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17/09/2019

Penthrox: Ne nous emballons pas

Methoxyflurane in Pre-Hospital Settings: A Review of Clinical Effectiveness, Cost-Effectiveness and Guidelines

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Beaucoup d'intérêt pour cet agent  tombé en désuétude en anesthéise du fait d'effets secondaires importants  mais utilisé comme antalgique. La HAS a émis un avis pour le moin mitigé. C'est également la position de l'agence du médicament canadienne qui reconnait des effets antalgiques réel mais sans avantage vrai par rapport à la morphine dans le domaine pré-hospitalier.

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The objective of this review is to evaluate the clinical effectiveness, cost-effectiveness, and evidence-based guidelines for the use of low-dose methoxyflurane for the management of moderate to severe pain associated with trauma or procedures in the pre-hospital setting.

29/07/2019

Penthrox: A risque d'hyperthermie maligne ?

An in-vitro model of malignant hyperthermia: differential effects of inhalation anesthetics on caffeine-induced muscle contractures.

 
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L'engouement en médecine d'urgence pour l'emploi du penthrox (1) se justifie notamment par sa simplicité de mise en oeuvre et la très grande rapidité d'obtention d'une analgésie qui reste cependant modérée (2). Cependant la HAS n'a pas retrouvé d'amélioration du service rendu pour cet agent d'anesthésie ancien. Dans les diverses publications, il n'est pratiquement jamais abordé le sujet du déclenchement d'une crise d'hyperthermie maligne. Pourtant cet agent est un agent déclencheur presqu'aussi "efficace" que l'halothane. Cette vieille publication l'atteste. Cceci étant dit il faut relativiser ce risque qui parait également dose dépendant sans que l'on sache bien à quel niveau se situe le seuil déclenchant (3) .
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Clinical concentrations of anesthetics augment caffeine-induced contracture of frog sartorius muscle; however, anesthetics differ in this characteristic. The potentiation was quantitated using six paired sartorius muscles for each specified concentration of anesthetic and controls. At a concentration of 1 MAC, the greatest potentiation occurred with 2 mM caffeine for all anesthetics studied. Under these conditions the order of magnitude of augmentations was: chloroform (15 times); halothane (11 times); methoxyflurane (10 times); cyclopropane (5 times); enflurane (4 times); isoflurane (3 times); diethyl ether (2 times); Baxter 3224 (2 times); fluroxene (1.4 times); nitrous oxide (1.3 times).

HTMA Methoxy.jpeg

Halothane at .5 MAC augments the 2 mM caffeine-induced contracture almost seven times, and at 2 MAC almost 13 times, whereas 2 MAC isoflurane potentiates the caffeine-induced contracture only four times and 4 MAC diethyl ether only two and a half times. It is postulated that those anesthetics that most potentiate caffeine-induced contracture may be the most potent triggering agents of malignant hyperthermia.

18/07/2019

ISR chez le traumatisé: Etomidate toujours pas convaincant

Pre-hospital emergent intubation in trauma patients: the influence of etomidate on mortality, morbidity and healthcare resource utilization.

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Cette publication revient sur le débat qui porte sur l'emploi de l'étomidate pour l'intubation préhospitalière. Son emploi est remis en cause par certains, notamment à cause de ses effets dépresseurs cortico-surrénaliens tout particulièrement en cas de sepsis. Les auteurs,  si ils ne rapportent pas d'effets délétères sur la mortalité, mettent en évidence une durée d'hospitalisation et de ventialtion plus longue dans le groupe ETO. Plusieurs informations méritent une lecture critique de ce travail. Le premier est la présence dans le groupe non-ETO de thiopental, responsable de nombreux décès lors de l'attaque de pearl harbour (1). La seconde est l'augmentation significative de défaillance cardio-vasculaire dan le groupe non-ETO. On peut se poser la question de l'impact du thiopental dans ce groupe. Le propofol peut également être à l'origine d'une instabilité hémodynamique et nécessite un vrai apprentissage. La quatrième réflexion porte sur le niveau de qualification, qui n'est pas précisé, des personnels réalisant ces intubations.

Ce document ne permet pa de remettre en question la recommandation d'emploi de la Kétamine pour l'ISR dans le cadre de la mise en condition de survie du blessé de guerre (2).

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 BACKGROUND:

Due to its favorable hemodynamic characteristics and by providing good intubation conditions etomidate is often used for induction of general anesthesia in trauma patients. It has been linked to temporary adrenal cortical dysfunction. The clinical relevance of this finding after a single-dose is still lacking appropriate evidence.

METHODS:

This retrospective multi-centre study is based on merged data from a German Helicopter Emergency Medical Service (HEMS) database and a large trauma patient registry. All trauma patients who were intubated prior to hospital admission with a documented Injury Severity Score ≥ 9 between 2008 and 2012 were eligible for analysis. The primary endpoint was hospital mortality. Other outcome measures were organ failures, sepsis, length of ventilation, as well as length of stay in hospital and ICU.

RESULTS:

One thousand six hundred ninety seven patients were enrolled into the study. Seven hundred sixty two patients received etomidate and 935 patients received other induction agents. The in-hospital mortality was similar in both groups (18.9% versus 18.2%; p = 0.71). Incidences of organ failures and sepsis were not increased in the etomidate group. However, health care resource utilization parameters were prolonged (after adjusting: + 1.3 days for ICU length of stay, p = 0.062; + 0.8 days for length of ventilation, p = 0.15; + 2,7 days for hospital length of stay, p = 0.034). A multivariable logistic regression analysis did not identify etomidate as an independent predictor of hospital mortality (OR: 1.10, 95% CI: 0.77-1.57; p = 0.60).

CONCLUSIONS:

This is the largest trial investigating outcome data for trauma patients who had received a single-dose of etomidate for induction of anesthesia. The use of etomidate did not affect mortality. The influence on morbidity and health care resource utilization remains unclear.

| Tags : etomidate, intubation

09/04/2019

Substituts au sang: Ils arrivent !

