E. Kirkman

A proactive approach to the coagulopathy of trauma: the rationale and guidelines for treatment.

Prevalence of coagulopathy in trauma According to the British Committee for Standards in Haematology and the American College of Pathologists, prolongation of the activated partial thromboplastin time (APTT) and prothrombin time (PT) to 1.5 times the mean normal value indicates a coagulopathy requiring blood product replacement [1-3]. A number of studies have indicated that coagulopathy is common after severe trauma and that it results from a number of causes including metabolic acidosis, hypothermia, dilution of coagulation factors by resuscitation fluids and consumption of coagulation factors [4-10]. Coagulopathy is especially associated with some forms of injury, e.g. brain injury, because of the release of tissue thromboplastins from damaged brain matter [11; 12]. A UK civilian study by Brohi et al [13], using the definitions given above, clearly demonstrated that major trauma patients (Injury Severity Score, ISS >15) can present at hospital with a coagulopathy: 24% of 1088 trauma patients (median ISS 20) analyzed on arrival at the Emergency Department (ED) were coagulopathic. The majority (75%) of patients had suffered blunt trauma and the median time from injury to hospital was 73 minutes; this is compared to 7.6% blunt force (motor vehicle crash, fall, assault, crush) in 876 patients on the UK military Joint Theatre Trauma Registry (01 April 2006 to 30 September 2007, OP HERRICK and OP TELIC only), and a median injury to ED handover time of 97 minutes for UK military priority 1 casualties [14]. The incidence of coagulopathy increased with severity of injury (assessed by ISS), independent of the volume of pre-hospital resuscitation fluid (reliably recorded by a physician). The authors comment that the patients had received minimal pre-hospital fluid resuscitation (median values of 500 ml crystalloid or 1000 ml colloid) and that the development of coagulopathy in these patients was unrelated to the volume or type of intravenous fluid given. A second survey [15] based on 8724 severely injured patients (96% blunt injuries) from the German Trauma Registry Database confirms the presence of coagulopathy in 34% of all severely injured patients arriving in the Emergency Department. This study used a similar definition of coagulopathy to that employed by Brohi et al [13] and identified a similar time to hospital. The presence of coagulopathy was positively associated with the volume of pre-hospital fluid, injury severity and delay between injury and arrival at hospital [15]. Even in patients with minimal pre-hospital resuscitation, coagulopathy was present in 10% of cases [15]. Despite the limited statistical analysis in this study it supports the conclusion that coagulopathy is present in a significant proportion of severely-injured patients by the time they arrive at hospital. Early coagulopathy was also reported by MacLeod et al [16] in a retrospective analysis of 7638 trauma patients admitted to a Level 1 Trauma Centre between Jan 1995 and Dec 2000, although as a group these patients were less severely injured (median ISS 9) than those described by Brohi et al [13]. Additionally, MacLeod et al [16] were unable to account for medication that might have contributed to the coagulopathy, for example warfarin treatment or pre-hospital fluid administration. A number of other smaller studies [17; 18] and anecdotal comments [19]] have also documented coagulopathy in trauma patients on arrival at hospital. Furthermore, early coagulopathy is associated with increased morbidity and mortality [13; 15; 16; 18]. Although it is always a concern that studies with negative conclusions are less likely to be published than those with a positive conclusion, the collective evidence strongly suggests that a proportion of severely injured patients are already coagulopathic by the time they arrive in the Emergency Department and the remainder are at high risk of rapidly developing a coagulopathy. Clearly the true incidence of coagulopathy will depend on the definition adopted. There is evidence that bleeding time and thromboelastographic measurements are better indicators of dilutional and hypothermia induced coagulopathy [20]. Using this methodology the true incidence of coagulopathy associated with major trauma may well be significantly higher than reported.

Preventable deaths after injury: why are the traditional 'vital' signs poor indicators of blood loss?

The concept of preventable deaths1 has stimulated debate about the identification and best ways oi avoiding such undesirable outcomes. A constant feature of the debate has been the finding of unsuspected and/or underestimated haemorrhage as a major contributor to such deaths.2Why is the presence of occult bleeding so difficult to diagnose? In many undergraduate text books of physiology it can be read that an increase in heart rate (HR) is almost invariably an accompaniment of severe haemorrhage and a tachycardia is one of the most valuable indicators of concealed bleeding. The widely acclaimed Advance Trauma Life Support (ATLS) courses emphasize the importance of progressive increases in HR and decreases in arterial blood pressure as the hallmarks of hypovolaemic shock.5 Also systolic blood pressure is included in the Revised Trauma Score (RTS),6 the basis of the physiological assessment of the injured patient incorporated into TRISS methodology.7 The continuing problem with the diagnosis of haemorrhage should lead to a questioning of the relationship between pulse rate and blood pressure and the magnitude of blood loss. Even during the First World War it was noted that traumatic shock was not always accompanied by a tachycardia8 and that blood pressure is of assistance in judging blood volume only when it is below a certain point, for there may be a considerable reduction of blood volume without any appreciable drop in the pressure.9 When blood pressure was recorded at very short intervals after the patient had been wounded two groups could be identified; hypertensive and

