Guidelines for the acute care of severe limb trauma patients

G Model ACCPM-100862; No. of Pages 16 Anaesth Crit Care Pain Med xxx (xxxx) xxx Contents lists available at ScienceDirect Anaesthesia Critical Care & Pain Medicine journal homepage: www.elsevier.com Guidelines Guidelines for the acute care of severe limb trauma patients§,§§ Julien Pottecher a,b,*, Hugues Lefort c, Philippe Adam d, Olivier Barbier e,f, Pierre Bouzat g, Jonathan Charbit h,i, Michel Galinski j,k, Delphine Garrigue l, Tobias Gauss m,n, Yannick Georg o, Sophie Hamada p, Anatole Harrois q, Romain Kedzierewicz f,r, Pierre Pasquier s,t, Bertrand Prunet f,t, Claire Roger u, Karim Tazarourte v,w, Stéphane Travers f,x, Lionel Velly y,z, Cédric Gil-Jardiné A, Hervé Quintard B a Service d’Anesthésie-Réanimation & Médecine Péri-Opératoire, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, 1 avenue Molière, 67098 Strasbourg Cedex, France Université de Strasbourg, FMTS, France c Structure des urgences, Hôpital d’Instruction des Armées Legouest, BP 9000, 57077 Metz Cédex 03, France d Service de Chirurgie Orthopédique et de Traumatologie, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, 1 Avenue Molière, 67098 Strasbourg Cedex, France e Service de Chirurgie Orthopédique et Traumatologie, Hôpital d’Instruction des Armées Sainte Anne, 2 boulevard Sainte Anne, 83000 Toulon, France f Ecole du Val de Grace, 2 place Alphonse Laveran, 75005 Paris, France g Université Grenoble Alpes, Pôle Anesthésie-Réanimation, Centre Hospitalo-Universitaire Grenoble-Alpes, Grenoble, France h Soins critiques DAR Lapeyronie, CHU Montpellier, France i Réseau OcciTRAUMA, Réseau Régional Occitanie de prise en charge des traumatisés sévères, France j Pôle urgences adultes – SAMU 33, Hôpital Pellegrin, CHU de Bordeaux 3300 Bordeaux, France k INSERM U1219, ISPED, Bordeaux Population Health Research Center INSERM U1219-‘‘Injury Epidemiology Transport Occupation’’ Team, F-33076 Bordeaux Cedex, France l Pôle d’Anesthésie Réanimation, Pôle de l’Urgence, CHU Lille, F-59000 Lille, France m Service d’Anesthésie-Réanimation, Hôpital Beaujon, DMU PARABOL, AP-HP Nord, Clichy, France n Université de Paris, Paris, France o Service de Chirurgie Vasculaire et Transplantation Rénale, Hôpitaux Universitaire de Strasbourg, Strasbourg, France p Département d’Anesthésie Réanimation, Hôpital Européen Georges Pompidou, APHP, Université de Paris, Paris, France q Département d’anesthésie-réanimation, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Saclay, 78 rue du Général Leclerc, 94275 Le Kremlin Bicêtre, France r Bureau de Médecine d’Urgence, Division Santé, Brigade de Sapeurs-Pompiers de Paris, 1 place Jules Renard, 75017 Paris, France s Département anesthésie-réanimation, Hôpital d’instruction des armées Percy, Clamart, France t Brigade de Sapeurs-Pompiers de Paris, Paris, France u Service de Réanimation Chirurgicale, Pôle Anesthésie Réanimation Douleur Urgence, CHU Carémeau, 30000 Nıˆmes, France v Service SAMU-Urgences, CHU Edouard Herriot, Hospices civils de Lyon, Lyon, France w Université Lyon 1 Hesper EA 7425, Lyon, France x 1ère Chefferie du Service de Santé, Villacoublay, France y Service d’Anesthésie Réanimation, CHU Timone Adultes, 264 rue St Pierre 13005 Marseille, France z MeCA, Institut de Neurosciences de la Timone – UMR 7289, Aix Marseille Université, Marseille, France A Pôle Urgences adultes SAMU-SMUR, CHU Bordeaux, Bordeaux Population Health – INSERM U1219 Université de Bordeaux, Equipe IETO, Bordeaux, France B Soins Intensifs, Hôpitaux Universitaires de Genève, Genève, Suisse b Validated by the SFAR Council on August 25th, 2020. Clinical guidelines issued by the French Society of Anaesthesia and Critical Care Medicine (Société Française d’Anesthésie et de Réanimation, SFAR), the French Society of Emergency Medicine (Société Française de Médecine d’Urgence, SFMU), the French Society of Orthopaedic and Trauma Surgery (Société Française de Chirurgie Orthopédique et Traumatologique, SOFCOT) the French-speaking Society of Vascular and Endovascular Surgery (Société de Chirurgie Vasculaire et Endovasculaire de Langue Française, SCVE), the French Army Health Service (Service de Santé des Armées, SSA) and the Val-de-Grâce School of Medicine (Ecole du Val-De-Grâce, EVG). * Corresponding author at: Service d’Anesthésie-Réanimation & Médecine Péri-Opératoire, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, 1 avenue Molière, 67098 Strasbourg Cedex, France. E-mail address: [email protected] (J. Pottecher). § §§ https://doi.org/10.1016/j.accpm.2021.100862 2352-5568/ C 2021 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved. Please cite this article as: J. Pottecher, H. Lefort, P. Adam et al., Guidelines for the acute care of severe limb trauma patients, Anaesth Crit Care Pain Med, https://doi.org/10.1016/j.accpm.2021.100862 G Model ACCPM-100862; No. of Pages 16 J. Pottecher, H. Lefort, P. Adam et al. Anaesth Crit Care Pain Med xxx (xxxx) xxx A R T I C L E I N F O A B S T R A C T Historique de l’article : Available online xxx Goal: To provide healthcare professionals with comprehensive multidisciplinary expert recommendations for the acute care of severe limb trauma patients, both during the prehospital phase and after admission to a Trauma Centre. Design: A consensus committee of 21 experts was formed. A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding (i.e., pharmaceutical, medical devices). The authors were advised to follow the rules of the Grading of Recommendations Assessment, Development and Evaluation (GRADE1) system to guide assessment of the quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised. Few recommendations remained non-graded. Methods: The committee addressed eleven questions relevant to the patient suffering severe limb trauma: 1) What are the key findings derived from medical history and clinical examination which lead to the patient’s prompt referral to a Level 1 or Level 2 Trauma Centre? 2) What are the medical devices that must be implemented in the prehospital setting to reduce blood loss? 3) Which are the clinical findings prompting the performance of injected X-ray examinations? 4) What are the ideal timing and modalities for performing fracture fixation? 5) What are the clinical and operative findings which steer the surgical approach in case of vascular compromise and/or major musculoskeletal attrition? 6) How to best prevent infection? 7) How to best prevent thromboembolic complications? 8) What is the best strategy to precociously detect and treat limb compartment syndrome? 9) How to best and precociously detect post-traumatic rhabdomyolysis and prevent rhabdomyolysis-induced acute kidney injury? 10) What is the best strategy to reduce the incidence of fat emboli syndrome and post-traumatic systemic inflammatory response? 11) What is the best therapeutic strategy to treat acute trauma-induced pain? Every question was formulated in a PICO (Patient Intervention Comparison Outcome) format and the evidence profiles were produced. The literature review and recommendations were made according to the GRADE1 methodology. Results: The experts’ synthesis work and the application of the GRADE method resulted in 19 recommendations. Among the formalised recommendations, 4 had a high level of evidence (GRADE 1+/ ) and 12 had a low level of evidence (GRADE 2+/ ). For 3 recommendations, the GRADE method could not be applied, resulting in an expert advice. After two rounds of scoring and one amendment, strong agreement was reached on all the recommendations. Conclusions: There was significant agreement among experts on strong recommendations to improve practices for severe limb trauma patients. C 2021 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved. Keywords: Guidelines Compartment syndrome Damage control Fat embolism syndrome Rhabdomyolysis Severe limb trauma patient Tourniquet 1. Introduction Expert coordinators Julien Pottecher (Strasbourg) Hugues Lefort (Metz) Hervé Quintard (Genève) Cédric Gil-Jardiné (Bordeaux) Limb injuries are a particularly common reason for emergency department visits, orthopaedic or operative surgical treatments and, for most severe cases, hospitalisations in acute care units. An extract from the TraumaBase1 National Registry on the 5th of March 2020 (gathering 15,823 patients admitted to a facility for severe trauma) revealed a substantial proportion of patients with significant limb trauma. For 50.1% of them, the Abbreviated Injury Scale (AIS) [1] ‘‘limb’’ was non-zero, 19.5% had an AIS > 2, 29.4% required orthopaedic intervention at Day 0 and, for 2.73%, osteoarticular trauma induced haemorrhagic shock. No French recommendation addresses their initial management during the acute phase in a holistic and transdisciplinary approach. The vast majority of limb(s) injuries do not have a severity criterion and do not have any functional or vital consequences for the injured patient. Conversely, severe limb(s) trauma (SLT), either single or multiple, have specific criteria of severity, assessed differently throughout the consecutive stages of care: prehospital phase, perioperative period, postoperative course or during hospitalisation in acute and then conventional units. Causal trauma may cause injury to one or more limbs resulting in the deliberate denomination of ‘‘severe limb(s) trauma’’. The common characteristics of SLT, the subject of this formalised expert recommendation (FER), are: a particularly significant locoregional decay, which induces excess mortality and/or leads to a definitive functional impairment and/or increases the length of