Artificial oxygen carriers- past, present and the future-a review of the most innovative and clinically relevant concepts.

Ferenz KB et Al. J Pharmacol Exp Ther. 2019 Mar 5. pii: jpet.118.254664. doi: 10.1124/jpet.118.254664.

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La question du transport de l'oxygène est fondamentale pour le traumatisé sévère. La recherche de transporteurs artificiels d'oxygène sont un axe fondamental de la recherche. Il se trouve qu'une entreprise bretonne fait partie des quelques équipes travaillant sur le sujet (voir ici)

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Blood transfusions are daily practice in hospitals. As these products are limited in availability and have various, harmful side-effects, researchers have pursued the goal to develop artificial blood components for about 40 years. Development of oxygen therapeutics and stem cells are more recent goals. Medline, clinicaltrials.gov, clinicaltrialsregister.eu and ANZCTR were searched up to November 2017 using search terms related to artificial blood products to identify new and ongoing research of the last 5 years. For already well-known products that are, however, important to the field or relevant to gain a better understanding, the reader is punctually referred to some important articles older than 5 years. This review includes not only clinically relevant substances such as heme-oxygenating carriers (HBOCs), PFOCs, stem cells and organ conservation, but also interesting pre-clinically advanced compounds depicting the pipeline of potential new products. In- depths insights into specific benefits and limitations of each substance, including the biochemical and physiological background are included. "Fancy" ideas such as Iron-based substances, O2-microbubbles, cyclodextranes or lugworms are also elucidated. To conclude, this systematic up-to-date review includes all actual achievements and ongoing clinical trials in the field of artificial blood products to pursue the dream of artificial oxygen carrier supply. Research is on the right track, but the task is demanding and challenging.

Lire aussi

05/04/2019

ISR: Ket/Celo SANS autre chose

Does the addition of fentanyl to ketamine improve haemodynamics, intubating conditions or mortality in emergency department intubation: A systematic review

01/04/2019

Oxsealife: LE cristalloïde de demain ?

The effect of a novel intravenous fluid (Oxsealife®) on recovery from haemorrhagic shock in pigs.
 

 

Blood transfusion is given according to haemoglobin thresholds aimed at restoration of arterial oxygen-carrying capacity. Patient survival after severe haemorrhagic shock depends on restoration of microvascular perfusion, tissue oxygen delivery, endothelial function and organ integrity. We investigated a novel crystalloid fluid designed for tissue oxygen delivery, Oxsealife® , with components that generate microvascular nitric oxide and scavenge reactive oxygen species generated during ischaemia-reperfusion injury. The amount of dissolved oxygen in blood progressively increased during step-wise in vitro haemodilution with this fluid, suggesting that the oxygen solubility coefficient of blood is dynamic, not static. We performed a pilot safety and efficacy study to compare resuscitation with this novel crystalloid vs. whole blood transfusion in a swine haemorrhagic shock model with animals bled to an arterial lactate oxygen debt target. Despite contributing no haemoglobin, viscosity nor oncotic potential, resuscitation with Oxsealife after severe haemorrhagic shock restored central haemodynamic parameters comparable to stored allogeneic blood transfusion. Tissue perfusion, oxygenation and metabolic outcomes were equivalent between treatment groups. Increased consumption of bicarbonate in animals given Oxsealife suggested greater capillary recruitment and enhanced clearance of acidic tissue metabolites. Serum markers of organ function, animal activity during recovery and histological analysis of tissue morphology and endothelial glycocalyx integrity confirmed functional recovery from haemorrhagic shock. We conclude that recovery of tissue oxygen delivery and organ function after haemorrhagic shock may not be dependent on treatments that increase haemoglobin levels. Oxsealife shows promise for treatment of severe haemorrhagic shock and may reduce the requirement for allogeneic blood products.

16/01/2019

Plyo prehospitalier: N'améliore pas la survie ?

The impact of prehospital administration of freeze-dried plasma on casualty outcome.

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Ce travail qui porte sur l'étude de l'impact, chez des blessés en choc hémorragique,  de la perfusion préhospitalière de PLyo confirme son intérêt en terme d'économie transfusionnelle mais pas en terme de mortalité. Les auteurs mettent en avant la taille de leur cohorte de blessés pour expliquer ce résultat négatif. On notera également les délais courts de transport.
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BACKGROUND:

Hemorrhage is the most common preventable cause of death in both civilian and military trauma. There is no consensus regarding the appropriate fluid resuscitation protocol. Plasma, as a resuscitative fluid, has substantial benefits as a volume expander, owing to its relatively high oncotic pressure and its positive effect on trauma-induced coagulopathy by replenishing the lost coagulation factors, rather than diluting the casualty's remaining factors. The Israel Defense Force Medical Corps decided to use freeze-dried plasma (FDP) as the fluid of choice for casualties in hemorrhagic shock in the prehospital setting. The aim of our study is to compare the differences of coagulation, perfusion measurements, resource utilization, and outcome between casualties receiving FDP to casualties who did not receive FDP in the prehospital setting.

METHODS:

This is a retrospective matched cohort study based on two groups of casualties (those treated with FDP vs. those without FDP treatment). The control group was compiled in three steps of precision for age, sex, mechanism of injury and maximum level of severity for each nine injured body regions. Data were collected from the IDF Trauma Registry and The National Israel Trauma Registry.

RESULTS:

The study group comprised 48 casualties receiving FDP and 48 controls with no differences in demographic, evacuation time, and injury characteristics. The FDP group demonstrated a lower level of hemoglobin (12.7 gr/dzl) (odds ratio [OR], 3.11; 95% confidence interval [CI], 1.10-8.80), lower level of international normalized ratio (1.1) (OR, 3.09; 95% CI, 1.04-9.14), and lower level of platelets (230 × 109/L) (OR, 3.06; 95% CI, 1.16-8.06). No other differences were found between the two groups.

