Past meets present: Reviving 80-year-old Canadian dried serum from World War II and its significance in advancing modern freeze-dried plasma for prehospital management of haemorrhage.

During World War II, Charles H. Best utilized Charles R. Drew's plasma isolation and drying technique to lead Canada's initiative to provide dried serum as a means of primary resuscitation for British casualties on the frontlines. Serum was likely utilized over plasma for its volume expansion properties without the risk of clotting during prolonged storage. We reconstituted dried serum from 1943 and discovered intact albumin, as well as anti-thrombin, plasminogen, protein C and protein S activity. Proteomic analysis identified 71 proteins, most prominent being albumin, and positive for hepatitis B by serological testing. Transmission of blood-borne diseases ended the programme, until modern advances in testing and pathogen reduction revived this technology. We tested the latest iteration of Canadian freeze-dried plasma (FDP), which was stored for 4 years, and demonstrated that its clotting capacity remained equivalent to fresh frozen plasma. We recommend that FDP is a strong alternative to contemporary prehospital resuscitation fluids (e.g. normal saline/lactated Ringer's) in managing prehospital haemorrhage where whole blood is unavailable.

Self-propelling thrombin powder enables hemostasis with no observable recurrent bleeding or thrombosis over 3 days in a porcine model of upper GI bleeding.

BACKGROUND AND AIMS: Hemostatic powders used to manage upper GI bleeding continue to exhibit high recurrent bleeding rates. Previously, self-propelling thrombin powder (SPTP) sprayed endoscopically managed severe Forrest class 1A bleeding. Here, we evaluate SPTP in a 3-day recovery model of diffuse ulcerated bleeding. METHODS: Five anesthetized pigs underwent an endoscopic mucosal snare resection to trigger diffuse ulcer bleeding and were treated with SPTP. The time to hemostasis and the amount of powder delivered were measured. Pigs were recovered and monitored. RESULTS: Five pigs achieved hemostasis in 4.5 ± 1.2 minutes At 3 days after the procedure, the pigs were rescoped and showed no recurrent bleeding. Measured blood parameters were not significantly different from baseline. There were no signs of foreign bodies or thromboembolism during gross necropsy and histopathology of key organs. CONCLUSIONS: SPTP is a promising novel material that stopped diffuse ulcer bleeding in 5 pigs without recurrent bleeding or adverse local or systemic events.

Virtual trauma patient simulation design using the McGill Simulation Complexity Score (MSCS): a breakthrough in trauma education.

BACKGROUND: Virtual patient simulations are interactive, computer-based cases. We designed scenarios based on the McGill Simulation Complexity Score (MSCS), a previously described objective complexity score. We aimed to establish validity of the MSCS and introduce a novel learning tool in trauma education at our institution. METHODS: After design of an easy and difficult patient scenario, we randomized medical students and residents to each perform 1 of the 2 scenarios. We conducted a 2-way analysis of variance of training level (medical student, resident) and scenario complexity (easy, difficult) to assess their effects on virtual time, the number of steps taken in the scenario, beneficial and harmful actions, and the ratio of beneficial over harmful actions. RESULTS: Virtual patient scenarios were successfully designed using the MSCS. Twenty-four medical students and 12 residents participated in the easy scenario (MSCS = 3), and 27 medical students and 12 residents did the difficult scenario (MSCS = 18). Though beneficial actions were similar between students and residents, sudents performed more harmful actions, particularly when the scenario was difficult. One virtual patient died in the easy scenario and 3 died in the difficult one (all medical students). Performance varied with level of complexity and there was significant interaction between level of training and number of steps, as well as with number of harmful actions. Decreasing performance with increasing level of complexity, as defined by the MSCS, suggests this score can accurately quantify difficulty. CONCLUSION: We established validity of the MSCS and showed its successful application on virtual patient scenario design.

Effect of special operational forces surgical resuscitation teams on combat casualty survival: A narrative review.

