London Trauma Conference Day 4

December 15, 2013 by  
Filed under All Updates, EMS, ICU, Resus, Trauma

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London Trauma Conference Day 4 by Dr Louisa Chan

It’s the last day of the conference and new this year is the Neurotrauma Masterclass running in parallel with the main track which focuses on in-hospital care.

We heard a little from Mark Wilson yesterday. He believes we are missing a pre-hospital trick in traumatic brain injury. Early intervention is the key (he has data showing aggressive intervention for extradural haemorrhage in patients with fixed dilated pupils has good outcomes in 75%).

Today he taught us neurosurgery over lunch. If you have a spare moment over then go to his website and you too can learn how to be a brain surgeon!

Dr Gareth Davies talks about Impact Brain Apnoea. Many will not heard of this phenomenon. Clinicians rarely see patients early enough in their injury timeline to witness

Essentially this term describes the cessation of breathing after head injury. It has been described in older texts (first mentioned in 1894!) The period of apnoea increases with the severity of the injury and if non fatal will then recover to normal over a period of time. Prolonged apnoea results in hypotension.

This is a brain stem mediated effect with no structural injury.

The effect is exacerbated by alcohol and ameliorated by ventilatory support during the apnoeic phase.

Associated with this response is a catecholamine surge which exacerbates the cardiovascular collapse and he introduces the concept of Central Shock.

So how does this translate into the real world?

Well, could we be miscategorising patients that die before they reach hospital as succumbing to hypovolaemic when in fact they had central shock?

These patients essentially present with respiratory arrest, but do well with supported ventilation. Identification of these patients by emergency dispatchers with airway support could mean the difference between life and death.

Read more about this at: http://www.sciencedirect.com/science/article/pii/S0025619611642547

Prof Monty Mythen spoke on fluid management in the trauma patient after blood (not albumin, HES or colloids) and Prof Mervyn Singer explained the genetic contribution to the development of MODS after trauma.

LTC-BrohiProf Brohi gave us the lowdown on trauma laparotomies – not all are the same! With important human factors advice:

1. Task focus kills
2. Situational awareness saves lives
3. The best communication is non verbal
4. Train yourself to listen

Prof Susan Brundage is a US trauma surgeon who has been recruited into the Bart’s and the London School of Medicine and the Royal College of Surgeons of England International Masters in Trauma Sciences for her trauma expertise.

She tells us that MOOCs and FOAM are changing education. Whilst education communities are being formed, she warns of the potential pitfalls of this form of education with a proportion of participants not fully engaged.

The Masters program is growing and if you’re interested you can read more here.

This has been a full on conference, with great learning points.

Hopefully see you next year!

Therapeutic hypothermia does not improve arrest outcome

November 18, 2013 by  
Filed under Acute Med, All Updates, EMS, Guidelines, ICU, Resus

A paper published today represents to me what’s great about science.

I am impressed with those investigators who had the wherewithall to subject previous therapeutic hypothermia studies to skeptical scrutiny and then design and conduct a robust multicentre trial to answer the question.

One of the criticisms of the original two studies was that those patients who were not actively cooled did not have their temperature tightly controlled, and therefore some were allowed to become hypERthermic, which is bad for brains.

This latest study showed no difference in survival or neurological outcome after cardiac arrest between target temperatures of 33°C and 36°C.

So controlling the temperature after cardiac arrest is still important, but cooling down to the recommended range of 32-4°C is not.

Cool.

Read the full study at the NEJM site.

Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest

NEJM November 17, 2013 Full text


BACKGROUND Unconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever.

METHODS In an international trial, we randomly assigned 950 unconscious adults after out-of-hospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33°C or 36°C. The primary outcome was all-cause mortality through the end of the trial. Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale.

RESULTS In total, 939 patients were included in the primary analysis. At the end of the trial, 50% of the patients in the 33°C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36°C group (225 of 466 patients) (hazard ratio with a temperature of 33°C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51). At the 180-day follow-up, 54% of the patients in the 33°C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36°C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78). In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar.