 

" In the total study population, seven (7.3%) casualties died in hospital, among which 8.3% were from the FDP group, compared with 6.2% from the control group"

CONCLUSION:

The use of FDP in the prehospital setting has logistic benefits and a positive effect on coagulation profile, with no other significant effects. Future studies need to be performed on larger groups to verify trends or nullify our hypotheses.

 

08/01/2019

TXA à l'avant: Peut être pas si simple !

Prehospital Tranexamic Acid Administration During Aeromedical Transport After Injury.

Boudreau RM et Al. J Surg Res. 2019 Jan;233:132-138
 
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Un article de plus qui doit faire interroger sur l'intérêt réel du TXA, notamment son administration quai systématique à l'avant et pointe la réalité des complications thrombo-emboliques. Une plus grande sélectivité dans les critères d'administration est discutée.
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BACKGROUND:

Tranexamic acid (TXA) has been shown to reduce mortality in the treatment of traumatic hemorrhage. This effect seems most profound when given early after injury. We hypothesized that extending a protocol for TXA administration into the prehospital aeromedical setting would improve outcomes while maintaining a similar safety profile to TXA dosed in the emergency department (ED).

MATERIALS AND METHODS:

We identified all trauma patients who received TXA during prehospital aeromedical transport or in the ED at our urban level I trauma center over an 18-mo period. These patients had been selected prospectively for TXA administration using a protocol that selected adult trauma patients with high-risk mechanism and concern for severe hemorrhage to receive TXA. Patient demographics, vital signs, lab values including thromboelastography, blood administration, mortality, and complications were reviewed retrospectively and analyzed.

RESULTS:

One hundred sixteen patients were identified (62 prehospital versus 54 ED). Prehospital TXA patients were more likely to have sustained blunt injury (76% prehospital versus 46% ED, P = 0.002). There were no differences between groups in injury severity score or initial vital signs.

TXA.jpeg

There were no differences in complication rates or mortality. Patients receiving TXA had higher rates of venous thromboembolic events (8.1% in prehospital and 18.5% in ED) than the overall trauma population (2.1%, P < 0.001).

CONCLUSIONS:

Prehospital administration of TXA during aeromedical transport did not improve survival compared with ED administration. Treatment with TXA was associated with increased risk of venous thromboembolic events. Prehospital TXA protocols should be refined to identify patients with severe hemorrhagic shock or traumatic brain injury.

 

30/12/2018

HEXACYL: Oui , mais attention à la MTE

Tranexamic acid administration is associated with an increased risk of posttraumatic venous thromboembolism.

 

BACKGROUND:

Tranexamic acid (TXA) is used as a hemostatic adjunct for hemorrhage control in the injured patient and reduces early preventable death. However, the risk of venous thromboembolism (VTE) has been incompletely explored. Previous studies investigating the effect of TXA on VTE vary in their findings. We performed a propensity matched analysis to investigate the association between TXA and VTE following trauma, hypothesizing that TXA is an independent risk factor for VTE.

METHODS:

This retrospective study queried trauma patients presenting to a single Level I trauma center from 2012 to 2016. Our primary outcome was composite pulmonary embolism or deep vein thrombosis. Mortality, transfusion, intensive care unit and hospital lengths of stay were secondary outcomes. Propensity matched mixed effects multivariate logistic regression was used to determine adjusted odds ratio (aOR) and 95% confidence intervals (95% CI) of TXA on outcomes of interest, adjusting for prespecified confounders. Competing risks regression assessed subdistribution hazard ratio of VTE after accounting for mortality.

RESULTS:

Of 21,931 patients, 189 pairs were well matched across propensity score variables (standardized differences <0.2). Median Injury Severity Score was 19 (interquartile range, 12-27) and 14 (interquartile range, 8-22) in TXA and non-TXA groups, respectively (p = 0.19). Tranexamic acid was associated with more than threefold increase in the odds of VTE (aOR, 3.3; 95% CI, 1.3-9.1; p = 0.02).

TXA.jpg

Tranexamic acid was not significantly associated with survival (aOR, 0.86; 95% CI, 0.23-3.25; p = 0.83). Risk of VTE remained elevated in the TXA cohort despite accounting for mortality (subdistribution hazard ratio, 2.42; 95% CI, 1.11-5.29; p = 0.03).

CONCLUSION:

Tranexamic acid may be an independent risk factor for VTE. Future investigation is needed to identify which patients benefit most from TXA, especially given the risks of this intervention to allow a more individualized treatment approach that maximizes benefits and mitigates potential harms.

| Tags : coagulopathie

19/10/2018

Morphine pour le blessé ? Un risque faible

Opioid analgesia on the battlefield: a retrospective review of data from Operation HERRICK.

Lewis P et Al. J R Army Med Corps. 2018 Sep;164(5):328-331.

BACKGROUND:

Acute pain secondary to trauma is commonly encountered on the battlefield. The use of morphine to manage pain during combat has been well established since the 19th century. Despite this, there is relatively little research on analgesia use in this environment. This study aims to review the use and complications of morphine and other opioids during Operation HERRICK.

 

METHODS: A database search of the Joint Theatre Trauma Registry was completed looking for all incidences of morphine, fentanyl or naloxone use from February 2007 to September 2014. Microsoft Excel was used to analyse the results.

RESULTS:

Opioid analgesia was administered to 5801 casualties. Morphine was administered 6742 times to 3808 patients. Fentanyl was administered 9672 times to 4318 patients. Naloxone was used 18 times on 14 patients, giving a complication rate of 0.24%. Opioid doses prior to naloxone administration range from 0 to 72 mg of morphine and from 0 to 100 mcg of fentanyl. Four casualties (two local civilians and two coalition forces) received naloxone despite no recorded opioids being administered. Opium abuse was prevalent among the local population in Afghanistan, and this could explain the rationale behind two local national casualties receiving naloxone without any documented opioids being given.

