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Objective: Advanced airway management (AAM) is a critical component of prehospital critical care. Airway management in flight can be more challenging because of spatial, ergonomic, and environmental factors. This study examines the frequency of in-flight intubation (IFI), first-pass success (FPS) rates, and definitive airway sans hypoxia/hypotension on first attempt (DASH-1A) across different locations of airway management., Methods: We conducted a retrospective database analysis of all patients transported between January 2016 and July 2021 who received AAM from a single air medical service. Patient records were reviewed for location of intubation, patient characteristics, and FPS and DASH-1A rates. The primary outcome was the frequency of IFI. The secondary outcomes included FPS and DASH-1A rates by location and type of transport asset., Results: During the study period, 473 patients required AAM. Three percent (15/473) of patients were intubated in an in-flight setting, 28% (130/473) were intubated on scene, and 70% (328/473) were intubated in a health care facility. The primary reason for IFI was unanticipated cardiac arrest or clinical deterioration. The overall FPS rate was 69% (328/473), and the DASH-1A rate was 49% (194/399). Based on the location of AAM, the FPS and DASH-1A rates were the lowest for on-scene intubations (56% [74/130] and 27% [20/74], respectively). Most of the on-scene AAM took place with rotor wing flight crews., Conclusion: Airway management occurs infrequently in an in-flight setting and is necessary because of patient deterioration or cardiac arrest. Based on our results, we identified opportunities for targeted AAM quality improvement and clinical governance., Competing Interests: Declaration of competing interest The author(s) have no relevant disclosures. There was no grant funding or financial support for this manuscript., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: This study aimed to compare current out-of-hospital transfusion (OHT) protocols in Canadian civilian critical care transport organizations (CCTO) to expert recommendations and explore the variability and potential benefits of standardizing OHT practices across Canada., Methods: A comprehensive cross-sectional study was conducted, encompassing all seven Canadian CCTOs that provide OHT. The study assessed adherence to expert recommendations and examined specific aspects of the transfusion process, such as indications for transfusion and cessation criteria., Results: The study found an 89% adherence to expert recommendations for OHT among Canadian CCTOs. It highlighted a strong alignment between current practices and recommendations, possibly attributed to collaborative frameworks like the CAN-PATT network. However, notable variability and ambiguity were observed in transfusion indications and cessation criteria. The study also emphasized the potential benefits of standardizing OHT practices, such as improved policy formulation, better interpretation of emerging literature, and evaluation of OHT efficacy., Conclusion: This cross-sectional study assessed how Canadian CCTOs implement OHT practices compared to expert-recommended practices. The findings underscore the importance of structured protocols in trauma management. Given the consistency in OHT protocol adoption and the comprehensive approach across CCTOs, there's a solid foundation for managing trauma patients in prehospital and transport settings across Canada. As OHT practices continue to evolve, sustained efforts are vital to refine, adapt, and elevate patient care standards in trauma management., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Background: Early resuscitation with blood components or products is emerging as best practice in selected patients with trauma and medical patients; as a result, out-of-hospital transfusion (OHT) programs are being developed based on limited and often conflicting evidence. This study aimed to provide guidance to Canadian critical care transport organizations on the development of OHT protocols., Methods: The study period was July 2021 to June 2022. We used a modified RAND Delphi process to achieve consensus on statements created by the study team guiding various aspects of OHT in the context of critical care transport. Purposive sampling ensured representative distribution of participants in regard to geography and relevant clinical specialties. We conducted 2 written survey Delphi rounds, followed by a virtual panel discussion (round 3). Consensus was defined as a median score of at least 6 on a Likert scale ranging from 1 ("Definitely should not include") to 7 ("Definitely should include"). Statements