CONCLUSIONS In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33°C did not confer a benefit as compared with a targeted temperature of 36°C.

Xenon – no bull?

August 31, 2013 by  
Filed under All Updates, ICU

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Xenon, an inert ‘noble’ gas with proven anaesthetic properties, has possible neuroprotective properties and appears to be also cardioprotective in this small study of post-cardiac arrest patients. Its high viscosity affects airway resistance, resulting in higher peak pressures and the need for a strategy to avoid gas trapping (ie. longer expiratory times as with asthma). Apparently it’s expensive, but these results suggest further study is warranted.

Feasibility and Cardiac Safety of Inhaled Xenon in Combination With Therapeutic Hypothermia Following Out-of-Hospital Cardiac Arrest
Crit Care Med. 2013 Sep;41(9):2116-24


OBJECTIVES: Preclinical studies reveal the neuroprotective properties of xenon, especially when combined with hypothermia. The purpose of this study was to investigate the feasibility and cardiac safety of inhaled xenon treatment combined with therapeutic hypothermia in out-of-hospital cardiac arrest patients.

DESIGN: An open controlled and randomized single-centre clinical drug trial (clinicaltrials.gov NCT00879892).

SETTING: A multipurpose ICU in university hospital.

PATIENTS: Thirty-six adult out-of-hospital cardiac arrest patients (18-80 years old) with ventricular fibrillation or pulseless ventricular tachycardia as initial cardiac rhythm.

INTERVENTIONS: Patients were randomly assigned to receive either mild therapeutic hypothermia treatment with target temperature of 33°C (mild therapeutic hypothermia group, n = 18) alone or in combination with xenon by inhalation, to achieve a target concentration of at least 40% (Xenon + mild therapeutic hypothermia group, n = 18) for 24 hours. Thirty-three patients were evaluable (mild therapeutic hypothermia group, n = 17; Xenon + mild therapeutic hypothermia group, n = 16).

MEASUREMENTS AND MAIN RESULTS: Patients were treated and monitored according to the Utstein protocol. The release of troponin-T was determined at arrival to hospital and at 24, 48, and 72 hours after out-of-hospital cardiac arrest. The median end-tidal xenon concentration was 47% and duration of the xenon inhalation was 25.5 hours. The frequency of serious adverse events, including inhospital mortality, status epilepticus, and acute kidney injury, was similar in both groups and there were no unexpected serious adverse reactions to xenon during hospital stay. In addition, xenon did not induce significant conduction, repolarization, or rhythm abnormalities. Median dose of norepinephrine during hypothermia was lower in xenon-treated patients (mild therapeutic hypothermia group = 5.30 mg vs Xenon + mild therapeutic hypothermia group = 2.95 mg, p = 0.06). Heart rate was significantly lower in Xenon + mild therapeutic hypothermia patients during hypothermia (p = 0.04). Postarrival incremental change in troponin-T at 72 hours was significantly less in the Xenon + mild therapeutic hypothermia group (p = 0.04).

CONCLUSIONS: Xenon treatment in combination with hypothermia is feasible and has favorable cardiac features in survivors of out-of-hospital cardiac arrest.

Targeted ICP reduction in TBI

December 13, 2012 by  
Filed under All Updates, ICU, Resus, Trauma

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A South American randomised controlled trial has demonstrated no improvement in mortality when traumatic brain injured patients had therapy targeted at keeping intracranial pressure below or equal to 20 mmHg as measured by an intraparenchymal monitor. The control group’s management was guided by neurologic examination and serial CT imaging(1).

Editorialist Dr Ropper summarises what we should do with this information well(2):

“[The authors]…do not advocate abandoning the treatment of elevated intracranial pressure any more than the authors of studies on wedge pressure reject the administration of fluid boluses in the treatment of shock”

BACKGROUND

Intracranial-pressure monitoring is considered the standard of care for severe traumatic brain injury and is used frequently, but the efficacy of treatment based on monitoring in improving the outcome has not been rigorously assessed.