stay. Operationally, SLT Experts Philippe Adam (Strasbourg) Olivier Barbier (Paris) Pierre Bouzat (Grenoble) Jonathan Charbit (Montpellier) Michel Galinski (Bordeaux) Delphine Garrigue (Lille) Tobias Gauss (Paris) Yannick Georg (Strasbourg) Sophie Hamada (Paris) Anatole Harrois (Paris) Romain Kedzierewicz (Paris) Pierre Pasquier (Paris) Bertrand Prunet (Paris) Claire Roger (Nı̂mes) Karim Tazarourte (Lyon) Stéphane Travers (Paris) Lionel Velly (Marseille) 2 G Model ACCPM-100862; No. of Pages 16 J. Pottecher, H. Lefort, P. Adam et al. Anaesth Crit Care Pain Med xxx (xxxx) xxx Table 1 Definition of severe trauma according to Vittel criteria [2]. ONE single criterion defines severe trauma Vital signs assessment on scene - Glasgow Coma Scale (GCS) < 13 - Oxygen saturation < 90% breathing room air - Systolic arterial pressure < 90 mmHg Mechanism of injury - Prehospital resuscitation - Mechanical ventilation - Fluid expansion > 1000 mL - Catecholamine infusion Anatomy of injuries - Medical history - Age > 65 y.o - Pregnancy (2nd or 3rd trimester) - Comorbidities (cardiac failure, respiratory failure, inherited or acquired coagulopathy) Victim being ejected, thrown or run over Death in same passenger compartment Fall > 20 feet or 6 m Explosion or blast Penetrating trauma Flail chest Burns Pelvic fractures - Amputation proximal to wrist and ankle - Acute limb ischaemia - Suspicion of spinal cord injury thus to give an estimate of the confidence that one can have from the quantitative analysis and a level of recommendation. The quality of evidence is divided into four categories: ‘‘high’’ if future research is unlikely to change confidence in effect estimation; ‘‘moderate’’ whether future research will likely change confidence in the estimate of the effect and could alter the estimate of the effect itself; ‘‘low’’ whether future research is very likely to have an impact on confidence in the estimate of the effect and likely to alter the estimate of the effect itself; ‘‘very low’’ if the estimate of the effect is very uncertain. The critical analysis of the quality of evidence is performed for each judgment criterion and then an overall level of evidence is defined based on the quality of evidence of the critical criteria. The final formulation of the recommendations is always binary, either positive or negative and either strong or weak: ‘‘strong’’ when it is recommended to do or not to do (GRADE 1+ or 1 ), ‘‘weak’’ if it is probably recommended to do or not to do (GRADE 2+ or 2 ). The strength of the recommendation is determined based on four key factors and validated by the experts after a vote, using the GRADE Grid method: the estimation of the effect; the overall level of evidence: the higher it is, the more likely the recommendation will be strong; the balance between desirable and undesirable effects: the more favourable it is, the more likely the recommendation will be strong; values and preferences: in case of uncertainty or great variability, the less likely the recommendation will be. These values and preferences should be best obtained from those involved (patient, physician, decision-maker); costs: the covers all limb(s) trauma that meets at least one of the Vittel criteria [2] (Table 1) and has an AIS classification greater than or equal to 3 (Appendix 1). In a non-exhaustive manner, SLT includes trauma involving amputation, degloving injury, limb crushing proximal to the ankle or wrist, acute limb ischaemia, ischaemic or haemorrhagic limb vascular injury, fractures of two proximal long bones (humerus or femur) and penetrating trauma proximal to the elbow or knee. As pelvic injuries were recently covered by a specific FER [3], they will not be discussed here. Concerning open limb fractures, the classification used in this FER is that introduced by Gustilo et al. and revised in 1984 [4] (Table 2). 2. Methods The Organising Committee, together with the experts’ coordinators, defined the issues to be dealt with and appointed the experts in charge of each of them. The questions were formulated in a Patient Intervention Comparison Outcome (PICO) format. Extensive bibliographic research was conducted using the PubMed1 and Cochrane1 databases and journals of the scientific societies associated with these guidelines. To be included in the analysis, the publications had to be deemed relevant by the expert group and published in English or French. The working method used to develop these recommendations is the GRADE1 method. This method makes it possible, after a quantitative analysis of the literature, to determine separately the quality of the evidence, and Table 2 Gustilo classification of open limb fractures [4]. Fracture Description Type 1 Type 2 Wound 1–10 cm wound Moderate soft tissue injury Wound Extensive soft tissue injury 3.A Type 3 3.B 3.C <1 cm Infection rate Contamination < 2% 2–5% Minimum Moderate Extensive >10 cm Impossible skin coverage Severe comminution Bone exposure, extensive periosteal stripping Severe comminution Associated vascular injury 3 5–10% 10–50% 25–50% G Model ACCPM-100862; No. of Pages 16 J. Pottecher, H. Lefort, P. Adam et al. Anaesth Crit Care Pain Med xxx (xxxx) xxx Table 3 Grading of initial clinical status in predicting perioperative risk. Stable clinical status Intermediate clinical status Unstable clinical status Haemodynamic condition & transfusion requirements Stable circulatory status - No vasopressor drug (norepinephrine) or < 2 mg/h - No blood transfusion - Lactate < 2.5 mmol/L Moderate circulatory shock - Vasopressor drug (norepinephrine) 2–4 mg/h - Transfusion 1–4 units of packed red blood cells - Lactate: 2.5–4 mmol/L Severe circulatory shock - Vasopressor drug (norepinephrine) > 4 mg/h - Transfusion  5 units of packed red blood cells - Lactate > 4 mmol/L Haemostasis Mild coagulopathy - PTr < 1.2 - Fibrinogen  1.5 g/L - Platelets  100 000 /mm3 Moderate coagulopathy - PTr 1.2–1.5 - Fibrinogen 1–1.5 g/L - Platelets 50–100 000/mm3 Severe coagulopathy - PTr >1.5 - Fibrinogen < 1 g/L - Platelets < 50 000/mm3 Central temperature Respiratory function Mild hypothermia > 35 8C Stable respiratory function PaO2/FiO2 >300 No rhabdomyolysis Moderate hypothermia 32–35 8C Moderate ARDS or hypoxaemia PaO2/FiO2 150–300 Severe rhabdomyolysis (myoglobin  10 000 UI/L) Status Variable Muscle involvement Severe hypothermia < 32 8C Severe ARDS or hypoxaemia PaO2/FiO2 < 150 Massive rhabdomyolysis (myoglobin  20 000 UI/L) Intermediate risk associated injuries High-risk associated injuries - ISS > 40 or an injury AIS  5 - ISS > 25 or an injury AIS = 4 - Moderate traumatic brain injury (GCS 9 12) - Severe Traumatic Brain injury - Thoracic Trauma Severity (TTS) score [54] 8–11 (GCS < 9) - Pulmonary contusion  2 lobes - Thoracic Trauma Severity (TTS) score [54]  12 - Aortic injury OIS 2 - Abdominal injury OIS  3 - Pulmonary contusion  3 lobes - or moderate haemoperitoneum - Massive air leak coming from lung - Moderate retroperitoneal haematoma (MTC [55] laceration score  6) - OIS grade  3 aortic injury before - Transitory or subclinical limb ischaemia surgery - OIS grade  4 abdominal injury and/ or requiring a haemostatic procedure - Massive retroperitoneal haematoma (MTC score [55]  10) - Bilateral diaphyseal or complex femoral fractures - Multiple diaphyseal or complex fractures - Critical limb ischaemia Associated injuries Mild associated injuries - ISS < 25 - Mild traumatic brain injury (GCS 13 15) - No extra-spine AIS  4 Requirements for associated emergent surgeries Low-risk surgery Intermediate or high-risk surgery - Laparotomy - Spine surgery in prone position - Multi-site orthopaedic surgery - Preventive embolisation - Vascular stenting Major high-risk surgery - Decompressive craniectomy - Resuscitative thoracotomy or lung resection - Resuscitative laparotomy - Pelvic clamp - Pelvic packing - Angioembolisation for pelvic or solid organ bleeding Therapeutic proposal Low-risk patient ! Early safe definitive orthopaedic surgery Intermediate-risk patient ! Initial resuscitation, temporary stabilisation and prompt individualised safe management (PRISM) High-risk patient ! Damage-control orthopaedics (mid-term stabilisation) followed by safe delayed definitive orthopaedic surgery AIS: abbreviated injury scale; GCS: glasgow coma score; ISS: injury severity score; MTC (score): Montpellier Trauma Centre (score); OIS: organ injury scale; PTr: prothrombin time ratio; TTS (score): thoracic trauma severity (score). Numbers refer to the reference list. frame. The following fields and questions were chosen for the collection and analysis of the literature. After summarising the work of the experts and applying the GRADE method, 19 recommendations were formalised. All recommendations were submitted to the Expert Panel for a GRADE Grid rating. After two rounds of quotations and various amendments, a strong agreement was reached on 100% of the recommendations. Of the recommendations, four are strong (Grade 1+/ ), twelve are weak (Grade 2+/ ), and for three recommendations, the GRADE1 method could not be applied, resulting in expert opinions. The present guidelines replace the previous recommendations from SFAR, SFMU, SOFCOT, SCVE and SSA on the same scope. The national societies represented by their experts encourage all practitioners to comply with these guidelines to ensure optimal quality of patient care. However, in applying these recommenda- higher the cost or use of resources, the lower the recommendation is likely to be. To establish a recommendation, at least 50% of participants must have an opinion and less than 20% must prefer the opposite proposal. To make a strong recommendation at least 70% of participants must agree. If the experts do not have studies on the subject, or if no data on the main criteria exist, no recommendation will be made. An expert opinion may be issued while clearly distinguishing it from the recommendations. An expert opinion is validated only if more than 70% of the participants agree. 