Severe Traumatic Brain Injury

ISOLATED BRAIN INJURY AS A CAUSE OF HYPOTENSION IN THE BLUNT TRAUMA PATIENT

Mahoney, E.J., et al, J Trauma 55(6):1065, December 2003

 

THE RELATIONSHIP OF INTRAOCULAR PRESSURE TO INTRACRANIAL PRESSURE
Ann Emerg Med 43(5):585, May 2004

METHODS: In this prospective study, from Ohio State University, the correlation between IOP and ICP was evaluated in 27 ICU patients without known glaucoma who were undergoing invasive monitoring of ICP due to a variety of conditions that included intracranial hemorrhage, ischemic stroke, trauma, tumor or shunt malfunction. A total of 76 measurements of IOP with a handheld Tono-Pen XL applanation tonometer were performed simultaneously with invasive ICP measurement.

RESULTS: At a cut-off of 20 mmHg as an indicator of pressure elevation, the sensitivity and specificity of IOP measurement for elevated ICP were each 100%. All patients with elevated ICP had increased IOP, and all with normal IOP had normal ICP. Although there was a high overall correlation between IOP and ICP (r=0.83), differences between the two parameters were increased with increasing pressure levels and the potential difference between the two techniques at higher ICP ranges could be as great as 40cm H2O.

CONCLUSIONS: Results from this pilot study require verification, but suggest that noninvasive measurement of IOP might prove to be a useful indicator of elevated ICP. 19 references (hiestand-1@medctr.osu.edu)
 

Signs on Herniation

Unilateral or bilateral unreactive, dilated pupil
Extensor posturing (decerebrate)
A sharp decline in GCS

 

decerebrate posturing=brainstem dysfunction

decorticate posturing=brainstem functioning

 

---

Reversal of Antiocogaulation and Antiplatelet Drugs

 

---

 

Cochrane Database Syst Rev. 2005 Oct 19;(4):CD001049. Related Articles, Links


Update of:
Cochrane Database Syst Rev. 2003;(2):CD001049.

Mannitol for acute traumatic brain injury.

Wakai A, Roberts I, Schierhout G.

St Vincent's Hospital, Department of Emergency Medicine, Dublin 4, Ireland. wakai@indigo.ie

BACKGROUND: Mannitol is sometimes effective in reversing acute brain swelling, but its effectiveness in the ongoing management of severe head injury remains unclear. There is evidence that, in prolonged dosage, mannitol may pass from the blood into the brain, where it might cause increased intracranial pressure. OBJECTIVES: To assess the effects of different mannitol therapy regimens, of mannitol compared to other intracranial pressure (ICP) lowering agents, and to quantify the effectiveness of mannitol administration given at other stages following acute traumatic brain injury. SEARCH STRATEGY: The review drew on the search strategy for the Injuries Group as a whole. We checked reference lists of trials and review articles, and contacted authors of trials. The searches were last updated in April 2005. SELECTION CRITERIA: Randomised trials of mannitol, in patients with acute traumatic brain injury of any severity. The comparison group could be placebo-controlled, no drug, different dose, or different drug. We excluded cross-over trials, and trials where the intervention was started more than eight weeks after injury. DATA COLLECTION AND ANALYSIS: The reviewers independently rated quality of allocation concealment and extracted the data. Relative risks (RR) and 95% confidence intervals (CI) were calculated for each trial on an intention to treat basis. MAIN RESULTS: In the acute management of comatose patients with severe head injury, the administration of high-dose mannitol resulted in reduced mortality (RR= 0.56; 95% CI 0.39 to 0.79) and reduced death and severe disability (RR= 0.58; 95% CI 0.47 to 0.72) when compared with conventional-dose mannitol. One trial compared ICP-directed therapy to 'standard care' (RR for death= 0.83; 95% CI 0.47 to 1.46). One trial compared mannitol to pentobarbital (RR for death= 0.85; 95% CI 0.52 to 1.38). One trial compared mannitol to hypertonic saline (RR for death= 1.25; 95% CI 0.47 to 3.33). One trial tested the effectiveness of pre-hospital administration of mannitol against placebo (RR for death= 1.75; 95% CI 0.48 to 6.38). AUTHORS' CONCLUSIONS: High-dose mannitol may be preferable to conventional-dose mannitol in the acute management of comatose patients with severe head injury. Mannitol therapy for raised ICP may have a beneficial effect on mortality when compared to pentobarbital treatment, but may have a detrimental effect on mortality when compared to hypertonic saline. ICP-directed treatment shows a small beneficial effect compared to treatment directed by neurological signs and physiological indicators. There are insufficient data on the effectiveness of pre-hospital administration of mannitol.
 

Vialet 2003 compared mannitol to hypertonic saline. Eligible
patients were those with severe head injury (GCS8) who required
intravenous infusions of an osmotic agent to treat episodes
of intracranial hypertension resistant to standard therapy (cerebrospinal
uid drainage, volume expansion and/or inotropic support,
hyperventilation). The mannitol group received 20% mannitol
solution. The hypertonic saline group received 7.5% hypertonic
saline. The infused volume was the same for both solutions:

2 ml/kg body weight in 20 minutes. The aim was to decrease ICP

to .25 mm Hg or to increase CPP to .70 mm Hg. In case the

rst infusion failed, the patient received a second infusion within

ten minutes after the end of the rst infusion. Treatment failure

was de ned as the inability to decrease ICP to .35 mm Hg or to

increase CPP to .70mmHg with two consecutive infusions of the

selected osmotic solution. In that case, the protocol was stopped,

and patients were followed up for mortality or 90-day neurologic

status. Because 20% mannitol can crystallize at ambient temperature,

injections could not be performed in a blinded manner.

Twenty patients were randomised, ten to each group. Outcome

was assessed at 90 days using the Glasgow Outcome Scale administered

by a practitioner who was blind to acute patient care.

 

One trial compared mannitol to hypertonic saline (Vialet 2003).

