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!”

Background
It is unclear whether decompressive craniectomy improves the functional outcome in patients with severe traumatic brain injury and refractory raised intracranial pressure.
Methods
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.
Results
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%).
Conclusions
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

Fluid Bolus in African Children with Severe Infection

Much discussion has already taken place in the blogosphere about the FEAST study of fluid resuscitation in septic children. Although a well conducted study, its external validity to Western populations is dubious, particularly in view of the proportion of malaria in the cohorts studied.

In the words of my emergency physician colleague Dr Fiona Rae from Wrexham, UK:

“Interesting. As they say, a completely different population in a resource limited setting so it doesn’t translate to UK practice. Majority of these children had malaria and if I read correctly 32% had Hb < 5g/dl. Also 20-40mls/kg is quite a lot of fluid these days as an initial bolus other than in the sort of severely shocked patients that they seemed to exclude. Their overall mortality also seems to be lower than expected for this population.

If you work in an environment without ITU and a high incidence of malaria then its a useful study. They are not the sort of children I see in my resus room with shock though.”
Nicely put Fi!
You can also read an analysis of this study on Dr G’s blog – where you can find other posts on critical care and emergency medicine.

Background
The role of fluid resuscitation in the treatment of children with shock and life-threatening infections who live in resource-limited settings is not established.
Methods
We randomly assigned children with severe febrile illness and impaired perfusion to receive boluses of 20 to 40 ml of 5% albumin solution (albumin-bolus group) or 0.9% saline solution (saline-bolus group) per kilogram of body weight or no bolus (control group) at the time of admission to a hospital in Uganda, Kenya, or Tanzania (stratum A); children with severe hypotension were randomly assigned to one of the bolus groups only (stratum B). Children with malnutrition or gastroenteritis were excluded. The primary end point was 48-hour mortality; secondary end points included pulmonary edema, increased intracranial pressure, and mortality or neurologic sequelae at 4 weeks.
Results
The data and safety monitoring committee recommended halting recruitment after 3141 of the projected 3600 children in stratum A were enrolled. Malaria status (57% overall) and clinical severity were similar across groups. The 48-hour mortality was 10.6% (111 of 1050 children), 10.5% (110 of 1047 children), and 7.3% (76 of 1044 children) in the albumin-bolus, saline-bolus, and control groups, respectively (relative risk for saline bolus vs. control, 1.44; 95% confidence interval [CI], 1.09 to 1.90; P=0.01; relative risk for albumin bolus vs. saline bolus, 1.01; 95% CI, 0.78 to 1.29; P=0.96; and relative risk for any bolus vs. control, 1.45; 95% CI, 1.13 to 1.86; P=0.003). The 4-week mortality was 12.2%, 12.0%, and 8.7% in the three groups, respectively (P=0.004 for the comparison of bolus with control). Neurologic sequelae occurred in 2.2%, 1.9%, and 2.0% of the children in the respective groups (P=0.92), and pulmonary edema or increased intracranial pressure occurred in 2.6%, 2.2%, and 1.7% (P=0.17), respectively. In stratum B, 69% of the children (9 of 13) in the albumin-bolus group and 56% (9 of 16) in the saline-bolus group died (P=0.45). The results were consistent across centers and across subgroups according to the severity of shock and status with respect to malaria, coma, sepsis, acidosis, and severe anemia.
Conclusions
Fluid boluses significantly increased 48-hour mortality in critically ill children with impaired perfusion in these resource-limited settings in Africa.

Mortality after Fluid Bolus in African Children with Severe Infection
NEJM May 26, 2011 Full text available

American airway management in the field

I often wonder why my US colleagues are so vehemently opposed to out-of-hospital tracheal intubation. This paper provides a clue. I would love it if any EMS providers out there could comment, as I find these results staggering.
The authors comment that the data set “contains data on over 4.3 million EMS events from 16 states (Alabama, Colorado, Florida, Hawaii, Iowa, Maine, Minnesota, Missouri, North Carolina, North Dakota, Nebraska, New Hampshire, New Jersey, New Mexico, Nevada, and Oklahoma) for the one-year period January 1, 2008–December 31, 2008. These states were the first to participate in the NEMSIS project. There are no estimates of the numbers of EMS agencies or EMS responses that are not included in NEMSIS. Hawaii, New Jersey, New Mexico and Oklahoma provided only partial data for the study period because of their implementation of NEMSIS during 2008.