that did not achieve consensus in the first 2 rounds were discussed and voted on during the panel discussion., Results: Seventeen subject experts participated in the study, all of whom completed the 3 Delphi rounds. After the study process was completed, a total of 39 statements were agreed on, covering the following domains: general oversight and clinical governance, storage and transport of blood components and products, initiation of OHT, types of blood components and products, delivery and monitoring of OHT, indications for and use of hemostatic adjuncts, and resuscitation targets of OHT., Interpretation: This expert consensus document provides guidance on OHT best practices. The consensus statements should support efficient and safe OHT in national and international critical care transport programs., Competing Interests: Competing interests: Brodie Nolan reports research funding from Canadian Blood Services and Physicians’ Services Incorporated Foundation. Andrew Shih reports payments for consulting on educational materials in relation to bleeding management from Octapharma Canada and payments for advisory board participation in relation to clotting factor concentrates from CSL Behring. He has received speaker honoraria from Octapharma Canada and CSL Behring. Octapharma Canada reimbursed travel expenses for attending a meeting for the FARES-II trial comparing clotting factor concentrates to plasma in cardiac surgery. He is vice-chair of the National Advisory Committee on Blood and Blood Products. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Introduction: Endotracheal intubation (ETI) is an infrequent but key component of prehospital and retrieval medicine. Common measures of quality of ETI are the first pass success rates (FPS) and ETI on the first attempt without occurrence of hypoxia or hypotension (DASH-1A). We present the results of a multi-faceted quality improvement program (QIP) on paramedic FPS and DASH-1A rates in a large regional critical care transport organization., Methods: We conducted a retrospective database analysis, comparing FPS and DASH-1A rates before and after implementation of the QIP. We included all patients undergoing advanced airway management with a first strategy of ETI during the time period from January 2016 to December 2021., Results: 484 patients met the inclusion criteria during the study period. Overall, the first pass intubation success (FPS) rate was 72% (350/484). There was an increase in FPS from the pre-intervention period (60%, 86/144) to the post-intervention period (86%, 148/173), p < 0.001. DASH-1A success rates improved from 45% (55/122) during the pre-intervention period to 55% (84/153) but this difference did not meet pre-defined statistical significance (p = 0.1). On univariate analysis, factors associated with improved FPS rates were the use of video-laryngoscope (VL), neuromuscular blockage, and intubation inside a healthcare facility., Conclusions: A multi-faceted advanced airway management QIP resulted in increased FPS intubation rates and a non-significant improvement in DASH-1A rates. A combination of modern equipment, targeted training, standardization and ongoing clinical governance is required to achieve and maintain safe intubation by paramedics in the prehospital and retrieval environment., (© 2023. The Author(s).)

Aim: This study examined the association between admission to a cardiac arrest centre and survival to hospital discharge for adults following out-of-hospital cardiac arrest (OHCA)., Methods: We undertook a multicentre retrospective observational study of patients transferred to hospital after OHCA of presumed cardiac aetiology in three ambulance services in England. We used propensity score matching to compare rates of survival to hospital discharge in patients admitted to OHCA centres (defined as either 24/7 PPCI availability or >100 OHCA admissions per year) to rates of survival of patients admitted to non-centres., Results: Between January 2017 and December 2018, 10,650 patients with OHCA were included in the analysis. After propensity score matching, admission to a hospital with 24/7 PPCI availability or a high volume centre was associated with an absolute improvement in survival to hospital discharge of 2.5% and 2.8%, respectively. The corresponding odds ratios and 95% confidence intervals were 1.69 (1.28-2.23) and 1.41 (1.14-1.75), respectively. The results were similar when missing values were imputed. In subgroup analyses, the association between admission to an OHCA centre and improved rates of survival was mainly seen in patients with OHCA due to shockable rhythms, with no or minimal potential benefit for patients with OHCA and asystole as first