This trial was randomised and single blind. Only patients with

head injury and persistent coma who required osmotherapy to treat

episodes of intracranial hypertension resistant to standard therapy

were included. For mannitol compared to hypertonic saline in

the treatment of refractory intracranial hypertension episodes in

comatose patients with severe head injury, the RR for death was

1.25 (95% CI 0.47 to 3.33).

 

---

 

Brain oedema peaks at 3–5 days after hemispheric strokes. Patients with brainstem or cerebellar strokes might develop substantial oedema in the first couple of days. Few patients develop enough oedema to warrant medical intervention.¹⁹³ Patients requiring intervention usually have large multilobar infarctions.^{194, 195, 196 and 197} Cerebellar infarctions with oedema can obstruct flow of cerebrospinal fluid, leading to acute hydrocephalus and increased intracranial pressure.¹⁹²

---

Hypertonic Saline Reduced Intracranial Pressure From Brain Trauma

Article content is available to ACEP members only; if you are an ACEP member, but do not have a Web account, please take a moment to create one now.

SAN FRANCISCO (EGMN)-Osmotic therapy using hypertonic saline reduced intracranial hypertension in 24 patients with traumatic brain injury while improving cerebral perfusion pressure and brain tissue oxygen levels, Dr. Archie Defillo reported.

The treatments caused no complications in these patients. Judging from the findings of this small series of patients, hypertonic saline appears to be a safe alternative to mannitol for osmotic therapy to control intracranial pressure after traumatic head injury, Dr. Defillo said at the annual meeting of the American Association of Neurological Surgeons.

With his associates, Dr. Defillo reviewed records on head trauma patients with intracranial pressure greater than 20 mm Hg for longer than 20 minutes in the absence of response to nociceptive stimuli, and who had not received other osmotic agents after traumatic brain injury. The 24 patients were infused with 30 ml of 23.4% sodium chloride solution over a 15-minute period. Patients with low hemoglobin levels received blood transfusion to maintain a constant oxygen delivery.

The hypertonic saline decreased intracranial pressure absolute values by a mean of 35% from baseline, consisting of a 10 mm Hg decrease in the first hour and an 8 mm Hg decrease sustained in hours 2-6, said Dr. Defillo of Hennepin County Medical Center, Minneapolis.

"Six millimeters of mercury can be the difference between profound ischemia and normal brain tissue oxygen values," he noted.

Cerebral perfusion pressures and brain tissue oxygen levels improved over the course of osmotic therapy. Cerebral perfusion pressures increased by a mean 14% (8 mm Hg/hr). Brain tissue oxygen levels showed a steady, linear increase ranging from 3% after the first hour of hypertonic saline to 25% by 6 hours after infusion.

Mean arterial pressures remained stable, with the only significant change being a 4 mm Hg decrease 6 hours after infusion.

The greatest benefit from hypertonic saline osmotic therapy was seen in patients with higher intracranial pressure or lower cerebral perfusion pressure.

Hypertonic saline does not cause the rebound effect that can be seen with mannitol, Dr. Defillo noted. Repeat doses of hypertonic saline were not associated with fluid depletion, hypovolemia, or hypertension.

The next research step should be a prospective trial comparing hypertonic saline with mannitol for osmotic therapy in head trauma patients, commentators suggested.

Traumatic brain injury can lead to increased intracranial pressure due to brain edema, blood clots, subdural hematomas, or other intracerebral hemorrhages. The mainstay of nonsurgical management is osmotic therapy.

Copyright 2006 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

 

Hypertonic Saline a Viable Treatment for Controlling Intracranial Pressure in Patients with Traumatic Brain Injury Contact:  Betsy van Die

