Tag Archives: neuroprotection

Is there nothing ketamine can't do?

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

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

How much oxygen after ROSC?

I reported a previous JAMA publication demonstrating an association between hyperoxia and mortality in patients resuscitated post-cardiac arrest. The same authors have published furthur data to better define the relationship between supranormal oxygen tension and outcome in postresuscitation patients. They hypothesised that a linear dose-dependent relationship would be present in the association between supranormal oxygen tension and in-hospital mortality.

Background– Laboratory and recent clinical data suggest that hyperoxemia after resuscitation from cardiac arrest is harmful; however, it remains unclear if the risk of adverse outcome is a threshold effect at a specific supranormal oxygen tension, or is a dose-dependent association. We aimed to define the relationship between supranormal oxygen tension and outcome in postresuscitation patients.

Methods and Results– This was a multicenter cohort study using the Project IMPACT database (intensive care units at 120 US hospitals). Inclusion criteria were age >17 years, nontrauma, cardiopulmonary resuscitation preceding intensive care unit arrival, and postresuscitation arterial blood gas obtained. We excluded patients with hypoxia or severe oxygenation impairment. We defined the exposure by the highest partial pressure of arterial oxygen (PaO(2)) over the first 24 hours in the ICU. The primary outcome measure was in-hospital mortality. We tested the association between PaO(2) (continuous variable) and mortality using multivariable logistic regression adjusted for patient-oriented covariates and potential hospital effects. Of 4459 patients, 54% died. The median postresuscitation PaO(2) was 231 (interquartile range 149 to 349) mm Hg. Over ascending ranges of oxygen tension, we found significant linear trends of increasing in-hospital mortality and decreasing survival as functionally independent. On multivariable analysis, a 100 mm Hg increase in PaO(2) was associated with a 24% increase in mortality risk (odds ratio 1.24 [95% confidence interval 1.18 to 1.31]. We observed no evidence supporting a single threshold for harm from supranormal oxygen tension.

Conclusion– In this large sample of postresuscitation patients, we found a dose-dependent association between supranormal oxygen tension and risk of in-hospital death.

Relationship Between Supranormal Oxygen Tension and Outcome After Resuscitation From Cardiac Arrest
Circulation. 2011 Jun 14;123(23):2717-2722
Australasian investigators provided the following critique of the original JAMA study:

Unfortunately, these investigators used only the first set of arterial blood gases in the ICU to assess oxygenation, excluded close to 30% of patients because of lack of arterial blood gas data and did not adjust for standard illness severity scores. Their conclusion that hyperoxia is a robust predictor of mortality in patients after resuscitation form cardiac arrest was therefore potentially affected by selection bias and by insufficient adjustment for major confounders. Thus, their results are of uncertain significance and require confirmation.

They undertook their own study of 12,108 patients:

INTRODUCTION: Hyperoxia has recently been reported as an independent risk factor for mortality in patients resuscitated from cardiac arrest. We examined the independent relationship between hyperoxia and outcomes in such patients.
METHODS: We divided patients resuscitated from nontraumatic cardiac arrest from 125 intensive care units (ICUs) into three groups according to worst PaO2 level or alveolar-arterial O2 gradient in the first 24 hours after admission. We defined ‘hyperoxia’ as PaO2 of 300 mmHg or greater, ‘hypoxia/poor O2 transfer’ as either PaO2 < 60 mmHg or ratio of PaO2 to fraction of inspired oxygen (FiO2 ) < 300, ‘normoxia’ as any value between hypoxia and hyperoxia and ‘isolated hypoxemia’ as PaO2 < 60 mmHg regardless of FiO2. Mortality at hospital discharge was the main outcome measure.

