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Transfusion en vol: Sécurité assurée

Risk Management Analysis of Air Ambulance Blood Product Administration in Combat Operations



Between June-October 2012, 61 flight-medic-directed transfusions took place aboard U.S. Army Medical Evacuation (medevac) helicopters in Afghanistan. This represents the initial experience for pre-hospital blood product transfusion by U.S. Army flight medics.


We performed a retrospective review of clinical records, operating guidelines, after-action reviews, decision and information briefs, bimonthly medical conferences, and medevac-related medical records.


A successful program was administered at 10 locations across Afghanistan. Adherence to protocol transfusion indications was 97%. There were 61 casualties who were transfused without any known instance of adverse reaction or local blood product wastage. Shock index (heart rate/systolic blood pressure) improved significantly en route, with a median shock index of 1.6 (IQR 1.2-2.0) pre-transfusion and 1.1 (IQR 1.0-1.5) post-transfusion (P < 0.0001). Blood resupply, training, and clinical procedures were standardized across each of the 10 areas of medevacoperations.


Potential risks of medical complications, reverse propaganda, adherence to protocol, and diversion and/or wastage of limited resources were important considerations in the development of the pilot program. Aviation-specific risk mitigation strategies were important to ensure mission success in terms of wastage prevention, standardized operations at multiple locations, and prevention of adverse clinical outcomes. Consideration of aviation risk mitigation strategies may help enable other helicopter emergency medical systems to develop remote pre-hospital transfusion capability. This pilot program provides preliminary evidence that blood product administration by medevac is safe.

| Tags : transfusion


Kétamine: Moins performant après !

Comparison of the effects of ketamine and morphine on performance of representative military tasks

Gaydos SJ et Al. J Emerg Med. 2015 Mar;48(3):313-24



When providing care under combat or hostile conditions, it may be necessary for a casualty to remain engaged in military tasks after being wounded. Prehospital care under other remote, austere conditions may be similar, whereby an individual may be forced to continue purposeful actions despite traumatic injury. Given the adverse side-effect profile of intramuscular (i.m.) morphine, alternative analgesics and routes of administration are of interest. Ketamine may be of value in this capacity.


To delineate performance decrements in basic soldier tasks comparing the effects of the standard battlefield analgesic (10 mg i.m. morphine) with 25 mg i.m. ketamine.


Representative military skills and risk propensity were tested in 48 healthy volunteers without pain stimuli in a double-blind, placebo-controlled, crossover design.


Overall, participants reported more symptoms associated with ketamine vs. morphine and placebo, chiefly dizziness, poor concentration, and feelings of happiness. Performance decrements on ketamine, when present, manifested as slower performance times rather than procedural errors.


Participants were more symptomatic with ketamine, yet the soldier skills were largely resistant to performance decrements, suggesting that a trained task skill (autonomous phase) remains somewhat resilient to the drugged state at this dosage. The performance decrements with ketamine may represent the subjects' adoption of a cautious posture, as suggested by risk propensity testing whereby the subject is aware of impairment, trading speed for preservation of task accuracy. These results will help to inform the casualty care community regarding appropriate use of ketamine as an alternative or opioid-sparing battlefield analgesic.

| Tags : douleur, analgésie


Albumine plutôt que fibrinogène ?

Influences of limited resuscitation with plasma or plasma protein solutions on hemostasis and survival of rabbits with noncompressible hemorrhage

Kheirabadi BS et Al. J Trauma Acute Care Surg. 2016;81: 42–49


Dans ce travail les auteurs évoquent la possibilité que les effets favorables d'une réanimation basée sur l'apport de plasma serait lié à l'apport de protéine et en particulier d'albumine qui aurait un effet tampon élevé, réduisant l'acidose métabolique, un des facteurs de la triade létale.



Plasma infusion with or without red blood cells is the current military standard of care for prehospital resuscitation of combat casualties. We examined possible advantages of early and limited resuscitation with fresh plasma compared with a single plasma protein or crystalloid solutions in an uncontrolled hemorrhage model in rabbits.


Anesthetized spontaneously breathing rabbits (3.3 ± 0.1 kg) were instrumented and subjected to a splenic uncontrolled hemorrhage. Rabbits in shock were resuscitated at 15 minutes with Plasma-Lyte (PAL; 30 mL/kg), PAL + fibrinogen (PAL + F; 30 mL + 100 mg/kg), fresh rabbit plasma (15 mL/kg), or 25% albumin (ALB; 5 mL/kg) solution, all given in two bolus intravenous injections (15 minutes apart) to achieve a mean arterial pressure of 65 mm Hg, n = 8 to 9/group. Animals were monitored for 2 hours or until death, and blood loss was measured. Blood samples and tissues were collected and analyzed.


There were no differences among groups in baseline measures and their initial bleeding volume at 15 minutes. At 60 minutes after injury, mean arterial pressure was higher with ALB than with crystalloids (PAL or PAL + F), but shock indices were not different despite the large differences in resuscitation volumes. Fibrinogen addition to PAL only increased clot strength. Plasma resuscitation increased survival rate (75%) without significant improvement in coagulation measures. Albumin administration replenished total plasma protein and increased survival rate to 100% (p < .05 vs. crystalloids). No histological adverse events were identified in the vital organs.



Fibrinogen administration added to a compatible crystalloid did not improve hemostatic outcomes. Plasma resuscitation increased survival rate; however, its effects did not differ from those obtained with 25% ALB at one-third of the volume. The ALB advantage was consistent with our previous findings in which 5% ALB was used at a volume equal to plasma. The benefit of plasma for resuscitation may be mostly due to its ALB content rather than its coagulation proteins


AL pour intuber: A ressortir de l'oubli

The Myth of Rescue Reversal in “Can’t Intubate, Can’t Ventilate” Scenarios

Naguib N. et Al. Anesth Analg. 2016 Jul;123(1):82-92


Ce travail met en avant l'insuffisance des démarches d'antagonisation pour restaurer une ventilation adéquate dans les situations de CICV. En ce qui concerne la gestion des voies aériennes en situation tactique, le principe de la préservation de la ventilation spontanée lors de l'accès aux voies aériennes mérite d'être rappelé. Si la réalisation d'une induction en séquence rapide reste la référence, en cas de difficulté prévisible le recours à une anesthésie locale doit être préférée (lire ce post).