CONCLUSION:

The use of opioids in a battlefield environment is extremely safe. Complication rates are similar to previously published data which is reassuring. The efficacy of different opioids was not covered by this study, and further analysis is required, particularly following the introduction of oral transmucosal fentanyl citrate and the availability of novel non-opioid analgesics.

| Tags : douleur

03/10/2018

Plaquettes et golden hour: Possible ?

Intravenous synthetic platelet (SynthoPlate) nanoconstructs reduce bleeding and improve 'golden hour' survival in a porcine model of traumatic arterial hemorrhage.

 

Traumatic non-compressible hemorrhage is a leading cause of civilian and military mortality and its treatment requires massive transfusion of blood components, especially platelets. However, in austere civilian and battlefield locations, access to platelets is highly challenging due to limited supply and portability, high risk of bacterial contamination and short shelf-life. To resolve this, we have developed an I.V.-administrable 'synthetic platelet' nanoconstruct (SynthoPlate), that can mimic and amplify body's natural hemostatic mechanisms specifically at the bleeding site while maintaining systemic safety.

41598_2018_21384_Fig1_HTML.jpg

Previously we have reported the detailed biochemical and hemostatic characterization of SynthoPlate in a non-trauma tail-bleeding model in mice. Building on this, here we sought to evaluate the hemostatic ability of SynthoPlate in emergency administration within the 'golden hour' following traumatic hemorrhagic injury in the femoral artery, in a pig model. We first characterized the storage stability and post-sterilization biofunctionality of SynthoPlate in vitro. The nanoconstructs were then I.V.-administered to pigs and their systemic safety and biodistribution were characterized. Subsequently we demonstrated that, following femoral artery injury, bolus administration of SynthoPlate could reduce blood loss, stabilize blood pressure and significantly improve survival. Our results indicate substantial promise of SynthoPlate as a viable platelet surrogate for emergency management of traumatic bleeding.

30/07/2018

Vitamine C pour la coagulopathie du traumatisé sévère

Interventional Vitamin C: A Strategy for Attenuation of Coagulopathy and Inflammation in a Swine Polytrauma Model

Reynolds PS et Al. J Trauma Acute Care Surg. 2018 DOI:10.1097/TA.0000000000001844

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L'emploi de vitamine C à haute dose est connue dans le cadre de la réanimation du brûlé (1). Elle limiterait la fuite capillaire du fait de propriétés anti-oxydantes. Les auteurs rapportent un intérêt expérimental modéré mais prometteur à leur avis.

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BACKGROUND

Coagulopathy and inflammation induced by hemorrhagic shock and traumatic injury are associated with increased mortality and morbidity. Vitamin C (VitC) is an antioxidant with potential protective effects on the pro-inflammatory and pro-coagulant pathways. We hypothesized that high-dose VitC administered as a supplement to fluid resuscitation would attenuate inflammation, coagulation dysfunction, and end-organ tissue damage in a swine model of polytrauma and hemorrhage.


METHODS

Male Sinclair swine (n = 24; mean body weight 27 kg) were anesthetized, intubated, mechanically ventilated, and instrumented for physiological monitoring. Following stabilization, swine were subjected to shock/traumatic injury (hypothermia, liver ischemia and reperfusion, comminuted femur fracture, hemorrhagic hypotension), resuscitated with 500mL of hydroxyethyl starch, and randomized to receive either intravenous saline (NS), low dose VitC (50mg/kg; LO), or high dose VitC (200 mg/kg; HI). Hemodynamics, blood chemistry, hematology, and coagulation function (ROTEM) were monitored to 4 hours post-resuscitation. Histological and molecular analyses were obtained for liver, kidney, and lung.


RESULTS

Compared to VitC animals, NS swine showed significant histological end-organ damage, elevated acute lung injury scores, and increased mRNA expression of tissue pro-inflammatory mediators (IL-1, IL-8, TNF), PAI-1, and TF. There were no statistically significant differences between treatment groups on MAP or univariate measures of coagulation function; however, NS showed impaired multivariate clotting function at 4 hours.


CONCLUSIONS

Although correction of coagulation dysfunction was modest, intravenous high-dose VitC may mitigate the pro-inflammatory/pro-coagulant response that contributes to multiple organ failure following acute severe polytrauma.

25/07/2018

Plasma et MEDEVAC, Obligation ? OUI

Prehospital plasma during air medical transport in trauma patients at risk for  hemorrhagic shock.

Sperry JL et Al. N Engl J Med. 2018 Jul 26;379(4):315-326

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Confirmation par l'étude PAMPER de tout l'intérêt de l'apport préhospitalier précoce d'au moins deux unités de plasma. Cette étude porte sur plus de 500 traumatisés graves essentiellement fermés, surtout secondaires à des AVP avec tout de même une motralité qui paraît très élevée. Il semblerait que l'administration avant l'arrivée en structure chirurgicale  (mesurée dans ce travail à 1h) soit déterminante. Cependant, elle n'inclue que 20% de plaies pénétrantes sans faire mention d'IED, ce qui limite fortement une extrapolation simple aux blessés par arme de guerre., ce d'autant que le tableau 2 montre que dans ce sous groupe le traitement conventionnel ferait mieux en terme de survie. Un éditorial abordant les problématiques "logistiques" liée à l'emploi du plasma accompagne cette publication (1). Lire également (23).

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BACKGROUND:

After a person has been injured, prehospital administration of plasma in addition to the initiation of standard resuscitation procedures in the prehospital environment may reduce the risk of downstream complications from hemorrhage and shock. Data from large clinical trials are lacking to show either the efficacy or the risks associated with plasma transfusion in the prehospital setting.