3. Results We voluntarily chose to deal with only eleven issues that we felt were the most likely to make progress and to have discussions to 4 G Model ACCPM-100862; No. of Pages 16 J. Pottecher, H. Lefort, P. Adam et al. Anaesth Crit Care Pain Med xxx (xxxx) xxx risk: terrorism, collapse, environmental. . .) and the status of the victim at the time of treatment (stable, in haemorrhagic shock, in cardiac arrest). On the one hand, a direct manual compression with a pressure-dressing relay to facilitate the stretching phase may thus be sufficient for a small simple haemorrhagic wound. On the other hand, a large, extremely devastating wound, an amputation, the presence of foreign bodies impossible to remove, in a context of abundant active haemorrhage, will require the use of a remote haemostasis strategy and the application of a tourniquet; note that in this context, the remote compression point is not sufficiently effective due to collateral circulation, but may be useful while the tourniquet is being applied to limit blood spoliation. In the event of multiple actions to be carried out in a very constrained time frame or in a hostile environment, the fastest, most effective and least personnel-consuming haemostasis technique should be used: the tactical tourniquet can bridge this gap and will be re-evaluated as soon as possible. Finally, when the patient’s condition is immediately catastrophic due to a haemorrhagic wound with no radial pulse, or cardiac arrest, the tourniquet should be applied immediately as it is the fastest and potentially unique lifesaving technique available (Table 3). With regard to the benefit-risk ratio of tourniquet application, several recent systematic reviews of the literature, based on the same fairly heterogeneous studies, agree on the effectiveness of the technique. Indeed, many of those reviews report an effectiveness ranging from 69% to 97%, depending on the studies and tourniquet models in stopping active haemorrhages with low morbidity, the origin of which is difficult to attribute to the tourniquet or to the pre-existing injury [13–16]. A recent study of a military population specifically focused on the risk of amputation: the application of a tourniquet was not associated with an increased risk of limb loss [17]. The multi-centre case-control study by Teixeira et al. published in 2019 and involving eleven Trauma Centres in Texas compared 186 patients with a tourniquet to 840 patients without a tourniquet [18]. After adjustment, the authors found that tourniquet application was associated with a significant increase in survival (OR: 5.86 [1.4–24.47]). The results on transfusion savings appear more mixed because of the inherent difficulty of having truly comparable groups [19–21]. tions, each practitioner must exercise her or his judgment, taking into account her or his expertise, the specifics of her or his institution or the constraints of the exercise of her or his care (conventional, isolated, exceptional situation, etc.), to determine the intervention method best suited to the patient’s condition. Question 1: In a patient with severe limb trauma, what are the anamnestic and clinical criteria of severity, which should prompt her/his admission to a severe trauma facility to reduce morbidity and mortality? R1 – In a patient with major limb injuries, it is recommended that the presence of one or more Vittel criteria in the prehospital setting prompt her/his admission to a specialised Trauma Centre. GRADE 1+ (STRONG AGREEMENT) Rationale Admitting patients with a suspicion of severe trauma to a specialised Trauma Centre reduces both their morbidity and mortality. Recently, an additional survival of 3–4 patients for every 100 patients admitted to a specialised trauma centre with an Injury Severity Score (ISS) greater than 15 was found as well as an additional survival of 11 patients for every 100 patients with an ISS greater than 24 in the United Kingdom [5]. Historically, the majority of studies showing a benefit from Trauma Centres have been conducted in the United States [6]. In this country, the suspicion of severe trauma is based on a prehospital triage published by the American College of Surgeons – Committee on Trauma (ACS-COT) [7]. In France, the recognition of a severe trauma patient is based on the Vittel criteria, inspired by North American triage criteria [2]. More specifically, for limb trauma, the existence of at least two long bone fractures, a proximal amputation above the wrist and/or above the ankle, and specific limb injuries such as degloving, crushing, or acute limb ischemia are specific features of severity. Question 2. In the patient with severe limb trauma, what therapeutic approaches should be implemented in the prehospital setting to reduce bleeding? R2.2 – If a tourniquet is applied, the experts suggest reevaluating its effectiveness, usefulness and location on the limb as soon as possible, including the prehospital phase, in order to limit its morbidity (the shortest possible application time and the smallest possible area of ischaemia). EXPERT OPINION (STRONG AGREEMENT) R2.1 – In the presence of active limb haemorrhage and inefficiency of direct compression, in case of amputation, foreign body within the haemorrhagic wound, lack of radial pulse (haemodynamic criteria) or multiple simultaneous actions to be carried out, application of a tourniquet is probably recommended. GRADE 2+ (STRONG AGREEMENT) Rationale Permanent monitoring and re-evaluation of haemostasis efficacy is absolutely crucial. Rationale Application time In order to obtain the best functional prognosis in limb-injured patients with vascular compromise, it is compulsory to restrict the time lag between injury and arrival to the operating theatre to less than one hour [22]. After this deadline, the risk of amputation increases significantly (from 6% to 11.7%; p < 0.01). In the absence of arterial injury, a tourniquet may be properly tolerated for a longer period of time [23]; however, this question has not been specifically addressed outside the context of elective surgery in the operating theatre. Iterative tourniquet releases for the sake of ischaemic sparing aggravate local (muscle injury) and systemic (rhabdomyolysis) morbidity [24,25]. The need to stop active bleeding in order to limit blood loss, the vicious circle of the lethal triad and death is beyond doubt [8–12]. The question, which therefore arises, is how to stop active limb haemorrhage. No randomised controlled study in humans has compared one mechanical haemostasis strategy to another in terms of survival. The extent of bleeding can vary considerably depending on whether it is from venous, bony, arterial or mixed origins. The therapeutic response will therefore be different according to the type of bleeding, its importance, the size of the wound, the accessibility of the limb and its injury, the time available (short if multiple haemorrhagic lesions coexist, multiple victims, particular exogenous 5 G Model ACCPM-100862; No. of Pages 16 J. Pottecher, H. Lefort, P. Adam et al. Anaesth Crit Care Pain Med xxx (xxxx) xxx (abolition of the pulses, pallor, neurological sensitive or motor deficits) or the presence of a murmur (thrill). These signs reflect a vascular injury and require either immediate surgical exploration or, if the patient is stabilised, a rapid radiological examination such as CT angiography or arteriography [27]. The presence of weak signs reveals an arterial injury in 3%–25% of cases [27,28]. Weak signs include an externalised bleeding of arterial origin during collection or transport, the location of an open or blunt trauma in the vicinity of a main vascular axis, the presence of a non-pulsatile haematoma next to an arterial path or the neurological deficit suggesting direct compression of a nerve. These weak signs prompt the performance of a radiological examination with intravenous opacification, generally a CT angiogram, in order to avoid unnecessary surgical exploration on the one hand and to uncover undiagnosed vascular lesion on the other hand. Particular attention should be paid to severe ligament injuries of the knee, dislocation or ligamentous lesions, which substantiate a wide acquisition window of injected whole-body CT that should cover the suspected area [29]. Physical examination should include the ankle-brachial index (ABI) measurement, facilitating the clinical diagnosis of vascular injury. The ABI is the ratio between the systolic blood pressure (SBP) measured at the ankle and the SBP measured at the arm. This measurement is performed with the patient in a supine position. Arterial flow is found with a Doppler probe positioned at an angle of 45 8. The first step consists in obtaining a reference SBP in a spare limb (arm) and to compare it to the value obtained at the ankle on the limb where a vascular injury is suspected. If the patient presents with a right-left asymmetry, the highest value is kept as a reference on the arm. On the lower limb, the cuff should be applied just above the malleolus. It is rapidly inflated until the flow signal disappears on Doppler examination, then slowly deflated until the distal flow signal corresponding to the systolic pressure