Ceci est parfaitement stipulé dans les RFE "Sédation et analgésie en structure d’urgence"  dont on rappelle après la présentation de l'abstract les termes de la question N3.



An unanticipated difficult airway during induction of anesthesia can be a vexing problem. In the setting of can't intubate, can't ventilate (CICV), rapid recovery of spontaneous ventilation is a reasonable goal. The urgency of restoring ventilation is a function of how quickly a patient's hemoglobin oxygen saturation decreases versus how much time is required for the effects of induction drugs to dissipate, namely the duration of unresponsiveness, ventilatory depression, and neuromuscular blockade. It has been suggested that prompt reversal of rocuronium-induced neuromuscular blockade with sugammadex will allow respiratory activity to recover before significant arterial desaturation. Using pharmacologic simulation, we compared the duration of unresponsiveness, ventilatory depression, and neuromuscular blockade in normal, obese, and morbidly obese body sizes in this life-threatening CICV scenario. We hypothesized that although neuromuscular function could be rapidly restored with sugammadex, significant arterial desaturation will occur before the recovery from unresponsiveness and/or central ventilatory depression in obese and morbidly obese body sizes.


We used published models to simulate the duration of unresponsiveness and ventilatory depression using a common induction technique with predicted rates of oxygen desaturation in various size patients and explored to what degree rapid reversal of rocuronium-induced neuromuscular blockade with sugammadex might improve the return of spontaneous ventilation in CICV situations.


Our simulations showed that the duration of neuromuscular blockade was longer with 1.0 mg/kg succinylcholine than with 1.2 mg/kg rocuronium followed 3 minutes later by 16 mg/kg sugammadex (10.0 vs 4.5 minutes). Once rocuronium neuromuscular blockade was completely reversed with sugammadex, the duration of hemoglobin oxygen saturation >90%, loss of responsiveness, and intolerable ventilatory depression (a respiratory rate of ≤4 breaths/min) were dependent on the body habitus and duration of oxygen administration. There is a high probability of intolerable ventilatory depression that extends well beyond the time when oxygen saturation decreases <90%, especially in obese and morbidly obese patients. If ventilatory rescue is inadequate, oxygen desaturation will persist in the latter groups, despite full reversal of neuromuscular blockade. Depending on body habitus, the duration of intolerable ventilatory depression after sugammadex reversal may be as long as 15 minutes in 5% of individuals.


The clinical management of CICV should focus primarily on restoration of airway patency, oxygenation, and ventilation consistent with the American Society of Anesthesiologist's practice guidelines for management of the difficult airway. Pharmacologic intervention cannot be relied upon to rescue patients in a CICV crisis.


Question 3 - Intubation sous ISR et sous AL : Quelles sont les modalités de réalisation d’une sédation et/ou d’une analgésie pour l’intubation trachéale ?

Les experts recommandent d’administrer une sédation pour toutes les indications de l’intubation trachéale, excepté chez le patient en arrêt cardiaque qui ne nécessite pas de sédation. Lorsque l’intubation trachéale est présumée diffi cile, il est possible d’effectuer une anesthésie locale réalisée de proche en proche, associée ou non à une sédation légère et titrée par voie générale

L’utilisation de médicaments anesthésiques lors de l’intubation trachéale a pour but de faciliter le geste et d’assurer le confort du patient. Cette sédation doit être rapidement réversible pour restaurer une ventilation effi cace en cas de diffi culté d’intubation. Le risque d’inhalation bronchique doit être minimisé au cours de la procédure et ce d’autant que les patients sont considérés comme ayant un estomac plein.

Les experts recommandent d’utiliser les techniques d’intubation en séquence rapide (ISR) associant un hypnotique d’action rapide (étomidate ou kétamine) et un curare d’action brève (succinylcholine) ........................................................

Lorsque l’intubation trachéale est présumée difficile, le protocole recommandé par les experts pour une intubation vigile est le suivant : - Lidocaïne entre 2 et 5% en pulvérisation de proche en proche - Complément de sédation intraveineuse pour intubation vigile : • midazolam : 1 mg par 1 mg IV • associé ou non à de la morphine : 2 mg par 2 mg IV




PLyo: Une révolution ? Pas vraiment, une redécouverte

 Dried plasma: state of the science and recent developments

Pusateri AE et Al. Transfusion. 2016 Apr;56 Suppl 2:S128-39


Les nouvelles modalités de transfusion mettent en avant le bénéfice de l'apport précoce de plasma. Les contraintes logistiques liées à l'emploi de plasma frais sont réelles. L'emploi  de plasma lyophilisé permet de raccourcir ce délai et peut représenter dans certaines conditions d'isolement la seule source disponibles de fractions coagulantes. Le plasma lyophylisé est un vieux monsieur, mais dont la place est fondamentale. Largement utilisé notamment par l'armée française pendant la guerre d'indocchine, le SSA a maintenu sa production jusqu'à ce que l'épidémie de VIH ne survienne. Depuis les années 1980, le SSA a travaillé sans relâche pour sécuriser un produit qui retrouve la place qui lui est due dans la  stratégie transfusionnelle du blessé de guerre (1)  Il s'agit donc d'une redécouverte avec un emploi effectif en opération dès 1996 (2), plutôt que de révolution. Le document proposé à la lecture fait le point sur cette historique et les développements à venir.  La lecture de ce document ne doit pas faire oublier la réflexion de plus en plus présente sur l'emploi  en situation d'isolement de l'intérêt de la transfusion de sang total, seule source de plaquettes, associé au recours à des fractions coagulantes comme le fibrinogène et les complexes prothrombiques. Une telle association représente probablement l'avenir de la réanimation hémostatique préhospitalière (3, 4).


Historical dried plasma development Event Selected References

1930s Plasma lyophilization developed in the 1930s.

1940—Large scale production of pooled, lyophilized plasma by both the US and British established for war time use (to meet logistical constraints of whole blood and frozen/liquid plasma).ans les années

1941—Spray dried plasma produced for the Swedish Defense Department. 21 WWII Production 20-22 British produced >500,000 U lyophilized plasma during WWII. US produced >6,000,000 U lyophilized plasma during WWII. US/British distributed world-wide. Sweden produced approximately 17,000 U spray dried plasma for Sweden and Finland.