METHODS:

To determine the efficacy and safety of prehospital administration of thawed plasma in injured patients who are at risk for hemorrhagic shock, we conducted a pragmatic, multicenter, cluster-randomized, phase 3 superiority trial that compared the administration of thawed plasma with standard-care resuscitation during air medical transport. The primary outcome was mortality at 30 days.

RESULTS:

A total of 501 patients were evaluated: 230 patients received plasma (plasma group) and 271 received standard-care resuscitation (standard-care group). Mortality at 30 days was significantly lower in the plasma group than in the standard-care group (23.2% vs. 33.0%; difference, -9.8 percentage points; 95% confidence interval, -18.6 to -1.0%; P=0.03). A similar treatment effect was observed across nine prespecified subgroups (heterogeneity chi-square test, 12.21; P=0.79). Kaplan-Meier curves showed an early separation of the two treatment groups that began 3 hours after randomization and persisted until 30 days after randomization (log-rank chi-square test, 5.70; P=0.02). The median prothrombin-time ratio was lower in the plasma group than in the standard-care group (1.2 [interquartile range, 1.1 to 1.4] vs. 1.3 [interquartile range, 1.1 to 1.6], P<0.001) after the patients' arrival at the trauma center. No significant differences between the two groups were noted with respect to multiorgan failure, acute lung injury-acute respiratory distress syndrome, nosocomial infections, or allergic or transfusion-related reactions.

CONCLUSIONS:

In injured patients at risk for hemorrhagic shock, the prehospital administration of thawed plasma was safe and resulted in lower 30-day mortality and a lower median prothrombin-time ratio than standard-care resuscitation. 

| Tags : coagulopathie

22/07/2018

Chitine: Prudence quand même ?

 Chitin and Its Effects on Inflammatory and Immune Responses

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Les pansements hémostatiques à base de chitine sont largement utilisés et ne semblent pas actuellement poser de problème allergique (1). Néanmoins se pose la question de leur innocuité immune. Le développement des allergies croisées avec les produits dérivés de la mer et l'emploi de chitine comme complément alimentaire sont autant de facteurs de rencontre avec un allergène vrai. De telles allergies croisées s'observent également avec d'autres composants tels que la paravalbumine et le collagène des produits de la mer. Les pansements hémostatiques ne contenant pas de chitine ne semble pas exposer à ce risque potentiel.

arton4104.jpg

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Chitin, a potential allergy-promoting pathogen-associated molecular pattern (PAMP), is a linear polymer composed of N-acetylglucosamine residues which are linked by β-(1,4)-glycosidic bonds. Mammalians are potential hosts for chitin-containing protozoa, fungi, arthropods, and nematodes; however, mammalians themselves do not synthetize chitin and thus it is considered as a potential target for recognition by mammalian immune system. Chitin is sensed primarily in the lungs or gut where it activates a variety of innate (eosinophils, macrophages) and adaptive immune cells (IL-4/IL-13 expressing T helper type-2 lymphocytes). Chitin induces cytokine production, leukocyte recruitment, and alternative macrophage activation. Intranasal or intraperitoneal administration of chitin (varying in size, degree of acetylation and purity) to mice has been applied as a routine approach to investigate chitin's priming effects on innate and adaptive immunity. Structural chitinpresent in microorganisms is actively degraded by host true chitinases, including acidic mammalian chitinases and chitotriosidase into smaller fragments that can be sensed by mammalian receptors such as FIBCD1, NKR-P1, and RegIIIc. Immune recognition of chitin also involves pattern recognition receptors, mainly via TLR-2 and Dectin-1, to activate immune cells to induce cytokine production and creation of an immune network that results in inflammatory and allergic responses. In this review, we will focus on various immunological aspects of the interaction between chitin and host immune system such as sensing, interactions with immune cells, chitinases as chitin degrading enzymes, and immunologic applications of chitin.

01/06/2018

Curare pour intuber: Oui, mais aussi !

Effects of avoidance or use of neuromuscular blocking agents on outcomes in tracheal intubation: a Cochrane systematic review.

 
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Il est communément admis que l'emploi de curares facilite l'intubation et réduit les complications liées à ce geste. C'est bien ce que confirme cette publication. Mais cette dernière conclue également à l'importance de peser le risque bénéfice risque. Dans les conditions extrêmes d'isolement et de prise en charge de trauma maxillo-faciaux/cranien ballistique l'objectif principal doit rester l'oxygénation des blessés/accidentés. Si l'induction en séquence rapide reste la référence, l'éventualité d'une intubation sans curare sous anesthésie locale doit être évoquée en cas de risque d'impossibilité de ventilation manuelle ou spontanée et de difficulté d'intubation. Dans tous les cas il reste nécessaire de pouvoir réaliser un abord chirurgical des voies aériennes.

Lire ici les recommandations de la SFAR: Intubation difficile en anesthésie, en réanimation

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Cohort studies have indicated that avoidance of neuromuscular blocking agents (NMBA) is a risk factor for difficult tracheal intubation. However, the impact of avoiding NMBA on tracheal intubation, possible adverse effects, and postoperative discomfort has not been evaluated in a systematic review of randomised trials. We searched several databases for trials published until January 2017. We included randomised controlled trials comparing the effect of avoiding vs using NMBA. Two independent authors assessed risk of bias and extracted data. The risk of random errors was assessed by trial sequential analysis (TSA). We included 34 trials (3565 participants). In the four trials judged to have low risk of bias, there was an increased risk of difficult tracheal intubation with no use of NMBA [random-effects model, risk ratio (RR) 13.27, 95% confidence interval (CI) 8.19-21.49, P<0.00001, TSA-adjusted CI 1.85-95.04]. The result was confirmed when including all trials, (RR 5.00, 95% CI 3.49-7.15, P<0.00001, TSA-adjusted CI 1.20-20.77). There was a significant risk of upper airway discomfort or injury by avoiding NMBA (RR=1.37, 95% CI 1.09-1.74, P=0.008, TSA-adjusted CI 1.00-1.86). None of the trials reported mortality. Avoiding NMBA was significantly associated with difficult laryngoscopy, (RR 2.54, 95% CI 1.53-4.21, P=0.0003, TSA-adjusted CI 0.27-21.75). In a clinical context, one must balance arguments for using NMBA when performing tracheal intubation.