RESULTS: Of 12,108 total patients, 1,285 (10.6%) had hyperoxia, 8,904 (73.5%) had hypoxia/poor O2 transfer, 1,919 (15.9%) had normoxia and 1,168 (9.7%) had isolated hypoxemia (PaO2 < 60 mmHg). The hyperoxia group had higher mortality (754 (59%) of 1,285 patients; 95% confidence interval (95% CI), 56% to 61%) than the normoxia group (911 (47%) of 1,919 patients; 95% CI, 45% to 50%) with a proportional difference of 11% (95% CI, 8% to 15%), but not higher than the hypoxia group (5,303 (60%) of 8,904 patients; 95% CI, 59% to 61%). In a multivariable model controlling for some potential confounders, including illness severity, hyperoxia had an odds ratio for hospital death of 1.2 (95% CI, 1.1 to 1.6). However, once we applied Cox proportional hazards modelling of survival, sensitivity analyses using deciles of hypoxemia, time period matching and hyperoxia defined as PaO2 > 400 mmHg, hyperoxia had no independent association with mortality. Importantly, after adjustment for FiO2 and the relevant covariates, PaO2 was no longer predictive of hospital mortality (P = 0.21).

CONCLUSIONS: Among patients admitted to the ICU after cardiac arrest, hyperoxia did not have a robust or consistently reproducible association with mortality. We urge caution in implementing policies of deliberate decreases in FiO2 in these patients.

Arterial hyperoxia and in-hospital mortality after resuscitation from cardiac arrest.
Crit Care. 2011 Mar 8;15(2):R90. [Epub ahead of print]
Open Access Full Text
What’s the best approach in the light of these differing results? My approach is to avoid hypoxia, since that’s probably bad, and to actively avoid overoxygenating as part of my general neuroprotection checklist in a post-cardiac arrest patient. It would seem prudent to follow the recommendations of ILCOR, summarised by the European Resuscitation Council guidelines as:

Recognition of the potential harm caused by hyperoxaemia after ROSC is achieved: once ROSC has been established and the oxygen saturation of arterial blood (SaO2) can be monitored reliably (by pulse oximetry and/or arterial blood gas analysis), inspired oxygen is titrated to achieve a SaO2 of 94–98%

Tympanic monitoring for targeted temperature management

As the authors of this study point out, the reliability of tympanic temperature monitoring is still under debate. Since invasive measures of core temperature employed in the ICU may not be practicable in the pre-hospital setting, it would be helpful to employ a simpler method in the field, particular if we are implementing targeted temperature management post-cardiac arrest. In this small study of ten patients (with 558 temperature measurements) there was a high degree of correlation between tympanic and oesophageal temperature (r=0.95, p<0.0001, 95% CI 0.93 to 0.96) and also between tympanic and bladder temperature (r=0.96, p<0.0001, 95% CI 0.95 to 0.97). This finding is apparently in keeping with results obtained from patients undergoing cardiac surgery.

Objective Prehospital induction of therapeutic hypothermia after cardiac arrest may require temperature monitoring in the field. Tympanic temperature is non-invasive and frequently used in clinical practice. Nevertheless, it has not yet been evaluated in patients undergoing mild therapeutic hypothermia (MTH). Therefore, a prospective observational study was conducted comparing three different sites of temperature monitoring during therapeutic hypothermia.
Methods Ten consecutive patients admitted to our medical intensive care unit after out-of-hospital cardiac arrest were included in this study. During MTH, tympanic temperature was measured using a digital thermometer. Simultaneously, oesophageal and bladder temperatures were recorded in a total of 558 single measurements.
Results Compared with oesophageal temperature, bladder temperature had a bias of 0.019°C (limits of agreement ±0.61°C (2SD)), and tympanic measurement had a bias of 0.021°C (±0.80°C). Correlation analysis revealed a high relationship for tympanic versus oesophageal temperature (r=0.95, p<0.0001) and also for tympanic versus bladder temperature (r=0.96, p<0.0001).
Conclusions That tympanic temperature accurately indicates both oesophageal and bladder temperatures with a very small discrepancy in patients undergoing MTH after cardiac arrest is demonstrated in this study. Although our results were obtained in the hospital setting, these findings may be relevant for the prehospital application of therapeutic hypothermia as well. In this case, tympanic temperature may provide an easy and non-invasive method for temperature monitoring.