OBJECTIVE: Prior studies describe airway management by single EMS agencies, regions or states. We sought to characterize out-of-hospital airway management interventions, outcomes and complications across the United States.
 
METHODS: Using the 2008 National Emergency Medical Services Information System (NEMSIS) Public-Release Data Set containing data from 16 states, we identified patients receiving advanced airway management, including endotracheal intubation (ETI), alternate airways (Combitube, Laryngeal Mask Airway (LMA), King LT, Esophageal-Obturator Airway (EOA)), and cricothyroidotomy (needle and open). We examined airway management success and complications in the full cohort and in key subsets (cardiac arrest, non-arrest medical, non-arrest injury, children <10 and 10-19 years, rapid-sequence intubation (RSI), population setting and US census region). We analyzed the data using descriptive statistics.
RESULTS: Among 4,383,768 EMS activations, there were 10,356 ETI, 2246 alternate airways, and 88 cricothyroidotomies. ETI success rates were: overall 6482/8418 (77.0%; 95% CI: 76.1-77.9%), cardiac arrest 3494/4482 (78.0%), non-arrest medical 616/846 (72.8%), non-arrest injury 417/505 (82.6%), children <10 years 295/397 (74.3%), children 10-19 years 228/289 (78.9%), adult 5829/7552 (77.2%), and rapid-sequence intubation 289/355 (81.4%). ETI success was success was lowest in the South US census region. Alternate airway success was 1564/1794 (87.2%). Major complications included: bleeding 84 (7.0 per 1000 interventions), vomiting 80 (6.7 per 1000) and esophageal intubation 12 (1.0 per 1000).
CONCLUSIONS: In this study characterizing out-of-hospital airway management across the United States, we observed low out-of-hospital ETI success rates. These data may guide national efforts to improve the quality of out-of-hospital airway management.

Out-of-hospital airway management in the United States
Resuscitation. 2011 Apr;82(4):378-85

Thrombolysis in submassive PE – still equipoise?

The AHA has produced a comprehensive guideline on venous thromboembolic disease. Here are some excerpts pertaining to resuscitation room decision making, particularly: ‘should I thrombolyse this patient?’

Definition for massive PE: Acute PE with sustained hypotension (systolic blood pressure <90 mm Hg for at least 15 minutes or requiring inotropic support, not due to a cause other than PE, such as arrhythmia, hypovolemia, sepsis, or left ventricular [LV] dysfunction), pulselessness, or persistent profound bradycardia (heart rate <40 bpm with signs or symptoms of shock).
Definition for submassive PE: Acute PE without systemic hypotension (systolic blood pressure ≥90 mm Hg) but with either RV dysfunction or myocardial necrosis.
RV dysfunction means the presence of at least 1 of the following:

  • RV dilation (apical 4-chamber RV diameter divided by LV diameter >0.9) or RV systolic dysfunction on echocardiography
  • RV dilation (4-chamber RV diameter divided by LV diameter >0.9) on CT
  • Elevation of BNP (>90 pg/mL)
  • Elevation of N-terminal pro-BNP (>500 pg/mL); or
  • Electrocardiographic changes (new complete or incomplete right bundle-branch block, anteroseptal ST elevation or depression, or anteroseptal T-wave inversion)

Myocardial necrosis is defined as either of the following:

  • Elevation of troponin I (>0.4 ng/mL) or
    Elevation of troponin T (>0.1 ng/mL)

Odds ratio for short-term mortality for RV dysfunction on echocardiography = 2.53 (95% CI 1.17 to 5.50).
Troponin elevations had an odds ratio for mortality of 5.90 (95% CI 2.68 to 12.95).
Definition for low risk PE: those with normal RV function and no elevations in biomarkers with short-term mortality rates approaching ≈ 1%

Recommendations for Initial Anticoagulation for Acute PE

  • Therapeutic anticoagulation with subcutaneous LMWH, intravenous or subcutaneous UFH with monitoring, unmonitored weight-based subcutaneous UFH, or subcutaneous fondaparinux should be given to patients with objectively confirmed PE and no contraindications to anticoagulation (Class I; Level of Evidence A).
  • Therapeutic anticoagulation during the diagnostic workup should be given to patients with intermediate or high clinical probability of PE and no contraindications to anticoagulation (Class I; Level of Evidence C).