presenting rhythm., Conclusion: Following OHCA, admission to a cardiac arrest centre is associated with a moderate improvement in survival to hospital discharge. A corresponding bypass policy would need to consider the resulting increased workload for OHCA centres., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: We describe the inter-rater agreement between Emergency Department (ED) clinicians and reporting radiologists in the interpretation of chest X-rays (CXRs) in patients presenting to ED with suspected COVID-19., Methods: We undertook a retrospective cohort study of patients with suspected COVID-19. We compared ED clinicians' and radiologists' interpretation of the CXRs according to British Society of Thoracic Imaging (BSTI) guidelines, using the area under the receiver operator curve (ROC area)., Results: CXRs of 152 cases with suspected COVID-19 infection were included. Sensitivity and specificity for 'classic' COVID-19 CXR findings reported by ED clinician was 84 and 83%, respectively, with a ROC area of 0.84 (95%CI 0.77 to 0.90). Accuracy improved with ED clinicians' experience, with ROC areas of 0.73 (95%CI 0.45 to 1.00), 0.81 (95%CI 0.73 to 0.89), 1.00 (95%CI 1.00 to 1.00) and 0.90 (95%CI 0.70 to 1.00) for foundation year doctors, senior house officers, higher speciality trainees and ED consultants, respectively ( p < 0.001)., Conclusions: ED clinicians demonstrated moderate inter-rater agreement with reporting radiologists according to the BSTI COVID-19 classifications. The improvement in accuracy with ED clinician experience suggests training of junior ED clinicians in the interpretation of COVID-19 related CXRs might be beneficial. Large-scale survey studies might be useful in the further evaluation of this topic., Advances in Knowledge: This is the first study to examine inter-rater agreement between ED clinicians and radiologists in regards to COVID-19 CXR interpretation.Further service configurations such as 24-hr hot reporting of CXRs can be guided by these data, as well as an ongoing, nationwide follow-up study., Competing Interests: Competing interests: The authors have no conflict of interest or source of funding to declare., (© 2020 The Authors. Published by the British Institute of Radiology.)

Background: Critical care transfers between hospitals are time critical high-risk episodes for unstable patients who often require urgent lifesaving intervention. This study aimed to establish the scale, nature and safety of current transfer practice in the South West Critical Care Network (SWCCN) in England., Methods: The SWCCN database contains prospectively collected data in accordance with national guidelines. It was interrogated for all adult (>15 years of age) patients from January 2012 to November 2017., Results: A total of 1124 inter-hospital transfers were recorded, with the majority (935, 83.2%) made for specialist treatment. The transferring team included a doctor in 998 (88.8%) and nurse in 935 (93.7%) transfers. In 204 (18.1%) transfers, delays occurred, with the commonest cause being availability of transport. Critical incidents occurred in 77 (6.9%)., Conclusions: This is the first published data on the transfer activity of a UK adult critical care network. It demonstrates that current ad-hoc provision is not meeting the longstanding expectations of national guidelines in terms of training, clinical experience and timeliness. The authors hope that this study may inform national conversation regarding the development of National Health Service commissioned inter-hospital transfer services for adult patients in England., (© The Intensive Care Society 2019.)

Aim: To examine the effect of prehospital critical care on survival following OHCA, compared to routine advanced life support (ALS) care., Methods: We undertook a prospective multi-centre cohort study including two ambulance services and six prehospital critical care services in the United Kingdom (UK), between September 2016 and October 2017. Inclusion criteria were adult patients with non-traumatic OHCA treated by either prehospital critical care teams or ALS paramedics. Patients who received prehospital critical care were matched to those receiving ALS using propensity score matching. Primary outcome was survival to hospital discharge; secondary outcome was survival to hospital admission., Results: The primary analysis included 658 patients with OHCA receiving prehospital critical care and 1847 patients receiving ALS care. Rates of survival to hospital discharge (primary outcome) were 11.9% in both groups; rates of survival to hospital admission (secondary outcome) were 34.4% and 27.7% in the prehospital critical care and ALS group, respectively. The corresponding