Anesthesia for Traumatic Brain Injury
Author: Shilpa Rao, MD
A 30-year-old male patient is emergently brought to the operating room following a motor vehicle accident earlier in the day. According to the emergency medical transport, he lost control of his vehicle and collided with a culvert, and he was not wearing a helmet at the time of the accident. Emergent non-contrast CT scan revealed a large left sided convex shaped hematoma, with a maximum width of 2.7 cm, with a 7 mm midline shift to the right. There was also associated fracture of the skull bone on the left. He is now booked for emergent decompressive craniotomy.
He arrives to the operating room with two large bore intravenous lines (18 G each) with Lactated Ringer’s solution wide open.
Past Medical History: Unable to obtain.
Physical Examination: Intubated on the field by the Emergency Medical Team, appropriate placement confirmed. Not conscious, not following commands, eyes are swollen and closed non-verbal with abnormal flexion, C-collar in place.
Cardiovascular system: sinus bradycardia, HR: 52 beats per minute, intermittently decreasing to 30s.BP 150/80 mmHg per last report.
Respiratory system: Coarse breath sounds bilaterally.
Central nervous system: unequal pupils, Left > right, blood noted in left ear canal.
Labs: Hemoglobin 12 gm/dl, basic metabolic panel: within normal limits, type and screen in progress.
Key Questions and discussion
1. What is Glasgow Coma Scale? Why is it important?
The Glasgow Coma Scale provides a practical method for assessment of impairment of conscious level in response to defined stimuli. It is based on a 15-point scale for estimating and categorizing the extent and outcomes of brain injury.1 This scale is widely used by all medical personnel and paramedics as being applicable to all acute medical and trauma events, and as part of initial and repeat assessment. The total score as well as the individual elements indicate the severity and prognosis of the inciting event. Generally, brain injury is classified as:
- Severe, GCS < 8–9
- Moderate, GCS 8 -12
- Minor, GCS ≥ 13
Tracheal intubation and severe facial/eye swelling or damage make it impossible to test the verbal and eye responses. In these circumstances, the score is given as 1 with a modifier attached (either “t” for intubation or “c” for eyes closed).2
To verbal command
|Best verbal Response||Oriented, conversing
No verbal response
Best Motor Response
|Obeys verbal commands
Localizes to pain
Withdrawal to pain
Abnormal flexion (decorticate)Abnormal extension (decerebrate)No motor response
Moderate to severe scores may warrant intubation and airway protection as these patients are at an increased risk of aspiration of gastric contents and/or respiratory depression.
In this patient, the GCS may be calculated as E1cV1tM3 = 5.
The GCS Pupils Score (GCS-P) was recently described.3 It is calculated by subtracting the Pupil Reactivity Score (PRS) from the GCS to yield a total score.
PRS is calculated as follows:
Pupils Unreactive to Light
Pupil Reactivity Score
Separately, the GCS score and pupil response were each correlated with outcome. Adding information about the pupil response to the GCS score increased the information yield. The performance of the simple GCS-P was similar to the performance of more complex methods of evaluating traumatic brain damage. The relationship between decreases in the GCS-P and deteriorating outcome was seen across the complete range of possible scores.3
2. What are the key components of a primary survey in a major trauma? Why is it important? (ATLS)
The primary survey comprises assessment and management of “ABCDE” – Airway maintenance, Breathing and Ventilation, Circulation / active bleeding, Disability/ neurologic assessment and Exposure and environment control. Ideally, most of these are performed by first responders arriving at the scene, prior to transfer to the hospital.
Basic pre-hospital skills include airway management (e.g., maneuvers to open an airway, airway adjuncts, and bag-mask ventilation), cardiopulmonary resuscitation and automated external defibrillation, hemorrhage control, and fracture and spine immobilization.
During this time, life threatening injuries are identified and resuscitation is simultaneously initiated. If the patient is not able to maintain his/her own airway, then basic airway maneuvers are tried first (head tilt/chin lift – caution needs to be exercised before moving the head in a suspected head injury or a C-spine injury patient.) The risk of concurrent cervical spine fracture in TBI patients is high, 1.7- 8.5%, and one should therefore have a high suspicion in all TBI patients. If these fail, immediate endotracheal intubation must be performed in order to secure the airway. This also facilitates mechanical ventilation and helps reduce intracranial pressure (ICP). Ongoing evaluation and treatment is required en-route to the hospital/ tertiary trauma center.