(847) 378-0517 or bvd@aans.org EMBARGOED FOR RELEASE ON APRIL 24 SAN FRANCISCO (April 24, 2006) - Controlling intracranial pressure (ICP) is an essential component of effectively treating patients with traumatic brain injury (TBI). TBI patients may develop increased ICP as a result of edema (brain swelling), blood clots, subdural hematomas, or other intracerebral hemorrhages. Because the brain is surrounded by the rigid skull, high ICP can cause compression or squeezing of the softer brain tissue, preventing enough blood from getting to the brain tissue. The result can be damage to brain cells. Even a short period of increased ICP can cause permanent damage. Raised ICP, along with hypotension and hypoxia, can increase the mortality rate in TBI patients by 70 percent. TBI survivors are often left with significant cognitive, behavioral, and speech disabilities, and some patients develop long-term medical complications, such as seizures. Osmotic therapy is the cornerstone of nonsurgical management of ICP. There are theoretical reasons why hypertonic saline (HTS) may be a more effective and safe osmotic agent than mannitol. Neurosurgeons at Hennepin County Medical Center (HCMC) in Minneapolis recently assessed the effectiveness of HTS as a single osmotic intervention for controlling ICP and its effect on cerebral perfusion pressure (CPP) and brain tissue oxygen (PtO2). The results of this study, Hypertonic Saline (HTS) and its Effect on Intracranial Pressure (ICP) and Brain Tissue Oxygen (PtO2), will be presented by Archie Defillo, MD, 4:15 to 4:30 p.m. on Monday, April 24, 2006, during the 74th Annual Meeting of the American Association of Neurological Surgeons in San Francisco. Co-authors are Gaylan L. Rockswold, MD, PhD, Jon Jancik, PharmD, and Sarah B. Rockswold, MD. HTS produces massive movement of water out of edematous swollen cells and into the blood vessels. This movement of water out of the brain can reduce swelling and improve cerebral blood flow. This specific action of HTS is due to its reflection coefficient of 1. The high numbers of particles in the solution pull water from a low-pressure compartment to a higher-pressure one. Compared with another osmotic diuretic such as mannitol, in which the reflection coefficient is 0.9 (allowing some leakage outside the blood vessels), HTS will not leak outside the capillaries in the presence of an intact blood-brain barrier. An analysis of 24 consecutive TBI patients (21 males and 3 females, ages 17-64, mean age: 37.5) admitted to the surgical intensive care unit (SICU) at HCMC was conducted. The use of other medications to control ICP was an exclusion criteria to prevent inaccurate results. Blood pressure (BP), mean arterial pressure (MAP), central venous pressure (CVP), heart rate, temperature, intake and output were monitored hourly. Serum sodium, osmolality, and arterial blood gases were checked every six hours. Hemoglobin levels, blood urea nitrogen (BUN), serum potassium, chloride, magnesium and phosphate levels were checked daily. The goal of the therapy was to maintain an ICP of less than 20 mmHg, a CPP between 55 and 70 mmHg, and PtO2 of 20mmHg or higher. When ICP increased to more than 20 mmHg, 30 milliliters of a 23.4-percent solution of HTS was administered as a single dose or repeated doses to control ICP levels. Hemoglobin levels less than 10 gr/dl were corrected via blood transfusion to maintain a constant oxygen delivery (VDO2). The following results were noted: Mean absolute value for ICP showed a 35 percent decrease compared to baseline. In the three different subgroups, the significant decrease occurred within the first hour after HTS infusion, with the following decreases noted: 26-percent in group 1, 51 percent in group 2, and 44 percent in group 3. CPP mean absolute value increased by 14 percent. CPP values were recorded in three subgroups: 40-54mmHg in group 1, 55-69mmHg in group 2, and 70 mmHg and higher in group 3. There was a mean increase of 40 percent in group 1, 12 percent in group 2, and 3 percent in group 3. In all groups, there was a sustained response for four hours after the initial infusion. PtO2 values were recorded in three different subgroups: 10-19 in group 1, 20-29 in group 2, and 31 mmHg and higher in group 3. None of the means were statistically different in the three subgroups; there was a steady linear increment ranging from 2.9 percent after the first hour to 25 percent by six hours after infusion. "There were no complications as a result of this treatment, so in conclusion, HTS is a viable option for decreasing ICP and improving CPP and PtO2 in TBI patients," said Dr. Defillo. "Studying a larger patient pool would provide an even better assessment of the effectiveness of HTS as a treatment option for TBI," concluded Dr. Defillo. Founded in 1931 as the Harvey Cushing Society, the American Association of Neurological Surgeons (AANS) is a scientific and educational association with more than 6,800 members worldwide. The AANS is dedicated to advancing the specialty of neurological surgery in order to provide the highest quality of neurosurgical care to the public. All active members of the AANS are certified by the American Board of Neurological Surgery, the Royal College of Physicians and Surgeons (Neurosurgery) of Canada or the Mexican Council of Neurological Surgery, AC. Neurological surgery is the medical specialty concerned with the prevention, diagnosis, treatment and rehabilitation of disorders that affect the entire nervous system, including the spinal column, spinal cord, brain and peripheral nerves.   # # # Media Representatives: If you would like to cover the meeting or interview a neurosurgeon "either on-site or via telephone" please contact the AANS Communications Department at (847) 378-0517 or call the Annual Meeting Press Room beginning Monday, April 24, at (415) 978-3511.

 

---

Arterial carbon dioxide partial pressure (Pa_CO2)
Because cerebral blood flow and Pa_CO2 are linearly related within physiologically relevant ranges, hyperventilation had become an entrenched practice in cerebral resuscitation. Reduction in Pa_CO2 was presumed to augment cerebral perfusion pressure favourably by reducing the cross-sectional diameter of the arterial circulation and thus cerebral blood volume. This would offset increases in intracranial pressure. Although the logic behind this practice can be appreciated, in fact, it is contradicted by direct examination of cerebral well being. The most salient evidence is derived from TBI investigations. These studies support a different concept, that being worsening of perfusion by hyperventilation-induced vasoconstriction in ischaemic tissue. Indeed, the volume of ischaemic tissue, elegantly assessed with positron emission tomography in TBI patients, was markedly increased when moderate hypocapnia was induced.²⁰ This is consistent with the only prospective trial of hyperventilation on TBI outcome, which observed a decreased number of patients with good or moderate disability outcomes when chronic hyperventilation was employed.⁴⁵ It remains unevaluated whether acute hyperventilation improves outcome from pending transtentorial herniation or when rapid surgical decompression of a haematoma (e.g. epidural) is anticipated. Within the context of focal ischaemic stroke, clinical trials have found no benefit from induced hypocapnia,^{17 62} although hyperventilation is sometimes employed in cases of refractory brain oedema. Use of hyperventilation during cardiopulmonary resuscitation may serve to increase mean intrathoracic pressure thereby decreasing perfusion pressure and is not advocated.⁵ Consequently, there are few data to support use of hyperventilation in the context of cerebral resuscitation.

 

