and in-vitro models for lab-on-chip based studies. The ablated areas were analyzed using electrical, mechanical, and surface analysis tools to understand change in physical structure and chemical properties of the laser ablated films. As proof-of-concept demonstrations of these technologies, four different devices are presented here: mechanical, electrochemical, and environmental sensors along with an in-vitro cell culture platform. All four devices are designed, fabricated, and characterized to highlight the capability of commercial laser processing systems in the production of the next generation, low-cost and flexible biomedical devices

Endoscopy

Endoscopy is a fast moving field, and new techniques are continuously emerging. In recent decades, endoscopy has evolved and branched out from a diagnostic modality to enhanced video and computer assisting imaging with impressive interventional capabilities. The modern endoscopy has seen advances not only in types of endoscopes available, but also in types of interventions amenable to the endoscopic approach. To date, there are a lot more developments that are being trialed. Modern endoscopic equipment provides physicians with the benefit of many technical advances. Endoscopy is an effective and safe procedure even in special populations including pediatric patients and renal transplant patients. It serves as the tool for diagnosis and therapeutic interventions of many organs including gastrointestinal tract, head and neck, urinary tract and others

Aerospace medicine and biology: A continuing bibliography with indexes, supplement 204

This bibliography lists 140 reports, articles, and other documents introduced into the NASA scientific and technical information system in February 1980

Artificial intelligence versus human intelligence in anaesthesia: who is winning?

Artificial intelligence (AI) plays a significant role especially in the light of the COVID-19 pandemic. The position of anaesthesiologists and their role in providing anaesthetic services initially was dominant. The AI ability to overtake the human’s capability in providing an accurate medical treatment may threaten the role of a doctor. The integration of AI in anaesthesia has been tremendous. Challenges in using this technology in anaesthesia are to determine, design, test the practicality, maintain dynamicity and market the technology. In the future, we hope AI may become the strongest weapon for anaesthesiologists to deliver the best anaesthesia services to patients and not as an enem

Examining the functional role of transporters in modulating drug absorption across lung epithelium

P-glycoprotein (P-gp – MDR-1), a 170 kDa glycosylated membrane bound protein, is a member of the ATP-binding cassette transporter family. The potential for P-gp to reduce drug absorption across lung epithelia is of significant interest; this is particularly so, given P-gp’s broad substrate specificity mediating efflux transport of a range of structurally unrelated substrates. Within lung, Pgp expression is evident in bronchial and alveolar epithelia with functional characterisation of P-gp transport capacity within lung epithelial cells currently restricted to respective in-vitro cell culture models. The aims of this project were to establish the relative mRNA expression of several ATP Binding Cassette (ABC), Solute Carrier (SLC) and Solute Carrier Organic Anion (SLCO) drug transporters within rat lung samples through use of RT-PCR; expression suggesting the potential to serve as targets for pulmonary drug delivery. Further, validation of an Isolated Perfused Rat Lung preparation for use in assessment of drug transport across the lung was conducted. In order to assess the functional significance of the ABC drug transporter, P-glycoprotein, on drugs instilled intra-tracheally to the IPRL set-up, use of the P-gp substrates; Rhodamine 123 (Rh123), digoxin, and flunisolide and the P-gp inhibitor, GF120918 was employed. Further, use of kinetic modelling was employed to establish pharmacokinetic parameters involved. Using the IPRL, the P-gp dependent pulmonary absorption of the P-gp substrate, Rh123, was demonstrated. Dose-dependent absorption, consistent with a saturable component in the molecule’s pulmonary absorption, was demonstrated. Further, the absorption of low dose Rh123 was promoted by the presence of the highly selective P-gp inhibitor GF120918, consistent with a functional role of P-gp mediated efflux within an intact lung; an efflux process which may limit the pulmonary absorption of a lung administered molecule. Further studies using this system and extending the range of molecules studied will provide greater understanding of the quantitative significance of P-gp in limiting pulmonary absorption across lung epithelium.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Respiratory complications of organophosphorus pesticide poisoning