A quick physical examination and use of FAST (Focused Assessment with Sonography in Trauma) of the chest and abdomen will help rule out life threatening conditions such as tension pneumothorax, hemothorax, flail chest, cardiac tamponade, hemoperitoneum etc. which warrant immediate attention. Again, the GCS is a useful tool for neurologic assessment and aids in determining patient outcome.
Further detailed examination can proceed once the primary survey is completed and resuscitation efforts are in progress.4
3. Why is airway protection and mechanical ventilation important in this patient?
Airway protection and mechanical ventilation are of utmost importance in this particular patient. He is unable to protect his own airway, which places him at risk of aspiration of gastric contents, respiratory depression leading to increased PaCO2 and further increased ICP.
In addition, he will require emergent decompressive craniotomy in the operating room, which warrants intubation and mechanical ventilation.
4. Do you think this patient has raised ICP? What are your plans to prevent a rise in ICP during induction and intubation?
Early signs of rising intracranial pressure include decreased level of consciousness, restlessness, irritability and confusion. With a continued increase, speech, voluntary movements, sensations and extraocular movements will slow. Additionally, T-wave elevation will develop on the electrocardiogram. As pressure increases near the medulla, the patient may experience projectile vomiting with no associated nausea, and cardiac arrhythmias can range from supraventricular tachycardia to severe bradycardia. As coma develops, reaction to painful stimuli will become reflexive and may disappear completely. When herniation of the brain is imminent, loss of extraocular movement will occur, with the pupils dilating, becoming unreactive and turning outward.5
This patient has raised ICP as evidenced by an inciting event (history of motor vehicle accident with head injury), and the clinical signs and symptoms he has presented with, including Cushing’s reflex (hypertension, bradycardia and apnea) to compensate for the increasing ICP. In addition, the CT scan reveals a midline shift of 2.7 cm, leading to compressive symptoms.
The techniques and medications used in airway management can increase ICP. Specifically, laryngoscopy and intubation can acutely increase ICP and can worsen existing brain injury, or cause stroke, encephalopathy or acute herniation. When time allows, if the patient is awake and assuming stable hemodynamics, pre-treatment with carefully titrated doses of short acting narcotics (e.g., fentanyl) (grade 2C evidence)6 and/or lidocaine intravenously can help blunt the sympathetic response to laryngoscopy and intubation. Extreme caution needs to be exercised while using narcotics in a patient who is unstable, obtunded and at increased risk of aspiration; it is wise to avoid narcotics in such a situation altogether until the airway is secured. In multiple small randomized trials, the short-acting beta blocker esmolol given at a dose of 2 mg/kg IV, has demonstrated the ability to control both heart rate and blood pressure responses to intubation.7,8
Positioning the patient head up by 15-30 degrees, also helps to lower the ICP, as well as lower aspiration risk. The choice of induction agent depends on the hemodynamic stability as discussed earlier
5. Assuming he was not yet intubated, how would you perform induction of anesthesia and intubation in this patient? Do you want to remove the C-collar for intubation? Would you consider Rapid Sequence induction?
The goals of anesthetic induction include:
- To minimize hemodynamic responses to laryngoscopy and intubation, which may affect ICP.
- To maintain cerebral perfusion pressure (CPP), which is defined as mean arterial pressure (MAP) – ICP (or central venous pressure, whichever is higher).
- To minimize C-spine movement during laryngoscopy and intubation.
- To rapidly and safely secure the endotracheal tube.
After attaching standard ASA monitors, adequate pre-oxygenation is performed with 100% oxygen. Since this is an emergent situation, with the possibility of inadequate airway assessment due to patient non co-operation, difficult airway equipment such as video-laryngoscope/ fiberoptic cart must be readily available. Adequate venous access needs to be ensured. Any induction agent can be used in appropriate doses, depending on the patient’s hemodynamic status. Etomidate (0.3 mg/kg IV) can be used for induction in patients with RSI, and might be advantageous because of its hemodynamically stable profile. Propofol (2mg/kg) can alternatively be used for induction, however large boluses might result in significant hypotension. Hypotension is detrimental in traumatic brain injury and must be avoided at all costs. A rapid sequence induction and intubation protects the airway from possible aspiration of gastric contents and can be performed.
However, no outcome studies have been performed to determine the best approach to airway management in these patients. The approach should be individualized, with the goal of rapidly and safely securing the airway.