20 Coles JP, Fryer TD, Coleman MR, et al. Hyperventilation following head injury: effect on ischemic burden and cerebral oxidative metabolism. Crit Care Med (2007) 35:568–78.[CrossRef][ISI][Medline]
21 Drummond JC, McKay LD, Cole DJ, Patel PM. The role of nitric oxide synthase inhibition in the adverse effects of etomidate in the setting of focal cerebral ischemia in rats. Anesth Analg (2005) 100:841–6.[Abstract/Free Full Text]
22 Elsersy H, Mixco J, Sheng H, Pearlstein RD, Warner DS. Selective gamma-aminobutyric acid type A receptor antagonism reverses isoflurane ischemic neuroprotection. Anesthesiology (2006) 105:81–90.[CrossRef][ISI][Medline]
23 Elsersy H, Sheng H, Lynch JR, Moldovan M, Pearlstein RD, Warner DS. Effects of isoflurane versus fentanyl-nitrous oxide anesthesia on long-term outcome from severe forebrain ischemia in the rat. Anesthesiology (2004) 100:1160–6.[CrossRef][ISI][Medline]
24 Fay T. Observations on generalized refrigeration in cases of severe cerebral trauma. Assoc Res Nerv Ment Dis Proc (1943) 24:611–19.
25 Franks NP, Honore E. The TREK K2P channels and their role in general anaesthesia and neuroprotection. Trends Pharmacol Sci (2004) 25:601–8.[CrossRef][Medline]
26 Gentile NT, Seftchick MW, Huynh T, Kruus LK, Gaughan J. Decreased mortality by normalizing blood glucose after acute ischemic stroke. Acad Emerg Med (2006) 13:174–80.[Abstract/Free Full Text]
27 Gluckman PD, Wyatt JS, Azzopardi D, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet (2005) 365:663–70.[ISI][Medline]
28 Goldstein A Jr, Wells BA, Keats AS. Increased tolerance to cerebral anoxia by pentobarbital. Arch Int Pharmacodyn Ther (1966) 161:138–43.[ISI][Medline]
29 Gray JJ, Bickler PE, Fahlman CS, Zhan X, Schuyler JA. Isoflurane neuroprotection in hypoxic hippocampal slice cultures involves increases in intracellular Ca2+ and mitogen-activated protein kinases. Anesthesiology (2005) 102:606–15.[CrossRef][ISI][Medline]
30 Harada H, Kelly PJ, Cole DJ, Drummond JC, Patel PM. Isoflurane reduces N-methyl-D-aspartate toxicity in vivo in the rat cerebral cortex. Anesth Analg (1999) 89:1442–7.[Abstract/Free Full Text]
31 Hellstrom-Westas L, Forsblad K, Sjors G, et al. Earlier Apgar score increase in severely depressed term infants cared for in Swedish level III units with 40% oxygen versus 100% oxygen resuscitation strategies: a population-based register study. Pediatrics (2006) 118:e1798–804.[Abstract/Free Full Text]
32 Higgins RD, Raju TN, Perlman J, et al. Hypothermia and perinatal asphyxia: executive summary of the National Institute of Child Health and Human Development workshop. J Pediatr (2006) 148:170–5.[CrossRef][ISI][Medline]
33 Hoffman WE, Charbel FT, Edelman G, Ausman JI. Thiopental and desflurane treatment for brain protection. Neurosurgery (1998) 43:1050–3.[CrossRef][ISI][Medline]
34 Jastremski M, Sutton-Tyrrell K, Vaagenes P, Abramson N, Heiselman D, Safar P. Glucocorticoid treatment does not improve neurological recovery following cardiac arrest. Brain Resuscitation Clinical Trial I Study Group. JAMA (1989) 262:3427–30.[Abstract]
35 Kaisti KK, Langsjo JW, Aalto S, et al. Effects of sevoflurane, propofol, and adjunct nitrous oxide on regional cerebral blood flow, oxygen consumption, and blood volume in humans. Anesthesiology (2003) 99:603–13.[CrossRef][ISI][Medline]
36 Kammersgaard LP, Jorgensen HS, Rungby JA, et al. Admission body temperature predicts long-term mortality after acute stroke: the Copenhagen Stroke Study. Stroke (2002) 33:1759–62.[Abstract/Free Full Text]
37 Klinger G, Beyene J, Shah P, Perlman M. Do hyperoxaemia and hypocapnia add to the risk of brain injury after intrapartum asphyxia? Arch Dis Child Fetal Neonatal Ed (2005) 90:F49–52.[Abstract/Free Full Text]
38 Kurth CD, Priestley M, Watzman HM, McCann J, Golden J. Desflurane confers neurologic protection for deep hypothermic circulatory arrest in newborn pigs. Anesthesiology (2001) 95:959–64.[CrossRef][ISI][Medline]
39 Lei B, Popp S, Capuano-Waters C, Cottrell JE, Kass IS. Lidocaine attenuates apoptosis in the ischemic penumbra and reduces infarct size after transient focal cerebral ischemia in rats. Neuroscience (2004) 125:691–701.[CrossRef][ISI][Medline]
40 Leonov Y, Sterz F, Safar P, et al. Mild cerebral hypothermia during and after cardiac arrest improves neurologic outcome in dogs. J Cereb Blood Flow Metab (1990) 10:57–70.[ISI][Medline]
41 McDonagh DL, Allen IN, Keifer JC, Warner DS. Induction of hypothermia after intraoperative hypoxic brain insult. Anesth Analg (2006) 103:180–1.[Abstract/Free Full Text]
42 Michenfelder J, Terry HJ, Daw E, Uihlein A. Induced hypothermia: physiologic effects, indications, and techniques. Surg Clin North Am (1965) 45:889.[ISI][Medline]
43 Michenfelder JD, Theye RA. Cerebral protection by thiopental during hypoxia. Anesthesiology (1973) 39:510–7.[ISI][Medline]
44 Mitchell SJ, Pellett O, Gorman DF. Cerebral protection by lidocaine during cardiac operations. Ann Thorac Surg (1999) 67:1117–24.[CrossRef][ISI][Medline]
45 Muizelaar JP, Marmarou A, Ward JD, et al. Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial. J Neurosurg (1991) 75:731–9.[ISI][Medline]
46 Nasu I, Yokoo N, Takaoka S, et al. The dose-dependent effects of isoflurane on outcome from severe forebrain ischemia in the rat. Anesth Analg (2006) 103:413–8.[Abstract/Free Full Text]
47 Nellgård B, Mackensen GB, Pineda J, Wellons JC 3rd, Pearlstein RD, Warner DS. Anesthetic effects on cerebral metabolic rate predict histologic outcome from near-complete forebrain ischemia in the rat. Anesthesiology (2000) 93:431–6.[CrossRef][ISI][Medline]

 

