Trials and guidelines in trauma burns and drowning

This collection of trauma trials and guidelines should serve as a sort of suggested reading material for the CICM Second Part exam candidate preparing for the increasingly unpredictable Fellowship exam, to supplement the increasingly inadequate practice of revising by doing past papers.  Trauma overlaps considerably with transfusion medicine for obvious reasons, and so some of the trials and guidelines here may be duplicates of those found in the corresponding haematology section. Most of these have come from Critical Care Reviews and The Bottom Line. Wherever possible, the original paper is linked from the name of the study, and the Bottom Line review is linked from the year of publication.

Transfusion trials

Boffard et al - 2005 - Factor VIIa in trauma; n=301 all over the world. RBC requirements reduced by 2.6 units and massive transfusion (>20 PRBCs) was required in fewer patients (14% vs 33%), more so in blunt vs penetrating trauma.

PROPPR - 2015 - blood product ratio of 1:1:1 vs 1:1:2 (FFP:platelets:RBCs); n=680 in the US. No difference in mortality (22.4 vs 26%).

PAMPer - 2018 - what if we give the FFP pre-hospital? n=501 in the US. Mortality was much better (23% vs. 33.0%)COMBAT

COMBAT - 2018 - prehospital FFP again, n=125 in the US. No difference in mortality (15% vs 10%)

ITACTIC 2020 - TEG/ROTEM vs. coags in trauma. Less product use? n=392 in Europe. No difference in product use; but also hardly any product use (only 67% and 36% of the groups got any blood products).

PREHO-PLYO - 2022 - why not prehospital lyophilised plasma? n=150 in France. No difference in the need for massive transfusion (10.3% vs  6.1%).

Re-PHILL - 2022 - why not prehospital lyophilised plasma and PRBCs? n=432 in the UK. No difference in composite outcome (64% vs 65%).

RESTRIC - 2023 - what if Hb 70-90 for severe trauma, instead 100-120? n=411 in Japan. No difference in survival (92.1% vs 91.3%)

PROCOAG - 2023 - what if prothrombin concentrate instead of FFP? n=327 in France. No difference in blood product use (12 vs 11 units of blood product), plus an increase in the risk of thrombotic events (35% vs 24%)

Tranexamic acid trials in trauma

CRASH-2 - 2010 - what if we give TXA to trauma patients? n=20,207 all over the world. Improved mortality (14.5% vs 16%), but they weren't very bleedy (only 5% of patients actually died of haemorrhage)

CRASH-3 2019 - what if TXA, but in TBI? n=12737, all over the world. No mortality difference (18.5% vs 19.8%), no difference in DVT/PE (1.6% vs 1.6%). Signal for better mortality in mild-moderate TBI (5.8% vs 7.5%).

PATCH-Trauma - 2023 - what if TXA, but prehospital? n=1310, in Australia NZ and Germany. Significantly reduced mortality at 24 hrs and 28 days but there was no difference in good-functioning survival at 6 months (53.7% vs 53.5%).

Miscellaneous trials in trauma

Bickell et al - 1994 - what if we don't haemodilute them with a million litres of fluid? n=598, in the US. Mean volume of 386 ml vs 2611 ml. Improved survival (70% vs. 62%)

HYPOLYTE - 2010 - why not some steroids? n=149 in France. Decreased risk of VAP (35.6% vs 51.3%) but increased duration of ventilation by six days.

REACT 2 - 2016 - pan-CT, or should we just scan the interesting bits? n=1403 in Europe. No difference in mortality (15.9% vs. 15.7%), but that won't stop anyone.

AVERT Shock - 2019 - low dose vasopressin, if you need more than 6 units of PRBCs. n=101 in the US. Significantly less non-PRBC product use (FFP, platelets and cryo).

Ho et al - 2019 - IVC filters for all? n=240 in Australia. No difference in PE or death (13.9% vs 14.4%); as a bonus 31.5% were never removed, eg. became lost to follow-up.