 
Patients treated with a fibrinolytic agent have faster restoration of lung perfusion. At 24 hours, patients treated with heparin have no substantial improvement in pulmonary blood flow, whereas patients treated with adjunctive fibrinolysis manifest a 30% to 35% reduction in total perfusion defect. However, by 7 days, blood flow improves similarly (≈65% to 70% reduction in total defect).
Thirteen placebo-controlled randomized trials of fibrinolysis for acute PE have been published, but only a subset evaluated massive PE specifically.
When Wan et al restricted their analysis to those trials with massive PE, they identified a significant reduction in recurrent PE or death from 19.0% with heparin alone to 9.4% with fibrinolysis (odds ratio 0.45, 95% CI 0.22 to 0.90).
Data from registries indicate that the short-term mortality rate directly attributable to submassive PE treated with heparin anticoagulation is probably < 3.0%. The implication is that even if adjunctive fibrinolytic therapy has extremely high efficacy, for example, a 30% relative reduction in mortality, the effect size on mortality due to submassive PE is probably < 1%. Thus, secondary adverse outcomes such as persistent RV dysfunction, chronic thromboembolic pulmonary hypertension, and impaired quality of life represent appropriate surrogate goals of treatment.
Data suggest that compared with heparin alone, heparin plus fibrinolysis yields a significant favorable change in right ventricular systolic pressure and pulmonary arterial pressure incident between the time of diagnosis and follow-up. Patients with low-risk PE have an unfavorable risk-benefit ratio with fibrinolysis. Patients with PE that causes hypotension probably do benefit from fibrinolysis. Management of submassive PE crosses the zone of equipoise, requiring the clinician to use clinical judgment.

An algorithm is proposed:

Two criteria can be used to assist in determining whether a patient is more likely to benefit from fibrinolysis: (1) Evidence of present or developing circulatory or respiratory insufficiency; or (2) evidence of moderate to severe RV injury.
Evidence of circulatory failure includes any episode of hypotension or a persistent shock index (heart rate in beats per minute divided by systolic blood pressure in millimeters of mercury) >1
The definition of respiratory insufficiency may include hypoxemia, defined as a pulse oximetry reading < 95% when the patient is breathing room air and clinical judgment that the patient appears to be in respiratory distress. Alternatively, respiratory distress can be quantified by the numeric Borg score, which assesses the severity of dyspnea from 0 to 10 (0=no dyspnea and 10=sensation of choking to death).
Evidence of moderate to severe RV injury may be derived from Doppler echocardiography that demonstrates any degree of RV hypokinesis, McConnell’s sign (a distinct regional pattern of RV dysfunction with akinesis of the mid free wall but normal motion at the apex), interventricular septal shift or bowing, or an estimated RVSP > 40 mm Hg.
Biomarker evidence of moderate to severe RV injury includes major elevation of troponin measurement or brain natriuretic peptides.
Two trials are currently ongoing that aim to assess effect of thrombolysis on patients with submassive PE: PEITHO and TOPCOAT

Recommendations for Fibrinolysis for Acute PE

  • Fibrinolysis is reasonable for patients with massive acute PE and acceptable risk of bleeding complications (Class IIa; Level of Evidence B).
  • Fibrinolysis may be considered for patients with submassive acute PE judged to have clinical evidence of adverse prognosis (new hemodynamic instability, worsening respiratory insufficiency, severe RV dysfunction, or major myocardial necrosis) and low risk of bleeding complications (Class IIb; Level of Evidence C).
  • Fibrinolysis is not recommended for patients with low-risk PE (Class III; Level of Evidence B) or submassive acute PE with minor RV dysfunction, minor myocardial necrosis, and no clinical worsening (Class III; Level of Evidence B).
  • Fibrinolysis is not recommended for undifferentiated cardiac arrest (Class III; Level of Evidence B).