Pupillary constriction is mediated via a parasympathetic pathway, which requires integrity of the third nerve and its nuclei in the brain, which lie close to areas involved in consciousness. Third nerve palsy initially causes mydriasis followed by loss of reactivity to light. Classically, ipsilateral third nerve palsy has been attributed to compression of the nerve on the free edge of the tentorium. It may also occur because of kinking of the nerve over the clivus or ‘buckling’ of the brainstem as a result of an increase in supra-tentorial pressure.80 In the presence of unilateral third nerve palsy, the consensual light reflex (opposite eye constricting in response to bright light) should still be present. Optic nerve injury (more common with frontal injuries) will impair both the direct and indirect responses and may lead to fixed or sluggish pupils, which may display spontaneous fluctuations (hippus).139
Bilaterally fixed pupils occur in around 20–30% of patients with severe head injury (GCS 8) after resuscitation: 70–90% of these patients will have poor outcome (vegetative or dead) when compared with around 30% with bilaterally reactive pupils.57 64 66 Unreactive pupils are associated with the presence of hypotension, lower GCS, and closed basal cisterns on CT.4 14 163 The underlying pathology influences the prognostic value of unreactive pupils: patients with epidural haematoma fare better than those with subdural haematoma.115 116 123 129 Unilaterally unreactive pupils have an outcome intermediate between bilaterally reactive and unreactive pupils. Pupil asymmetry is associated with an operable mass lesion in around 30% of patients.18

 

Table 7 Marshall CT classification of TBI

 

Category Definition Diffuse injury I (no visible pathology) No visible intra-cranial pathology seen on CT scan Diffuse injury II Cisterns are present with midline shift < 5 mm and/or lesion densities present   No high- or mixed-density lesion > 25 ml, may include bone fragments and foreign bodies Diffuse injury III Cisterns compressed or absent with mid-line shift 0–5 mm No high- or mixed-density lesion > 25 ml Diffuse injury IV Mid-line shift > 5 mm No high- or mixed-density lesion > 25 ml Evacuated mass lesion Any lesion surgically evacuated Non-evacuated mass lesion High- or mixed-density lesion > 25 ml, not surgically evacuated

---

Table 8 Outcome related to Marshall CT classification. TCDB, Traumatic Coma Data Bank; EBIC, European Brain Injury Consortium. Outcome is defined using the Glasgow Outcome Scale

 

Category Outcome94 Frequency Unfavourable (dead, vegetative, severe disability) Favourable (mild disability, good recovery) TCDB94 European Nimodipine trial64 EBIC survey105 Diffuse injury I (no visible pathlogy) 38 62 7 8 12 Diffuse injury II 65 35 24 33 28 Diffuse injury III 84 16 21 11 10 Diffuse injury IV 94 6 4 4 2 Evacuated mass lesion 77 23 37 38 48 Non-evacuated mass lesion 89 11 5 4 –

 

---

 

 

 

Hypotension
Numerous observational studies have confirmed the association between systemic hypotension occurring at any point after injury and poor outcome.¹⁶ The largest study,¹⁹ a prospective review of more than 700 patients from the American TCDB, found that a single episode of hypotension during the period from injury through resuscitation was associated with an approximate doubling of mortality and a parallel increase in morbidity in survivors. This association persists when age and the presence or absence of hypoxia and extra-cranial injuries are taken into account. Similar associations have been found in other studies. A prospective Australian study³⁸ found that early (resuscitation) and late (definitive care) hypotension were separately and additively associated with increased mortality. The duration and number of episodes of hypotension are correlated with mortality.⁹⁰ The findings in children are similar provided appropriate correction of adequate arterial pressure is made for age.¹¹⁸ Retrospective data¹¹⁷ suggest that intra-operative hypotension is also important, with a three-fold increase in mortality in those patients experiencing intra-operative hypotension. The precise mechanism for the enhanced susceptibility of the injured brain to hypotension is not clear,^{33 143} but up to 90% of head-injured patients have been found to have evidence of ischaemic damage at autopsy.⁴⁸

  Hypoxia
Most,^{19 68 93} but not all⁹⁰ observational studies in TBI have found an association between observed early hypoxia [Sp_O2 < 90% or <7.9 kPa (60 mm Hg)] and poor outcome. The association is not as strong as for hypotension, and may be less important in children.¹¹⁸ Hypoxia may be a marker of the severity of brain or systemic injury, or it may be a secondary insult to the at risk brain. It may also be a surrogate marker for marked hypercapnia, which would be expected to lower cerebral perfusion pressure. Animal work suggests that, in rats, the combination of hypoxia and percussive trauma leads to a small increase in oedema formation when compared with the percussive trauma alone, presumably because of the increasing inability of injured cells to maintain ionic homeostasis.¹⁶⁴