Tympanic temperature during therapeutic hypothermia
Emerg Med J. 2011 Jun;28(6):483-5

Targeted temperature management guidelines

Okay – rather than ‘therapeutic hypothermia’, the recommended phrase now is ‘targeted temperature management’. Several critical care authorities got together to produce clinical recommendations on this topic. Here are a few interesting points from the document:
On coagulation:
Hypothermia affects platelet function and prolongs the prothrombin time and partial thromboplastin time. These effects are masked when laboratory analysis is performed at 37°C, suggesting that any risk will be mitigated by rewarming.
Although not mentioned in the abstract, the authors examined the role of TTM in raised intracranial pressure (ICP):
Sufficient evidence exists to conclude that TTM does decrease ICP compared to unstructured temperature management. However, there is no sufficient evidence to make a recommendation regarding the use of targeted hypothermia to control elevated ICP to improve patent-important outcomes in TBI. The jury makes NO RECOMMENDATION regarding the use of TTM as an ICP control strategy to improve outcomes in brain injuries regardless of cause (trauma, hemorrhage, or ischemic stroke).
Regarding acute liver failure with severe cerebral edema:
there are currently no RCTs. There is a case series suggesting a strongly favorable effect. This is a powerful argument for support of an RCT evaluating TTM alone or in combination with hepatic dialysis strategies

OBJECTIVE: Representatives of five international critical care societies convened topic specialists and a nonexpert jury to review, assess, and report on studies of targeted temperature management and to provide clinical recommendations.
DATA SOURCES: Questions were allocated to experts who reviewed their areas, made formal presentations, and responded to questions. Jurors also performed independent searches. Sources used for consensus derived exclusively from peer-reviewed reports of human and animal studies.
STUDY SELECTION: Question-specific studies were selected from literature searches; jurors independently determined the relevance of each study included in the synthesis.

  1. The jury opines that the term “targeted temperature management” replace “therapeutic hypothermia.”
  2. The jury opines that descriptors (e.g., “mild”) be replaced with explicit targeted temperature management profiles.
  3. The jury opines that each report of a targeted temperature management trial enumerate the physiologic effects anticipated by the investigators and actually observed and/or measured in subjects in each arm of the trial as a strategy for increasing knowledge of the dose/duration/response characteristics of temperature management. This enumeration should be kept separate from the body of the report, be organized by body systems, and be made without assertions about the impact of any specific effect on the clinical outcome.
  4. The jury STRONGLY RECOMMENDS targeted temperature management to a target of 32°C-34°C as the preferred treatment (vs. unstructured temperature management) of out-of-hospital adult cardiac arrest victims with a first registered electrocardiography rhythm of ventricular fibrillation or pulseless ventricular tachycardia and still unconscious after restoration of spontaneous circulation (strong recommendation, moderate quality of evidence).
  5. The jury WEAKLY RECOMMENDS the use of targeted temperature management to 33°C-35.5°C (vs. less structured management) in the treatment of term newborns who sustained asphyxia and exhibit acidosis and/or encephalopathy (weak recommendation, moderate quality of evidence).

Targeted temperature management in critical care: A report and recommendations from five professional societies
Crit Care Med. 2011 May;39(5):1113-1125

Decompressive craniectomy for high ICP head trauma

Bilateral decompressive craniectomy for severe diffuse traumatic brain injury and intracranial hypertension that was refractory to first line therapies did not improve neurological outcome. This was the Australasian DECRA study.