IMPORTANCE: The most common cause of preventable death on the conventional battlefield or on special operations force (SOF) missions is hemorrhage. SOF missions may take place in remote and austere locations. Many preventable deaths in combat occur within 30 min of wounding. Therefore, SOF damage control resuscitation (DCR) and damage control surgery (DCS) teams may improve combat casualty survival in the SOF environment. OBJECTIVE: To determine the effect of SOF DCR and DCS teams on combat casualty survival. Also, to describe commonalities in team structure, logistics, and blood product usage. DESIGN: A narrative review of the English literature used a Medline and Embase search strategy. The authors were contacted for more details as required. The risk of bias was assessed using the Cochrane Collaboration's ROBINS-I tool. Pooling of data was not done to the heterogeneity of studies. RESULTS: Weak evidence was identified showing a clinical benefit of SOF DCR and DCS teams. Conflicting evidence from less rigorous studies was also found. The overall risk of bias using ROBINS-I was serious to critical. Several commonalities in team structure, training, and logistics were found. CONCLUSIONS AND RELEVANCE: There is conflicting evidence regarding the effect SOF DCR and DCS teams have on combat casualty survival. There is no strong evidence that SOF DCR and DCS teams cause harm. More robust data collection is recommended to evaluate these teams.

Freeze-dried plasma: From damage control resuscitation to coronavirus disease 2019 therapy.

BACKGROUND: Freeze-dried plasma (FDP) is a promising blood component for prehospital resuscitation given its logistic advantages over fresh frozen plasma (FFP). COVID-19 convalescent (CC) plasma has been used to treat coronavirus disease 2019 (COVID-19) patients, and its corresponding FDP has potential use during future pandemics. Therefore, we conducted the study to determine if the hemostatic and immunological properties of plasma can be retained after lyophilization. STUDY DESIGN AND METHODS: Hemostatic tests were conducted with Rotational Thromboelastometry (ROTEM) and a Stago analyzer. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG (Immunoglobulin G) and neutralizing activity were analyzed using Meso Scale Diagnostics immunoassay kits. RESULTS: There were no differences in ROTEM parameters and Stago measurements for prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen and D-dimer concentrations, and antithrombin, factor V, VIII, and protein S activities between FFP and FDP for either pre-COVID-19 or CC samples. Differences were observed in INTEM clotting time and PT and PTT when comparing reconstituted FDP stored at 4°C for 24 h or room temperature for 4 h to healthy control. Both CC-FFP and CC-FDP showed two orders of magnitude higher concentrations of IgG antibodies against SARS-CoV-2 antigens than pre-COVID-19-FFP and pre-COVID-19-FDP and healthy control. Similarly, the CC samples showed approximately 4-fold higher %-inhibition of receptor binding than the pre-COVID-19 samples. There were no differences in either the antibody levels or neutralization activity between CC-FFP and CC-FDP. DISCUSSION: We demonstrated that FDP and CC-FDP retained the same hemostatic and antibody functional activities relative to their initial plasma sources, supporting clinical evaluation of their benefits in severe trauma and COVID-19 patients.

Retention of hemostatic and immunological properties of frozen plasma and COVID-19 convalescent apheresis fresh-frozen plasma produced and freeze-dried in Canada.