A commonly used practice is removing the anterior half of a semi-rigid collar and having an assistant provide manual in-line stabilization during intubation. This maneuver is achieved with the assistant standing at the head or side of the bed and using the fingers and palms of both hands to stabilize the patient’s occiput and mastoid processes to gently counteract the forces of airway intervention. However, Nolan et al found that, when compared with sniffing position, manual inline stabilization decreased laryngoscopic view of the glottis in 45% of patients, that 22% of patients had a grade III (epiglottis only) view with inline stabilization, and that using a gum-elastic bougie greatly increased the rate of successful intubation within 45 seconds.9
While manual inline stabilization anchors the occiput and the torso anchors the lower cervical spine, it is likely that laryngoscopic forces can still be translated to the mid-cervical spine. It is important to note that the anterior collar should be replaced after the airway is secured and the collar should be worn during other movements such as from a stretcher to an operating room (OR) table.10
It is important to avoid nasotracheal intubation in this patient due to the possibility of basilar skull fracture as is suggested by the blood in the ear canal.
6. What intraoperative monitors would you like to use and why?
Apart from standard ASA monitors, an arterial line is useful for invasive hemodynamic monitoring and to check serial arterial blood gases for hemoglobin, glucose, electrolytes, etc. A Foley catheter is required to monitor urine output.
The use of end tidal carbon dioxide monitoring along with PaCO2 correlation is useful in avoiding hypercarbia which can increase ICP as well as hypocarbia which may worsen cerebral ischemia.
A central venous catheter may be placed if the patient requires Hypertonic saline (3% or higher concentrations) infusions or for long term venous access in the Intensive Care unit. This can be done under ultrasound guidance. In addition to the time concerns, placement of a jugular line will almost certainly require movement of the cervical spine, which should be avoided in TBI patients. Placement of a subclavian line is associated with higher risk of pneumothorax, which can rapidly increase PaCO2 and ICP. Hence the risks and benefits must be carefully considered. However, surgery should not be delayed for the placement of these lines due to its emergent nature.
If the patient already has an external ventricular drain (EVD) in situ, ICP can be monitored through the EVD transducer via a three way stopcock. This is useful in determining cerebral perfusion pressure and facilitates drainage of CSF to reduce ICP.
7. Discuss fluid management in this patient. What is your intravenous fluid of choice?
In general, patients with elevated ICP do not need to be severely fluid restricted.11 Patients should be kept euvolemic and normo- to hyperosmolar. This can be achieved by avoiding all free water (including D5W, 0.45 percent (half normal) saline, and enteral free water) and employing only isotonic fluids (such as 0.9 percent (normal) saline). Serum osmolality should be kept >280 mOsm/L, and often is kept in the 295 to 305 mOsm/L range. Hyponatremia is common in the setting of elevated ICP, particularly in conjunction with subarachnoid hemorrhage.
Similarly, the value of colloid compared to crystalloid fluid resuscitation in patients with elevated ICP has been studied, but findings have been inconclusive with respect to the superior approach. A subgroup analysis in one large study, however, suggested that in patients with traumatic brain injury, fluid resuscitation with albumin was associated with a higher mortality as compared with normal saline.12
8. After opening the bone flap, the surgeon states that the dura is still tense and requests further brain relaxation. What are the techniques you can employ to facilitate this?
Patients with elevated ICP should be positioned head up, to maximize venous outflow from the head. It is important to avoid excessive flexion or rotation of the neck, restrictive neck taping, and minimizing stimuli that could induce Valsalva responses, such as endotracheal suctioning.