Emergency Medicine Ireland reviews the paper here.
Another study on decompressive craniectomy, the RESCUE-ICP study, is ongoing, with 306/400 patients now recruited. The RESCUE-ICP investigators make the following comment on the DECRA trial:
“The study showed a significant decrease in intracranial pressure in patients in the surgical group. However, although ICP was lowered by surgery, ICP was not excessively high in the medical group (mean ICP below 24 mmHg pre-randomisation).
RESCUE-ICP differs from DECRA in terms of ICP threshold (25 vs 20 mmHg), timing of surgery (any time after injury vs within 72 hours post-injury), acceptance of contusions and longer follow up (2 years).
The cohort profiles and criteria for entry and randomisation between the DECRA and RESCUE-ICP are therefore very different. Hence the results from the DECRA study should not deter recruitment into RESCUE-ICP. Randomising patients into the RESCUE-ICP study is now even more important!”

It is unclear whether decompressive craniectomy improves the functional outcome in patients with severe traumatic brain injury and refractory raised intracranial pressure.
From December 2002 through April 2010, we randomly assigned 155 adults with severe diffuse traumatic brain injury and intracranial hypertension that was refractory to first-tier therapies to undergo either bifrontotemporoparietal decompressive craniectomy or standard care. The original primary outcome was an unfavorable outcome (a composite of death, vegetative state, or severe disability), as evaluated on the Extended Glasgow Outcome Scale 6 months after the injury. The final primary outcome was the score on the Extended Glasgow Outcome Scale at 6 months.
Patients in the craniectomy group, as compared with those in the standard-care group, had less time with intracranial pressures above the treatment threshold (P<0.001), fewer interventions for increased intracranial pressure (P<0.02 for all comparisons), and fewer days in the intensive care unit (ICU) (P<0.001). However, patients undergoing craniectomy had worse scores on the Extended Glasgow Outcome Scale than those receiving standard care (odds ratio for a worse score in the craniectomy group, 1.84; 95% confidence interval [CI], 1.05 to 3.24; P=0.03) and a greater risk of an unfavorable outcome (odds ratio, 2.21; 95% CI, 1.14 to 4.26; P=0.02). Rates of death at 6 months were similar in the craniectomy group (19%) and the standard-care group (18%).
In adults with severe diffuse traumatic brain injury and refractory intracranial hypertension, early bifrontotemporoparietal decompressive craniectomy decreased intracranial pressure and the length of stay in the ICU but was associated with more unfavorable outcomes

Decompressive Craniectomy in Diffuse Traumatic Brain Injury
N Engl J Med. 2011 Apr 21;364(16):1493-502

Predicting neurological outcome after cardiac arrest

Predicting neurological recovery after successful cardiac arrest resuscitation has always been tricky, with clinical signs on day one being unreliable, but absent pupillary responses or absent or extensor motor responses to painful stimuli being predictive of a poor outcome on day three. However, the use of therapeutic hypothermia, and its frequent associated need for sedation, appear to make even these downstream assessments inclined to give false positive predictions for a poor outcome, potentially resulting in withdrawal of intensive care in patients who may have recovered. A review recommends a multimodal approach to prognostication.
Regarding physical examination, the authors state:

In summary, therapeutic hypothermia and sedation required for induced cooling might delay recovery of motor reactions up to 5–6 days after cardiac arrest. Corneal/ pupillary reflexes and myoclonus are more robust predic- tors of poor outcome after cardiac arrest, but their absence is not an absolute predictor of dismal prognosis