BACKGROUND: Randomized clinical trial data show that early plasma transfusion may save lives among trauma patients. Supplying plasma in remote environments is logistically challenging. Freeze-dried plasma (FDP) offers a possible solution. STUDY DESIGN AND METHODS: A Terumo BCT plasma freeze-drying system was evaluated. We compared pooled frozen plasma (FP) units with derived Terumo BCT FDP (TFDP) units and pooled COVID-19 convalescent apheresis fresh-frozen plasma (CC-AFFP) with derived CC-TFDP units. Parameters measured were: coagulation factors (F) II; V; VII; VIII; IX; XI; XIII; fibrinogen; Proteins C (PC) and S (PS); antithrombin (AT); α2 -antiplasmin (α2 AP); ADAMTS13; von Willebrand Factor (vWF); thrombin-antithrombin (TAT); D-dimer; activated complement factors 3 (C3a) and 5 (C5a); pH; osmolality; prothrombin time (PT); and activated partial thromboplastin time (aPTT). Antibodies to SARS-CoV-2 in CC-AFFP and CC-TFDP units were compared by plaque reduction assays and viral protein immunoassays. RESULTS: Most parameters were unchanged in TFDP versus FP or differed ≤15%. Mean aPTT, PT, C3a, and pH were elevated 5.9%, 6.9%, 64%, and 0.28 units, respectively, versus FP. CC-TFDP showed no loss of SARS-CoV-2 neutralization titer versus CC-AFFP and no mean signal loss in most pools by viral protein immunoassays. CONCLUSION: Changes in protein activities or clotting times arising from freeze-drying were <15%. Although C3a levels in TFDP were elevated, they were less than literature values for transfusable plasma. SARS-CoV-2-neutralizing antibody titers and viral protein binding levels were largely unaffected by freeze-drying. In vitro characteristics of TFDP or CC-TFDP were comparable to their originating plasma, making future clinical studies appropriate.

Resuscitative endovascular balloon occlusion of the aorta in Canada: a context-specific position paper from the Canadian Collaborative for Urgent Care Surgery (CANUCS).

SummaryResuscitative endovascular balloon occlusion of the aorta (REBOA) is a well-described intervention for noncompressible torso hemorrhage. Several Canadian centres have included REBOA in their hemorrhagic shock protocols. However, REBOA has known complications and equipoise regarding its use persists. The Canadian Collaborative on Urgent Care Surgery (CANUCS) comprises surgeons who provide acute trauma care and leadership in Canada, with experience in REBOA implementation, use, education and research. Our goal is to provide evidence- and experience-based recommendations regarding institutional implementation of a REBOA program, including multidisciplinary educational programs, attention to device and care pathway logistics, and a robust quality assurance program. This will allow Canadian trauma centres to maximize patient benefits and minimize risks of this potentially life-saving technology.

Ex vivo hemostatic and immuno-inflammatory profiles of freeze-dried plasma.

BACKGROUND: Hemorrhage is a leading cause of preventable death in civilian and military trauma. Freeze-dried plasma is promising for hemostatic resuscitation in remote prehospital settings, given its potential benefits in reducing blood loss and mortality, long storage at ambient temperatures, high portability, and rapid reconstitution for transfusion in austere environments. Here we assess the ex vivo characteristics of a novel Terumo's freeze-dried plasma product (TFDP). STUDY DESIGN AND METHODS: Rotational thromboelastometry (ROTEM) tests (INTEM, EXTEM, and FIBTEM) were conducted on plasma samples at 37°C with a ROTEM delta-machine using standard reagents and procedures. The following samples were analyzed: pooled plasma to produce TFDP, TFDP reconstituted, and stored immediately at -80°C, reconstituted TFDP stored at 4°C for 24 h and room temperature (RT) for 4 h before freezing at -80°C. Analysis of plasma concentrations of selected cytokines, chemokines, and vascular molecules was performed using a multiplex immunoassay system. One-way ANOVA with post hoc tests assessed differences in hemostatic and inflammatory properties. RESULTS: No significant differences in ROTEM variables (coagulation time [CT], clot formation time, α-angle, maximum clot firmness, and lysis index 30) between the TFDP-producing plasma and reconstituted TFDP samples were observed. Compared to control plasma, reconstituted TFDP stored at 4°C for 24 h or RT for 4 h showed a longer INTEM CT. Levels of immuno-inflammatory mediators were similar between frozen plasma and TFDP. CONCLUSIONS: TFDP is equivalent to frozen plasma with respect to global hemostatic and immuno-inflammatory mediator profiles. Further investigations of TFDP in trauma-induced coagulopathy models and bleeding patients are warranted.

Evaluation of trauma-induced coagulopathy in the fibrinogen in the initial resuscitation of severe trauma trial.