^{1 Acheson MB, Livingston RR, Richardson ML, Stimac GK. High-resolution CT scanning in the evaluation of cervical spine fractures: comparison with plain film examinations. Am J Roentgenol (1987) 148:1179–85.[Abstract/Free Full Text]
2 Adams JH, Doyle D, Ford I, Gennarelli TA, Graham DI, McLellan DR. Diffuse axonal injury in head injury: definition, diagnosis and grading. Histopathology (1989) 15:49–59.[ISI][Medline]
3 Alderson P, Roberts I. Corticosteroids in acute traumatic brain injury: systematic review of randomised controlled trials. Br Med J (1997) 314:1855–9.[Abstract/Free Full Text]
4 Andrews BT, Levy ML, Pitts LH. Implications of systemic hypotension for the neurological examination in patients with severe head injury. Surg Neurol (1987) 28:419–22.[CrossRef][ISI][Medline]
5 Arango MF, Mejia-Mantilla JH. Magnesium for acute traumatic brain injury. Cochrane Database Syst Rev (2006) 4. doi:10.1002/14651858. CD005400.pub2.
6 Balestreri M, Czosnyka M, Chatfield DA, et al. Predictive value of Glasgow Coma Scale after brain trauma: change in trend over the past ten years. J Neurol Neurosurg Psychiatry (2004) 75:161–2.[Abstract/Free Full Text]
7 Bernard F, Menon DK, Matta BF. Corticosteroids after traumatic brain injury: new evidence to support their use. Crit Care Med (2006) 34:583.[CrossRef][ISI][Medline]
8 Berne JD, Velmahos GC, El-Tawil Q, et al. Value of complete cervical helical computed tomographic scanning in identifying cervical spine injury in the unevaluable blunt trauma patient with multiple injuries: a prospective study. J Trauma (1999) 47:896–902.[ISI][Medline]
9 Bickell WH, Wall MJ Jr, Pepe PE, et al. Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. N Engl J Med (1994) 331:1105–9.[Abstract/Free Full Text]
10 Blumbergs PC, Jones NR, North JB. Diffuse axonal injury in head trauma. J Neurol Neurosurg Psychiatry (1989) 52:838–41.[Abstract]
11 Boto GR, Gomez PA, De La Cruz J, Lobato RD. Severe head injury and the risk of early death. J Neurol Neurosurg Psychiatry (2006) 77:1054–9.[Abstract/Free Full Text]
12 Bouma GJ, Muizelaar JP, Choi SC, Newlon PG, Young HF. Cerebral circulation and metabolism after severe traumatic brain injury: the elusive role of ischemia. J Neurosurg (1991) 75:685–93.[ISI][Medline]
13 Bouma GJ, Muizelaar JP, Stringer WA, Choi SC, Fatouros P, Young HF. Ultra-early evaluation of regional cerebral blood flow in severely head-injured patients using xenon-enhanced computerized tomography. J Neurosurg (1992) 77:360–8.[ISI][Medline]
14 Braakman R, Gelpke GJ, Habbema JD, Maas AI, Minderhoud JM. Systematic selection of prognostic features in patients with severe head injury. Neurosurgery (1980) 6:362–70.[ISI][Medline]
15 Brain Trauma Foundation. Guidelines for Prehospital Management of Traumatic Brain Injury (2000) New York: Brain Trauma Foundation.
16 Brain Trauma Foundation. Management and Prognosis of Severe Traumatic Brain Injury (2000) New York: Brain Trauma Foundation.
17 Canavero S, Bonicalzi V, Narcisi P. Safety of magnesium-lidocaine combination for severe head injury: the Turin lidomag pilot study. Surg Neurol (2003) 60:165–9.[CrossRef][ISI][Medline]
18 Chesnut RM, Gautille T, Blunt BA, Klauber MR, Marshall LE. The localizing value of asymmetry in pupillary size in severe head injury: relation to lesion type and location. Neurosurgery (1994) 34:840–5.[ISI][Medline]
19 Chesnut RM, Marshall LF, Klauber MR, et al. The role of secondary brain injury in determining outcome from severe head injury. J Trauma (1993) 34:216–22.[ISI][Medline]
20 Chesnut RM, Marshall SB, Piek J, Blunt BA, Klauber MR, Marshall LF. Early and late systemic hypotension as a frequent and fundamental source of cerebral ischemia following severe brain injury in the Traumatic Coma Data Bank. Acta Neurochir Suppl (Wien) (1993) 59:121–5.[Medline]
21 Choi SC, Barnes TY, Bullock R, Germanson TA, Marmarou A, Young HF. Temporal profile of outcomes in severe head injury. J Neurosurg (1994) 81:169–73.[ISI][Medline]
22 Choi SC, Narayan RK, Anderson RL, Ward JD. Enhanced specificity of prognosis in severe head injury. J Neurosurg (1988) 69:381–5.[ISI][Medline]
23 Clifton GL, Ziegler MG, Grossman RG. Circulating catecholamines and sympathetic activity after head injury. Neurosurgery (1981) 8:10–14.[ISI][Medline]
24 Cochran A, Scaife ER, Hansen KW, Downey EC. Hyperglycemia and outcomes from pediatric traumatic brain injury. J Trauma (2003) 55:1035–8.[ISI][Medline]
25 Cohan P, Wang C, McArthur DL, et al. Acute secondary adrenal insufficiency after traumatic brain injury: a prospective study. Crit Care Med (2005) 33:2358–66.[CrossRef][ISI][Medline]
26 Davis DP, Dunford JV, Ochs M, Park K, Hoyt DB. The use of quantitative end-tidal capnometry to avoid inadvertent severe hyperventilation in patients with head injury after paramedic rapid sequence intubation. J Trauma (2004) 56:808–14.[ISI][Medline]
27 Davis DP, Heister R, Poste JC, Hoyt DB, Ochs M, Dunford JV. Ventilation patterns in patients with severe traumatic brain injury following paramedic rapid sequence intubation. Neurocrit Care (2005) 2:165–71.[CrossRef][ISI][Medline]
28 Davis DP, Idris AH, Sise MJ, et al. Early ventilation and outcome in patients with moderate to severe traumatic brain injury. Crit Care Med (2006) 34:1202–8.[CrossRef][ISI][Medline]
29 Davis DP, Peay J, Sise MJ, et al. The impact of prehospital endotracheal intubation on outcome in moderate to severe traumatic brain injury. J Trauma (2005) 58:933–9.[ISI][Medline]