odds ratios for survival to hospital discharge and survival to hospital admission with prehospital critical care were 1.06 (95% confidence interval 0.75-1.49) and 1.39 (95% confidence interval 1.10-1.75), respectively. Results were consistent across subgroups and sensitivity analyses., Conclusions: Despite a positive association with the secondary outcome of survival to hospital admission, prehospital critical care was not associated with increased rates of survival to hospital discharge following OHCA., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: This research aimed to answer the following questions: What are the costs of prehospital advanced life support (ALS) and prehospital critical care for out-of-hospital cardiac arrest (OHCA)? What is the cost-effectiveness of prehospital ALS? What improvement in survival rates from OHCA would prehospital critical care need to achieve in order to be cost-effective?, Setting: A single National Health Service ambulance service and a charity-funded prehospital critical care service in England., Participants: The patient population is adult, non-traumatic OHCA., Methods: We combined data from previously published research with data provided by a regional ambulance service and air ambulance charity to create a decision tree model, coupled with a Markov model, of costs and outcomes following OHCA. We compared no treatment for OHCA to the current standard of care of prehospital ALS, and prehospital ALS to prehospital critical care. To reflect the uncertainty in the underlying data, we used probabilistic and two-way sensitivity analyses., Results: Costs of prehospital ALS and prehospital critical care were £347 and £1711 per patient, respectively. When costs and outcomes of prehospital, in-hospital and postdischarge phase of OHCA care were combined, prehospital ALS was estimated to be cost-effective at £11 407/quality-adjusted life year. In order to be cost-effective in addition to ALS, prehospital critical care for OHCA would need to achieve a minimally economically important difference (MEID) in survival to hospital discharge of 3%-5%., Conclusion: This is the first economic analysis to address the question of cost-effectiveness of prehospital critical care following OHCA. While costs of either prehospital ALS and/or critical care per patient with OHCA are relatively low, significant costs are incurred during hospital treatment and after discharge in patients who survive. Knowledge of the MEID for prehospital critical care can guide future research in this field., Trial Registration Number: ISRCTN18375201., Competing Interests: Competing interests: JVVF and JRB work as prehospital doctors with a regional prehospital critical care team., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Background and Aims: Prehospital critical care for out-of-hospital cardiac arrest (OHCA) is a complex and largely unproven intervention. During research to examine this intervention, we noted significant differences in stakeholders' views about research, randomisation, and the funding of prehospital critical care for OHCA. We aimed to answer the following questions: What are stakeholders' priorities for prehospital research? What are stakeholders' views on randomisation of prehospital critical care? How do stakeholders consider allocation of resources in prehospital care?, Methods: We undertook an explanatory qualitative framework analysis of interviews and focus group with 5 key stakeholder groups: patients and public, air ambulance charities, ambulance service commissioners, prehospital researchers, and prehospital critical care providers., Results: We undertook 3 focus group discussions with a total of 23 participants and 8 interviews with a total of 9 participants. Despite sharing a common appreciation of the concepts of scientific enquiry, fairness, and beneficence, the 5 relevant stakeholder groups displayed divergent views of research and funding strategies regarding the intervention of prehospital critical care for the condition of OHCA. The reasons for this divergence could largely be explained through the different personal experiences and situational contexts of each stakeholder group. Many aspects of the strategies suggested by the stakeholder groups only partially aligned with principles of traditional evidence-based medicine, but were held with strong conviction., Discussion: Analysis of the views of 5 stakeholder groups regarding research and the funding of prehospital critical care for OHCA revealed shared values but a variety of different strategies to achieve these. This knowledge can help researchers in similar fields in the planning and presentation of their research, to maximise impact on decision making.