METHODS
We conducted a multicenter, controlled trial in which 324 patients 13 years of age or older who had severe traumatic brain injury and were being treated in intensive care units (ICUs) in Bolivia or Ecuador were randomly assigned to one of two specific protocols: guidelines-based management in which a protocol for monitoring intraparenchymal intracranial pressure was used (pressure-monitoring group) or a protocol in which treatment was based on imaging and clinical examination (imaging–clinical examination group). The primary outcome was a composite of survival time, impaired consciousness, and functional status at 3 months and 6 months and neuropsychological status at 6 months; neuropsychological status was assessed by an examiner who was unaware of protocol assignment. This composite measure was based on performance across 21 measures of functional and cognitive status and calculated as a percentile (with 0 indicating the worst performance, and 100 the best performance).

RESULTS
There was no significant between-group difference in the primary outcome, a composite measure based on percentile performance across 21 measures of functional and cognitive status (score, 56 in the pressure-monitoring group vs. 53 in the imaging–clinical examination group; P=0.49). Six-month mortality was 39% in the pressure-monitoring group and 41% in the imaging–clinical examination group (P=0.60). The median length of stay in the ICU was similar in the two groups (12 days in the pressure-monitoring group and 9 days in the imaging–clinical examination group; P=0.25), although the number of days of brain-specific treatments (e.g., administration of hyperosmolar fluids and the use of hyperventilation) in the ICU was higher in the imaging–clinical examination group than in the pressure-monitoring group (4.8 vs. 3.4, P=0.002). The distribution of serious adverse events was similar in the two groups.

CONCLUSIONS
For patients with severe traumatic brain injury, care focused on maintaining monitored intracranial pressure at 20 mm Hg or less was not shown to be superior to care based on imaging and clinical examination

1. A Trial of Intracranial-Pressure Monitoring in Traumatic Brain Injury
N Eng J Med 367;26:2471-2381 Full Text

2. Brain in a Box
N Eng J Med DOI: 10.1056/NEJMe1212289 Full Text

Magnesium doesn’t improve SAH outcome

September 23, 2012 by  
Filed under Acute Med, All Updates, ICU, Resus

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A multicentre RCT showed intravenous magnesium sulphate does not improve clinical outcome after aneurysmal subarachnoid haemorrhage, therefore routine administration of magnesium cannot be recommended.
Magnesium for aneurysmal subarachnoid haemorrhage (MASH-2): a randomised placebo-controlled trial
Lancet 2012 July 7; 380(9836): 44–49 Free full text


Background Magnesium sulphate is a neuroprotective agent that might improve outcome after aneurysmal subarachnoid haemorrhage by reducing the occurrence or improving the outcome of delayed cerebral ischaemia. We did a trial to test whether magnesium therapy improves outcome after aneurysmal subarachnoid haemorrhage.

Methods We did this phase 3 randomised, placebo-controlled trial in eight centres in Europe and South America. We randomly assigned (with computer-generated random numbers, with permuted blocks of four, stratified by centre) patients aged 18 years or older with an aneurysmal pattern of subarachnoid haemorrhage on brain imaging who were admitted to hospital within 4 days of haemorrhage, to receive intravenous magnesium sulphate, 64 mmol/day, or placebo. We excluded patients with renal failure or bodyweight lower than 50 kg. Patients, treating physicians, and investigators assessing outcomes and analysing data were masked to the allocation. The primary outcome was poor outcome—defined as a score of 4–5 on the modified Rankin Scale—3 months after subarachnoid haemorrhage, or death. We analysed results by intention to treat. We also updated a previous meta-analysis of trials of magnesium treatment for aneurysmal subarachnoid haemorrhage. This study is registered with controlled-trials.com (ISRCTN 68742385) and the EU Clinical Trials Register (EudraCT 2006-003523-36).