Keeping patients appropriately sedated and relaxed while under anesthesia can decrease ICP by reducing metabolic demand, ventilator – patient dyssynchrony, venous congestion, and the sympathetic responses of hypertension and tachycardia. Again, continued mechanical ventilation to lower PaCO2 to 26 to 30 mmHg has been shown to rapidly reduce ICP through vasoconstriction and a decrease in the volume of intracranial blood; a 1 mmHg change in PaCO2 is associated with a 3 percent change in CBF.13 There are several more recent recommendations against hyperventilation in the first 24 hours after TBI. In the first 24 hours after injury, even mild hyperventilation will cause vasoconstriction and ischemia in the injured brain areas and worsens neurological outcomes. The only time that hyperventilation can be considered in the first 24 hours is if ICP is critically high and there is a concern for immediate herniation. Even in this scenario, the period of hyperventilation should be very brief.14
Some of the specific medications to be considered in this setting include:
Osmotic diuretics: Mannitol is the most commonly used agent. It reduces brain volume by drawing free water out of the brain tissue and into the circulation, to be excreted by the kidneys, thereby reducing ICP and improving Cerebral Blood flow. The commonly used dose is 1 gm/kg bolus of a 20% solution. Onset is usually within 15-20 minutes, and the duration of action is 4-8 hours. Some of the complications associated with mannitol therapy include volume depletion, initially hyponatremia and subsequentlyhypernatremia. If very high doses of hypertonic mannitol are infused, or if the drug is given to patients with preexisting renal failure, mannitol is retained in the circulation. The ensuing rise in plasma osmolality, similar to that produced by hyperglycemia, results in the osmotic movement of water and potassium out of cells leading to extracellular fluid volume expansion (and possibly pulmonary edema), hyponatremia, metabolic acidosis (by dilution), and hyperkalemia.15,16
Hypertonic Saline: Hypertnonic saline is an effective agent to reduce ICP. This agent has been used in a wide range of concentrations, from 3%, most commonly used as a continuous infusion, to 23.4%, which is typically used in intermittent boluses. When used as a continuous infusion, 3 percent NaCl may be titrated to a sodium goal of approximately 145 to 155 mEq/L. Hypertonic saline should be administered via a central venous catheter because of the risk of extravasation injury when used with peripheral intravenous (IV) access. Short-term use via peripheral IV access is permissible in the setting of acute ICP elevation, however, while central access is obtained.17,18
- If the patient has a functioning EVD, CSF can be drained carefully to reduce ICP, and the stopcock closed after the required amount is drained.
- Other aspects of management include:
- Anti-seizure medications: The incidence of early post-traumatic seizures (within the first week or two) may be as high as 30 percent in patients with severe TBI.19 Reasons to prevent early seizures include the risk of status epilepticus, which has a high fatality rate in this setting, and the potential of convulsions to aggravate a systemic injury, in addition to further increasing ICP.20
In addition, a case series suggest that approximately 15 to 25% of patients with coma and severe head injury will have non-convulsive seizures identified on continuous monitoring with electroencephalography (EEG), the clinical significance of which is unclear. Intravenous levetiracetam 500-1000 mg every 12 hours is commonly used for up to 7 days for seizure prophylaxis. A randomized clinical trial that compared levetiracetam with phenytoin for seizure prophylaxis in neurosurgical ICU patients (89 percent with TBI) revealed equivalent efficacy for seizure prevention but improved six-month functional outcomes with levetiracetam.21
– Deep Venous Thrombosis (DVT) Prophylaxis: Intermittent Pneumatic Compression Stockings are commonly used. Although DVT risk can be further reduced with antithrombotic therapy, this has to be weighed against the potential risk of hemorrhage expansion, which is greatest in the first 24 to 48 hours.2
–Glucose Control: Both hyper- and hypoglycemia are associated with worsened outcome in a variety of neurologic conditions including severe TBI and hence need to be avoided. Hyperglycemia is particularly common in TBI patients, hence frequent glucose monitoring and control is imperative during the perioperative period.. This has been presumed to be at least in part related to aggravation of secondary brain injury. Several mechanisms for this are proposed, including increased tissue acidosis from anaerobic metabolism, free radical generation, and increased blood-brain barrier permeability.23 Insulin needs to be used judiciously to avoid hypoglycemia, which can also be detrimental in these patients.