30 Davis DP, Serrano JA, Vilke GM, et al. The predictive value of field versus arrival Glasgow Coma Scale score and TRISS calculations in moderate-to-severe traumatic brain injury. J Trauma (2006) 60:985–90.[ISI][Medline]
31 Davis DP, Stern J, Sise MJ, Hoyt DB. A follow-up analysis of factors associated with head-injury mortality after paramedic rapid sequence intubation. J Trauma (2005) 59:486–90.[Medline]
32 Demetriades D, Kuncir E, Velmahos GC, Rhee P, Alo K, Chan LS. Outcome and prognostic factors in head injuries with an admission Glasgow Coma Scale score of 3. Arch Surg (2004) 139:1066–8.[Abstract/Free Full Text]
33 DeWitt DS, Jenkins LW, Prough DS. Enhanced vulnerability to secondary ischemic insults after experimental traumatic brain injury. New Horiz (1995) 3:376–83.[Medline]
34 Diringer MN. Is aggressive treatment of hyperglycemia for everyone? Crit Care Med (2006) 34:930–1.[CrossRef][ISI][Medline]
35 Eisenberg HM, Gary HE Jr, Aldrich EF, et al. Initial CT findings in 753 patients with severe head injury. A report from the NIH Traumatic Coma Data Bank. J Neurosurg (1990) 73:688–98.[ISI][Medline]
36 Excellence, National Institute of Clinical. Head Injury Triage, Assessment, Investigation and Early Management of Head Injury in Infants Children and Adults. Clinical Guideline 4 (2003) London: NICE.
37 Farin A, Deutsch R, Biegon A, Marshall LF. Sex-related differences in patients with severe head injury: greater susceptibility to brain swelling in female patients 50 years of age and younger. J Neurosurg (2003) 98:32–6.[ISI][Medline]
38 Fearnside MR, Cook RJ, McDougall P, McNeil RJ. The Westmead Head Injury Project outcome in severe head injury. A comparative analysis of pre-hospital, clinical and CT variables. Br J Neurosurg (1993) 7:267–79.[ISI][Medline]
39 Forsyth RJ, Jayamoni B, Paine TC. Monoaminergic agonists for acute traumatic brain injury. Cochrane Database Syst Rev (2006) 4. doi:10.1002/14651858. CD003984.pub2.
40 Gale JL, Dikmen S, Wyler A, Temkin N, McLean A. Head injury in the Pacific Northwest. Neurosurgery (1983) 12:487–91.[ISI][Medline]
41 Gausche M, Lewis RJ, Stratton SJ, et al. Effect of out-of-hospital pediatric endotracheal intubation on survival and neurological outcome: a controlled clinical trial. JAMA (2000) 283:783–90.[Abstract/Free Full Text]
42 Gennarelli TA, Spielman GM, Langfitt TW, et al. Influence of the type of intracranial lesion on outcome from severe head injury. J Neurosurg (1982) 56:26–32.[ISI][Medline]
43 Gentry LR, Godersky JC, Thompson B, Dunn VD. Prospective comparative study of intermediate-field MR and CT in the evaluation of closed head trauma. Am J Roentgenol (1988) 150:673–82.[Abstract/Free Full Text]
44 Gill MR, Reiley DG, Green SM. Interrater reliability of Glasgow Coma Scale scores in the emergency department. Ann Emerg Med (2004) 43:215–23.[CrossRef][ISI][Medline]
45 Glass TF, Fabian MJ, Schweitzer JB, Weinberg JA, Proctor KG. The impact of hypercarbia on the evolution of brain injury in a porcine model of traumatic brain injury and systemic hemorrhage. J Neurotrauma (2001) 18:57–71.[CrossRef][ISI][Medline]
46 Goldstein B, Kelly MM, Bruton D, Cox C. Inflicted versus accidental head injury in critically injured children. Crit Care Med (1993) 21:1328–32.[ISI][Medline]
47 Graham DI. The pathology of brain ischaemia and possibilities for therapeutic intervention. Br J Anaesth (1985) 57:3–17.[Free Full Text]
48 Graham DI, Ford I, Adams JH, et al. Ischaemic brain damage is still common in fatal non-missile head injury. J Neurol Neurosurg Psychiatry (1989) 52:346–50.[Abstract]
49 Group ALS. Advanced Paediatric Life Support: the Practical Approach (2005) London: BMJ Books/Blackwell.
50 Helmy A, Vizcaychipi M, Gupta AK. Traumatic brain injury: intensive care management. Br J Anaesth (2007) 99:32–42.[Abstract/Free Full Text]
51 Harders A, Kakarieka A, Braakman R. Traumatic subarachnoid hemorrhage and its treatment with nimodipine. German tSAH Study Group. J Neurosurg (1996) 85:82–9.[ISI][Medline]
52 Hare GMT, Kavanagh BP, Mazer CD, et al. Hypercapnia increases cerebral tissue oxygen tension in anesthetized rats. Can J Anaesth (2003) 50:1061–8.[Abstract/Free Full Text]
53 Hartl R, Gerber LM, Iacono L, Ni Q, Lyons K, Ghajar J. Direct transport within an organized state trauma system reduces mortality in patients with severe traumatic brain injury. J Trauma (2006) 60:1250–6.[ISI][Medline]
54 Havill JH, Sleigh JW, Davis GM, et al. Observer error and prediction of outcome—grading of head injury based on computerised tomography. Crit Care Resusc (2001) 3:15–8.[Medline]
55 Haydel MJ, Preston CA, Mills TJ, Luber S, Blaudeau E, DeBlieux PM. Indications for computed tomography in patients with minor head injury. N Engl J Med (2000) 343:100–5.[Abstract/Free Full Text]
56 Healey C, Osler TM, Rogers FB, et al. Improving the Glasgow Coma Scale score: motor score alone is a better predictor. J Trauma (2003) 54:671–8.[ISI][Medline]
57 Heiden JS, Small R, Caton W, Weiss M, Kurze T. Severe head injury. Clinical assessment and outcome. Phys Ther (1983) 63:1946–51.[ISI][Medline]
58 Hodgkinson DW, Berry E, Yates DW. Mild head injury—a positive approach to management. Eur J Emerg Med (1994) 1:9–12.[CrossRef][Medline]
59 Hogan GJ, Mirvis SE, Shanmuganathan K, Scalea TM. Exclusion of unstable cervical spine injury in obtunded patients with blunt trauma: is MR imaging needed when multi-detector row CT findings are normal? Radiology (2005) 237:106–13.[Abstract/Free Full Text]