BACKGROUND: Coagulopathic bleeding is frequently present after major trauma. However, trauma-induced coagulopathy (TIC) remains incompletely understood. This laboratory analysis of blood samples derived from our completed trial on fibrinogen in the initial resuscitation of severe trauma (FiiRST) was conducted to evaluate TIC and associated responses to fibrinogen replacement. STUDY DESIGN AND METHODS: We conducted a retrospective evaluation of TIC in 45 FiiRST trial patients based on rotational thromboelastometry (ROTEM), international normalized ratio (INR), and biomarkers for hemostasis and endotheliopathy. Whole blood was analyzed by ROTEM. Plasma was analyzed for INR and biomarkers. RESULTS: Overall, 19.0% and 30.0% of the FiiRST trial patients were coagulopathic on admission defined by EXTEM maximum clot firmness out of the range of 40-71 mm and INR >1.2, respectively. The FiiRST patients showed lower fibrinogen, factor II and V levels, protein C and antiplasmin activities, higher activated protein C, tissue plasminogen activator, d-dimer, and thrombomodulin concentrations at admission than healthy controls. Most of the biomarkers changed their activities during 48-h hospitalization, but were at abnormal levels even 48-h after admission. The fibrinogen treatment reduced hypofibrinogenemia and increased factor XIII level, but had no significant effects on other biomarkers levels. Limited development of endotheliopathy was indicated by syndean-1, thrombomodulin, and sE-selectin. CONCLUSIONS: About 19%-30% of the trauma patients in the FiiRST trial were coagulopathic on hospital admission depending on the definition of TIC. Analyses of the TIC biomarkers demonstrated that hemostasis would not return to normal after 48-h hospitalization, and fibrinogen replacement improved hypofibrinogenemia.

Management of Open Abdomen After Trauma Laparotomy: A Comparative Analysis of Dynamic Fascial Traction and Negative Pressure Wound Therapy Systems.

BACKGROUND: Management of the post-traumatic open abdomen (OA) using negative pressure wound therapy (NPWT) alone is associated with low rates of primary fascial closure. The abdominal reapproximation anchor (ABRA) system exerts dynamic medial fascial traction and may work synergistically with NPWT to facilitate primary fascial closure. METHODS: Patients with an OA following trauma laparotomy between 2009 and 2018 were identified from a prospectively maintained institutional database. Patients treated with ABRA in conjunction with NPWT (ABRA) versus NPWT alone (NPWT) were compared in terms of primary fascial closure rate, number of surgeries to closure, tracheostomy duration, length of stay and incidence of entero-atmospheric fistula. Multivariable linear regression was performed to identify predictors of tracheostomy duration. RESULTS: We identified 48 patients [ABRA, 12 and NPWT, 36]. The ABRA group was significantly younger (25 vs. 37 years, p = 0.027) and included a lower proportion of males (58% vs. 89%, p = 0.032). Groups were similar with respect to the incidence of hollow viscus injury, injury severity score and abdominal abbreviated injury score. Compared to the NPWT group, the ABRA group had a significantly higher rate of primary fascial closure (100% vs. 28%, p < 0.001), fewer surgeries to abdominal closure (2 vs. 2.5, p = 0.023) and shorter duration of tracheostomy (15.5 vs. 36 days, p = 0.008). There were no differences in length of stay or incidence of entero-atmospheric fistula. On multivariable linear regression, ABRA placement was an independent predictor of shorter tracheostomy duration, after adjusting for covariates (ß = - 0.294, p = 0.036). CONCLUSION: For the post-traumatic OA, ABRA coupled with NPWT achieves a higher rate of primary fascial closure compared to NPWT alone, while requiring fewer surgeries and a shorter duration of tracheostomy.

The Financial Burden of Road Traffic Injuries in Mozambique: A Hospital-Related Cost-of-Illness Study of Maputo Central Hospital.