Of the 800,000 suicides recorded globally every year, over a third are due to pesticide ingestion, the majority of which occur in rural Asia with organophosphorus (OP) compounds. These anticholinesterase pesticides cause an acute cholinergic syndrome characterised by decreased consciousness, excessive airway secretions and respiratory failure. A combination of these clinical features is the most common cause of death. Up to 30% of OP pesticide poisoned patients are admitted to the Intensive Care Unit (ICU) for tracheal intubation and lung ventilation, but up to half die. It is not understood why the case fatality for intubated poisoned patients is so high, but one hypothesis is that the patients, when unconscious, aspirate their stomach contents (including the OP and the solvent present in its agricultural formulation) causing a toxic lung injury which contributes to the observed high mortality. In this PhD, I aimed to characterise the lung injury caused by OP pesticide self-poisoning through both indirect (ingestion) and direct (aspiration) means. To achieve this, I analysed data from previous toxicological minipig work and designed and conducted a specific minipig pulmonary aspiration study which was complemented by an experimental OP poisoning ex vivo lung perfusion model and human data from pesticide poisoned patients in Sri Lanka. I first investigated the pulmonary pathophysiology resulting from orogastric administration of OP pesticide without aspiration. Analysis of my group’s Gottingen minipig in vivo work demonstrated that orogastric placement of agricultural OP (dimethoate EC40) produced lung injury via exposure to blood-borne pesticide. Pathological lung changes consisted of alveolar and interstitial oedema, pulmonary haemorrhage and modest neutrophilia with increased concentrations of protein, IL-6 and IL-8 when compared with controls, but with low concentrations of TNF-α and IL-10 in bronchoalveolar lavage fluid (BALF). In a second study, OP poisoned minipigs had increased concentrations of BALF protein, neutrophils, IL-8 and CRP six hours after orogastric poisoning when compared with their baseline values. Electron microscopy images of both studies demonstrated damage to the alveolar capillary membrane secondary to systemic OP poisoning. Prior to conducting the main pulmonary aspiration study in minipigs, there was considerable refinement of the processes involved through use of: (i) pilot aspiration and dose ranging studies; (ii) the development of a specific pulmonary histopathological scoring system; and (iii) employment of modern human anaesthetic equipment and intensive care patient management protocols. After this period of model development, an in vivo 48 hour study using Gottingen minipigs (n=26) was conducted to investigate the pulmonary pathophysiology in animals given either sham bronchoscopy (sham control) or 0.5 mL/kg of: saline (saline control), porcine gastric juice [GJ], OP (dimethoate EC40) + GJ [OP+GJ], or solvent (cyclohexanone) + GJ [Solv+GJ] into the right lung under bronchoscopic guidance. The results showed that in a minipig model OP and GJ placed into one lung created a direct (right) and indirect (left) lung injury significantly different to controls, and in some respects worse than GJ alone 48 hours after poisoning. The direct lung injury caused by OP+GJ was characterised by significantly worse pathology (p=0.0003) in terms of: pulmonary neutrophilia, alveolar haemorrhage, necrosis, oedema and fibrin deposition, when compared with sham controls at 48 hours. Lungs injured directly with OP+GJ also had significantly higher concentrations of BALF neutrophils (p≤0.01), protein (p≤0.05), IL-6 (p≤0.01), IL-8 (p≤0.01) and CRP (p≤0.05) at 24 hours, and BALF protein (p≤ 0.01), and CRP (p≤ 0.05) when compared with sham controls at 48 hours. The BALF from OP+GJ minipigs at 48 hours also had higher numbers of aerobic bacteria than other groups, suggesting the development of pneumonia could be a source of additional lung injury. Lung damage might also have resulted from a reduction in the surfactant component responsible for the lowering of alveolar surface tension. Direct lung injury with OP+GJ caused a proportional reduction of beneficial pulmonary surfactant phosphatidylcholine (PC) species 16:0/16:0 [29(±4) % vs. 38(±4) %] when compared with sham controls at 48 hours. Unlike the other groups, OP+GJ (direct and indirectly-injured) lungs had type 2 alveolar cell ultrastructural morphological differences in the lamellar bodies that stored the surfactant. The lamellar bodies were more numerous and more dense in the OP+GJ lungs compared with other groups and could signify a failure of surfactant release or some other pathology pertinent to OP aspiration lung injury. Computed tomography analysis showed that direct lung injury with OP+GJ caused significantly more lung tissue to be poorly or non-aerated [77 (±13) % ; p≤0.0001 when compared with sham] as opposed to 62 (±27) % in GJ, 53(±13)% in sham and 47(±0.2)% in saline control animals by 47.5 hours and was mainly due to pulmonary haemorrhage and oedema fluid. The key differences between aspiration of OP+GJ versus GJ alone was that the majority of inflammatory