1945—Hepatitis 23 Hepatitis as a result of plasma transfusion recognized by the end of WWII. Believed that benefits outweighed the risk.

1945-1952—Hepatitis 24 Attempts at pathogen reduction and reducing pool size not successful. Several deaths in clinical studies of ultraviolet irradiated pooled plasma.


—Department of the Army (Circular 73) directed that, because of the risk of serum hepatitis, the higher cost, and the need to use it for the production of specific globulins, plasma would not be used “to support blood volume” unless dextran was not available. 

—Serum albumin replaced plasma as primary resuscitative product for US Forces in Korea. 

1968—National Research Council Committee on Plasma and Plasma Substitutes recommended that “the use of whole, pooled human plasma be discouraged and even discontinued unless a clear cut case can be made for its unique requirements.” 

The French Military Blood Institute produced dried plasma from 1949 to 1984, and provided over 40,000 units to French military forces during the Indochina War. In 1985, production was discontinued due to risk of HIV infection.

Acide tranexaminique systématique: La roue tournerait-elle ?

Acute Fibrinolysis Shutdown after Injury Occurs Frequently and Increases Mortality: A Multicenter Evaluation of 2,540 Severely Injured Patients

Moore HB et Al. J Am Coll Surg. 2016 Apr;222(4):347-55. 


La recommandation n°15 de la RFE Portant sur la réanimation du choc hémorragique stipule qu' il est recommandé d'administrer de l'acide tranexamique dès que possible chez les patients traumatisés à la dose de 1 g en bolus intraveineux en 10 min suivi de 1 g perfusé sur 8 h chez les patients traumatisés. Cette administration ne doit pas être initiée au delà de la 3e heure suivant la survenue d'un traumatisme avec choc hémorragique. Si l'étude CRASH-2 a montré que l'acide tranexamique réduisait significativement la mortalité. De nouvelles données disponibles depuis alimentent la discussion (1). Trois états du système de fibrinolyse peuvent être retrouvés: normal, hyperfibrinolyse, inhibition Les deux derniers sont associés à une surmortalité mais la fréquence des états d'inhibition de l'inhibition ne plaiderait pas pour une administration systématique mais ciblée d'exacyl. En qui nous concerne il faut à nouveau insister sur la précocité de l'administration d'exacyl dans l'heure chez les blessés sévères, pour lesquels le bénéfice en terme de mortalité est le plus grand (2). Une réflexion pour un emploi optimisé est en MARCHE (3, 4)



Fibrinolysis is a physiologic process that maintains microvascular patency by breaking down excessive fibrin clot. Hyperfibrinolysis is associated with a doubling of mortality. Fibrinolysis shutdown, an acute impairment of fibrinolysis, has been recognized as a risk factor for increased mortality. The purpose of this study was to assess the incidence and outcomes of fibrinolysis phenotypes in 2 urban trauma centers.


Injured patients included in the analysis were admitted between 2010 and 2013, were 18 years of age or older, and had an Injury Severity Score (ISS) > 15. Admission fibrinolysis phenotypes were determined by the clot lysis at 30 minutes (LY30): shutdown ≤ 0.8%, physiologic 0.9% to 2.9%, and hyperfibrinolysis ≥ 3%. Logistic regression was used to adjust for age, arrival blood pressure, ISS, mechanism, and facility.


There were 2,540 patients who met inclusion criteria. Median age was 39 years (interquartile range [IQR] 26 to 55 years) and median ISS was 25 (IQR 20 to 33), with a mortality rate of 21%. Fibrinolysis shutdown was the most common phenotype (46%) followed by physiologic (36%) and hyperfibrinolysis (18%). Hyperfibrinolysis was associated with the highest death rate (34%), followed by shutdown (22%), and physiologic (14%, p < 0.001). The risk of mortality remained increased for hyperfibrinolysis (odds ratio [OR] 3.3, 95% CI 2.4 to 4.6, p < 0.0001) and shutdown (OR 1.6, 95% CI 1.3 to 2.1, p = 0.0003) compared with physiologic when adjusting for age, ISS, mechanism, head injury, and blood pressure (area under the receiver operating characteristics curve 0.82, 95% CI 0.80 to 0.84).


Fibrinolysis shutdown is the most common phenotype on admission and is associated with increased mortality. These data provide additional evidence of distinct phenotypes of coagulation impairment and that individualized hemostatic therapy may be required.



| Tags : coagulopathie


The 2015 Remote Damage Control Resuscitation Symposium



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Succinylcholine et frigo: Non fondé ?

Froid et suxaméthonium : une recommandation non fondée

Dewachter P et AL. Ann. Fr. Med. Urgence DOI 10.1007/s13341-015-0600-1

Morceaux choisis:

L’Agence nationale de sécurité du médicament et des produits de santé (ANSM) a publié en 2012 une recommandation destinée aux médecins anesthésistes-réanimateurs et urgentistes décrivant les conditions d’utilisation du chlorure de suxaméthonium. .......Cette recommandation faisait suite à une enquête rétrospective de pharmacovigilance sur les réactions allergiques induites par les curares qui mettait en évidence une augmentation des notifications de réactions allergiques attribuées au suxaméthonium........Néanmoins, l’hypothèse émise par l’ANSM ne résiste pas à l’évaluation scientifique. En effet, aucune étude n’a démontré que le suxaméthonium conservé à température ambiante favorise la survenue d’une réaction allergique, ce qui avait déjà été souligné lors de la publication de cette recommandation..........................En revanche, depuis 20 ans, plusieurs équipes européennes et nord-américaines ont confirmé la stabilité des solutions de chlorure de suxaméthonium à température ambiante ou lors de variations extrêmes de température................... La succinylcholine (50 mg/mL) préservée dans l’ampoule est stable pendant deux mois à température ambiante (25°C) [5] alors que la solution à 20 mg/mL reste stable au moins sept jours après exposition à des variations extrêmes de température (de -6°C à +54°C).......................Par ailleurs, la solution de succinylcholine (20 mg/mL) conservée dans une seringue en plastique est stable trois mois à 25°C et deux mois à 40°C . Enfin, la stabilité de la succinylcholine stockée à bord d’ambulances, respectivement pendant sept mois [8] et un an , a été évaluée après exposition aux variations climatiques auxquelles ces équipes sont exposées. La succinylcholine (20 mg/mL) est stable pendant environ trois mois quand elle est soumise à des températures moyennes variant de -9°C à +32°C [8] alors que la solution à 100 mg/mL est stable pendant un peu plus d’un mois quand elle est exposée de -8°C à +36°C. D’autres études ont également confirmé la stabilité de la succinylcholine (10 mg/ml) dans une seringue en plastique pendant sept jours [9] et pendant au moins cinq mois, quand celle-ci est conservée dans l’ampoule (20 et 50 mg/ml) ..........Plus récemment, la stabilité de la succinylcholine à température ambiante (25°C) a été confirmée par l’ANSM pour qui les résultats obtenus sont « conformes aux spécifications à péremption décrites dans le dossier d’AMM................Ce rapport de conclure que « les données relatives à la qualité ne semblent donc pas être en mesure d’expliquer l’augmentation des réactions anaphylactiques sur la période étudiée............Le turn-over prévisible de l’utilisation du suxaméthonium stocké à température ambiante rend ainsi son utilisation possible par les équipes de Samu. En effet, l’éventuelle morbidité – voire mortalité – induite par cette recommandation ne peut être occultée. Nombreux sont les patients qui devant bénéficier d’une induction à séquence rapide, ont été intubés sans curare par les équipes qui ne disposaient pas d’un réfrigérateur à bord alors que l’appréciation de la balance risque/ bénéfice penche en faveur de l’utilisation du suxaméthonium dans cette situation clinique