Recommendations for Catheter Embolectomy and Fragmentation

  • Depending on local expertise, either catheter embolectomy and fragmentation or surgical embolectomy is reasonable for patients with massive PE and contraindications to fibrinolysis (Class IIa; Level of Evidence C).
  • Catheter embolectomy and fragmentation or surgical embolectomy is reasonable for patients with massive PE who remain unstable after receiving fibrinolysis (Class IIa; Level of Evidence C).
  • For patients with massive PE who cannot receive fibrinolysis or who remain unstable after fibrinolysis, it is reasonable to consider transfer to an institution experienced in either catheter embolectomy or surgical embolectomy if these procedures are not available locally and safe transfer can be achieved (Class IIa; Level of Evidence C).
  • Either catheter embolectomy or surgical embolectomy may be considered for patients with submassive acute PE judged to have clinical evidence of adverse prognosis (new hemodynamic instability, worsening respiratory failure, severe RV dysfunction, or major myocardial necrosis) (Class IIb; Level of Evidence C).
  • Catheter embolectomy and surgical thrombectomy are not recommended for patients with low-risk PE or submassive acute PE with minor RV dysfunction, minor myocardial necrosis, and no clinical worsening (Class III; Level of Evidence C).

 
Management of Massive and Submassive Pulmonary Embolism, Iliofemoral Deep Vein Thrombosis, and Chronic Thromboembolic Pulmonary Hypertension
Circulation. 2011 Apr 26;123(16):1788-1830 (Free Full Text)

FAST 1 success rates in the field

Three quarters of attempts to place the FAST 1 sternal intraosseous device were successful…

Introduction: Access to the vascular system of the critically ill or injured adult patient is essential for resuscitation. Whether due to trauma or disease, vascular collapse may delay or preclude even experienced medical providers from obtaining standard intravenous (IV) access. Access to the highly vascular intramedullary space of long bones provides a direct link to central circulation. The sternum is a thin bone easily identified by external landmarks that contains well-vascularized marrow. The intraosseous (IO) route rapidly and reliably delivers fluids, blood products, and medications. Resuscitation fluids administered by IV or IO achieve similar transit times to central circulation. The FAST-1 Intraosseous Infusion System is the first FDA-approved mechanical sternal IO device. The objectives of this study were to: (1) determine the success rate of FAST-1 sternal IO device deployment in the prehospital setting; (2) compare the time of successful sternal IO device placement to published data regarding time to IV access; and (3) describe immediate complications of sternal IO use.
Methods: All paramedics in the City of Portsmouth, Virginia were trained to correctly deploy the FAST-1 sternal IO device during a mandatory education session with the study investigators. The study subjects were critically ill or injured adult patients in cardiac arrest treated by paramedics during a one-year period. When a patient was identified as meeting study criteria, the paramedic initiated standard protocols; the FAST-1 sternal IO was substituted for the peripheral IV to establish vascular access. Time to deployment was measured and successful placement was defined as insertion of the needle, with subsequent aspiration and fluid flow without infiltration.
Results: Over the one-year period, paramedics attempted 41 FAST-1 insertions in the pre-hospital setting. Thirty (73%) of these were placed successfully. The mean time to successful placement was 67 seconds for 28 attempts; three of the 31 insertions did not have times recorded by the paramedic. Paramedics listed the problems with FAST-1 insertion, including: (1) difficulty with adhesive after device placement (3 events); (2) failure of needles to retract and operator had to pull the device out of the skin (2 events); and (3) slow flow (1 event). Emergency department physicians noted two events of minor bleeding around the site of device placement.
Conclusion: This is the first study to prospectively evaluate the prehospital use of the FAST-1 sternal IO as a first-line device to obtain vascular access in the critically ill or injured patient. The FAST-1 sternal IO device can be a valuable tool in the paramedic arsenal for the treatment of the critically ill or injured patient. The device may be of particular interest to specialty disaster teams that deploy in austere environments.