03/01/2018

Fibrinogène: En 1er chez les canadiens

Fibrinogen Concentrate in the Special Operations Forces Environment

Sanders S et al. Military Medecine, 00, 0/0:1, 2017

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Un choix raisonné et différent (Apport de 6 g de fibrinogène) des armées françaises qui s'intègre dans les nouvelles stratrégies transfusionnelles de prise en charge du blessé de guerre où la place de la transfusion de sang frais le fibrinogène et le plasma ont une place essentielle (1,2)

Aller sur le forum coagulopathie

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Introduction:

Hemorrhage is the most common cause of death among Special Operations Force (SOF) soldiers. Bringing remote damage control resuscitation into the far-forward combat environment is logistically challenging, as it requires blood products that generally require a robust cold chain. Alternatively, lyophilized products such as fibrinogen concentrate, which does not require thawing or blood group compatibility testing before use, might be advantageous in damage control resuscitation in the battlefield. In this report, we review the evidence for the use of fibrinogen concentrate in the Canadian SOF environment.

Materials and Methods:

The literature on the use of fibrinogen concentrate in the trauma setting was reviewed by Canadian Forces Services Working Group, in three separate meetings. Multiple stakeholders were consulted to obtain authoritative perspectives from subject matter experts on the use of fibrinogen concentrate in the Canadian SOF environment.

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We also conducted a comparison review of fibrinogen content, pathogen risk, shelf life, and methods required for use for fresh frozen plasma, cryoprecipitate, and fibrinogen concentrate relevant to their application in the far-forward combat environment.

Results:

Indications and a protocol for the use of fibrinogen as an adjunct to fresh whole blood were formulated based on a literature review and clinical expert opinion. Alternative strategies and other lyophilized blood products were considered before selecting fibrinogen concentrate as the lyophilized blood product of choice. Fibrinogen concentrate is an ABO-universal blood product with an excellent safety profile. Training was conducted by subject matter experts within civilian trauma centers and at military training facilities. The clinical efficacy and safety were confirmed by monitoring the use of fibrinogen concentrate in deployed combat settings.

Conclusion:

Fibrinogen concentrate is a useful adjunct to remote damage control resuscitation in the SOF environment. Fibrinogen concentrate was found to be robust for transport into the SOF environment and is widely accepted among SOF operators and medics

24/12/2017

AAST 2017: Utilité du TXA encore questionnée

Late TXA utilization is associated with Iincreased blood product transfusion: A secondary analysisof the pragmatic randomized optimal platelet and plasma ratios  (PROPPR) study

Aravind K. et AL . Session: XIIIA: Papers 45-54: Preclincial/Translational Science Paper 52

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Ce poster présenté au dernier AAST 2017 est une ré-interprétation de données de l'étude POPR. Il semblerait qu'au delà des premières heures l'administration précoce (dans la 1ère heure) de TXA n'améliore pas la survie à 24h et un mois. L'administration tardive (après la 1ère heure mais avant la 3ème) majorerait les besoins transfusionnels. Les auteurs de ce poster attirent l'attention sur la disparité des groupes comparés, ce qui peut expliquer leurs résultats.

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Introduction:

Exsanguination is the leading cause of preventable death after trauma. In addition to a balanced ratio blood component strategy, tranexamic acid (TXA) is used as an adjunct in hemorrhaging patients. This secondary analysis was performed to determine the incidence of TXA utilization and outcome in patients predicted to receive a massive transfusion (MT) in level 1 trauma centers.

Methods:

Trauma patients who were predicted to require a MT and admitted to 12 level I North American trauma centers were studied. Patients were divided into those who received TXA and those who did not. We examined 3 hour, 24 hour, and 30 day mortality. We also examined incidence of thromboembolic events, blood product administration within the first 24 hours, length of stay (hospital free days), ICU free days, as well as development of complications including acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), sepsis, and multisystem organ failure (MOF). In our multivariate analysis, we controlled for Injury Severity Score (ISS), Glasgow Coma Scale (GCS), treatment group, mechanism of injury, hypotension and/or tachycardia on admission, geriatric patient (age > 65), and site as independent variables.

Results:

137 out of 680 (20.1%) patients in the PROPPR study received TXA with 130 patients receiving TXA within the first 3 hours after admission. Other adjunctive therapies administered included cryoprecipitate (25.4%), and others (6.6%). The incidence of TXA administration did not differ between the ratio groups (50.3% vs 47.4%, p=0.55), but patients receiving TXA were more severely injured with a median ISS of 34(21) vs 26(20), p<0.01  and a lower median(IQR) GCS of 9(12) vs 14(12),  p<0.01. Multivariate linear regression analysis revealed no association between TXA administration and blood transfusion requirements (Table 1). Further analysis revealed that patients who received late (from >1 hour to ≤3 hours after arrival) TXA (41 patients) experienced increased blood requirements in the first 24 hours (Table 1) compared to those remaining 543 patients that did not receive TXA. There was no difference in blood product requirement in those patients who received TXA early (≤1 hour) (89 patients) versus those that did not receive TXA. In patients that receiv ed TXA, there was an increased incidence of ARDS(OR (95% CI) 1.99 (1.06,3.73), p=0.03), AKI (1.90 (1.13,3.20), p=0.01), and MOF (4.18 (1.52,11.48), p<0.01) even when controlling for the factors mentioned above. There was also a difference in adjusted 3 hour mortality (OR (95% CI) 0.22 (0.07,0.73), p=0.01) but not 24 hour (0.61 (0.30,1.24), p=0.18) or 30 day mortality (1.42 (0.78,2.59), p=0.25) for any TXA administration. There was no difference in adjusted thromboembolic events or adjusted length of stay. Subgroup analysis with additional variables that were found to have a difference between groups with a p​<0.20 were added to the regression model including hematocrit, platelet count, international normalized ratio, creatinine, lactate, and R value on thrombelastography. This analysis showed an increase in PRBC transfusion with late TXA administration (16 out of 232 patients, 7.51 (0.46,14.56), p=0.04), but showed no difference in FFP or platelet administration.