The Development of an Experimental Model of Contaminated Muscle Injury in Rabbits

Extent of tissue trauma and contamination determine outcome in extremity injury. In contrast to fracture, osteomyelitis, and closed muscle injury studies, there are limited small animal models of extremity muscle trauma and contamination. To address this we developed a model of contaminated muscle injury in rabbits. Twenty-eight anesthetized New Zealand White rabbits underwent open controlled injury of the flexor carpi ulnaris (FCU). Twenty-two animals had subsequent contamination of the injured muscle with Staphylococcus aureus. All animals were sacrificed at 48 hours and the level of muscle injury and contamination determined by quantitative histological and microbiological analysis. A 1-kg mass dropped 300 mm onto the mobilized FCU resulted in localized necrosis of the muscle belly. Delivery of a mean challenge of 3.71 × 106 cfu/100 µL S aureus by droplet spread onto the injured muscle produced a muscle contamination of 8.79 × 106 cfu/g at 48 hours. Ipsilateral axillary lymph nodes demonstrated clinically significant activation. All animals had normal body temperature and hematological parameters throughout and blood and urinalysis culture at autopsy were negative for organisms. This model allows reproducible muscle injury and contamination with the organism ubiquitous to extremity wound infection at a level sufficient to allow quantitative assessment of subsequent wound care interventions without incurring systemic involvement.

Microcirculatory perfusion shows wide inter-individual variation and is important in determining shock reversal during resuscitation in a porcine experimental model of complex traumatic hemorrhagic shock

BackgroundTraumatic hemorrhagic shock (THS) is a leading cause of preventable death following severe traumatic injury. Resuscitation of THS is typically targeted at blood pressure, but the effects of such a strategy on systemic and microcirculatory flow remains unclear. Failure to restore microcirculatory perfusion has been shown to lead to poor outcomes in experimental and clinical studies. Systemic and microcirculatory variables were examined in a porcine model of complex THS, in order to investigate inter-individual variations in flow and the effect of microcirculatory perfusion on reversal of the shock state.MethodsBaseline standard microcirculatory variables were obtained for 22 large white pigs using sublingual incident dark field (IDF) video-microscopy. All animals were subjected to a standardised hind-limb injury followed by a controlled haemorrhage of approximately 35xa0% of blood volume (shock phase). This was followed by 60xa0min of fluid resuscitation with either 0.9xa0% saline or component blood products and a target SBP of 80xa0mmHg (early resuscitation phase). All animals were then given blood products to a target SBP of 110xa0mmHg for 120xa0min (mid-resuscitation phase), and a further 100xa0min (late resuscitation phase). IDF readings were obtained at the midpoint of each of these phases. Cardiac output was measured using a pulmonary artery catheter. Animals were divided into above average (A) and below average (B) perfused vessel density (PVD) groups based on the lowest recorded PVD measurement taken during the shock and early resuscitation phases.ResultsThere was minimal inter-individual variation in blood pressure but wide variation of both systemic and microcirculatory flow variables during resuscitation. During shock and early resuscitation, group A (nu2009=u200910) had a mean PVD of 10.5 (SDu2009±u20092.5) mm/mm2 and group B (nu2009=u200912) 5.5 (SDu2009±u20094.1) mm/mm2. During the later resuscitation phases, group A maintained a significantly higher PVD than group B. Group A initially had a higher cardiac output, but the difference between the groups narrowed as resuscitation progressed. At the end of resuscitation, group A had significantly lower plasma lactate, higher lactate clearance, lower standard base deficit and smaller mixed venous-arterial CO2 gradient. There was no significant difference in blood pressure between the two groups at any stage.ConclusionThere was a wide variation in both macro- and microcirculatory flow variables in this pressure-targeted experimental model of THS resuscitation. Early changes in microvascular perfusion appear to be key determinants in the reversal of the shock state during resuscitation. Microcirculatory flow parameters may be more reliable markers of physiological insult than pressure-based parameters and are potential targets for goal-directed resuscitation.

UK defence medical services guidance for the use of recombinant factor VIIa (rFVIIa) in the deployed military setting.

Use of recombinant Factor VIIa (rFVIIa) for trauma is currently an ‘off label’ use. There are reports of rFVIIa contributing to the successful outcome of military trauma patients. This paper sets out the current position of the UK Defence Medical Services with regard to using rFVIIa in military trauma.