Evaluation of success rate and access time for an adult sternal intraosseous device deployed in the prehospital setting
Prehosp Disaster Med 2011;26(2):127–129

It's a bit quiet in here

Blogging has slowed a bit as I’ve been travelling to the UK and am running courses here all week.
Just in case you’re desperate to read something useful, I came across a guideline on The Management of Diabetic Ketoacidosis in Adults by the Joint British Diabetes Societies Inpatient Care Group
The guideline contain the following approaches:

  • Measurement of blood ketones, venous (not arterial) pH and bicarbonate and their use as treatment markers
  • Monitoring of ketones and glucose using bedside meters when available and operating within their quality assurance range
  • Replacing ‘sliding scale’ insulin with weight-based fixed rate intravenous insulin infusion (IVII)
  • Use of venous blood rather than arterial blood in blood gas analysers
  • Monitoring of electrolytes on the blood gas analyser with intermittent laboratory confirmation
  • Continuation of long acting insulin analogues (Lantus® or Levemir®) as normal
  • Involvement diabetes specialist team as soon as possible

There is also a section on ‘Controversial Areas’, discussing such issues as bicarbonate therapy, rate of fluid therapy, and even 0.9% saline versus Hartmann’s (Ringer’s Lactate) solution, although this part was desperately disappointing, with the following bizarre excuse given for not recommending the latter:
In theory replacement with glucose and compound sodium lactate (Hartmann’s solution) with potassium, would prevent hyperchloraemic metabolic acidosis, as well as allow appropriate potassium replacement. However, at present this is not readily available as a licensed infusion fluid.
Apart from that, this appears to be an interesting and potentially useful document.
The Management of Diabetic Ketoacidosis in Adults
Joint British Diabetes Societies Inpatient Care Group

Intubation checklist

Perhaps you’ve read the blog post and heard the podcast about the excellent NAP4 airway audit…..now you can start putting the learning points into action with the intubation checklist, developed by the regional trainee-led collaborative ‘RTIC Severn’. Thanks to Dr Tim Bowles for the link:

I’ve used an RSI checklist for both in-and-out of hospital intubations for the last seven years. The beauty of this one is the potential for it to become a standard within and between hospitals, so wherever you work the team will be on the same page when preparing for intubation.
Further details are at http://saferintubation.com

NAP 4 Podcast

Check out EMCrit.org for our Podcast interview with Professor Jonathan Benger, the Emergency Physician who contributed to the design, execution, and analysis of the important NAP 4 national airway audit, which has important learning points for all of us involved in pre-hospital, emergency, or ICU airway management.

EMCrit Podcast
2016 Update
An important follow up study showing the effect of the NAP 4 Audit:
A national survey of the impact of NAP4 on airway management practice in United Kingdom hospitals: closing the safety gap in anaesthesia, intensive care and the emergency department
Br. J. Anaesth. (2016) 117 (2): 182-190.

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

Status epilepticus review

A review on status epilepticus, differentiating complex partial status from generalised convulsive status:

PURPOSE OF REVIEW: Status epilepticus is one of the most common emergencies in neurology, and every third patient does not respond to adequate first-line treatment. Refractory status epilepticus may be associated with increased morbidity and mortality, and new treatment options are urgently required. This review critically discusses recently published data regarding the role of ‘new’ antiepileptic drugs, the efficacy and safety of anesthetic agents, and the overall clinical outcome that is an integral part of treatment decisions.
RECENT FINDINGS: In complex partial status epilepticus, levetiracetam may be administered after failure of first-line and/or second-line agents. Lacosamide may be an interesting new adjunct, but reliable data are pending. In the treatment of refractory generalized convulsive status epilepticus, propofol seems to be as efficient as barbiturates. The latter are associated with prolonged ventilation times due to redistribution kinetics, whereas the former bears the risk of propofol infusion syndrome if administered continuously. Even after prolonged treatment with anesthetics over weeks, survival with satisfactory functional outcome is possible.
SUMMARY: Unambiguous recommendations regarding treatment strategies for refractory status epilepticus are limited by a lack of reliable data. Therefore, randomized controlled trials or at least prospective observational studies based on strict protocols incorporating long-term outcome data are urgently required.

Treatment strategies for refractory status epilepticus
Curr Opin Crit Care. 2011 Apr;17(2):94-100