reappears. The measurements should be repeated two or three times, the average value being kept. These measurements are taken at the level of the pedal artery and the posterior tibial artery. The lowest value is kept and used for the calculation of the ABI. In a series of 93 patients, Lynch and Johansen [30] demonstrated that an ABI < 0.9 had a satisfactory sensitivity (87%) and a good specificity (97%) for diagnosing vascular injury. In a recent meta-analysis (eight studies, 2161 patients with a prevalence of 15% for penetrating extremity trauma and arterial injuries), deSouza et al. [31] concluded that in the absence of clinical signs suggesting a vascular injury (neither strong, nor weak sign) and in the presence of normal ABI, the probability of vascular injury was virtually zero (negative likelihood ratio of 0.01; 95% CI [0.0–0.1]) and did require additional exploratory examination. Arteriography was historically the first-line examination to rule out arterial injury in traumatic limbs. The latest generation of CTs have established the CT angiography as the first-line radiological examination for the exploration of limb vessels [32]. A whole-body exploration is currently possible in a single injection with protocols adapted to the severe trauma patient and including a good exploration of the limbs [33]. The speed of its completion and its integration into the overall lesion assessment argue in favour of CT angiography. In a prospective study comparing the effectiveness of CT angiography with arteriography, Seamon et al. [34] demonstrated 100% sensitivity and specificity of CT angiography, faster access and lower cost of treatment. A recent meta-analysis investigated the performance of CT angiography for the detection of vascular injuries in limb trauma patients [35]. Out of 11 studies analysed involving a total number of 891 patients, the sensitivity and specificity were 96.2% and 99.2%, respectively. Diagnostic arteriography remains a second-line imaging modality when the CT angiography is not contributing, for example in the event of artefacts related to the presence of metal fragments. Reassessment of requirement and/or location of a tourniquet Excluding extreme situations (haemorrhagic shock patient without a perceived radial pulse, cardiac arrest or crush syndrome), the need to maintain a tourniquet applied beforehand by the paramedical team may be reconsidered. This is all the truer as it was implemented in a hostile environment or with multiple actions to be carried out simultaneously under fire (tactical tourniquet). To do so, first apply a pressure dressing on the wound (possibly completed by a haemostatic dressing). Then gradually loosen the tourniquet. Either there is a resumption of bleeding, in which case the tourniquet is immediately tightened, or there is no resumption of bleeding, in which case the tourniquet is completely loosened but left in place around the limb. Thus, may a resumption of bleeding occur during the course of treatment (mobilisation during stretching, increase in blood pressure, etc.), the tourniquet would already be correctly positioned and quickly clamped again. The location, possibly too proximal, of a tactical tourniquet placed before the arrival of the emergency medical team must also be re-assessed in order to restrict the ischaemic zone. If tourniquet application appears mandatory (haemorrhagic shock, cardiac arrest), a second tourniquet, distal to the first should ideally be applied, before loosening the proximal one, so as to avoid any recurrence of blood spoliation. Tourniquet-related secondary injuries Lacking prospective randomised study, the incidence of tourniquet-induced secondary injuries is difficult to assess. Moreover, accountability is challenging to establish since persisting injuries may either be due to the tourniquet itself or to the initial trauma. In their 2018 meta-analysis, Beaucreux et al. [26] reported a variable incidence of the numerous complications, either local (compartmental syndrome requiring fasciotomy [between 2% and 18%], localised infection [between 7% and 9%], paresis due to nerve palsy [between 1% and 6%], deep vein thrombosis [9%], amputation [between 12% and 59%]), systemic (rhabdomyolysis [2%], acute renal failure [2%–3%]) or persistent (rare permanent paralysis [less than 1%]). Question 3: In a patient suffering from a severe limb trauma, what are the clinical findings which should prompt the performance of injected x-ray examinations in order not to miss vascular injuries and thus reduce the morbidity? R3 – In order not to miss a vascular injury in a severe limb trauma patient, it is probably recommended to perform a CT angiography in the presence of one or more of the following findings: - Externalised bleeding of arterial origin Vicinity of the injury site to a main vascular axis Presence of a non-expanding haematoma Isolated neurological deficit Ankle-brachial index (ABI) less than 0.9 GRADE 2+ (STRONG AGREEMENT) Rationale Clinical signs suggesting a vascular injury are classically separated into "strong" (hard) and "weak" (soft) signs. The strong signs consist in a significant externalised bleeding, a rapidly expanding or pulsatile haematoma, an ischaemic syndrome 6 G Model ACCPM-100862; No. of Pages 16 J. Pottecher, H. Lefort, P. Adam et al. Anaesth Crit Care Pain Med xxx (xxxx) xxx Question 4: In the severe limb trauma patient, what are the ideal timing and modalities for performing fracture fixation to reduce morbidity and mortality? to a secondary displacement [36–42]. Many retrospective studies reported an association between delayed surgical management of shaft fractures and ARDS occurrence or fat embolism syndrome [37,43–48]. Two studies found a reduced incidence of ARDS in patients operated on in the first 24 h, compared to those with delayed surgical management [38,43]. The time threshold was even set earlier (10 h) in a study focusing on fat embolism syndrome [44]. Previous studies mostly analysed lower limb fractures, most often femoral shaft fracture. Early safe definitive orthopaedic surgery is thus the standard of care in this context, especially in patients without any severe associated injury [49]. Early definitive osteosynthesis of diaphyseal fracture may however induce severe complications in case of severe trauma [50–52]. Many systemic complications were indeed reported in this specific setting, mainly related to massive operative blood loss, lactic acidosis, hypothermia and large systemic release of proinflammatory mediators. All these phenomena fuel a feed-forward loop leading to multiple organ failure [50]. The specific surgeryinduced inflammatory trigger, so called ‘‘second hit’’, was identified long years ago [51]. Intramedullary nailing of long bone shaft fractures is the main culprit involved because of pressureinduced vascular leakage of bone marrow [51,52]. Thus, early intramedullary nailing of femur shaft was associated with the development of significant chest injuries including ARDS, longer durations of mechanical ventilation, ICU or hospital lengths of stays [53]. Initial haemodynamic instability is a an aggravating factor for this morbi-mortality risk, which prompts an initial stabilisation by aggressive resuscitation and management of other emergent injuries [42,53]. A sequential surgical approach (damage control orthopaedic surgery – DCO) was therefore proposed in this context to perform a simplified temporary stabilisation at the initial phase, followed by a delayed osteosynthesis surgery. This strategy is adapted to the risk. Indeed, the modalities of initial stabilisation of unstable fractures are determined according to clinical status, physiological stability and injury assessment (early appropriate care). To identify patients at risk of developing secondary multiple organ failure or systemic complications, CT scan is a key exam in detecting massive bleeding or unstable R4.1 – In the absence of severe visceral injury, circulatory shock, or respiratory failure, an early definitive osteosynthesis of diaphyseal fractures is recommended within the 24 first hours to reduce the incidence of local and systemic complications. This is particularly true for femoral and tibial shaft fractures, which are at high-risk of respiratory complications, such as ARDS or fat embolism syndrome. GRADE 1+ (STRONG AGREEMENT) R4.2 – In the presence of one or several severe visceral injuries (including brain, thorax, abdomen, pelvis or spinal cord), circulatory shock, or respiratory failure, a delayed definitive osteosynthesis of diaphyseal fractures is probably recommended within the first 24 h to reduce the incidence of systemic complications related to surgical hit, perioperative blood loss, coagulopathy or fat embolism syndrome. For femoral and tibial shaft fractures, a temporary stabilisation (external fixator or osseous traction) is most often necessary. Once clinical status is stabilised, a safe definitive osteosynthesis should be performed as early as possible. GRADE 2+ (STRONG AGREEMENT) Rationale A global and appropriate approach is necessary for each patient using a multidisciplinary discussion, based on clinical status and assessment of injuries. Early stabilisation of mechanically unstable shaft fractures in severe trauma patients is a priority during their initial management. It aims at reducing early and late complications such as fat embolism syndrome, respiratory compromise, prolonged local bleeding, or tissue injuries (cutaneous, vascular or nervous) related Fig. 1. Guidance on appropriate early or delayed safe definitive orthopaedic surgery based on clinical and injury criteria. 