Conclusion: Early TXA use was not associated with improved outcomes. Late TXA use was associated with increased blood product resuscitation. TXA administration in general was associated with improved 3 hour mortality. This did not translate to an improvement in mortality at 24 hours or 30 days. There was a significant increase in the incidence of ARDS, AKI, and MOF in patients who received TXA but this analysis is limited by the differences in the 2 populations despite attempts to control for them

08/05/2017

Hémorragie: De la glace sur le visage ?

Face Cooling Increases Blood Pressure during Simulated Blood Loss

B. Johnson et Al. Proceedings of Experimental Biology 2017 Chicago 

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Une constatation qui ne devrait pas surprendre ceux qui s'intéressent à la médecine de plongée et au réflexe d'immersion (1, 2, 3, 4), dont le facteur principal de déclenchement est l'exposition de la face à de l'eau froide.

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Introduction

Blood loss causes central hypovolemia and in severe instances, it can decrease blood pressure and lead to cardiovascular decompensation. Simple and quick interventions that can be used to prevent cardiovascular decompensation in pre-hospital settings could be a valuable tool for first responsders. Cooling the forehead and cheeks using an ice/water slurry mixture has been shown to increase blood pressure for over 15 minutes. Therefore, face cooling could be used to mitigate decreases in blood pressure during blood loss.

Purpose

We tested the hypothesis that face cooling during simulated blood loss will increase blood pressure. Methods Ten healthy participants (22 ± 2 years, 3 women) completed two randomized trials on separate days. Both trials began with 30 mmHg of lower body negative pressure (LBNP) to simulate blood loss for 6 minutes. Then, either a 2.5 L plastic bag of an ice/water slurry mixture (0 ± 0°C) (LBNP+FC) or a 2.5 L plastic bag of thermoneutral water (34 ± 1°C) (LBNP+SHAM) was placed on the forehead and eyes and 30 mmHg of LBNP was maintained for an additional 15 minutes.

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We continuously measured blood pressure (Penaz method), heart rate (ECG), stroke volume (Modelflow), cardiac output, total peripheral resistance, and forehead temperature throughout the protocol.

Results

Forehead temperature did not change from LBNP (34.2 ± 0.6°C) to LBNP+SHAM (33.9 ± 1.4°C, P > 0.999) and decreased from LBNP (34.4 ± 0.5°C) to LBNP+FC (11.0 ± 1.6°C, P < 0.001). Mean arterial pressure did not change from LBNP (82 ± 10 mmHg) to LBNP+SHAM (80 ± 8 mmHg, P = 0.978), but markedly increased during LBNP+FC. The peak increase from LBNP (77 ± 9 mmHg) was observed after 3 minutes of LBNP+FC (98 ± 15 mmHg, P < 0.001). Heart rate during LBNP (76 ± 14 bpm, P = 0.978) was not different from LBNP+SHAM (75 ± 13 bpm). Heart rate was lower throughout LBNP+FC beginning at 2 minutes of FC (60 ± 16 bpm) versus LBNP (80 ± 19 bpm, P < 0.001). Stroke volume did not change from LBNP (72 ± 15 mL) to LBNP+SHAM (67 ± 18 mL, P = 0.857). However, stroke volume increased from LBNP (78 ± 16 mL) to LBNP+FC, and peaked after 5 minutes of FC (97 ± 32 mL, P < 0.001). Cardiac output did not change from LBNP (5.4 ± 1.0 L/min) to LBNP+SHAM (4.9 ± 1.0 L/min, P > 0.415). Cardiac output slightly decreased from LBNP (6.2 ± 1.5 L/min) to 2 minutes of LBNP+FC (5.3 ± 1.6 L/min, P = 0.038). Total peripheral resistance did not change from LBNP (15.6 ± 3.7 mmHg/L/min) to LBNP+SHAM (17.3 ± 3.2 mmHg/L/min, P = 0.613). Total peripheral resistance throughout LBNP+FC was greater than LBNP. The peak increase in total peripheral resistance was observed after 2 minutes of LBNP+FC (20.0 ± 6.2 mmHg/L/min) versus LBNP (13.2 ± 3.9 mmHg/L/min, P < 0.001).  

Conclusions

Face cooling during simulated moderate blood loss increases blood pressure through an increase in total peripheral resistance. Although more research is warranted, face cooling during blood loss is a potential simple and quick intervention that could delay cardiovascular decompensation.  Support or Funding InformationUniversity at Buffalo IMPACT Award

| Tags : choc, hémorragie

15/01/2017

ISR: Plutôt kétamine ?

Significant modification of traditional rapid sequence induction improves safety and effectiveness of pre-hospital trauma anaesthesia.

Lyon RM et Al. Crit Care. 2015 Apr 1;19:134

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Faut-il utiliser la kétamine ou l'étomidate ? Le travail présenté milite pour l'emploi de la kétamine, mais ceci reste controversé (voir également ici)). C'est aussi le choix présenté dans la procédure du sauvetage au combat, du fait de la polyvalence d'emploi de la kétamine tant dans ses indications que de ses voies d'administration. On rappelle quand même que si l'ISR facilite grandement les conditions de l'intubation oro-trachéale en médecine préhospitalière métropolitaine, nos conditions spécifiques d'exercice ne correspondent pas à cette dernière. Avant de réaliser une telle induction, encore faut-il être valider l'indication de l'intubation au milieu de nulle part. Par ailleurs  la réalisation de ce geste sous anesthésie locale doit également être envisagée. Ceci est conforme aux recommandations sur le sujet. 