markers (e.g. BALF protein, IL-6 and CRP) appeared to increase from 24-48 hours in OP+GJ treated animals, but decreased in GJ pigs, possibly signifying resolution. Treatment with GJ alone produced less severe histopathological damage, bacterial BALF numbers and percentage of poorly and non-aerated lung tissue. Importantly, there was less evidence of indirect lung injury within the GJ pigs when compared with animals treated with OP+GJ. Solvent placed into the lung seemed to offer some form of protection from the effects of GJ aspiration. This was dramatically demonstrated by the histopathology scores, proportional percentage of beneficial phosphatidylcholine (PC) species 16:0/16:0 and the percentage of poorly and non-aerated lung tissue all approaching control animal levels by 48 hours in minipigs that had Solv+GJ placed in the directly-injured (right) lung. Further evidence of benefit was provided by statistically significant reductions (p≤ 0.05) in BALF concentrations of IL-8, IL-6 and CRP in minipigs which had aspirated Solv+GJ when compared with OP+GJ and/or GJ minipig groups at 24 hours. The pathophysiology of aspirated OP+GJ was also investigated in a pilot ovine ex vivo lung perfusion (EVLP) model (n=4). Lungs directly-injured with OP+GJ had higher concentrations of total protein (4300 mg/L vs. 350 mg/L) with a proportional reduction of beneficial pulmonary surfactant phosphatidylcholine species 16:0/16:0 (27% vs.34%) when compared with control lungs. Analysis of toll-like receptor (TLR) lung tissue expression in the OP+GJ directly and indirectly-injured lungs indicated that inflammatory mechanisms might also involve upregulation of TLR 3 and 5, unlike other lung injuries e.g. those induced with lipopolysaccharide, which typically upregulates TLR 2 and 4. To compare OP-induced lung injury in humans and the minipigs, a small feasibility study was conducted in the ICUs of the University of Peradeniya hospital, Sri Lanka. Unfortunately, ethics review and recruitment proved more difficult than expected and we failed to recruit to target. We did however find raised BALF concentrations of IL-6, IL-8 and CRP and low concentrations of TNF, IL-1β, IL-10 in intubated OP poisoned patients at 24 hours when compared with controls. We also found that two plasma micro-RNA biomarkers thought to be involved in inflammation and lung injury, MiR-21 and MiR-146a, had significantly reduced expression in OP-poisoned patients with aspiration compared to non-intubated control patients from the UK (p=0.008 and p=0.0083 respectively). The work from this thesis has allowed the characterisation of both indirect and direct lung injuries caused by OP pesticide ingestion and aspiration. The minipig model showed that at 48 hours the lung injury created by aspiration of OP+GJ appeared more severe than GJ alone, but the addition of the solvent cyclohexanone seemed protective and even beneficial in the context of GJ aspiration. The cytokine expression profiles from both the human and minipig work, combined with the preliminary TLR lung tissue analysis from the EVLP model, suggest that OP+GJ aspiration is unlike normal GJ aspiration and classic ARDS. Increased concentrations of aerobic bacteria in the minipig OP+GJ lungs at 48 hours and evidence of suppression of plasma miR-21 and miR-146a in OP poisoned patients could be linked, and may involve cholinergic immune system modulation. These molecular mechanisms need to be investigated further in both in vitro and in vivo models. These discoveries indicate the complex nature of the pulmonary injury that occurs after OP pesticide poisoning, and suggests that damage is not caused by gastric contents alone. Preliminary findings indicate that aspiration of OP+GJ could create favourable conditions for the development of aspiration or ventilator-associated pneumonia but this would need confirmation in larger clinical studies. The potential roles of micro RNA as a biomarker of OP poisoning and lung injury, and solvent as a therapy for aspiration should be explored in further pre-clinical studies

A dual nozzle 3D printing system for super soft composite hydrogels

Due to their inability to sustain their own weight, 3D printing materials as soft as human tissues is challenging. Hereby we describe the development of an extrusion additive manufacturing (AM) machine able to 3D print super soft hydrogels with micro-scale precision. By designing and integrating new subsystems into a conventional extrusion-based 3D printer, we obtained hardware that encompasses a range of new capabilities. In particular, we integrated a heated dual nozzle extrusion system and a cooling platform in the new system. In addition, we altered the electronics and software of the 3D printer to ensure fully automatized procedures are delivered by the 3D printing device, and super-soft tissue mimicking parts are produced. With regards to the electronics, we added new devices to control the temperature of the extrusion system. As for the software, the firmware of the conventional 3D printer was changed and modified to allow for the flow rate control of the ink, thus eliminating overflows in sections of the printing path where the direction/speed changes sharply