Background: Improving survival after out-of-hospital cardiac arrest (OHCA) is a priority for modern emergency medical services (EMS) and prehospital research. Advanced life support (ALS) is now the standard of care in most EMS. In some EMS, prehospital critical care providers are also dispatched to attend OHCA. This systematic review presents the evidence for prehospital critical care for OHCA, when compared to standard ALS care., Methods: We searched the following electronic databases: PubMed, EmBASE, CINAHL Plus and AMED (via EBSCO), Cochrane Database of Systematic Reviews, DARE, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, NIHR Health Technology Assessment Database, Google Scholar and ClinicalTrials.gov. Search terms related to cardiac arrest and prehospital critical care. All studies that compared patient-centred outcomes between prehospital critical care and ALS for OHCA were included., Results: The review identified six full text publications that matched the inclusion criteria, all of which are observational studies. Three studies showed no benefit from prehospital critical care but were underpowered with sample sizes of 1028-1851. The other three publications showed benefit from prehospital critical care delivered by physicians. However, an imbalance of prognostic factors and hospital treatment in these studies systematically favoured the prehospital critical care group., Conclusion: Current evidence to support prehospital critical care for OHCA is limited by the logistic difficulties of undertaking high quality research in this area. Further research needs an appropriate sample size with adjustments for confounding factors in observational research design., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Survival rates from out-of-hospital cardiac arrest (OHCA) remain low, despite remarkable efforts to improve care. A number of ambulance services in the United Kingdom (UK) have developed prehospital critical care teams (CCTs) which attend critically ill patients, including OHCA. However, current scientific evidence describing CCTs attending OHCA is sparse and research to date has not demonstrated clear benefits from this model of care., Methods: This prospective, observational study will describe the effect of CCTs on survival from OHCA, when compared to advanced-life-support (ALS), the current standard of prehospital care in the UK. In addition, we will describe the association between individual critical care interventions and survival, and also the costs of CCTs for OHCA. To examine the effect of CCTs on survival from OHCA, we will use routine Utstein variables data already collected in a number of UK ambulance trusts. We will use propensity score matching to adjust for imbalances between the CCT and ALS groups. The primary outcome will be survival to hospital discharge, with the secondary outcome of survival to hospital admission. We will record the critical care interventions delivered during CCT attendance at OHCA. We will describe frequencies and aim to use multiple logistic regression to examine possible associations with survival. Finally, we will undertake a stakeholder-focused cost analysis of CCTs for OHCA. This will utilise a previously published Emergency Medical Services (EMS) cost analysis toolkit and will take into account the costs incurred from use of a helicopter and the proportion of these costs currently covered by charities in the UK., Discussion: Prehospital critical care for OHCA is not universally available in many EMS. In the UK, it is variable and largely funded through public donations to charities. If this study demonstrates benefit from CCTs at an acceptable cost to the public or EMS commissioners, it will provide a rationale to increase funding and service provision. If no clinical benefit is found, the public and charities providing these services can consider concentrating their efforts on other areas of prehospital care., Trial Registration: ISRCTN registry ID ISRCTN18375201 .

Aim: To assess the impact of a pre-hospital critical care team (CCT) on survival from out-of-hospital cardiac arrest (OHCA)., Methods: We undertook a retrospective observational study, comparing OHCA patients attended by advanced life support (ALS) paramedics with OHCA patients attended by ALS paramedics and a CCT between April 2011 and April 2013 in a single ambulance service in Southwest England. We used multiple logistic regression to control for an anticipated imbalance of prognostic factors between the groups. The primary outcome was survival to hospital discharge. All data were collected independently of the research., Results: 1851 cases of OHCA were included in the analysis, of which 1686 received ALS paramedic treatment and 165 were attended by both ALS paramedics and a CCT. Unadjusted rates of survival to hospital discharge were significantly higher in the CCT group, compared to the ALS paramedic group (15.8% and 6.5%, respectively, p<0.001). After adjustment using multiple logistic regression, the effect of CCT treatment was no longer statistically significant (OR 1.54, 95% CI 0.89-2.67, p=0.13). Subgroup