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INTRODUCTION:

Rapid Sequence Induction of anaesthesia (RSI) is the recommended method to facilitate emergency tracheal intubation in trauma patients. In emergency situations, a simple and standardised RSI protocol may improve the safety and effectiveness of the procedure. A crucial component of developing a standardised protocol is the selection of induction agents. The aim of this study is to compare the safety and effectiveness of a traditional RSI protocol using etomidate and suxamethonium with a modified RSI protocol using fentanyl, ketamine and rocuronium.

METHODS:

We performed a comparative cohort study of major trauma patients undergoing pre-hospital RSI by a physician-led Helicopter Emergency Medical Service. Group 1 underwent RSI using etomidate and suxamethonium and Group 2 underwent RSI using fentanyl, ketamine and rocuronium. Apart from the induction agents, the RSI protocol was identical in both groups. Outcomes measured included laryngoscopy view, intubation success, haemodynamic response to laryngoscopy and tracheal intubation, and mortality.

RESULTS:

Compared to Group 1 (n = 116), Group 2 RSI (n = 145) produced significantly better laryngoscopy views (p = 0.013) and resulted in significantly higher first-pass intubation success (95% versus 100%; p = 0.007). A hypertensive response to laryngoscopy and tracheal intubation was less frequent following Group 2 RSI (79% versus 37%; p < 0.0001). A hypotensive response was uncommon in both groups (1% versus 6%; p = 0.05). Only one patient in each group developed true hypotension (SBP < 90 mmHg) on induction.

CONCLUSIONS:

In a comparative, cohort study, pre-hospital RSI using fentanyl, ketamine and rocuronium produced superior intubating conditions and a more favourable haemodynamic response to laryngoscopy and tracheal intubation. An RSI protocol using fixed ratios of these agents delivers effective pre-hospital trauma anaesthesia.

| Tags : kétamine, airway

15/12/2016

Sang total: Pas que chaud, de banque aussi

Coagulation function of stored whole blood is preserved for 14 days in austere conditions: A ROTEM feasibility study during a Norwegian antipiracy mission and comparison to equal ratio reconstituted blood.

 
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L'emploi du sang total fait un retour en force dans les stratégies transfusionnelles actuelles (1) bien sûr dans un contexte militaire mais aussi dans toutes les situations d'isolement comme les expéditions et le milieu maritime. (2). On pense alors sang frais. En fait la conservation à +4°c de ce sang en banque appropriée n'altère ni les fonctions plaquettaires ni la fonctionnalité du fibrinogène. Ces données permettent donc d'ouvrir la porte à la mise à disposition de ce type de produit en contexte militaire ou d'isolement ne permettant pas la conservation des produits sanguins dans les mêmes condition qu'une banque de sang hospitalière (3). On rappelle quand même que la conservation du sang total en banque de sang n'est pas franchement une nouveauté et que c'est sous cette forme qu'il est disponible dans nombre de pays.
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BACKGROUND:

Formulation of a medical preparedness plan for treating severely bleeding casualties during naval deployment is a significant challenge because of territory covered during most missions. The aim of this study was to evaluate the concept of "walking blood bank" as a supportable plan for supplying safe blood and blood products.

METHODS:

In 2013, the Royal Norwegian Navy conducted antipiracy operations from a frigate, beginning in the Gulf of Aden and ending in the Indian Ocean. Crews were on 24-hour emergency alert in preparation for an enemy assault on the frigate. Under an approved command protocol, a "walking blood bank," using crew blood donations, was established for use on board and on missions conducted in rigid-hulled inflatable boats, during which freeze-dried plasma and leukoreduced, group O low anti-A/anti-B titer, cold-stored whole blood were stored in Golden Hour Boxes. Data demonstrating the ability to collect, store, and provide whole blood were collected to establish feasibility of implementing a whole blood-focused remote damage-control resuscitation program aboard a naval vessel. In addition, ROTEM data were collected to demonstrate feasibility of performing this analysis on a large naval vessel and to also measure hemostatic efficacy of cold-stored leukoreduced whole blood (CWB) stored during a period of 14 days. ROTEM data on CWB was compared with reconstituted whole blood.

RESULTS:

Drills simulating massive transfusion activation were conducted, in which 2 U of warm fresh whole blood with platelet sparing leukoreduction were produced in 40 minutes, followed by collection of two additional units at 15-minute increments. The ROTEM machine performed well during ship-rolling, as shown by the overlapping calculated and measured mechanical piston movements measured by the ROTEM device. Error messages were recorded in 4 (1.5%) of 267 tests. CWB yielded reproducible ROTEM results demonstrating preserved fibrinogen function and platelet function for at least 3.5 weeks and 2 weeks, respectively. The frequency of ROTEM tests were as follows: EXTEM (n = 88), INTEM (n = 85), FIBTEM (n = 82), and APTEM (n = 12). CWB results were grouped. Compared with Days 0 to 2, EXTEM maximum clot firmness was significantly reduced, beginning on Days 10 to 14; however, results through that date remained within reference ranges and were comparable with the EXTEM maximum clot firmness for the reconstituted whole blood samples containing Day 5 room temperature-stored platelets.

CONCLUSION:

A "walking blood bank" can provide a balanced transfusion product to support damage-control resuscitation/remote damage-control resuscitation aboard a frigate in the absence of conventional blood bank products. ROTEM analysis is feasible to monitor damage-control resuscitation and blood product quality. ROTEM analysis was possible in challenging operational conditions.