Findings 1204 patients were enrolled, one of whom had his treatment allocation lost. 606 patients were assigned to the magnesium group (two lost to follow-up), 597 to the placebo (one lost to follow-up). 158 patients (26·2%) had poor outcome in the magnesium group compared with 151 (25·3%) in the placebo group (risk ratio [RR] 1·03, 95% CI 0·85–1·25). Our updated meta-analysis of seven randomised trials involving 2047 patients shows that magnesium is not superior to placebo for reduction of poor outcome after aneurysmal subarachnoid haemorrhage (RR 0·96, 95% CI 0·86–1·08).

Interpretation Intravenous magnesium sulphate does not improve clinical outcome after aneurysmal subarachnoid haemorrhage, therefore routine administration of magnesium cannot be recommended.

Hypothermia after long down times

September 11, 2012 by  
Filed under Acute Med, All Updates, EMS, ICU, Resus

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You receive a patient resuscitated from cardiac arrest to a perfusing rhythm in your emergency department. History suggests a long ‘down time': There was a ten minute duration of ‘no-flow’ (time from collapse to the start of resuscitation attempts).

Would this make you more likely or less likely to initiate targeted temperature management (TTM) and cool the patient to the recommended 32-34 degrees?

A recent study supports the suggestion that a longer no-flow time is associated with greater odds of survival with TTM compared with no TTM, than patients with shorter no-flow times. In other words, cooling the patient is more likely to make a difference in the ‘long down time’ patient, even though the overall survival in that group is obviously less.


Aim Mild therapeutic hypothermia has shown to improve long-time survival as well as favorable functional outcome after cardiac arrest. Animal models suggest that ischemic durations beyond 8 min results in progressively worse neurologic deficits. Based on these considerations, it would be obvious that cardiac arrest survivors would benefit most from mild therapeutic hypothermia if they have reached a complete circulatory standstill of more than 8 min.

Methods In this retrospective cohort study we included cardiac arrest survivors of 18 years of age or older suffering a witnessed out-of-hospital cardiac arrest, which remain comatose after restoration of spontaneous circulation. Data were collected from 1992 to 2010. We investigated the interaction of ‘no-flow’ time on the association between post arrest mild therapeutic hypothermia and good neurological outcome. ‘No-flow’ time was categorized into time quartiles (0, 1–2, 3–8, >8 min).

Results One thousand-two-hundred patients were analyzed. Hypothermia was induced in 598 patients. In spite of showing a statistically significant improvement in favorable neurologic outcome in all patients treated with mild therapeutic hypothermia (odds ratio [OR]: 1.49; 95% confidence interval [CI]: 1.14–1.93) this effect varies with ‘no-flow’ time. The effect is significant in patients with ‘no-flow’ times of more than 2 min (OR: 2.72; CI: 1.35–5.48) with the maximum benefit in those with ‘no-flow’ times beyond 8 min (OR: 6.15; CI: 2.23–16.99).

Conclusion The beneficial effect of mild therapeutic hypothermia increases with cumulative time of complete circulatory standstill in patients with witnessed out-of-hospital cardiac arrest.

The beneficial effect of mild therapeutic hypothermia depends on the time of complete circulatory standstill in patients with cardiac arrest
Resuscitation. 2012 May;83(5):596-601

Hyperosmolar therapy

September 2, 2012 by  
Filed under Acute Med, All Updates, EMS, ICU, Kids, Resus, Trauma

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A great review article from the New England Journal of Medicine summaries the current knowledge base regarding the use of hypertonic saline and mannitol for raised intracranial pressure.

Hyperosmolar Therapy for Raised Intracranial Pressure 
N Engl J Med. 2012 Aug 23;367(8):746-52

Full text access is only available to New England Journal subscribers, but I’ve summarised some of the interesting bits in a short quiz you can take to test your knowledge. Just 13 True/False questions.

Take the Hyperosmolar Therapy Quiz

If you liked the quiz and want to use it at your local teaching sessions, here’s a Keynote Version and a PowerPoint Version

Severe Traumatic Brain Injury in Children

February 21, 2012 by  
Filed under All Updates, Guidelines, ICU, Kids, Resus

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The Brain Trauma Foundation has released updated guidelines on traumatic brain injury in children.