TBL Mini - 2022 - rib fixation for flail chest? n=211. Two extra ventilator-free days in the operative group (22.7 vs 20.6), but did not reach clinical significance

Free online resources

Guidelines in trauma

Head and facial injury guidelines

Neck and spinal injury guidelines

Chest injury guidelines

Abdominal and pelvic injury guidelines

Trauma resuscitation guidelines

VTE prophylaxis in trauma

Burns guidelines

Drowning guidelines

Miscellaneous guidelines

References

Sperry, Jason L., et al. "Western Trauma Association critical decisions in trauma: penetrating neck trauma." Journal of Trauma and Acute Care Surgery 75.6 (2013): 936-940.

Schmidt, Andrew C., et al. "Wilderness medical society clinical practice guidelines for the treatment and prevention of drowning: 2019 update." Wilderness & Environmental Medicine 30.4 (2019): S70-S86.

Dehghan, Niloofar, et al. "Operative vs nonoperative treatment of acute unstable chest wall injuries: A randomized clinical trial." JAMA surgery 157.11 (2022): 983-990.

Crombie, Nicholas, et al. "Resuscitation with blood products in patients with trauma-related haemorrhagic shock receiving prehospital care (RePHILL): a multicentre, open-label, randomised, controlled, phase 3 trial." The Lancet Haematology 9.4 (2022): e250-e261.

Sims, Carrie A., et al. "Effect of low-dose supplementation of arginine vasopressin on need for blood product transfusions in patients with trauma and hemorrhagic shock: a randomized clinical trial." JAMA surgery 154.11 (2019): 994-1003.

Ho, Kwok M., et al. "A multicenter trial of vena cava filters in severely injured patients." New England Journal of Medicine 381.4 (2019): 328-337. 

Sperry, Jason L., et al. "Prehospital plasma during air medical transport in trauma patients at risk for hemorrhagic shock." New England Journal of Medicine 379.4 (2018): 315-326.

Sierink, Joanne C., et al. "Immediate total-body CT scanning versus conventional imaging and selective CT scanning in patients with severe trauma (REACT-2): a randomised controlled trial." The Lancet 388.10045 (2016): 673-683.

Holcomb, John B., et al. "Transfusion of plasma, platelets, and red blood cells in a 1: 1: 1 vs a 1: 1: 2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial." Jama 313.5 (2015): 471-482.

Bickell, William H., et al. "Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries." New England Journal of Medicine 331.17 (1994): 1105-1109.

Hayakawa, Mineji, et al. "The Restrictive Red Blood Cell Transfusion Strategy for Critically Injured Patients (RESTRIC) trial: a cluster-randomized, crossover, non-inferiority multicenter trial of restrictive transfusion in trauma." Journal of Intensive Care 11.1 (2023): 1-14.

Moore, Hunter B., et al. "Plasma-first resuscitation to treat haemorrhagic shock during emergency ground transportation in an urban area: a randomised trial." The Lancet 392.10144 (2018): 283-291.

Jost, Daniel, et al. "Prehospital lyophilized plasma transfusion for trauma-induced coagulopathy in patients at risk for hemorrhagic shock: a randomized clinical trial." JAMA Network Open 5.7 (2022): e2223619-e2223619.

Roquilly, Antoine, et al. "Hydrocortisone therapy for patients with multiple trauma: the randomized controlled HYPOLYTE study." Jama 305.12 (2011): 1201-1209.

Rappold, Joseph F., et al. "Venous thromboembolism prophylaxis in the trauma intensive care unit: an American Association for the Surgery of Trauma Critical Care Committee Clinical Consensus Document." Trauma surgery & acute care open 6.1 (2021): e000643.

Ley, Eric J., et al. "Updated guidelines to reduce venous thromboembolism in trauma patients: a Western Trauma Association critical decisions algorithm." The journal of trauma and acute care surgery 89.5 (2020): 971.

Bouzat, Pierre, et al. "Efficacy and safety of early administration of 4-factor prothrombin complex concentrate in patients with trauma at risk of massive transfusion: the PROCOAG randomized clinical trial." JAMA 329.16 (2023): 1367-1375.

Boffard, Kenneth David, et al. "Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: two parallel randomized, placebo-controlled, double-blind clinical trials." Journal of Trauma-Injury Infection and Critical Care 59.1 (2005): 8-18.