BACKGROUND: Road traffic injuries (RTIs) are increasingly being recognized for their significant economic impact. Mozambique, like other low-income countries, suffers staggering rates of road traffic collisions. To our knowledge, this is the first study to estimate direct hospital costs of RTIs using a bottom-up, micro-costing approach in the Mozambican context. This study aims to calculate the direct, inpatient costs of RTIs in Mozambique and compare it to the financial capacity of the Mozambican public health care system. METHODS: This was a retrospective, single-centre study. Charts of all patients with RTIs admitted to Maputo Central Hospital over a period of 2 months were reviewed. The costs were recorded and analysed based on direct costs, human resource costs, and overhead costs. Costs were calculated using a micro-costing approach. RESULTS: In total, 114 patients were admitted and treated for RTIs at Maputo Central Hospital during June-July 2015. On average, the hospital cost per patient was US$ 604.28 (IQR 1033.58). Of this, 44% was related to procedural costs, 23% to diagnostic imaging costs, 17% to length-of-stay costs, 9% to medication costs, and 7% to laboratory test costs. The average annual inpatient cost of RTIs in Mozambique was almost US$ 116 million (0.8% of GDP). CONCLUSION: The financial burden of RTIs in Mozambique represents approximately 40% of the annual public health care budget. These results help highlight the economic impact of trauma in Mozambique and the importance of an organized trauma system to reduce such costs.

Perioperative Mortality Rates as a Health Metric for Acute Abdominal Surgery in Low- and Middle-Income Countries: A Systematic Review and Future Recommendations.

BACKGROUND: Approximately 5 billion people do not have access to safe, timely, and affordable surgical and anesthesia care, with this number disproportionately affecting those from low-middle-income countries (LMICs). Perioperative mortality rates (POMRs) have been identified by the World Health Organization as a potential health metric to monitor quality of surgical care provided. The purpose of this systematic review was to evaluate published reports of POMR and suggest recommendations for its appropriate use as a health metric. METHODS: The protocol was registered a priori with PROSPERO. A peer-reviewed search strategy was developed adhering with the PRISMA guidelines. Relevant articles were identified through Medline, Embase, CENTRAL, CDSR, LILACS, PubMed, BIOSIS, Global Health, Africa-Wide Information, Scopus, and Web of Science databases. Two independent reviewers performed a primary screening analysis based on titles and abstracts, followed by a full-text screen. Studies describing POMRs of adult emergency abdominal surgeries in LMICs were included. RESULTS: A total of 7787 articles were screened of which 7466 were excluded based on title and abstract. Three hundred and twenty-one articles entered full-text screen of which 70 articles met the inclusion criteria. Variables including timing of POMR reporting, intraoperative mortality, length of hospital stay, complication rates, and disease severity score were collected. Complication rates were reported in 83% of studies and postoperative stay in 46% of studies. 40% of papers did not report the specific timing of POMR collection. 7% of papers reported on intraoperative death. Additionally, 46% of papers used a POMR timing specific to the duration of their study. Vital signs were discussed in 24% of articles, with disease severity score only mentioned in 20% of studies. CONCLUSION: POMR is an important health metric for quantifications of quality of care of surgical systems. Further validation and standardization are necessary to effectively use this health metric.

Deployment of second-generation resuscitative endovascular balloon occlusion of the aorta for unresponsive hypotension in a polytrauma patient

Summary: Noncompressible hemorrhagic control remains one of the most challenging areas in damage control medicine and continues to be a leading cause of preventable death. For decades, emergency thoracotomy or laparotomy and aortic cross clamping have remained the gold standard intervention. Recently, there has been a movement toward less invasive techniques for noncompressible hemorrhagic control, such as resuscitative endovascular balloon occlusion of the aorta (REBOA). The REBOA technique involves inflation of an endovascular balloon within the abdominal aorta proximal to the vascular injury to temporarily inhibit bleeding. Although the literature is robust on this new technique, skepticism remains about whether REBOA is superior to aortic cross clamping, as it has been associated with complications including organ and limb ischemia, limb amputation, femoral aneurysm, and thrombosis.