Most of the recommendations are Grade C and therefore based on limited evidence.


Indications for ICP monitoring

Use of intracranial pressure (ICP) monitoring may be considered in infants and children with severe traumatic brain injury (TBI) (Grade C).

Four lines of evidence support the use of ICP monitoring in children with severe TBI:

  • a frequently reported high incidence of intracranial hypertension in children with severe TBI
  • a widely reported association of intracranial hypertension and poor neurologic outcome
  • the concordance of protocol-based intracranial hypertension therapy and best-reported clinical outcomes
  • and improved outcomes associated with successful ICP-lowering therapies.

Threshold for treatment of intracranial hypertension
Treatment of intracranial pressure (ICP) may be considered at a threshold of 20 mm Hg (Grade C).

Sustained elevations in ICP (>20 mm Hg) are associated with poor outcome in children after severe TBI.
Normal values of blood pressure and ICP are age-dependent (lower at younger ages), so it is anticipated that the optimal ICP treatment threshold may be age-dependent.

Cerebral perfusion pressure thresholds
A CPP threshold 40–50 mm Hg may be considered. There may be age-specific thresholds with infants at the lower end and adolescents at the upper end of this range (Grade C).

Survivors of severe pediatric TBI undergoing ICP monitoring consistently have higher CPP values vs. nonsurvivors, but no study demonstrates that active maintenance of CPP above any target threshold in pediatric TBI reduces mortality or morbidity.

CPP should be determined in a standard fashion with ICP zeroed to the tragus (as an indicator of the foramen of Monro and midventricular level) and MAP zeroed to the right atrium with the head of the bed elevated 30°.

Advanced neuromonitoring
If brain oxygenation monitoring is used, maintenance of partial pressure of brain tissue oxygen (PbtO2) >10 mm Hg may be considered.

Neuroimaging
In the absence of neurologic deterioration or increasing intracranial pressure (ICP), obtaining a routine repeat computed tomography (CT) scan >24 hrs after the admission and initial follow-up study may not be indicated for decisions about neurosurgical intervention (Grade C).

Hyperosmolar therapy
Hypertonic saline should be considered for the treatment of severe pediatric traumatic brain injury (TBI) associated with intracranial hypertension. Effective doses for acute use range between 6.5 and 10 mL/kg (of 3%) (Grade B).

Hypertonic saline should be considered for the treatment of severe pediatric TBI associated with intracranial hypertension. Effective doses as a continuous infusion of 3% saline range between 0.1 and 1.0 mL/kg of body weight per hour administered on a sliding scale. The minimum dose needed to maintain intracranial pressure (ICP)

Temperature control
Moderate hypothermia (32–33°C) beginning early after severe traumatic brain injury (TBI) for only 24 hrs’ duration should be avoided.
Moderate hypothermia (32–33°C) be- ginning within 8 hrs after severe TBI for up to 48 hrs’ duration should be considered to reduce intracranial hypertension.
If hypothermia is induced for any indication, rewarming at a rate of >0.5°C/hr should be avoided (Grade B).

Moderate hypothermia (32–33°C) be- ginning early after severe TBI for 48 hrs, duration may be considered (Grade C).
Note: after completion of these guidelines, the committee became aware that the Cool Kids trial of hypothermia in pediatric TBI was stopped because of futility. The implications of this development on the recommendations in this section may need to be considered by the treating physician when details of the study are published.

Cerebrospinal fluid drainage
Cerebrospinal fluid (CSF) drainage through an external ventricular drain may be considered in the management of increased intracranial pressure (ICP) in children with severe traumatic brain injury (TBI).
The addition of a lumbar drain may be considered in the case of refractory intracranial hypertension with a functioning external ventricular drain, open basal cis- terns, and no evidence of a mass lesion or shift on imaging studies (Grade C).

Barbiturates
High-dose barbiturate therapy may be considered in hemodynamically stable patients with refractory intracranial hypertension despite maximal medical and surgical management.
When high-dose barbiturate therapy is used to treat refractory intracranial hy- pertension, continuous arterial blood pressure monitoring and cardiovascular support to maintain adequate cerebral perfusion pressure are required (Grade C).