Gammon DL, et al (2008) Alteration in prehospital drug concentration after thermal exposure. Am J Emerg Med 26:566–73.

Agence Nationale de Sécurité du Médicament et des Produits de Santé (2013) Enquête officielle de pharmacovigilance relative aux réactions anaphylactiques liées à l’utilisation des curares. 21 mai 2013. 

| Tags : intubation


Le graal plaquettaire hémostatique ?

Thrombosomes: a platelet-derived hemostatic agent for control of noncompressible hemorrhage

Fitzpatrick GM et Al. Transfusion. 2013 Jan;53 Suppl 1:100S-106S


Un thrombosome est en quelque sorte une plaquette lyophilisée dans laquelle l'eau est remplacée par un sucre particulier: le trehalose. Ré exposé à une atmosphère humide, il se réhydrate pour retrouver toutes ses propriétés. Cela ne semble pas être une simple théorie car il initierai une génération de thrombine permettant la formation d'un caillot de manière satisfaisante. Des thrombosmes, du fibrinogène et du PLyo, on peut espérer !


BACKGROUND: Uncontrolled hemorrhage is responsible for ~80% of the potentially survivable deaths in combat and over 40% of early mortality in the under 65 age group in the United States. Providing an easily used infusible hemostatic agent to first responders could significantly reduce these fatalities. We report on an infusible lyophilized platelet-derived hemostatic agent stabilized with trehalose and polysucrose prior to and during lyophilization.

STUDY DESIGN AND METHODS: Characterization included determining the particle population size range, surface marker expression GPIb, GPIIbIIIa, and Annexin V binding. Function was assessed by aggregation, thromboelastography, and thrombin generation. Pharmacokinetics, biodistribution, and immunogenicity established using Indium111 labeled Thrombosomes in healthy New Zealand white rabbits (NZWRs), efficacy in thrombocytopenic NZWR, and safety in NZWRs, canines, and nonhuman primates.

RESULTS: Thrombosomes retained GPIIbIIIa expression (98.71% 0.18 of the rehydrated particles), a reduced expression of GPIb (47.77% 6.65), and Annexin V binding (86.05% 2.65). Aggregation to all agonists except thrombin in buffer (78.15% 2.5) was <50%. Thrombin generation and thromboelastography results demonstrated a concentration gradient that was consistent from lot to lot. There were no observed adverse events in any safety study and blood loss was reduced by >80% in the thrombocytopenic ear bleed model.

CONCLUSION: Our in vitro characterization studies in conjunction with preclinical animal safety and efficacy studies demonstrated lot consistency in manufacturing, maintenance of hemostatic functions of Thrombosomes, safety at high dose concentrations, and the potential to provide an effective hemostatic agent at the site of injury.  


Cyanokit pour l'hémorragie massive ?

A prospective, randomized trial of intravenous hydroxocobalamin versus whole blood transfusion compared to no treatment for class III hemorrhagic shock resuscitation in a prehospital swine model

Bebarta VS et Al. Acad Emerg Med.2015 Mar;22(3):321-30


La prise en charge des hémorragies traumatiques en préhospitalier est basée sur la miseen oeuvre des moyens d'arrêts de ces dernières et l'initiation d'une stratégie raisonnée de remplissage vasculaire et de transfusion. L'apport équilibrée de CGR, de plasma,de fractions coagulantes et même de plaquettes fait partie de cette démarche de damage control resuscitation de même que l'apport d'acide tranexaminique pour s'opposer à une fibrinolyse précoce souvent présente. D'autres axes de recherches sont proposés. AInsi l'hydroxocobalamine, connue en tant qu'antidote de l'acide cynahydrique permettrait sur des cochons auxquels on aurait soustrait 20 ml/kg de sang de préserver la pression artérielle et la lactatémie de manière identique à celle obtenue par l'apport de sang total. 



The objective was to compare systolic blood pressure (sBP) over time in swine that have had 30% of their blood volume removed (Class III shock) and treated with intravenous (IV) whole blood or IV hydroxocobalamin, compared to nontreated control animals.


Thirty swine (45 to 55 kg) were anesthetized, intubated, and instrumented with continuous femoral and pulmonary artery pressure monitoring. Animals were hemorrhaged a total of 20 mL/kg over a 20-minute period. Five minutes after hemorrhage, animals were randomly assigned to receive 150 mg/kg IV hydroxocobalamin solubilized in 180 mL of saline, 500 mL of whole blood, or no treatment. Animals were monitored for 60 minutes thereafter. A sample size of 10 animals per group was determined based on a power of 80% and an alpha of 0.05 to detect an effect size of at least a 0.25 difference (>1 standard deviation) in mean sBP between groups. sBP values were analyzed using repeated-measures analysis of variance (RANOVA). Secondary outcome data were analyzed using repeated-measures multivariate analysis of variance (RMANOVA).