7 G Model ACCPM-100862; No. of Pages 16 J. Pottecher, H. Lefort, P. Adam et al. Anaesth Crit Care Pain Med xxx (xxxx) xxx cases. Fig. 1 summarises different strategies of management of severe lower limb shaft fractures in severe trauma patients. injuries [54,55]. Accordingly, DCO and initial temporary stabilisation of femoral shaft fractures showed a significant reduction of both operative delays and blood loss in unstable or severe trauma patients [56–58]. Pape et al. [49] have moreover observed in a randomised prospective trial (EPOFF study) a significant decrease of respiratory complications during postoperative phase in a subgroup of patients (‘‘borderline patients’’) considered ‘‘at-risk’’, based on clinical status. Note that the most severely injured patients were excluded from this randomisation. They were considered too serious to tolerate an early definitive osteosynthesis. Other studies focusing on management of lower limb shaft fractures confirmed the higher morbi-mortality with early definitive osteosynthesis [42,58,59]. DCO strategy in upper limb shaft fractures in contrast did not clearly demonstrate its superiority in terms of perioperative complications and outcome. The grading of patients based on their risk to develop systemic complications is therefore a prior objective to determine an individualised management, considering safe conditions and benefit/risk balance; this is the PRompt Individualised Safe Management (PRISM). Even if clinical criteria remain debated to decide a PRISM approach, haemorrhagic and circulatory status, acute traumatic coagulopathy, respiratory failure and (either suspected or documented) intracranial hypertension were used in most series [43,58,60]. Bilateral femoral shaft fractures were also frequently considered an indication for PRISM, as well as the global severity of trauma (ISS  40) [61,62]. Thus, a reduction of mortality rate was found in large populations of severe trauma patients affected by a femoral shaft fracture when the definitive osteosynthesis was delayed 12–24 h, prioritising an aggressive resuscitation and a temporary stabilisation [42]. Subscribing to this rational, Pape et al. [59] proposed the identification of patients atrisk upon admission based on clinical status, thorough injury assessment and trauma severity. Other authors proposed several classifications, which also included clinical status and injury assessment [60]. Table presents a summary of clinical and injury criteria to triage trauma patients and to determine early appropriate care. It is noteworthy that patients may change category according to their early evolution and response to initial resuscitation (Fig. 1). Furthermore, the choice of temporary stabilisation device has to be made according to both anatomical constraints and anticipated delay for final osteosynthesis. Skeletal tractions are effective devices, however, they do not guarantee a continuous keeping of fracture site and limb axis. Furthermore, tractions impede patient’s mobilisation and badly protect against fat embolism syndrome. In contrast, external fixators may be considered more invasive but guarantee however a safe and continuous stabilisation. A French study recently demonstrated that external fixators provided a 15% reduction of ARDS incidence compared to skeletal tractions in case of femoral shaft fracture [63]. The temporary stabilisation by external fixators should therefore be preferred to skeletal tractions when definitive osteosynthesis is not anticipated in the next 24–36 h. Finally, when DCO and temporary stabilisation have been chosen during the initial phase, a delayed definitive osteosynthesis has to be scheduled as early as possible, once stable clinical status is obtained. Several variables have thus to be daily re-assessed following a dynamic approach in order to identify the optimal moment for final osteosynthesis. This concept, taking benefit/risk into account, is named safe definitive orthopaedic surgery. A frequent re-assessment (haemodynamic and respiratory status, acid-base status, coagulation function. . .) would allow a timely reintervention in numerous cases (36–48 h) with reduced morbidity and shorter hospital length of stay. Anyway, DCO strategy is all the more effective as the safe definitive orthopaedic surgery can be achieved in reasonable timing, within the first two weeks in most Question 5: In the severe limb trauma patient with vascular injury and/or major mangled limb injuries, what are the findings on which the surgical strategy should be based to decide either limb salvage or amputation, in case of haemodynamic stability and in case of haemorrhagic shock? R5.1 – In case of haemodynamic stability, it is probably recommended that the limb be salvaged. GRADE 2+ (STRONG AGREEMENT) Rationale The clinical criteria for unfavourable outcome after a severe limb trauma are patient’s comorbidities, associated organ injuries, initial nerve damage, major substance loss, proximal vascular damage, associated bone fractures, delays in therapeutic management, the cause of the trauma and the proximal level of traumatic amputation. Nevertheless, the psychological outcome and the quality of life (assessed by the Sickness Impact Profile and Short Form-36 scales, respectively) remain superior when limb reimplantation is successful [64]. Early secondary amputation may be performed in the event of an unfavourable outcome. Ladlow et al. [65] conclude that there is no obstacle to continued limb rescue if it is surgically feasible, since trauma patients subjected to delayed amputations have a functional outcome equivalent to those treated with immediate amputations. There is little difference in hospital length of stay between the two treatment options [66–68]. Patients with a limb salvage strategy often require several interventions and are more likely to be re-hospitalised [67,69]. Amputation may be preferable for a shorter rehabilitation period, fewer additional surgeries and less likelihood of rehospitalisation, while reconstruction may have better psychological outcomes. Amputation, whether initial or secondary, has additional functional benefits if performed distal to the knee. Ultimately, equivalent functional results are possible with both options, so management should be based on the condition of the limbs, the importance of comorbidities, the patient’s preferences and the surgeon’s own expertise [64]. Busse et al. [67] observed a 67% recovery rate of sensitivity at two years in a cohort of 601 patients, 55 of whom had initial nerve damage, authenticated on the basis of lack of plantar sensitivity. R5.2 – In case of haemorrhagic shock associated with severe limb trauma complicated with vascular injury or mangled extremity, it is probably recommended to apply a damage control strategy. No single gravity criterion requires amputation. GRADE 2+ (STRONG AGREEMENT) Rationale The choice of a damage control strategy should encompass the patient’s condition, the operator’s experience and has to be funded of a collegial discussion. The clinical situations associated with haemorrhagic shock favouring a decision of initial amputation are: complete traumatic amputation [70], large loss of substance making skin coverage impossible (and/or with major infectious risks), proven section of the tibial nerve [71], multiple fractures with bone loss or ischaemic vascular lesions [72]. Delhey et al. [73] found 8.5% of patients who had undergone reconstruction 8 G Model ACCPM-100862; No. of Pages 16 J. Pottecher, H. Lefort, P. Adam et al. Anaesth Crit Care Pain Med xxx (xxxx) xxx the SFAR guidelines on surgical antibiotic prophylaxis (SAP) [84]. For limb trauma with open fracture, the use of antibiotic prophylaxis was associated with lower early infection rates in two meta-analyses [85,86]. However, it is noteworthy to highlight that 1) the randomised controlled trials with low biases have been conducted decades ago 2) the vast majority of observational studies investigating the potential benefit of open fracture antibiotic prophylaxis exhibit several methodological biases. It is highly unlikely that a randomised controlled trial comparing antibiotic prophylaxis versus no antibiotic prophylaxis will be conducted in the future. The choice of molecule to be administered depends on the type of open fracture according to Anderson-Gustilo classification [4] (Table 2), on SAP guidelines and local ecology. The optimal time window to administer antibiotic prophylaxis remains uncertain. A prospective study including 1104 patients has shown a higher infection rate (7.4% vs. 4.7%) when SAP was administered beyond the first 3 h post trauma [83]. On the opposite, a recent systematic review in 2014 failed to show any influence of the timing of antibiotic prophylaxis administration due to low level of evidence [87]. The use of adjunctive local antibiotics is associated with a reduced infection rate after open limb fractures (14.4 % (95% CI: 10.5–18.5%) vs. 4% (95% CI: 0.0–9.4%; OR = 0.17) with no definitive evidence of efficacy, lacking randomised controlled trial [88]. To date, no argument supports extending antibiotic prophylaxis beyond the 72nd hour, which is the duration recommended by the different guidelines from Surgical Societies [89,90]. In a metaanalysis published in 2015, enrolling 1104 patients, no statistical difference in infection rates was observed between patients receiving prolonged (3–5 days) antibiotic therapy compared to shorter antibiotic course (1 day) [86]. Nevertheless, the level of evidence