9 Closed chest compressions reduce survival in a model of haemorrhage-induced traumatic cardiac arrest

Background Closed chest compressions (CCC) are a key component of resuscitation from medical causes of cardiac arrest, but when haemorrhage, the leading cause of preventable battlefield deaths, is the likely cause there is little evidence to support their use. Resuscitation protocols for traumatic cardiac arrest (TCA) highlight the importance of addressing reversible causes, such as the administration of fluids to treat hypovolaemia. This study evaluated whether CCC were beneficial following haemorrhage-induced TCA and additionally whether resuscitation with blood improved physiological outcomes. Methods The study was conducted with the authority of UK Animals (Scientific Procedures) Act 1986 using 39 terminally anesthetised Large White pigs (35u2009kg, 29–40u2009kg) instrumented for invasive physiological monitoring. Following instrumentation and baseline measurements, animals underwent tissue injury (captive bolt to the right thigh) and controlled haemorrhage (30% blood volume). Mean arterial blood pressure (MAP) was maintained at 45u2009mmHg for 60u2009min, followed by a further controlled haemorrhage to a MAP of 20u2009mmHg. As arterial blood and pulse pressures spontaneously deteriorated further over a 5u2009min period, the randomised resuscitation protocol was initiated as follows: CCC (n=6); IV 0.9% saline (Sal n=8); IV autologous whole blood (WB n=8); IV saline +chest compressions (Sal +CCC n=9); and IV whole blood +chest compressions (WB +CCC n=8). 3×10u2009ml/kg fluid boluses were administered using the Belmont Rapid Infuser (200u2009ml/min). CCC were performed using the LUCAS II Chest Compression System. Outcome was attainment of return of spontaneous circulation (ROSC) 15u2009min post-resuscitation. ROSC was categorised by MAP (MAP ≥50 mmHg=ROSC; MAP >20 <50 mmHg=partial ROSC; MAP ≤20 mmHg=dead). Figure 1 Results Outcome was significantly worse in the group that received CCC compared to WB and Sal groups (6/6 dead versus 0/8 and 0/8 respectively) (p<0.0001). A significantly higher number of animals attained ROSC in WB compared to Sal group (6/8 versus 0/8 ROSC and 2/8 versus 8/8 partial ROSC respectively) (p=0.0069). There were some none significant differences between WB and WB+CCC groups (6/8 versus 5/8 ROSC, 2/8 versus 1/8 partial ROSC and 0/8 versus 2/8 dead respectively) (p=0.4411). No animals attained ROSC in the Sal and Sal+CCC groups however significantly more animals died in the Sal+CCCu2009group (0/8 versus 0/9 ROSC, 8/8 versus 2/9 partial ROSC and 0/8 versus 7/9 dead respectively) (p=0.0023). Conclusions CCC were associated with increased mortality compared to intravenous fluid resuscitation. Resuscitation with whole blood demonstrated the greatest physiological benefit as demonstrated by highest numbers of animals achieving ROSC.

Blood salvage technology after combat injury

Transfusion support is a critical component of modern combat casualty care. Experiences in the recent wars in Iraq and Afghanistan have seen the refinement of the concept of damage control resuscitation[1][1] with the introduction of multiple, innovative developments such as platelet apheresis in

An evaluation of the normal range of StO2 measurements at rest and following a mixed exercise protocol

Background Assessment of local tissue oxygenation (StO2) using near infrared spectroscopy is an emerging technique in medical practice with applications in trauma/sepsis management, diagnosis of acute compartment syndrome and assessment of tissue viability. Despite this, there have been little published data on the range of StO2 values in normal subjects. Methods StO2 measurements were recorded in 105 infantry soldiers using an INVOS System Monitor (Somanetics) from both deltoids, the anterior compartment of the leg and the frontal lobe of the brain. Measurements were taken at rest and following completion of a mixed exercise protocol, consisting of overarm pull-ups, sit-ups and a 3-mile run. Results StO2 values at rest were found to have a wide normal range with a skew left distribution. Mean StO2 was similar between the deltoids (left deltoid 80%, right deltoid 79%), but significantly different between other anatomical sites (leg 68%, brain 73%). However, all sites demonstrated a similar lower range cut-off at approximately 40%. Following exercise, there was a significant increase in StO2 values at all sites (left deltoid by 3.1±2.0%, right deltoid by 2.6±2.3%, leg by 8.0±2.3% and brain by 8.6±1.9%), which persisted for at least 10u2005min. Conclusions There were statistically significant differences in mean StO2 values recorded at different anatomical sites, although the reference ranges were wide and substantially overlapped. StO2 increased at all sites after exercise with the effect persisting for at least 10u2005min. The interaction between exercise and pathological phenomena remains unknown and is an area for further study.

The cytocam video microscope. a new method for visualising the microcirculation using incident dark field (IDF) technology

Imaging the microcirculation provides valuable information regarding perfusion in a range of shock states. We report a new microcirculatory assessment device, the Braedius Cytocam, an Incident Dark Field (IDF) video microscope, and compare it with the most commonly used precursor device, the Microvision Microscan which utilises side stream dark field (SDF) imaging.

Guidelines for using animal models in blast injury research

Blast injury is a very complex phenomenon and frequently results in multiple injuries. One method to investigate the consequences of blast injuries is with the use of living systems (animal models). The use of animals allows the examination and evaluation of injury mechanisms in a more controlled manner, allowing variables such as primary or secondary blast injury for example, to be isolated and manipulated as required. To ensure a degree of standardisation across the blast research community a set of guidelines which helps researchers navigate challenges of modelling blast injuries in animals is required. This paper describes the guidelines for Using Animal Models in Blast Injury Research developed by the NATO Health Factors and Medicine (HFM) Research Task Group 234.