– Induced or therapeutic hypothermia: Hypothermia has remained a controversial issue in the debate concerning the management of elevated ICP. It is currently not recommended as a standard treatment for increased ICP in any clinical setting, except perhaps as a last resort in refractory intracranial hypertension. Hypothermia decreases cerebral metabolism and may reduce ICP. A systematic review of 37 randomized controlled trials, including 3110 subjects, of mild to moderate hypothermia (32 to 35°C) following TBI concluded that there was no high-quality evidence that hypothermia is beneficial following TBI for the goal of improving meaningful long-term outcomes.24
– Temperature Control: Fever worsens outcome after stroke and probably severe head injury, presumably by aggravating secondary brain injury. Fever also worsens ICP control through an increase in metabolic demand, blood flow, and blood volume. Early (within 2.5 Hours), short term (48 hours post injury) prophylactic hypothermia is not recommended to improve outcomes in patients with diffuse injury.25 Current approaches emphasize maintaining normothermia through the use of antipyretic medications, surface-cooling devices, or endovascular temperature management catheters. While induced normothermia using endovascular cooling and a continuous feedback-loop system has been shown to lower the fever burden and improve ICP control following TBI.26
– Glucocorticoids: Administration of exogenous glucocorticoids were associated with a worse outcome in a large randomized clinical trial of their use in moderate to severe head injury, and are therefore contraindicated after TBI.27
–Barbiturates: Pentobarbital and thiopental infusions may be used to manage elevated ICP refractory to other therapies. While effective for the control of ICP, the use of barbiturate coma has not been shown to improve outcomes following TBI. These agents profoundly decrease cerebral metabolic demand, CBF, and cerebral blood volume. 28,29
Ultimately, surgical treatment is the mainstay of therapy and is potentially lifesaving. Decompressive craniectomy removes the rigid confines of the bony skull, increasing the potential volume of the intracranial contents and circumventing the Monroe-Kellie doctrine. There is a growing body of literature supporting the efficacy of decompressive craniectomy in certain clinical situations. It has been demonstrated that in patients with elevated ICP, craniectomy alone lowered ICP 15%, but opening the dura in addition to the bony skull resulted in an average decrease in ICP of 70%.30
Clinical trials of decompressive craniectomy in TBI suggest that the procedure is effective in controlling ICP and is lifesaving in patients who have failed medical therapy. However, patients who require decompressive craniectomy for the management of intracranial hypertension following TBI have suffered particularly severe brain injury and may be left in a state of severe disability or worse. Conclusions from clinical trials are somewhat limited in short follow-up time; functional recovery following severe TBI may be delayed beyond one year of follow-up.
A randomized trial (DECRA) in 155 adults with severe diffuse TBI and ICP >20 mmHg for 15 minutes within a one-hour period despite first-tier therapies compared bifrontal craniectomy with continued medical 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 and a greater risk of an unfavorable outcome.31
The RESCUEicp trial used more broadly applicable eligibility criteria; 408 patients ages 10 to 65 years old with refractory ICP >25 mmHg for 1 to 12 hours despite medical therapy were randomized to continued medical therapy or craniectomy appropriate to the nature of injury. Patients requiring hematoma evacuation were included. Control of ICP was improved in the surgical arm. At six months, patients in the surgical group had lower mortality (27 versus 49 percent) but higher rates of vegetative state (8.5 versus 2.1 percent), lower severe disability (dependent on others for care in the home; 22 versus 14 percent), and upper severe disability (independent within but not outside of the home; 15 versus 8 percent), these outcomes likely reflecting those of patients who would not otherwise have survived. Rates of moderate disability and good recovery were similar between the two groups (23 versus 20 percent and 4 versus 7 percent, respectively). The intention to treat analysis with 37 percent crossover from medical to surgical treatment likely diluted the apparent treatment effect. A prespecified analysis of outcomes at one year revealed that the surgical group had a higher rate of favorable outcomes (defined as better than lower severe disability or, i.e. functionally independent within the home or better) of 45 versus 32 percent.32
9. The surgery proceeds with evacuation of the hematoma. You notice a decrease in the Hemoglobin to 6 gm/dl. Would you transfuse?
The transfusion goal is to maintain oxygen carrying capacity and improve clinical outcomes, while at the same time avoiding unnecessary blood transfusions.
In the setting of trauma, loss of circulating blood volume from hemorrhage is the most common cause of shock. Inadequate oxygenation, mechanical obstruction (e.g., cardiac tamponade, tension pneumothorax), neurologic dysfunction (e.g., high-spinal cord injury), and cardiac dysfunction represent other potential causes or contributing factors. Hemorrhagic shock is a common and frequently treatable cause of death in injured patients and is second only to traumatic brain injury as the leading cause of death from trauma.33,34
Resuscitation should begin with crystalloids, and blood products are given as soon as the need is recognized, especially in the setting of ongoing blood loss. This improves oxygen carrying capacity and hemoglobin alone is not a reliable indicator in acute bleeding. Multiple factors should be taken into consideration prior to making a clinical decision, including patient’s age, co morbidities, symptoms and ongoing bleeding.