remains low due to the lack of well-designed randomised controlled trial investigating this question. Finally, it is essential to incorporate antibiotic prophylaxis into a bundle of preventive strategies to reduce infectious complications after limb trauma (Fig. 2). attempts in a "borderline" population of 481 out of 926 patients, defined by an ISS > 20, a thoracic AIS > 2, an abdominal or pelvic AIS > 2, initial systolic blood pressure (SBP) < 90 mmHg, an ISS > 40 without thoracic injury and limb trauma associated with bilateral radiological pulmonary contusion. In this borderline population, the mortality of non-reimplanted patients was 30.5% compared to 17.7% in the general population. The lower the ISS score and base excess and the closer the SAP, haemoglobin and prothrombin time are to physiological values, the safer reimplantation appears to be [73]. A Mangled Extremity Severity Score (MESS) above 7 and a Mangled Upper Extremity Injury (MESI) score above 20 are widely regarded as acceptable thresholds to guide initial amputation [74]. However, Kumar et al. [75], in a recent prospective study, found only a 43.2% amputation rate in the population of patients with a MESS score > 8. Out of 230 patients with vascular lesions, a MESS score of 8 was associated with an increase in the length of hospital stay, but not with the risk of amputation: 81.3% of the limbs saved, only 18.7% had secondary amputations with MESS > 8. No statistical difference was found between the MESS score and the amputation rate [75]. Ray et al. [76] proposed a MESS score > 11 to facilitate the choice of initial amputation, implying an unfavourable evolution in 75% of cases in their cohort of 108 patients. However, in multivariate analysis, the MESS score does not appear to be an independent risk factor for severity and should not be considered in isolation [76]. The level of amputation, above or below the knee, has a major impact in terms of function, which is the converse to the level of amputation [77]. Delays in ischaemia reversal are frequently used to argue for amputation. In the early phase, cold ischaemia lasting more than six hours increases the risk of reimplantation failure to 87% vs. 61% below this time. Vascular surgery techniques, such as the use of a vascular shunt, are now making it possible to improve the prognosis [78]. The time to ischaemia should be considered as a relative criterion rather than an independent predictive marker of amputation [79]. For secondary amputations, a long delay synonymous with frequent rehospitalisation and impaired functional prognosis has an unfavourable psychological impact [80,81]. R6.2 – It is probably not recommended to perform systematic perioperative microbiological sampling after severe limb trauma with open fracture. GRADE 2- (STRONG AGREEMENT) Question 6. What are the preventive infection strategies in severe limb trauma patients to reduce morbidity and mortality? Rationale R6.1 – In severe limb trauma patients with open fracture, it is probably recommended to administer antibiotic prophylaxis as soon as possible and for a maximal duration of 48 h to 72 h (excepted for proven infection). GRADE 2+ (STRONG AGREEMENT) Early infection rates complicating open limb trauma reported in the literature vary considerably from 6 to 44%, according to the definition of infection used [91–95]. In order to predict and/or diagnose patients at risk of infection after open limb trauma, preor perioperative microbiological sampling procedures have been assessed in several observational studies conducted in the last 20 years [91–95]. In a retrospective study including 245 patients, perioperative microbiological sampling was found to have no value in 47% of cases. Preoperative microbiological cultures were positive in 8% of infected patients, whereas 7% of patients with negative cultures developed postoperative infections. Perioperative microbiological sampling seems more sensitive to detect patients at risk of infection compared to preoperative samples. Nevertheless, the causative pathogen was found in 0–56% of perioperative samples according to the study considered [91,94– 97], leading authors of these studies to conclude that systematic perioperative microbiological samples were unnecessary. Although infrequent, invasive fungal infections complicating severe limb trauma are associated with high mortality rate (7.8%) and significant morbidity, including a high rate of limb amputations [98,99]. Fungal species such as Mucorales, Aspergillus, Rationale Preventing infectious complications is crucial in limb trauma management with open fracture. Occurrence of infection is associated with an increased morbidity and mortality, mainly due to osteomyelitis and consolidation impairment. Increased infectious risk has been reported in limb trauma with open fracture. After limb trauma with closed fracture, the infection rate is about 1%, whereas an infection rate ranging from 6 to 44% has been reported after limb trauma with open fracture depending on the type of fracture, comorbidities and definition criteria considered for proven infection [82,83]. For closed limb trauma, antibiotic prophylaxis administration depends on the surgical procedure applied and should be in line with 9 G Model ACCPM-100862; No. of Pages 16 J. Pottecher, H. Lefort, P. Adam et al. Anaesth Crit Care Pain Med xxx (xxxx) xxx Fig. 2. Measures to prevent the risk of infection in a patient with severe limb injury. are considered to be at high risk of VTE [105]; tibia, ankle, or foot fractures, Achilles tendon rupture and immobilisation in a cast are considered to be at moderate risk of VTE [105]. Beyond the risk associated with the fracture site, the risk associated with the patient must also be assessed individually [106]. There are several scores and lists of criteria, which generally group the same risk factors (GEMnet guideline [107], NICE guideline [108], L-TRiP(cast) score [109], Risk Assessment Profile Score [110]. The diagnosis of DVT remains a diagnostic challenge, as clinical clues are rough and found in less than 10% of patients [111]. Systematic investigation of all patients by combined venous ultrasound-Doppler is not currently recommended [112]. The prevention of VTE in these patients therefore requires assessing: Scedosporium and Fusarium represent the most common species among civilian casualties. In 50–70% of cases, bacterial co-infection has been reported. In combat casualties, the main factors associated with post-traumatic invasive fungal infection are large-volume blood transfusions, above the knee amputation and blast limb injury [100], whereas in civilian population, the number of injuries, mechanism of injury, environmental contamination and rhabdomyolysis have been identified as risk factors [101]. Despite high morbidity and mortality rates associated with invasive fungal infections, there is no current evidence to warrant systematic perioperative microbiological samples seeking fungi among civilian casualties. A study performed in military population has demonstrated the benefit of an early fungal screening strategy on reducing diagnosis and treatment delay and improving prognosis [102]. Similar evidence is currently not available for civilians. Microbiological samples to identify post-traumatic invasive fungal infections could be performed in case of extended and persistent skin necrosis or presence of moistures in wounds. 1) A risk related to the injured area 2) A personalised patient risk assessment 3) The opportunity to set up intermittent mechanical compression device (rarely possible in cases of lower limb trauma) 4) The opportunity of early pharmacological thromboprophylaxis [113] 5) Potential contraindications to pharmacological thromboprophylaxis. In case of major risk of VTE, partial interruption of the inferior vena cava by a vena cava filter should be considered [112]. In this situation, it is suggested to use an optional venous filter and it is recommended to plan filter removal from the outset, remotely from the trauma (grade 2+ recommendation in the 2011 SFAR recommendations [105]). The combined use of a vena cava filter and thromboprophylaxis in polytrauma patients was compared to thromboprophylaxis alone in a meta-analysis [114]. No difference was shown in mortality. To avoid one pulmonary embolism, the number of trauma patients needed to treat with vena cava filter ranged from 109 to 962. Question 7. In the severe limb trauma patient, what are the methods of thromboprophylaxis, which can reduce morbidity and mortality? R7.1 It is strongly recommended to initiate early pharmacologic thromboprophylaxis with low molecular weight heparin (LMWH), after haemorrhage control and haemostasis, timing of which will be determined by the type of injury. GRADE 1+ (STRONG AGREEMENT) R7.2 It is not recommended to propose systematic insertion of vena cava filter, unless absolute contraindication for both pharmacological and mechanical treatment (i.e., pneumatic compression devices) in patients at major risk. GRADE 1- (STRONG AGREEMENT) Concerning the choice of drug treatments for VTE prophylaxis, LMWHs have been the reference for more than 20 years [105,115,116]. Some studies comparing direct oral anticoagulants show a greater reduction in DVT with fondaparinux compared to nadroparin for lower limb trauma with added VTE risk factors [117,118]. Regarding timing of initiation, the introduction of pharmacological thromboprophylaxis within the first 36 h after trauma appears safe in all patients, including those with solid organ damage or traumatic brain injury (provided intracerebral bleeding remains stable on two successive CT scans) without a significant increase in bleeding risk [119]. However, in an isolated traumatic injury of the lower limb without persisting bleeding, it is probably necessary to come closer to the classical postoperative introduction time, i.e., within the 6 h following trauma or surgery. Rationale Venous thromboembolism (VTE), a combination of deep vein thrombosis (DVT) and pulmonary embolism (PE), is a lifethreatening complication in severe limb trauma patients. It is one of the preventable hospital deaths in trauma patients who survive their injuries [103]. Apart from multiple traumas, patients with isolated lower limb fractures (potentially immobilised by splint, cast or external fixator), present an increased risk of VTE and more precisely deep vein thrombosis [104]. The risk is not the same according to the fracture site: femur fracture and proximal tibia fracture (shinbone) 10 G Model ACCPM-100862; No. of Pages 16 J. Pottecher, H. Lefort, P. Adam et al. Anaesth Crit Care Pain Med xxx (xxxx) xxx Rationale Question 8. In patients with severe limb trauma, what therapeutic strategy can reduce the morbidity and mortality associated with the occurrence of compartment syndrome? Raising CPK levels above five times normal (approximately 1000 IU L 1) is a sign of rhabdomyolysis [127]. In a population of patients with crush syndrome following an earthquake [128], CPK levels above 75,000 IU L 1 were associated with a high incidence of acute kidney injury (> 80%). Myoglobin is responsible for intraluminal kidney tubular obstruction resulting in reduced glomerular filtration rate. In some studies, it appears that the measurement of plasma myoglobin, which has an earlier peak plasma concentration than CPKs, may be more sensitive and specific than CPKs in identifying the risk of acute kidney injury, which is correlated with increased mortality [129,130]. This assessment will be usefully complemented by plasma potassium test for hyperkalaemia and a measurement of kidney function by means of plasma creatinine test. R8 – In patients with severe limb trauma, the experts suggest performing an early fasciotomy in cases of newly formed compartment syndrome to reduce the incidence of functional impact. EXPERTS OPINION (STRONG AGREEMENT) Rationale In patients with severe limb(s) trauma, the following risk factors are associated with an increased risk of developing compartment syndrome: fracture, crush injury, haemorrhagic injury or reperfusion of an ischaemic lesion, and hypotension [120,121]. In patients with severe limb(s) trauma presenting one or more compartment syndrome risk factors, experts suggest investigating repetitively (every 30 min to 2 h), during the first 24 h, the presence of one among the following clinical signs: pain (spontaneous or on tensioning by flexion or passive extension), tension, paraesthesia, paresis and/or an increase of the measure of compartmental pressure monitoring. Paleness, paralysis, and decreased pulse are signs that are too late for their absence to reassure the clinician. Indeed, the Anglo-Saxon four P’s are pain, pain with passive stretch, paraesthesia and paresis. Pulselessness and Pallor are too late signs which, when present, often reflect the irreversible nature of compartment syndrome [121–125]. These clinical signs are nevertheless difficult to look for, in particular in patients receiving sedation or presenting with altered level of consciousness. Finally, these clinical signs have a low sensitivity for the diagnosis of compartment syndrome, but a high negative predictive value [123]. Also, a measurement of compartment pressure  30 mmHg and/or differential pressure (diastolic blood pressure – compartment pressure < 30 mmHg) are useful tests for the diagnosis of compartment syndrome [121]. In patients with severe limb(s) trauma presenting with established compartment syndrome, the treatment is based on early fasciotomy in case of recently formed compartment syndrome. This fasciotomy involves a wide incision of the skin, subcutaneous tissue, and fascia. Fasciotomy should allow opening of all the compartments in a same segment and may require one or more incision of skin and aponeuroses [126]. R9.2 – Concerning measures to prevent acute kidney injury in patients suffering from post-traumatic acute rhabdomyolysis after limb trauma, recommendations are those of the 2016 French recommendations Acute kidney injury in perioperative and intensive care. GRADE 2+ (STRONG AGREEMENT) Rationale The 2016 French recommendations Acute kidney injury in perioperative and intensive care apply to the prevention of acute kidney injury in patients suffering from acute post-traumatic rhabdomyolysis after limb trauma [131]. There are currently no randomised controlled trials focusing on the treatment of rhabdomyolysis and the 2012 recommendations [132,133] are based on retrospective, animal or case-report studies. Acute kidney injury, which is initially ‘‘functional’’ by kidney hypoperfusion and then becomes ‘‘organic’’ by acute tubular necrosis and intraluminal tubular obstruction, is one of the most feared complications of rhabdomyolysis. Indeed, it can rapidly become life threatening. Beyond the rapid correction of the initial hypovolaemia, which is an emergency, the continuation of vascular replenishment, aimed at hypervolaemia to generate hyperdiuresis, must be tailored to the patient’s general condition. This correction of volume deficit is performed with balanced crystalloids. The volume to be administered remains debated. In 2011, a retrospective study of 638 earthquake victims concluded that volumes greater than 6 L were required in patients with severe rhabdomyolysis (CPK > 15,000 IU L 1) to prevent acute kidney injury and the need for renal replacement therapy, whereas 3–6 L per day were deemed sufficient in moderate rhabdomyolysis [134]. Although there are no randomised controlled trials, most retrospective studies report that patients who eventually developed acute kidney injury had a longer time to initiate volume resuscitation compared to those who did not [135]. The management of kidney injury built up after rhabdomyolysis has no specificity. The experts refer to the French recommendations for acute kidney injury in perioperative period and intensive care units [131]. Question 9. In patients with acute post-traumatic rhabdomyolysis following limb traumatic injury, how to detect and prevent acute kidney injury? R9.1 – In order to detect acute kidney injury in patients suffering from post-traumatic acute rhabdomyolysis after limb traumatic injury, it is probably recommended to perform: Question 10. In patients suffering severe limb trauma, how to prevent both fat embolism and systemic inflammatory response syndromes (including ARDS)?  A repeated bio-assessment combining plasma myoglobin, plasma creatine phosphokinase (CPK) and kalaemia measurements  Bladder catheterisation to monitor hourly urine output and urine pH, which should be maintained  6.5. R10.1 – It is probably recommended to perform surgical stabilisation (either definitive osteosynthesis or external fixation) of long bone fractures within the first 24 post-traumatic hours to decrease respiratory complications, including ARDS and fat emboli syndrome. GRADE 2+ (STRONG AGREEMENT) GRADE 2+ (STRONG AGREEMENT) 11 G Model ACCPM-100862; No. of Pages 16 J. Pottecher, H. Lefort, P. Adam et al. Anaesth Crit Care Pain Med xxx (xxxx) xxx Rationale subsequent definitive osteosynthesis surgery in a two-step strategy must also be included in the final decision. Early surgical stabilisation of long bone fractures aims at facilitating patients’ mobilisation, limiting secondary displacement of fractures and initiating early healing process. The literature includes many retrospective cohort studies, which have reported an association between long-bone surgery delay and the occurrence of ARDS or fat embolism. Two studies found a decreased incidence of ARDS in patients operated on within the first 24 h (versus > 24 h) [38,43]. Another study also reported a lower risk of fat embolism in patients operated on within the first 10 h (versus > 10 h) [44]. However, no studies report an increased risk of ARDS or fat embolism in patients receiving surgical treatment within the first 24 h (versus > 24 h) [45–48,136]. The previously cited studies focused on lower limb fractures, specifically femoral shaft fractures. The experts therefore point out that this recommendation primarily concerns femoral shaft fractures. Finally, the delay in surgical management also depends on the associated lesions (ongoing haemorrhage or cerebral injury with intracranial hypertension) whose management takes precedence over long bones fractures (see Recommendations 4.1 and 4.2.). R10.3 – It is probably not recommended to use corticosteroids to prevent fat embolism syndrome in patients with long bone fractures. GRADE 2- (STRONG AGREEMENT) Rationale A meta-analysis was conducted in 2009, investigating the effects of corticosteroids to prevent fat embolism following long bone fractures [140]. Seven studies, of which 6 were performed between 1977 and 1987, were included in this meta-analysis for a total of 430 patients. The relative risk for fat embolism was 0.22 in patients who received corticosteroids as compared to those who did not (p < 0.05, confidence interval not given). Although corticosteroids significantly prevented fat embolism syndrome, the external validity of this meta-analysis is relatively weak. Patients were indeed admitted following long