analysis of OHCA with first monitored rhythm of ventricular fibrillation or pulseless ventricular tachycardia showed similar results., Conclusion: Pre-hospital critical care for OHCA was not associated with significantly improved rates of survival to hospital discharge. These results are in keeping with previously published studies. Further research with a larger sample size is required to determine whether CCTs can improve outcome in OHCA., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Emergency medical services in the UK are facing the challenge of responding to an increasing number of calls, often for non-emergency care, while also providing critical care to the few severely ill or injured patients. In response, paramedic training in the UK has been extended and there are regional strategies to improve prehospital critical care (PHCC). We describe the clinical competencies of three groups of prehospital providers in the UK with the aim of informing future planning of the delivery of PHCC., Methods: We used a data triangulation approach to obtain lists of competencies for paramedics, critical care paramedics (CCPs) and PHCC physicians of the Great Western Ambulance Service. Data sources were professional guidance documents, equipment available to the provider, log sheets of prehospital care episodes, direct observations and a survey of providers., Results: We identified 389, 441 and 449 competencies for paramedics, CCPs and PHCC physicians, respectively. Competencies of CCPs and PHCC physicians which exceeded those of paramedics can be arranged in four distinct clusters: induction and maintenance of anaesthesia, procedural sedation, advanced cardiovascular management and complex invasive interventions., Discussion: Paramedics possess a considerable number of competencies which allow them to diagnose and treat a variety of conditions. CCPs and PHCC physicians possess a few additional critical care competencies which are potentially life-saving but are required infrequently and can carry significant risks. Concentration of training and clinical exposure for a small group of providers in critical care teams can help optimising benefits and reducing risks of PHCC., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives: Paramedic-delivered prehospital critical care is an established concept in a number of emergency medical services around the world and, more recently, has been introduced to the UK. This review identifies and describes the available evidence relating to paramedics who routinely provide prehospital critical care as primary scene response (critical care paramedics, or CCP)., Methods: A systematic search of electronic databases was performed: CENTRAL, EMBASE, MEDLINE (through EMBASE and Web of Knowledge) and Web of Science (through Web of Knowledge)., Results: The search identified 12 relevant publications, one of which was a randomised controlled trial. The remaining 11 were retrospective studies. Five studies compared CCPs with physician-led care. Three of these publications demonstrated improved outcomes with physician care, while two showed no difference. Four further publications examined CCPs versus non-physician-led care and found improved outcomes (two studies), mixed effects (one study) and no difference (one study) for CCPs. Finally, three publications addressed the addition of skills to CCP competencies. A randomised controlled trial of CCP rapid sequence induction (RSI) and tracheal intubation demonstrated improved neurologic outcomes. CCP tube thoracostomy was shown to have similar complication rates to the same procedure performed in the emergency department, while addition of a non-invasive ventilation protocol to CCP practice had no effect on long-term mortality., Conclusions: There is limited evidence to support the concept of paramedic-delivered prehospital critical care. The best available evidence suggests a benefit from prehospital RSI carried out by CCPs in patients with severe traumatic brain injury, but the impact of CCPs remains unclear for many conditions. Further high-quality research in this area would be welcome., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Critical care paramedics (CCPs) have been introduced by individual ambulance trusts in England, but there is a lack of national coordination of training and practice. We conducted an online survey of NHS ambulance services to provide an overview of the current utilization and role of CCPs in England. The survey found significant variations in training, competencies and the working patterns of the ∼90 CCPs working in five ambulance services. All ambulance trusts currently employing CCPs are planning on increasing CCP numbers, whereas 'insufficient financial means' and 'insufficient scientific evidence' are the two major barriers to CCP utilization. The CCP model established in five ambulance services in England is unique within Europe. With increasing numbers of CCPs, concerns about lack of supportive scientific evidence and clinical need should be addressed. Optimal delivery of prehospital critical care in England remains controversial.