PURPOSE OF REVIEW: Therapeutic hypothermia and aggressive management of postresuscitation disease considerably improved outcome after adult cardiac arrest over the past decade. However, therapeutic hypothermia alters prognostic accuracy. Parameters for outcome prediction, validated by the American Academy of Neurology before the introduction of therapeutic hypothermia, need further update.
RECENT FINDINGS: Therapeutic hypothermia delays the recovery of motor responses and may render clinical evaluation unreliable. Additional modalities are required to predict prognosis after cardiac arrest and therapeutic hypothermia. Electroencephalography (EEG) can be performed during therapeutic hypothermia or shortly thereafter; continuous/reactive EEG background strongly predicts good recovery from cardiac arrest. On the contrary, unreactive/spontaneous burst-suppression EEG pattern, together with absent N20 on somatosensory evoked potentials (SSEP), is almost 100% predictive of irreversible coma. Therapeutic hypothermia alters the predictive value of serum markers of brain injury [neuron-specific enolase (NSE), S-100B]. Good recovery can occur despite NSE levels >33 μg/l, thus this cut-off value should not be used to guide therapy. Diffusion MRI may help predicting long-term neurological sequelae of hypoxic-ischemic encephalopathy.
SUMMARY: Awakening from postanoxic coma is increasingly observed, despite early absence of motor signs and frank elevation of serum markers of brain injury. A new multimodal approach to prognostication is therefore required, which may particularly improve early prediction of favorable clinical evolution after cardiac arrest.
Predicting neurological outcome after cardiac arrest

Curr Opin Crit Care. 2011 Jun;17(3):254-9

Hyperbaric O2 for the sick and the well with CO poisoning

A French study, large by hyperbaric oxygen trial standards, did not confirm that hyperbaric oxygen therapy improves recovery from pure CO poisoning. In addition, in comatose patients, repeating hyperbaric oxygen therapy resulted in worse outcomes compared to one session.

I don't care if it doesn't work - something looking like a retro-sci-fi time machine is COOL.

INTRODUCTION: Although hyperbaric oxygen therapy (HBO) is broadly used for carbon monoxide (CO) poisoning, its efficacy and practical modalities remain controversial.
OBJECTIVES: To assess HBO in patients poisoned with CO.
DESIGN: Two prospective randomized trial on two parallel groups.
SETTING: Critical Care Unit, Raymond Poincaré Hospital, Garches, France.
SUBJECTS: Three hundred eighty-five patients with acute domestic CO poisoning.
INTERVENTION: Patients with transient loss of consciousness (trial A, n = 179) were randomized to either 6 h of normobaric oxygen therapy (NBO; arm A0, n = 86) or 4 h of NBO plus one HBO session (arm A1, n = 93). Patients with initial coma (trial B, n = 206) were randomized to either 4 h of NBO plus one HBO session (arm B1, n = 101) or 4 h of NBO plus two 2 HBO sessions (arm B2, n = 105). PRIMARY ENDPOINT: Proportion of patients with complete recovery at 1 month.
RESULTS: In trial A, there was no evidence for a difference in 1-month complete recovery rates with and without HBO [58% compared to 61%; unadjusted odds ratio, 0.90 (95% CI, 0.47-1.71)]. In trial B, complete recovery rates were significantly lower with two than with one HBO session [47% compared to 68%; unadjusted odds ratio, 0.42 (CI, 0.23-0.79)].
CONCLUSION: In patients with transient loss of consciousness, there was no evidence of superiority of HBO over NBO. In comatose patients, two HBO sessions were associated with worse outcomes than one HBO session.

Hyperbaric oxygen therapy for acute domestic carbon monoxide poisoning: two randomized controlled trials
Intensive Care Med. 2011 Mar;37(3):486-92

Salt or sugar on the brain

A meta-analysis suggests hypertonic saline may be more effective at lowering intracranial pressure than mannitol. An accompanying editorial cleverly entitled ‘Salt or sugar on the brain: Does it matter except for taste?’ suggests one reason hypertonic saline (HTS) has not replaced mannitol in clinical practice is that too many different regimens of HTS, in terms of concentration, dose, bolus vs. continuous infusions, and plus or minus supplementation of colloids, have been utilised. Because only 112 patients with 184 episodes of increased ICP were treated with each medication in this meta-analysis, the editorialist agrees with the authors in suggesting a larger randomised study is needed.