bone fractures without associated major injuries and time to surgery was more than 5 days. This prolonged time before surgery may account for the high incidence of fat embolism (18%) in the control group (patients who did not receive corticosteroids). Moreover, the administered dose of corticosteroids was especially high, ranging from 6 to 30 mg/kg of methylprednisolone. Currently, the early surgical care of patients presenting with long bone fractures does not expose to such a high rate of fat embolism. In addition, similar high dose of corticosteroids showed detrimental effects in patients with traumatic brain injury (increased mortality) and patients with spinal cord injury (increased risk of infection) [141,142]. Inhalational steroids were tested against placebo in a recent study conducted in 70 patients (35 patients in each group) with lower limb long bone fractures and showed a fourfold reduction in the risk of fat embolism: 2 versus 9 episodes of fat embolism in those receiving corticosteroids and those who did not, respectively (p = 0.022) [143]. However, in this study, patients had surgery more than 48 h following admission, which may account for the high rate of fat embolism in the control group (25%). R10.2 – In first intention, it is probably recommended to perform a definitive osteosynthesis of long-bone fractures to prevent ARDS and fat emboli syndrome. In haemodynamically unstable patients or in patients with severe preoperative respiratory compromise, the benefit-risk ratio between definitive osteosynthesis or external fixation should be the subject of a multidisciplinary discussion. GRADE 2+ (STRONG AGREEMENT) Rationale Several surgical techniques were assessed in patients with long bone shaft fractures. These studies focused on femoral shaft fractures. The definitive reference treatment is osteosynthesis by intramedullary nailing or plate osteosynthesis. The alternative is a two-step strategy by first applying external fixation (damage control) at the initial phase, followed by definitive osteosynthesis at a distance. The definitive initial treatment with intramedullary nailing may trigger larger systemic inflammation (circulating cytokine concentrations) than the two-step strategy [137]; however, studies do not report a reduced incidence of ARDS when a two-step strategy (versus definitive nailing treatment) is applied to an unselected population of trauma patients [57,138,139]. In a prospective multicentre study, which randomised 165 severe trauma patients with femoral shaft fracture to either immediate intramedullary nailing (n = 94) or initial external fixation and subsequent nailing (n = 71), the proportions of ARDS (25% versus 23%) and acute lung injury (ALI) (10% versus 8.6%) were not different between the two strategies [49]. In the ‘‘borderline’’ sub-population (42 patients defined as having bilateral pulmonary contusion, or ISS > 40 without associated chest trauma, or a combination of chest trauma (AIS 2–4) and an ISS > 20, or abdominal pelvic trauma with initial shock) after adjustment on initial severity, the odds ratio for ALI was 6.69 (1.01–44.08; p = 0.048) in the immediate nailing group while the odds ratio for ARDS was non-significant (2.01 (0.13–31.91); p = 0.618). In contrast, in stable patients (123 nonborderline patients), definitive osteosynthesis treatment was associated with shorter ventilation time [49]. Experts suggest taking into account the centre’s expertise in the use of osteosynthesis and external fixation techniques as well as the patient’s physiological situation to decide on the most appropriate strategy for ‘‘borderline’’ patients. The need for Question 11. In the severe limb trauma patients, what are the therapeutic modalities to control acute pain? R11 – Experts suggest that in the event of severe limb trauma, the use of a multimodal analgesia strategy should be promoted and that the benefit/risk ratio of the chosen molecules should be assessed taking volaemia and muscle damage into account. EXPERT OPINION (STRONG AGREEMENT) Rationale Concerning acute pain assessment and management after severe limb trauma, the experts refer to SFMU’s recommendations (sedation and analgesia in emergency medicine [144]) and SFAR’s recommendations (updating the recommendations on postoperative pain [145] and improved rehabilitation after major orthopaedic surgery of the lower limb [146]). Indeed, the mean principles summarised in these 3 recommendations are applicable to severe limb trauma patients, except particularities discussed below. Expert recommendations on sedation and analgesia in emergency medicine published in 2010 [144] advocated pain control as soon as possible. 12 G Model ACCPM-100862; No. of Pages 16 J. Pottecher, H. Lefort, P. Adam et al. Anaesth Crit Care Pain Med xxx (xxxx) xxx severe limb trauma patient are an integral part of his treatment and are probably important to alleviate his stress, but no comparative prospective studies support the effectiveness of this practice. Numeric rating scale (NRS) has been validated in emergency medicine [144]. It strongly correlates to results obtained with analogic visual scale (VAS) and can be used in 96% of patients in this context [147]. Acute pain in non-communicating patients has to be assessed with BOS-3 scale, the only validated scale for acute pain assessment in all these adult patients whatever their age [148]. Efficiency of morphine has been clearly demonstrated to relieve acute pain. The technique of choice recommended in this context is intravenous titration [144]. Protocolisation is an essential element of technique efficiency [149]. In emergency department, a morphine titration adequately performed is efficient in 82% of cases [150]. The protocol of morphine titration is described in the SFMU’s recommendations. A loading dose of morphine is not compulsory [151]. Multimodal analgesia is based on the principle of combining drugs and/or techniques with different and synergistic pathways in order to improve analgesia, to reduce the risk of dose-dependent side effects, particularly those associated with opioids [144]. Paracetamol and morphine have an additive interaction [152]. Lowdose ketamine (from 0.15 to 0.3 mg kg 1) in association with morphine allows for analgesia improvement and for a reduction in the required morphine dose [153]. In the out-of-hospital setting, which lacks intravenous access, some other techniques may be used. For instance, methoxyflurane has been demonstrated efficient on moderate to severe traumarelated pain and takes the advantage of being administrated by inhalation [154]. However, there is no data on its administration in severe limb trauma and potential related risks. Nitrous oxide and oxygen mixture is efficient in trauma-induced pain and has no major side effects, provided the contraindications are observed [144,155]. Two randomised controlled trials have shown that intranasal sufentanil was effective on pain relief after trauma, provided the proper device was used, but it also induced a significant rate of side effects [156,157]. The performance of a locoregional anaesthesia (LRA) will depend on the accessibility of the puncture site relative to the injury location but also on the moment of its realisation. Recommendations for carrying out a LRA in emergency medicine context were proposed in 2010 [144] and updated in 2012 [150]. Selected LRA were femoral block (by the ilio-fascial route [IFB] or by direct access, provided a nerve locating device was used). The other blocks could only be truncal and distal in this context (hand and foot) [144,158,159]. Some observational studies, including a low number of patients, have shown that femoral nerve block was feasible in out-of-hospital setting [158,159]. In the emergency department, IFB was more effective than intravenous morphine for pain relief in children [159]. In the hospital, a thorough evaluation should be performed by the anaesthesiologist to determine the most appropriate LRA (either plexic or perimedullary), which will cover both surgery and postoperative analgesia. By decreasing the intensity of acute pain and limiting the use of opioids, which are two factors that contribute to the sustainability of pain, multimodal analgesia may be of interest in this situation [144,150]. However, the phenomena by which acute pain becomes chronic and the associated mechanisms of hyperalgesia are still poorly known in emergency medicine. No study has shown the value of a particular management to reduce the risk of chronic pain in this context. A Cochrane1 review of effective pharmacological means to prevent chronic pain after surgery found that only lowdose ketamine given perioperatively was associated with reduced risk [160]. The use of ketamine, gabapentin or locoregional anaesthesia techniques in the first 24 h did not show any benefit in terms of prevention of post-amputation phantom limb pain [161–163]. Finally, psychological support and reinsurance to the Funding This work was sponsored by the Société française d’anesthésie et de réanimation (SFAR) and the Société française de médecine d’urgence (SFMU). Conflict of interest The authors declare that they have no competing interests Appendix 1. Supplementary data Supplementary material related to this article can be found, in the online version, at doi:https://doi.org/10.1016/j.accpm.2021. 100862. References [1] Loftis KL, Price JP, Gillich PJ, Cookman KJ, Brammer AL, St Germain T, et al. Development of an expert based ICD-9-CM and ICD-10-CM map to AIS 2005 update 2008. 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