Decompressive craniectomy for the treatment of intracranial hypertension
Decompressive craniectomy (DC) with duraplasty, leaving the bone flap out, may be considered for pediatric patients with traumatic brain injury (TBI) who are showing early signs of neurologic deterioration or herniation or are developing intracranial hypertension refractory to medical management during the early stages of their treatment (Grade C).

Hyperventilation
Avoidance of prophylactic severe hyperventilation to a PaCO2 If hyperventilation is used in the management of refractory intracranial hypertension, advanced neuromonitoring for evaluation of cerebral ischemia may be considered (Grade C).

Corticosteroids
The use of corticosteroids is not recommended to improve outcome or reduce intracranial pressure (ICP) for children with severe traumatic brain injury (TBI) (Grade B).

Analgesics, sedatives, and neuromuscular blockade
Etomidate may be considered to control severe intracranial hypertension; however, the risks resulting from adrenal suppression must be considered.
Thiopental may be considered to control intracranial hypertension.
In the absence of outcome data, the specific indications, choice and dosing of analgesics, sedatives, and neuromuscular-blocking agents used in the management of infants and children with severe traumatic brain injury (TBI) should be left to the treating physician.
*As stated by the Food and Drug Administration, continuous infusion of propofol for either sedation or the management of refractory intracranial hypertension in infants and children with severe TBI is not recommended (Grade C).

The availability of other sedatives and analgesics that do not suppress adrenal function, small sample size and single-dose administration in the study discussed previously, and limited safety profile in pediatric TBI limit the ability to endorse the general use of etomidate as a sedative other than as an option for single-dose administration in the setting of raised ICP.

Glucose and nutrition
The evidence does not support the use of an immune-modulating diet for the treatment of severe traumatic brain injury (TBI) to improve outcome (Grade B).

In the absence of outcome data, the specific approach to glycemic control in the management of infants and children with severe TBI should be left to the treating physician (Grade C).

Antiseizure prophylaxis
Prophylactic treatment with phenytoin may be considered to reduce the incidence of early posttraumatic seizures (PTS) in pediatric patients with severe traumatic brain injury (TBI) (Grade C).

The incidence of early PTS in pediatric patients with TBI is approximately 10% given the limitations of the available data. Based on a single class III study (4), prophylactic anticonvulsant therapy with phenytoin may be considered to reduce the incidence of early posttraumatic seizures in pediatric patients with severe TBI. Concomitant monitoring of drug levels is appropriate given the potential alterations in drug metabolism described in the context of TBI. Stronger class II evidence is available supporting the use of prophylactic anticonvulsant treatment to reduce the risk of early PTS in adults. There are no compelling data in the pediatric TBI literature to show that such treatment reduces the long-term risk of PTS or improves long-term neurologic outcome.

Guidelines for the Acute Medical Management of Severe Traumatic Brain Injury in Infants, Children, and Adolescents-Second Edition
Pediatr Crit Care Med 2012 Vol. 13, No. 1 (Suppl.)
Read online
Download PDF (617k)
Other Brain Trauma Foundation Guidelines

Is there nothing ketamine can’t do?

September 25, 2011 by  
Filed under All Updates, ICU, Kids, Resus

As well as the benefits of cardiovascular stability, maintenance of cerebral perfusion pressure, possibly lowering ICP and providing other neuroprotective benefits, ketamine may have other advantages. These are reviewed in a British Journal of Anaesthesia article from which I’ve selected those benefits of interest to practitioners of emergency medicine and critical care.