There were no significant differences between hemodynamic parameters of IV hydroxocobalamin versus whole blood versus control group at baseline (MANOVA; Wilks' lambda; p = 0.868) or immediately posthemorrhage (mean sBP = 47 mm Hg vs. 41 mm Hg vs. 37 mm Hg; mean arterial pressure = 39 mm Hg vs. 28 mm Hg vs. 34 mm Hg; mean serum lactate = 1.2 mmol/L vs. 1.4 mmol/L vs. 1.4 mmol/L; MANOVA; Wilks' lambda; p = 0.348). The outcome RANOVA model detected a significant difference by time between groups (p < 0.001). Specifically, 10 minutes after treatment, treated animals showed a significant increase in mean sBP compared to nontreated animals (mean sBP = 76.3 mm Hg vs. 85.7 mm Hg vs. 51.1 mm Hg; p < 0.001). RMANOVA modeling of the secondary data detected a significant difference in mean arterial pressure, heart rate, and serum lactate (p < 0.001). Similar to sBP, 10 minutes after treatment, treated animals showed a significant increase in mean arterial pressure compared to nontreated animals (mean arterial pressure = 67.7 mm Hg vs. 61.4 mm Hg vs. 40.5 mm Hg). By 10 minutes, mean heart rate was significantly slower in treated animals compared to nontreated animals (mean heart rate = 97.3 beats/min vs. 95.2 beats/min vs. 129.5 beats/min; p < 0.05). Serum lactate, an early predictor of shock, continued to rise in the control group, whereas it did not in treated animals. Thirty minutes after treatment, serum lactate values of treated animals were significantly lower compared to nontreated animals (p < 0.05). This trend continued throughout the 60-minute observation period such that 60-minute values for lactate were 1.4 mmol/L versus 1.1 mmol/L versus 3.8 mmol/L. IV hydroxocobalamin produced a statistically significant increase in systemic vascular resistance compared to control, but not whole blood, with a concomitant decrease in cardiac output.


Intravenous hydroxocobalamin was more effective than no treatment and as effective as whole blood transfusion, in reversing hypotension and inhibiting rises in serum lactate in this prehospital, controlled, Class III swine hemorrhage model.

| Tags : choc


1/1/1 ou 1/1/2 ?

Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial

Holcomb JB et All. JAMA Surg. 2013 Feb;148(2):127-36


La reconnaissance et la mise en place de la meilleure stratégie thérapeutique du choc hémorragique traumatique sont des enjeux fondamentaux qui se posent aux équipes de réanimation préhospitalières et hospitalières. L'application du concepts du damage control resuscitation (1) vise par la mise en place d'un stratégie raisonnée d'arrêt des hémorragies (2), d'un remplissage vasculaire mesuré (3) et d'une politique transfusionnelle spécifique (4). Parmi ces mesures, il apparaît important de garantir l'apport équilibré de plasma, de plaquettes et de CGR dans un ration  élevé 1/1/1 ou 1/1/2. Deux études se sont attachées à ce point: L'étude PROMMTT et l'étude PROPPR ici présentée. La première confirme le bénéfice d'une telle stratégie avec une moindre mortalité chez les patients bénéficiant de rapport élevé supérieur mais uniquement dans les 6 premières heures. L'étude PROPPR semble confirmer ces données avec une moindre mortalité précoce par hémorragie mais ne réussit pas à confirmer l'intérêt d'un ratio 1/1/1 par rapport à un ratio 1/1/2 sur la mortalité à long terme.



Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials.


To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio.


Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013.


Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local standard-of-care interventions (uncontrolled).


Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis, blood product volumes transfused, complications, incidence of surgical procedures, and functional status.


No significant differences were detected in mortality at 24 hours (12.7% in 1:1:1 group vs 17.0% in 1:1:2 group; difference, -4.2% [95% CI, -9.6% to 1.1%]; P = .12) or at 30 days (22.4% vs 26.1%, respectively; difference, -3.7% [95% CI, -10.2% to 2.7%]; P = .26). Exsanguination, which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6% in 1:1:2 group; difference, -5.4% [95% CI, -10.4% to -0.5%]; P = .03). More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group (86% vs 78%, respectively; P = .006). Despite the 1:1:1 group receiving more plasma (median of 7 U vs 5 U, P < .001) and platelets (12 U vs 6 U, P < .001) and similar amounts of red blood cells (9 U) over the first 24 hours, no differences between the 2 groups were found for the 23 prespecified complications, including acute respiratory distress syndrome, multiple organ failure, venous thromboembolism, sepsis, and transfusion-related complications.


Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups.

| Tags : hémorragie


Kétamine: Prudence quand même

Is ketamine ready to be used clinically for the treatment of depression ?

Colleen L. Med J Aust 2015 Dec 14;203(11):425.

A single dose of ketamine produces rapid antidepressant effects, but attaining lasting remission remains a challenge

Il existe un engouement très important pour l'emploi de kétamine pour la prise en charge de la dépression (1,2). Pour autant il ne faut pas oublier les effets secondaires de cette dernière lorsqu'elle est administrée de manière chronique. De nombreuses données issues de l'emploi récréatif de la kétamine mettent en avant de nombreux effets secondaires comme  l'hépatotoxicité, les dysfonctions vésicales et, possiblement des troubles cognitifs. Même si aucun effets de ce type n'est retrouvé lors d'emploi encadré médicalement, la prudence reste de mise.

| Tags : kétamine; ptsd


Coagulopathie: Du fibrinogène avant tout

Trauma-induced coagulopathy: impact of the early coagulation support protocol on blood product consumption, mortality and costs

Nardi G et al. Critical Care (2015) 19:83


Le damage control resuscitation fait largement appel à l'apport de plasma, concentrés de globules rouges et de plaquettes dans un rapport de 1/1/1 (1). Malgré la relative correction de la coagulopathie la survie à long terme ne semble pas être améliorée (2). Aussi certains proposent d'avoir plutôt recours à l'administration précoce de fibrinogène plutôt que l'administration de plasma. Le travail suivant qui propose l'apport précoce de  2g de fibrinogène est en faveur d'une telle démarche.



Hemorrhage is the principal cause of death in the first few hours following severe injury. Coagulopathy is a frequent complication of critical bleeding. A network of Italian trauma centers recently developed a protocol to prevent and treat trauma-induced coagulopathy. A pre-post cohort multicenter study was conducted to assess the impact of the early coagulation support (ECS) protocol on blood products consumption,mortality and treatment costs.