Objectives: Prehospital anaesthesia using rapid sequence induction (RSI) is carried out internationally and in the UK despite equivocal evidence of clinical benefit. It is a core skill of the prehospital critical care service established by the Great Western Ambulance Service NHS Trust (GWAS) in 2008. This retrospective analysis of the service's first 150 prehospital RSIs describes intubation success rates and complications, thereby contributing towards the ongoing debate on its role and safety., Methods: Within the GWAS critical care team, RSI is only carried out in the presence of a qualified physician and critical care paramedic (CCP). The role of the intubating practitioner is interchangeable between physician and CCP. Data were collected retrospectively from RSI audit forms and electronic patient monitor printouts., Results: GWAS physician and CCP teams undertook 150 prehospital RSIs between June 2008 and August 2011. The intubation success rate was 82, 91 and 97% for the first, second and third attempts, respectively. Successful intubation on the first attempt was achieved in 58 (85%) and 64 (78%) patients for physicians and CCPs, respectively. RSI complications included hypoxaemia (10.2%), hypotension (9.7%) and bradycardia (1.3%)., Conclusion: Prehospital RSI can be carried out safely, with intubation success rates and complications comparable with RSI in the emergency department. The variation in the intubation success rates between individual practitioners highlights the importance of ongoing performance monitoring, coupled with high standards of clinical governance and training.

Purpose: To compare the ability of the ultrasmall superparamagnetic iron oxide (USPIO) SHU555C vs. gadopentetate dimeglumine (Gd-DTPA) to detect antigen-induced monoarthritis with MRI., Materials and Methods: Twelve seven-week-old female rats with an antigen-induced monoarthritis of the right knee were randomly assigned to two groups. Animals in group I (N = 6) underwent MRI using T1-weighted gradient-echo sequences before injection and at 2, 9, 17, 25, 33, 40, 47, 55, and 63 minutes postinjection (p.i.) of Gd-DTPA on day 1, and before injection and at 3, 23, 43, and 123 minutes p.i. of SHU555C on day 2. Animals in group II (N = 6) were imaged before injection and at 3, 23, 43, and 123 minutes p.i. using identical sequences. Signal-to-noise ratios (SNRs) and relative enhancement (DeltaSI%) of arthritic and normal synovium were determined from region-of-interest (ROI) measurements in consensus reading by two experienced radiologists. Data were tested for significant differences between the two agents and between the arthritic and normal knees using a mixed-effect model and F-tests (P < 0.05). Joints were processed for histopathology as the gold standard., Results: USPIO and Gd-DTPA showed significant enhancement differences (P < 0.001). USPIO provided a progressive and persistent enhancement of arthritic joints while Gd-DTPA provided an early and rapidly declining enhancement. Maximal enhancement in synovitis was 400% at 40-120 minutes p.i. of USPIO vs. 300% at two minutes p.i. of Gd-DTPA. USPIO provided a significant higher difference in enhancement between the arthritic and normal synovium than Gd-DTPA (P < 0.001). Histopathology confirmed marked inflammatory synovial changes in all arthritis-induced right knee joints and normal synovium in all left knee joints., Conclusion: Both USPIO and Gd-DTPA detect arthritis by positive T1-enhancement. Compared to standard Gd-DTPA, the USPIO SHU555C provides a comparable maximal T1-enhancement (at two minutes p.i for Gd-DTPA and between 43 and 123 minutes p.i. for SHU555C), but in addition it provides a prolonged T1-enhancement of synovitis and a higher difference between the relative enhancement of arthritic and normal synovium., (Copyright 2006 Wiley-Liss, Inc.)

Purpose: To optimize contrast agent dose and pulse sequence parameters in order to achieve a maximal T1 enhancement in arthritic knee joints with ultra small superparamagnetic iron oxides (USPIO)-enhanced MRI., Materials and Methods: Antigen-mediated arthritis was induced in the right knee of nine Sprague Dawley rats. The arthritic knee joint as well as the contralateral normal knee were investigated in a 2 Tesla MR scanner before as well as in short intervals up to 2 h after USPIO injection, using T1-weighted gradient echo (GE) sequences. Three rats each received intravenous injections of the new USPIO SHU 555 C (SH U 555 C, Schering AG, Berlin) at doses of 40, 100 and 200 micromol Fe/kg. Pulse sequence parameters of the GE-sequence were optimized by varying flip angles (alpha) and echo times (TE). Changes in signal intensities (SI) of the arthritic knee and contralateral normal knee were quantified as DeltaSI (%) = /([SIpost - SIpre] / SIpre) x 100 %/ and compared with histopathology., Results: Histology of the arthritic knees demonstrated a marked inflammatory proliferation of the synovium. The USPIO SH U 555 C caused a significant increase in signal intensity of the arthritic joints on T1-weighted MR images (p < 0.05). This effect was optimized using a flip angle of 60-70 degrees, a minimal TE and a dose of 200 micromol Fe/kg. Visually the contralateral normal knee did not show any USPIO enhancement., Conclusion: Inflammation can be depicted with marked T1 enhancement by the USPIO SH U 555 C using high contrast agent doses and optimized MR pulse sequence parameters.