 

 

Additional Beneficial Effects of Ketamine

  • the dysphoric, or ‘emergence’ reactions associated with ketamine may be reduced by pre-administration or co-administration of sedatives, such as benzodiazepines, propofol, dexmedetomidine, or droperidol.
  • ketamine potentiates opioid analgesia in multiple settings, reducing opioid total dose and in some groups of patients reducing postoperative desaturation
  • ketamine has possible anti-inflammatory effects demonstrated in some types of surgical patients
  • ketamine may prevent awareness, recall, or both during general anaesthesia

Ketamine: new uses for an old drug?
Br J Anaesth. 2011 Aug;107(2):123-6

CRASH-2 and head injury

August 14, 2011 by  
Filed under All Updates, ICU, Resus, Trauma

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The overall effect of the antifibrinolytic drug tranexamic acid on outcome from major trauma was assessed in the CRASH-2 trial, reported here and here. Its effect on a nested cohort of 270 patients from the trial who had traumatic brain injury has now been published1.

Previous evaluation in nontraumatic subarachnoid haemorrhage patients showed tranexamic acid to be associated with cerebral ischaemia, whereas in CRASH-2 (in which a lower dose of tranexamic acid was used) there was a trend to fewer ischaemic lesions as well as smaller haematoma growth and decreased mortality. None of these outcomes were statistically significant so further research is warranted.

An accompanying editorial2 states:

…the CRASH-2 study also justifies a re-evaluation of the possible benefit of low dose short term TXA in patients with other types of intracranial haemorrhage. Many patients with aneurysmal subarachnoid haemorrhage still have to wait for one or two days before the aneurysm is occluded. In addition, at least 30% of patients with spontaneous intracerebral haemorrhage experience substantial haematoma growth in the first 24 hours after the onset of the haemorrhage. As well as the CRASH-2 trial we therefore need new trials investigating short course low dose TXA in patients with aneurysmal subarachnoid haemorrhage and intracerebral haemorrhage.

It looks like considerable enthusiasm for this drug will be around for a while. I look forward to more outcome data, particularly in regard to this challenging group of patients with traumatic and non-traumatic intracranial bleeding.


OBJECTIVE: To assess the effect of tranexamic acid (which reduces bleeding in surgical patients and reduces mortality due to bleeding in trauma patients) on intracranial haemorrhage in patients with traumatic brain injury.

METHODS: A nested, randomised, placebo controlled trial. All investigators were masked to treatment allocation. All analyses were by intention to treat. Patients 270 adult trauma patients with, or at risk of, significant extracranial bleeding within 8 hours of injury, who also had traumatic brain injury.

INTERVENTIONS: Patients randomly allocated to tranexamic acid (loading dose 1 g over 10 minutes, then infusion of 1 g over 8 hours) or matching placebo.

MAIN OUTCOME MEASURES: Intracranial haemorrhage growth (measured by computed tomography) between hospital admission and then 24-48 hours later, with adjustment for Glasgow coma score, age, time from injury to the scans, and initial haemorrhage volume.

RESULTS: Of the 133 patients allocated to tranexamic acid and 137 allocated to placebo, 123 (92%) and 126 (92%) respectively provided information on the primary outcome. All patients provided information on clinical outcomes. The mean total haemorrhage growth was 5.9 ml (SD 26.8) and 8.1 mL (SD 29.2) in the tranexamic acid and placebo groups respectively (adjusted difference -3.8 mL (95% confidence interval -11.5 to 3.9)). New focal cerebral ischaemic lesions occurred in 6 (5%) patients in the tranexamic acid group versus 12 (9%) in the placebo group (adjusted odds ratio 0.51 (95% confidence interval 0.18 to 1.44)). There were 14 (11%) deaths in the tranexamic acid group and 24 (18%) in the placebo group (adjusted odds ratio 0.47 (0.21 to 1.04)).

CONCLUSIONS: This trial shows that neither moderate benefits nor moderate harmful effects of tranexamic acid in patients with traumatic brain injury can be excluded. However, the analysis provides grounds for further clinical trials evaluating the effect of tranexamic acid in this population

1. Effect of tranexamic acid in traumatic brain injury: a nested randomised, placebo controlled trial (CRASH-2 Intracranial Bleeding Study)
BMJ. 2011 Jul 1;343:d379 (free text available)

2. Tranexamic acid for traumatic brain injury
BMJ. 2011 Jul 1;343:d3958

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