We prospectively collected data from all severely injured patients (Injury Severity Score (ISS) >15) admitted to two trauma centers in 2013 and compared these findings with the data for 2011. Patients transfused with at least 3 units of packed red blood cells (PRBCs) within 24 hours of an accident were included in the study. In 2011, patients with significant hemorrhaging were treated with early administration of plasma with the aim of achieving a high (≥1:2) plasma-to-PRBC ratio. In 2013, the ECS protocol was the treatment strategy. Outcome data, blood product consumption and treatment costs were compared between the two periods.


The two groups were well matched for demographics, injury severity (ISS: 32.9 in 2011 versus 33.6 in 2013) and clinical and laboratory data on admission. In 2013, a 40% overall reduction in PRBCs was observed, together with a 65% reduction in plasma and a 52% reduction in platelets. Patients in the ECS group received fewer blood products: 6.51 units of PRBCs versus 8.14 units. Plasma transfusions decreased from 8.98 units to 4.21 units (P <0.05), and platelets fell from 4.14 units to 2.53 units (P <0.05). Mortality in 2013 was 13.5% versus 20% in 2011 (13 versus 26 hospital deaths, respectively) (nonsignificant). When costs for blood components, factors and point-of-care tests were compared, a €76,340 saving in 2013 versus 2011 (23%) was recorded.



The introduction of the ECS protocol in two Italian trauma centers was associated with a marked reduction in blood product consumption, reaching statistical significance for plasma and platelets, and with a non-significant trend toward a reduction in early and 28-daymortality. The overall costs for transfusion and coagulation support (including point-of-care tests) decreased by 23% between 2011 and 2013.

| Tags : coagulopathie


Kétamine pour le PTSD: Oui!

Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder. A Randomized Clinical Trial

Feder A. et Al. JAMA Psychiatry. 2014 Jun;71(6):681-8. doi: 10.1001/jamapsychiatry.2014.62


Importance  Few pharmacotherapies have demonstrated sufficient efficacy in the treatment of posttraumatic stress disorder (PTSD), a chronic and disabling condition.

Objective  To test the efficacy and safety of a single intravenous subanesthetic dose of ketamine for the treatment of PTSD and associated depressive symptoms in patients with chronic PTSD.

Design, Setting, and Participants  Proof-of-concept, randomized, double-blind, crossover trial comparing ketamine with an active placebo control, midazolam, conducted at a single site (Icahn School of Medicine at Mount Sinai, New York, New York). Forty-one patients with chronic PTSD related to a range of trauma exposures were recruited via advertisements.

Interventions  Intravenous infusion of ketamine hydrochloride (0.5 mg/kg) and midazolam (0.045 mg/kg).

Main Outcomes and Measures  The primary outcome measure was change in PTSD symptom severity, measured using the Impact of Event Scale–Revised. Secondary outcome measures included the Montgomery-Asberg Depression Rating Scale, the Clinical Global Impression–Severity and –Improvement scales, and adverse effect measures, including the Clinician-Administered Dissociative States Scale, the Brief Psychiatric Rating Scale, and the Young Mania Rating Scale.

Results  Ketamine infusion was associated with significant and rapid reduction in PTSD symptom severity, compared with midazolam, when assessed 24 hours after infusion (mean difference in Impact of Event Scale–Revised score, 12.7 [95% CI, 2.5-22.8]; P = .02). Greater reduction of PTSD symptoms following treatment with ketamine was evident in both crossover and first-period analyses, and remained significant after adjusting for baseline and 24-hour depressive symptom severity. Ketamine was also associated with reduction in comorbid depressive symptoms and with improvement in overall clinical presentation. Ketamine was generally well tolerated without clinically significant persistent dissociative symptoms.



Conclusions and Relevance  This study provides the first evidence for rapid reduction in symptom severity following ketamine infusion in patients with chronic PTSD. If replicated, these findings may lead to novel approaches to the pharmacologic treatment of patients with this disabling condition.

| Tags : ptsd


Et l'albumine ?

Is limited prehospital resuscitation with plasma more beneficial than using a synthetic colloid? An experimental study in rabbits with parenchymal bleeding

Kheirabadi BS et Al. J Trauma Acute Care Surg. 2015;78: 752-759


Il existe de grands débats sur la manière optimale d'assurer le remplissage vasculaire des blessés de guerre. Pour certains le fluide de référence est un hydroxyéthylamidon, pour d'autres un cristalloïde isotonique et en ce qui nous concerne les deux avec la mise en avant du sérum salé hypertonique premier suivi d'HEA. Actuellement il existe une tendance à promouvoir une autre stratégie faisant appel pour les blessés les plus graves au plasma voire la transfusion de sang frais. L'étude proposée avait pour objectif de confirmer l'intérêt d'une démarche "plasma premier". Une des surprises a été de constater que ce n'est pas cette dernière qui permettait d'obtenir le meilleur taux de survie mais l'emploi d'albumine, et ce de loin. Ces données expérimentales certes très partielles permettent aux auteurs (?)  de rediscuter les conclusions de travaux anciens notamment de l'étude SAFE (1,2). Les solutés d'albumine utilisés par cette dernière ont une osmolarité de 260 mosm/kg (versus 305 mosm/kg pour le sérum salé). Les effets délétères notamment chez le traumatisé crânien pourraient être dus non pas à  l'extravasation d'albumine dans le parenchyme cérébral lésé mais à l'hypoosmolarité de l'albumex 4%, ces deux mécanismes concourrant à la plus grande fréquence d'HTIC dans le groupe albumine (3).  A méditer



Reports of survival benefits of early transfusion of plasma with red blood cells (1:1 ratio) in trauma patients suggest that plasma may be a better fluid to replace Hextend for battlefield resuscitation. We studied possible advantages of prehospital resuscitation with plasma compared with Hextend or albumin in a model of uncontrolled hemorrhage.


Male New Zealand white rabbits (3.3 T 0.1 kg) were anesthetized, instrumented, and subjected to a splenic injury with uncontrolled bleeding. Ten minutes after injury (mean arterial pressure [MAP] G 40 mm Hg), the rabbits received small and equal volumes (15 mL/kg) of rabbit plasma (n = 10), Hextend (n = 10), or 5% human albumin (n = 9) or no fluid. Fluids were administered in two bolus injections (20 minutes apart) and targeted to aMAP of 65 mm Hg. Animals were monitored for 2.5 hours or until death, and their blood losses were measured. Arterial blood samples were collected at different times and analyzed for ABG, CBC, and coagulation tests.