In summary, there is excellent clinical trial evidence that suggests that a restrictive policy of transfusion at a hemoglobin concentration of 7 to 8 g/dL should guide transfusion decisions in most patients. The use of transfusion thresholds that restrict transfusion to this hemoglobin concentration are safe in most patient populations, may improve clinical outcomes, and will reduce unnecessary transfusion.35
In addition to the above, all trauma patients are required to have large bore intravenous access and / or central venous access, and an active type and screen.
10. What are the important post-operative concerns in this patient. Do you wish to extubate this patient at the end of the surgery?
Although post-operative extubation is preferred in most elective neurosurgeries to facilitate neurological exams, this patient has severe traumatic brain injury, hence is it important to continue close hemodynamic and ICP monitoring as well as mechanical ventilation in the post-operative period. This allows sufficient time for neurological recovery, as well as assessment of any further injuries that may need to be addressed.
Some of the important physiologic changes in the peri-operative period include disruption of cerebral autoregulation, leading to cerebral edema and decreased cerebral perfusion pressure, in addition to disruption of ionic homeostasis, neurotransmitter release, mitochondrial dysfunction, apoptosis and inflammatory responses. The central mechanisms of dysregulation after brain injury may contribute to the development and progression of extra cerebral organ dysfunction by promoting systemic inflammation that have the potential for medical complications. Complications such as pneumonia, sepsis, or multiple organ dysfunction syndrome are the leading causes of late morbidity and mortality in many types of brain damage.36
11. How does the approach to management differ if this was a pregnant patient?
Although the basics of management (ABCDE as discussed earlier) remain the same, the approach to evaluation and management of Traumatic Brain Injury in a pregnant patient is influenced by the gestational age of the patient. The obstetrical service should be consulted as early as possible to determine the gestational age and viability of the fetus. The approach includes saving the mother first and then the fetus. Some of the considerations include:
- Normal anatomic and physiologic changes related to pregnancy need to be considered when evaluating these patients.
- Maintaining adequate oxygenation and cardiac perfusion in the mother is of utmost importance in this patient.
- Caesarean delivery for maternal resuscitation is only warranted if the uterus is above the umbilicus, which can compress the vena cava, reduce venous return and impede maternal resuscitation.
- Caesarean delivery for fetal indication is warranted if the gestational age is above 23 weeks due to possible neonatal viability beyond this gestational age.
- Left uterine displacement to achieve a 30 degree tilt by placing pillows/wedge etc. is critical in maximizing cardiac output and improving resuscitation efforts.
- External chest compressions are more difficult in pregnancy due to reduced chest compliance and aortocaval compression in the supine position in later stages of pregnancy.
- Fetal assessment can be performed by continuous fetal heart rate monitoring, ultrasound assessment of fetus and placenta, non-stress test, etc. Ultrasound examination is important in diagnosing abruptio placentae, feto-maternal bleeding, uterine rupture, etc., especially if abdominal trauma is involved.37
- Paul M.Brennan, Gordon Murray et al. Simplifying the use of prognostic information in traumatic brain injury. Part 1 : The GCS-Pupils score: an extended index of clinical severity. Journal of Neurosurgery June 2018. Vol.12 : 6, 1612-1620.
- Committee on Trauma, American College of Surgeons(2008). ATLS: Advanced Trauma Life Support Program for Doctors (8th ed.). Chicago: American College of Surgeons
- Molnar C, Nemes C, Szabo S, Fulesdi B. Harvey Cushing, a pioneer of neuroanesthesia. J Anesth 22(4): 483–6, 2008.
- Hussain AM, Sultan ST. Efficacy of fentanyl and esmolol in the prevention of haemodynamic response to laryngoscopy and endotracheal intubation. J Coll Physicians Surg Pak 2005; 15:454.
- Oda Y, Nishikawa K, Hase I, Asada A. The short-acting beta1-adrenoceptor antagonistsesmolol and landiolol suppress the bispectral index response to tracheal intubation during sevoflurane anesthesia. AnesthAnalg 2005; 100:733.
- Nolan JP, Wilson ME. Orotracheal intubation in patients with potential cervical spine injuries. An indication for the gum elastic bougie. 1993;48:630–3
- Naola Austin et al. Airway management in cervical spine injury. Int J CritIllnInj Sci. 2014 Jan-Mar; 4(1): 50–56.
- Tranmer BI, Iacobacci RI, Kindt GW. Effects of crystalloid and colloid infusions on intracranial pressure and computerized electroencephalographic data in dogs with vasogenic brain edema. Neurosurgery 1989; 25:173.