Objectives: We sought to compare the ability of 3 ultrasmall superparamagnetic iron oxides (USPIOs) to detect and characterize antigen-induced arthritis with MR imaging., Materials and Methods: A monoarthritis was induced in the right knee of 18 rats. The left knee served as a normal control. Knees underwent magnetic resonance (MR) imaging before, up to 2 hours, and 24 hours after injection (p.i.) of 200 mumol Fe/kg SHU 555 C (n= 6), ferumoxtran-10 (n = 6), or ferumoxytol (n = 6), using T2-2D-SE 100/20,40,60,80/90 (TR/TE/flipangle), T2*-3D-spoiled gradient recalled (SPGR) 100/15/38, and T1-3D-SPGR 50/1,7/60 sequences., Results: Quantitative signal to noise ratio and DeltaSI data of arthritic knees on T1- and T2*-weighted MR images showed no significant differences between the 3 USPIOs (P > 0.05). At 2 hours p.i., SNR and DeltaSI data were significantly increased from baseline on T1-weighted images and significantly decreased on T2*-weighted images (P < 0.001). At 24 hours p.i., the T1-enhancement returned to baseline, whereas the T2*-enhancement remained significantly elevated (P < 0.001). Immunostains demonstrated an USPIO compartmentalization in macrophages in the arthritic synovium., Conclusions: Based on the relatively small number of animals in our study group, inflammation in antigen-induced arthritis can be equally detected and characterized with any of the three USPIOs evaluated.

Rationale and Objectives: The objective is to compare three different ultrasmall superparamagnetic iron oxides (USPIOs) for magnetic resonance (MR) imaging of normal bone marrow in rodents., Materials and Methods: Femoral bone marrow in 18 Sprague-Dawley rats was examined by using MR imaging before and up to 2 and 24 hours postinjection (PI) of 200 mumol of Fe/kg of SHU555C (n = 6), ferumoxtran-10 (n = 6), or ferumoxytol (n = 6), using T1-weighted (50 ms/1.7 ms/60 degrees = repetition time [TR]/echo time [TE]/flip angle) and T2*-weighted (100 ms/15 ms/38 degrees = TR/TE/flip angle) three-dimensional spoiled gradient recalled echo sequences. USPIO-induced bone marrow was evaluated qualitatively and quantified as signal-to-noise ratio (SNR) and change in signal intensity (DeltaSI) values. A mixed-effect model was fitted to the SNR and DeltaSI values, and differences among USPIOs were tested for significance by using F tests., Results: At 2 hours PI, all three USPIOs showed marked positive signal enhancement on T1-weighted images and a corresponding marked signal loss on T2*-weighted images. At 24 hours PI, the T1 effect of all three USPIOs disappeared, whereas T2*-weighted images showed persistent signal loss on SHU555C and ferumoxytol-enhanced MR images, but not ferumoxtran-10-enhanced MR images. Corresponding SNR and DeltaSI values on T2*-weighted MR images at 24 hours PI were significantly different from baseline for SHU555C and ferumoxytol, but not ferumoxtran-10., Conclusion: All three USPIO contrast agents, ferumoxtran-10, ferumoxytol, and SHU555C, can be applied for MR imaging of bone marrow. Ferumoxtran-10 apparently reveals a different kinetic behavior in bone marrow than ferumoxytol and SHU555C.