There were no differences in baseline measures among groups. Splenic injury caused similar hemorrhages (9.1 T 0.4 mL/kg at 10 minutes) and decreased MAP in all subjects. Subsequent resuscitation initiated additional bleeding. At 60 minutes after injury (20 minutes after resuscitation), longer activated partial thromboplastin time and lower fibrinogen concentrations were apparent compared with baseline values with differences among groups. Thrombelastography analysis indicated faster and stronger clot formation with plasma and albumin resuscitation than with Hextend use. Shock indices were increased in all groups, but smaller changes were measured in the albumin group. Total blood loss did not differ among resuscitated rabbits but was higher (p G 0.05) than among nonresuscitated animals. Survival rates were 11% (untreated), 40% (Hextend and plasma), and 89% (albumin, p G 0.05).

Albuminie COT.jpg


Resuscitation with plasma or albumin better preserved coagulation function than did Hextend. However, despite these improvements, plasma resuscitation did not reduce blood loss or improve survival, while albumin administration seemed beneficial

Lent/régulier: Mieux pour le crâne ?

Resuscitation speed affects brain injury in a large animal model of traumatic brain injury and shock

Sillesen M et Al. Scand J Trauma Resusc Emerg Med. 2014 Aug 14;22:46


En matière de remplissage vasculaire,  on s'intéresse souvent à la nature des solutés et aux quantités perfusées. On s'intéresse moins aux vitesses de perfusion. Pourtant cette dernière a son importance. Le travail présenté est intéressant car il rapport qu'outre la nature du soluté importante mais aussi sa vitesse d'administration. Ainsi il semblerait que dans un modèle expérimental de traumatisme crânien l'emploi de solutés cristalloïdes de sérum salé isotonique soit responsable d'une augmentation de l'oedeme cérébal et du volume des lésions intracraniennes quel que soit le régime d'administration. Ce travail retrouve par ailleurs l'intérêt sur la maîtrise de l'oedeème cérébral  de l'apport de fraction coagulantes de manière procédurée par rapport au bolus. Si l'on replace ce document dans le contexte d'isolement et de maintien en survie de nos blessés notamment cranio-cérébraux en état de choc, cela implique une formation spécifique des équipes qui devront par ailleurs pouvoir disposer d'équipements adaptés comme celui_ci (1)



Optimal fluid resuscitation strategy following combined traumatic brain injury (TBI) and hemorrhagic shock (HS) remain controversial and the effect of resuscitation infusion speed on outcome is not well known. We have previously reported that bolus infusion of fresh frozen plasma (FFP) protects the brain compared with bolus infusion of 0.9% normal saline (NS). We now hypothesize reducing resuscitationinfusion speed through a stepwise infusion speed increment protocol using either FFP or NS would provide neuroprotection compared with a highspeed resuscitation protocol.


23 Yorkshire swine underwent a protocol of computer controlled TBI and 40% hemorrhage. Animals were left in shock (mean arterial pressure of 35 mmHg) for two hours prior to resuscitation with bolus FFP (n = 5, 50 ml/min) or stepwise infusion speed increment FFP (n = 6), bolus NS (n = 5, 165 ml/min) or stepwise infusion speed increment NS (n = 7). Hemodynamic variables over a 6-hour observation phase were recorded. Following euthanasia, brains were harvested and lesion size as well as brain swelling was measured.


Bolus FFP resuscitation resulted in greater brain swelling (22.36 ± 1.03% vs. 15.58 ± 2.52%, p = 0.04), but similar lesion size compared with stepwise resuscitation. This was associated with a lower cardiac output (CO: 4.81 ± 1.50 l/min vs. 5.45 ± 1.14 l/min, p = 0.03). In the NS groups, bolus infusion resulted in both increased brain swelling (37.24 ± 1.63% vs. 26.74 ± 1.33%, p = 0.05) as well as lesion size (3285.44 ± 130.81 mm(3) vs. 2509.41 ± 297.44 mm3, p = 0.04). This was also associated with decreased cardiac output (NS: 4.37 ± 0.12 l/min vs. 6.35 ± 0.10 l/min, p < 0.01).


In this clinically relevant model of combined TBI and HS, stepwise resuscitation protected the brain compared with bolusresuscitation.



| Tags : tbi, remplissage


Dépakine chez le blessé cranien en choc ?

Treatment with a histone deacetylase inhibitor, valproic acid, is associated with increased platelet activation in alarge animal model of traumatic brain injury and hemorrhagic shock

Dekker SE et Al. J Surg Res. 2014 Jul;190(1):312-8



Le concept du damaged control resuscitation fait appel en partie à de nouvelles modalités transfusionnelles et d'emploi de fractions coagulantes. D'autres approches sont possibles comme celles visant à restuarer la fonction plaquettaire. C'est ce que permettrait l'adminsitration de médicaments appartenant à la classe des inhibiteurs des histone deacetylase et dont les effets neuroprotecteurs pourraient ainsi être mis à profit.  Le document proposé semble conforter cette approche.

Documents reliés: 1, 2, 3



We have previously shown that resuscitation with fresh frozen plasma (FFP) in a large animal model of traumatic brain injury (TBI) and hemorrhagic shock (HS) decreases the size of the brain lesion, and that addition of a histone deacetylase inhibitor, valproic acid (VPA), provides synergistic benefits. In this study, we hypothesized that VPA administration would be associated with a conservation of platelet function as measured by increased platelet activation after resuscitation.


Ten swine (42-50 kg) were subjected to TBI and HS (40% blood loss). Animals were left in shock for 2 h before resuscitation with either FFP or FFP+VPA (300 mg/kg). Serum levels of platelet activation markers transforming growth factor beta, CD40 L, P-selectin, and platelet endothelial cell adhesion molecule (PECAM) 1 were measured at baseline, postresuscitation, and after a 6-h observation period. Platelet activation markers were also measured in the brain whole cell lysates and immunohistochemistry.