- SAFE Study Investigators, Australian and New Zealand Intensive Care Society Clinical Trials Group, Australian Red Cross Blood Service, et al. Saline or albumin for fluid resuscitation in patients with traumatic brain injury. N Engl J Med 2007; 357:874.
- McLone D. Pediatric Neurosurgery: Surgery of the Developing Nervous System, 4th, W.B. Saunders, Philadelphia 2001. p.626.
- Godoy DA, Seifi A, Garza D, Lubillo-Montenegro S, Murillo-Cabezas F. Hyperventilation Therapy for Control of Posttraumatic Intracranial Hypertension. Front Neurol. 2017 Jul 17;8:250.
- Manninen PH, Lam AM, Gelb AW, Brown SC. The effect of high-dose mannitol on serum and urine electrolytes and osmolality in neurosurgical patients. Can J Anaesth 1987; 34:442.
- Fanous AA, Tick RC, Gu EY, Fenstermaker RA. Life-Threatening Mannitol-Induced Hyperkalemia in Neurosurgical Patients. World Neurosurg 2016; 91:672.e5.
- Shackford SR, Bourguignon PR, Wald SL, et al. Hypertonic saline resuscitation of patients with head injury: a prospective, randomized clinical trial. J Trauma 1998; 44:50.
- Ware ML, Nemani VM, Meeker M, et al. Effects of 23.4% sodium chloride solution in reducing intracranial pressure in patients with traumatic brain injury: a preliminary study. Neurosurgery 2005; 57:727.
- Temkin NR. Risk factors for posttraumatic seizures in adults. Epilepsia 2003; 44 Suppl 10:18.
- Vespa PM, Nuwer MR, Nenov V, et al. Increased incidence and impact of nonconvulsive and convulsive seizures after traumatic brain injury as detected by continuous electroencephalographic monitoring. J Neurosurg 1999; 91:750.
- Szaflarski JP, Sangha KS, Lindsell CJ, Shutter LA. Prospective, randomized, single-blinded comparative trial of intravenous levetiracetam versus phenytoin for seizure prophylaxis. Neurocrit Care 2010; 12:165.
- Norwood SH, Berne JD, Rowe SA, et al. Early venous thromboembolism prophylaxis with enoxaparin in patients with blunt traumatic brain injury. J Trauma 2008; 65:1021.
- Rovlias A, Kotsou S. The influence of hyperglycemia on neurological outcome in patients with severe head injury. Neurosurgery 2000; 46:335.
- Lewis SR, Evans DJW, Butler AR, Schofield-Robinson OJ, Alderson P. Hypothermia for traumatic brain injury. Cochrane Database of Systematic Reviews 2017, Issue 9. Art. No.: CD001048
- Puccio AM, Fischer MR, Jankowitz BT, et al. Induced normothermia attenuates intracranial hypertension and reduces fever burden after severe traumatic brain injury. Neurocrit Care 2009; 11:82.
- Roberts I, Yates D, Sandercock P, et al. Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial. Lancet 2004; 364:1321.
- Roberts I, Sydenham E. Barbiturates for acute traumatic brain injury. Cochrane Database Syst Rev 2012; 12:CD000033.
- Brain Trauma Foundation, American Association of Neurological Surgeons, Congress of Neurological Surgeons, et al. Guidelines for the management of severe traumatic brain injury. XI. Anesthetics, analgesics, and sedatives. J Neurotrauma 2007; 24 Suppl 1:S71.
- Jourdan C, Convert J, Mottolese C, et al. [Evaluation of the clinical benefit of decompression hemicraniectomy in intracranial hypertension not controlled by medical treatment]. Neurochirurgie 1993; 39:304.
- Cooper DJ, Rosenfeld JV, Murray L, et al. Decompressive craniectomy in diffuse traumatic brain injury. N Engl J Med 2011; 364:1493.
- Hutchinson PJ, Kolias AG, Timofeev IS, et al. Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension. N Engl J Med 2016; 375:1119.
- Britt LD, Weireter LJ Jr, Riblet JL, et al. Priorities in the management of profound shock. SurgClin North Am 1996; 76:645.
- Siegel JH. The effect of associated injuries, blood loss, and oxygen debt on death and disability in blunt traumatic brain injury: the need for early physiologic predictors of severity. J Neurotrauma 1995; 12:579.
- Kosaku Kinoshita. Traumatic Brain Injury: pathophysiology for neurocritical care. J.Intensive Care. 2016;4:29