Intermittent use of resuscitative endovascular balloon occlusion of the aorta in penetrating gunshot wound of the lower extremity

Summary: The use of resuscitative endovascular balloon occlusion of the aorta (REBOA) in penetrating injuries is an emerging adjunct in the civilian trauma surgeon's toolbox for the management of traumatic hemorrhagic shock. Furthermore, within the Canadian civilian context, little has been reported with regard to its use as an assisted damage-control measure in vascular reconstruction of the lower extremity. We report a case of penetrating gunshot injury of the lower extremity where the preoperative deployment of REBOA had a remarkable positive impact in the resuscitation phase and the intraoperative control of blood loss. A description of the procedure and the advantage gained from REBOA are discussed.

No. 3 Canadian General Hospital (McGill) in the Great War: service and sacrifice.

SUMMARY: During the Great War, McGill University fielded a full general hospital to care for the wounded and sick among the Allied forces fighting in France and Belgium. The unit was designated No. 3 Canadian General Hospital (McGill) and included some of the best medical minds in Canada. Because the unit had a relationship with Sir William Osler, who was a professor at McGill from 1874 to 1885, the unit received special attention throughout the war, and legendary Canadian medical figures, such as John McCrae, Edward Archibald and Francis Scrimger, VC, served on its staff. The unit cared for thousands of victims of the war, and its trauma care advanced through the clinical innovation and research demanded by the nature of its work. Although No. 3 Canadian General Hospital suffered tragedies as well, such as the deaths of John McCrae and Osler's only son Revere, by the war's end the McGill hospital was known as one of the best medical units within the armies in France.

After the war is over: the role of General Sir Arthur Currie in the development of academic medicine in Canada

Summary: Canadian universities faced a challenge with the return of a large cohort of battle-hardened students and faculty from the First World War. General Sir Arthur Currie, considered one of the few successful generals of the war, returned to a welcome of silence in Canada. McGill University exploited the opportunity to recruit him as its president. Currie oversaw a campaign of building construction and faculty development at McGill that also had a significant effect on the rest of Canada. Through his fostering of the Montreal Neurological Institute and the recruitment of Dr. Wilder Penfield, Currie facilitated the development of multidisciplinary medicine, which integrates clinical care with research ­ an aspiration still held by specialty medicine in Canada today.

No. 3 Canadian General Hospital (McGill) in the Great War: service and sacrifice.

SUMMARY: During the Great War, McGill University fielded a full general hospital to care for the wounded and sick among the Allied forces fighting in France and Belgium. The unit was designated No. 3 Canadian General Hospital (McGill) and included some of the best medical minds in Canada. Because the unit had a relationship with Sir William Osler, who was a professor at McGill from 1874 to 1885, the unit received special attention throughout the war, and legendary Canadian medical figures, such as John McCrae, Edward Archibald and Francis Scrimger, VC, served on its staff. The unit cared for thousands of victims of the war, and its trauma care advanced through the clinical innovation and research demanded by the nature of its work. Although No. 3 Canadian General Hospital suffered tragedies as well, such as the deaths of John McCrae and Osler's only son Revere, by the war's end the McGill hospital was known as one of the best medical units within the armies in France.

The University of Toronto's lasting contribution to war surgery: how Maj. L. Bruce Robertson fundamentally transformed thinking toward blood transfusion during the First World War.

SUMMARY: During the Great War, Canadian military surgeons produced some of the greatest innovations to improve survival on the battlefield. Arguably, the most important was bringing blood transfusion practice close to the edge of the battlefield to resuscitate the many casualties dying of hemorrhagic shock. Dr. L. Bruce Robertson of the Canadian Army Medical Corps was the pioneering surgeon from the University of Toronto who was able to demonstrate the benefit of blood transfusions near the front line and counter the belief that saline was the resuscitation fluid of choice in military medicine. Robertson would go on to survive the Great War, but would be taken early in life by influenza. Despite his life and career being cut short, Robertson's work is still carried on today by many military medical organizations who strive to bring blood to the wounded in austere and dangerous settings. This article has an Appendix, available at canjsurg.ca.