OBJECTIVES: Randomized trials have suggested that hypertonic saline solutions may be superior to mannitol for the treatment of elevated intracranial pressure, but their impact on clinical practice has been limited, partly by their small size. We therefore combined their findings in a meta-analysis.
DATA SOURCES: We searched for relevant studies in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, and ISI Web of Knowledge.
STUDY SELECTION: Randomized trials were included if they directly compared equiosmolar doses of hypertonic sodium solutions to mannitol for the treatment of elevated intracranial pressure in human subjects undergoing quantitative intracranial pressure measurement.
DATA EXTRACTION: Two investigators independently reviewed potentially eligible trials and extracted data using a preformed data collection sheet. Disagreements were resolved by consensus or by a third investigator if needed. We collected data on patient demographics, type of intracranial pathology, baseline intracranial pressure, osms per treatment dose, quantitative change in intracranial pressure, and prespecified adverse events. Our primary outcome was the proportion of successfully treated episodes of elevated intracranial pressure.
DATA SYNTHESIS: Five trials comprising 112 patients with 184 episodes of elevated intracranial pressure met our inclusion criteria. In random-effects models, the relative risk of intracranial pressure control was 1.16 (95% confidence interval, 1.00-1.33), and the difference in mean intracranial pressure reduction was 2.0 mm Hg (95% confidence interval, -1.6 to 5.7), with both favoring hypertonic saline over mannitol. A mild degree of heterogeneity was present among the included trials. There were no significant adverse events reported.
CONCLUSIONS: We found that hypertonic saline is more effective than mannitol for the treatment of elevated intracranial pressure. Our meta-analysis is limited by the small number and size of eligible trials, but our findings suggest that hypertonic saline may be superior to the current standard of care and argue for a large, multicenter, randomized trial to definitively establish the first-line medical therapy for intracranial hypertension.

Hypertonic saline versus mannitol for the treatment of elevated intracranial pressure: A meta-analysis of randomized clinical trials
Crit Care Med. 2011 Mar;39(3):554-9

Pre-hospital transcranial Doppler

The SAMU (Service d’aide médicale urgente) guys have had a run of interesting pre-hospital publications lately. In this study, one of their ultrasound-wielding physicians travelled in a car to meet comatose head injured patients in a large semi-rural territory area with up to a 120–160-min transport time to a hospital with emergency neurosurgical capability. Pre-hospital transcranial Doppler was done, the results of which appear to have influenced treatment decisions, including the pre-hospital administration of noradrenaline (norepinephrine). I think this study has answered the ‘can it be done?’ question, but further work is needed to determine whether it really makes a difference to outcome.

Background: Investigation of the feasibility and usefulness of pre-hospital transcranial Doppler (TCD) to guide early goal-directed therapy following severe traumatic brain injury (TBI).
Methods: Prospective, observational study of 18 severe TBI patients during pre-hospital medical care. TCD was performed to estimate cerebral perfusion in the field and upon arrival at the Level 1 trauma centre. Specific therapy (mannitol, noradrenaline) aimed at improving cerebral perfusion was initiated if the initial TCD was abnormal (defined by a pulsatility index >1.4 and low diastolic velocity).
Results: Nine patients had a normal initial TCD and nine an abnormal one, without a significant difference between groups in terms of the Glasgow Coma Scale or the mean arterial pressure. Among patients with an abnormal TCD, four presented with an initial areactive bilateral mydriasis. Therapy normalized TCD in five patients, with reversal of the initial mydriasis in two cases. Among these five patients for whom TCD was corrected, only two died within the first 48 h. All four patients for whom the TCD could not be corrected during transport died within 48 h. Only patients with an initial abnormal TCD required emergent neurosurgery (3/9). Mortality at 48 h was significantly higher for patients with an initial abnormal TCD.
Conclusions: Our preliminary study suggests that TCD could be used in pre-hospital care to detect patients whose cerebral perfusion may be impaired.

Pre-hospital transcranial Doppler in severe traumatic brain injury: a pilot study
Acta Anaesthesiol Scand. 2011 Apr;55(4):422-8