Circulating P-selectin levels were significantly higher in the FFP+VPA group compared with the FFP alone group (70.85±4.70 versus 48.44±7.28 ng/mL; P<0.01). Likewise, immunohistochemistry data showed elevated P-selectin in the VPA treatment group (22.30±10.39% versus 8.125±3.94%, P<0.01). Serum sCD40L levels were also higher in the FFP+VPA group (3.21±0.124 versus 2.38±0.124 ng/mL; P<0.01), as was brainsCD40L levels (1.41±0.15 versus 1.22±0.12 ng/mL; P=0.05). Circulating transforming growth factor beta levels were elevated in the FFP+VPA group, but this did not reach statistical significance (11.20±1.46 versus 8.09±1.41 ng/mL; P=0.17). Brain platelet endothelial cell adhesion molecule 1 levels were significantly lower in the FFP+VPA group compared with the FFP group (5.22±2.00 pg/mL versus 7.99±1.13 pg/mL; P=0.03).


In this clinically relevant large animal model of combined TBI+HS, the addition of VPA to FFP resuscitation results in an early upregulation of platelet activation in the circulation and the brain. The previously observed neuroprotective effects of VPA may be due to a conservation of platelet function as measured by a higher platelet activation response after resuscitation.

| Tags : tbi, coagulopathie


Mg++: Médicament de la coagulopathie ?

Both acute delivery of and storage with magnesium sulfate promote cold-stored platelet aggregation and coagulation function

Meledeo MA et Al. J Trauma Acute Care Surg. 2015 Oct;79(4 Suppl 2):S139-45


Il y a quelque mois était publié un travail de recherche portant sur  l'intérêt de l'administration de Adénosine/Lidocaïne/Mg2+ ALM (1, 2, 3). Une hypothèse faite par les auteurs  serait que L'ALM agirait comme un antifibrinolytique en activant la voie du thrombin-activatable fibrinolysis inhibitor (TAFI) plutôt que celle de la protéine C. Cette action passerait par un mécanisme antiinflammatoire, une modification de la polarité endothéliale et une action sur la fonction plaquettaire. Le travail expérimental dont l'abstract est présenté met en avant l'intérêt de l'adminsitration de magnésium pour la restauration de la fonction plaquettaire après conservation de palquettes d'aphérèse au delà de 5 jours. U



The platelet storage lesion causes loss of function and viability over time. A new paradigm for platelet storage is desired to enable safer, more effective transfusions while reducing waste. We hypothesized that repletion of Mg, which is chelated by citrate anticoagulant, could reduce platelet storage lesion severity when given in conjunction with storage at a refrigerated temperature.


Apheresis platelet units were collected from healthy donors and stored at 22°C or 4°C. On Days 0, 2, 4, and 8, samples were collected for analyses of receptor-mediated aggregation, coagulation, adhesion to collagen under flow, and viability. In the first series, samples were given anacute dose of MgSO4 before testing; in the second series, storage bags were supplemented with 0-, 3-, or 6-mM MgSO4.


Acutely delivered MgSO4 induced a more rapid coagulation time in apheresis platelets, further enhanced by storage at 4°C. Plateletadhesion to a collagen surface while exposed to arterial shear rates (920 s) was enhanced by MgSO4 supplementation-acute MgSO4 had a large effect on adhesion of fresh platelets, which diminished more rapidly in 22°C samples, while storage with MgSO4 showed significant benefits even out to Day 4 at both temperatures. Although 4°C storage improves the longevity of platelet aggregation responses to agonists, MgSO4 supplementation did not change those responses.


Acute MgSO4 reduces clot time likely through the transient increase of free Ca. Limited differences between platelet function inacute delivery of and storage with MgSO4 diminish the possibility that Mg-induced metabolic inhibition of platelets synergizes with 4°C storage. Regardless, magnesium supplementation to platelets is an exciting possibility in transfusion because the adhesion response of 22°C-stored platelets on Day 4 is significantly enhanced when stored with 6-mM MgSO4

| Tags : coagulopathie


Quelle place pour les facteurs de la coagulation ?


Clic sur l'image pour suivre la conférence


Célo: Au frigo, c'est vraiment mieux

Impact of Temperature Exposure on Stability of Drugs in a Real-World Out-of-Hospital Setting

De Winter S. et Al. Ann Emerg Med. 2013 Oct;62(4):380-387


Le maintien au frais des médicaments de l'urgence est réglementé. Malheureusement le maintien à +4c de plusieurs médicaments de l'urgence n'est pas toujours possible. Ce travail plutôt récent confirme la sensibilité des ces derniers aux conditions de stockage. Il faut donc dès lors envisager le renouvellement très régulier de ces produits quand ils sont stockés de manière non conforme aux spécifications des fabriquants et quand les conditions sont extrêmes avoir recours à des solutions de transports comme celui-ci


Study objective:

The aim of this study is to determine the content of 5 important emergency medical services

(EMS) drugs after being stored at the recommended refrigerated temperature, room temperature, or in an emergency physician transport vehicle operating under real-world working conditions.


Adrenaline hydrochloride, cisatracurium besylate, lorazepam, methylergonovine maleate, and succinylcholine chloride were stored for 1 year under the 3 conditions. For each storage condition, samples of the drugs were taken after 1, 2, 3, and 4 weeks and after 2, 4, 6, 8, 10, and 12 months. For adrenaline hydrochloride, however, the samples were taken after 1, 2, 4, 6, 8, 10, and 12 months. The samples were analyzed with a validated high-performance liquid chromatography assay. A drug was considered stable if its content was above 90%.


Adrenaline hydrochloride and methylergonovine maleate remained stable for 1 year at room temperature and in the emergency physician transport vehicle. At room temperature and in the emergency physician transport vehicle, lorazepam became unstable within 4 weeks. Succinylcholine chloride was stable for 2 months at room temperature and for 1 month in the emergency physician transport vehicle. Cisatracurium besylate became unstable within 4 months at room temperature. However, it remained stable for 4 months in the emergency physician transport vehicle.


When stored at room temperature or in the emergency physician transport vehicle, lorazepam became unstable within weeks, whereas succinylcholine chloride and cisatracurium besylate became unstable within months. Adrenaline hydrochloride and methylergonovine maleate remained stable for several months, even under room temperature and emergency physician transport vehicle conditions. Thus, real-world EMS working conditions pose challenges for maintaining optimal efficacy of these important EMS drugs.