60 Holly LT, Kelly DF, Counelis GJ, Blinman T, McArthur DL, Cryer HG. Cervical spine trauma associated with moderate and severe head injury: incidence, risk factors, and injury characteristics. J Neurosurg (2002) 96:285–91.[ISI][Medline]
61 Hukkelhoven CWPM, Steyerberg EW, Rampen AJJ, et al. Patient age and outcome following severe traumatic brain injury: an analysis of 5600 patients. J Neurosurg (2003) 99:666–73.[ISI][Medline]
62 Iida H, Tachibana S, Kitahara T, Horiike S, Ohwada T, Fujii K. Association of head trauma with cervical spine injury, spinal cord injury, or both. J Trauma (1999) 46:450–2.[ISI][Medline]
63 Ikonomidou C, Turski L. Why did NMDA receptor antagonists fail clinical trials for stroke and traumatic brain injury? Lancet Neurol (2002) 1:383–6.[CrossRef][ISI][Medline]
64 Injury ESGoNiSH. A multicenter trial of the efficacy of nimodipine on outcome after severe head injury. J Neurosurg (1994) 80:797–804.[ISI][Medline]
65 Jennett B. Epidemiology of head injury. J Neurol Neurosurg Psychiatry (1996) 60:362–9.[ISI][Medline]
66 Jennett B, Teasdale G, Braakman R, Minderhoud J, Knill-Jones R. Predicting outcome in individual patients after severe head injury. Lancet (1976) 1:1031–4.[ISI][Medline]
67 Jennett B, Teasdale G, Galbraith S, et al. Severe head injuries in three countries. J Neurol Neurosurg Psychiatry (1977) 40:291–8.[Abstract]
68 Jeremitsky E, Omert L, Dunham CM, Protetch J, Rodriguez A. Harbingers of poor outcome the day after severe brain injury: hypothermia, hypoxia, and hypoperfusion. J Trauma (2003) 54:312–9.[ISI][Medline]
69 Johnstone AJ, Lohlun JC, Miller JD, et al. A comparison of the Glasgow Coma Scale and the Swedish Reaction Level Scale. Brain Inj (1993) 7:501–6.[ISI][Medline]
70 Jones PA, Andrews PJ, Midgley S, et al. Measuring the burden of secondary insults in head-injured patients during intensive care. J Neurosurg Anesthesiol (1994) 6:4–14.[ISI][Medline]
71 Kakarieka A, Braakman R, Schakel EH. Clinical significance of the finding of subarachnoid blood on CT scan after head injury. Acta Neurochir (Wien) (1994) 129:1–5.[CrossRef][Medline]
72 Klauber MR, Barrett-Connor E, Marshall LF, Bowers SA. The epidemiology of head injury: a prospective study of an entire community-San Diego County, California, 1978. Am J Epidemiol (1981) 113:500–9.[Abstract/Free Full Text]
73 Klauber MR, Marshall LF, Luerssen TG, Frankowski R, Tabaddor K, Eisenberg HM. Determinants of head injury mortality: importance of the low risk patient. Neurosurgery (1989) 24:31–6.[ISI][Medline]
74 Knoller N, Levi L, Shoshan I, et al. Dexanabinol (HU-211) in the treatment of severe closed head injury: a randomized, placebo-controlled, phase II clinical trial. Crit Care Med (2002) 30:548–54.[CrossRef][ISI][Medline]
75 Kobayashi S, Nakazawa S, Otsuka T. Clinical value of serial computed tomography with severe head injury. Surg Neurol (1983) 20:25–9.[CrossRef][ISI][Medline]
76 Kuday C, Uzan M, Hanci M. Statistical analysis of the factors affecting the outcome of extradural haematomas: 115 cases. Acta Neurochir (Wien) (1994) 131:203–6.[CrossRef][Medline]
77 Laird AM, Miller PR, Kilgo PD, Meredith JW, Chang MC. Relationship of early hyperglycemia to mortality in trauma patients. J Trauma (2004) 56:1058–62.[ISI][Medline]
78 Lam AM, Winn HR, Cullen BF, Sundling N. Hyperglycemia and neurological outcome in patients with head injury. J Neurosurg (1991) 75:545–51.[ISI][Medline]
79 Langham J, Goldfrad C, Teasdale G, Shaw D, Rowan K. Calcium channel blockers for acute traumatic brain injury. Cochrane Database Syst Rev (2003) [Update of Cochrane Database Syst Rev. 2000;(2):CD000565; PMID: 10796727], CD000565.
80 Larner AJ. False localising signs. J Neurol Neurosurg Psychiatry (2003) 74:415–8.[Abstract/Free Full Text]
81 Levi L, Guilburd JN, Linn S, Feinsod M. The association between skull fracture, intracranial pathology and outcome in pediatric head injury. Br J Neurosurg (1991) 5:617–25.[ISI][Medline]
82 Link TM, Schuierer G, Hufendiek A, Horch C, Peters PE. Substantial head trauma: value of routine CT examination of the cervicocranium. Radiology (1995) 196:741–5.[Abstract]
83 Lobato RD, Rivas JJ, Cordobes F, et al. Acute epidural hematoma: an analysis of factors influencing the outcome of patients undergoing surgery in coma. J Neurosurg (1988) 68:48–57.[ISI][Medline]
84 Lokkeberg AR, Grimes RM. Assessing the influence of non-treatment variables in a study of outcome from severe head injuries. J Neurosurg (1984) 61:254–62.[ISI][Medline]
85 Lu J, Marmarou A, Choi S, et al. Mortality from traumatic brain injury. Acta Neurochir Suppl (2005) 95:281–5.[Medline]
86 Luber SD, Brady WJ, Brand A, Young J, Guertler AT, Kefer M. Acute hypoglycemia masquerading as head trauma: a report of four cases. Am J Emerg Med (1996) 14:543–7.[CrossRef][ISI][Medline]
87 Maas AI, Dearden M, Teasdale GM, et al. EBIC-guidelines for management of severe head injury in adults. European Brain Injury Consortium. Acta Neurochir (Wien) (1997) 139:286–94.[CrossRef][Medline]
88 Maas AIR, Hukkelhoven CWPM, Marshall LF, Steyerberg EW. Prediction of outcome in traumatic brain injury with computed tomographic characteristics: a comparison between the computed tomographic classification and combinations of computed tomographic predictors. Neurosurgery (2005) 57:1173–82.[ISI][Medline]
89 Maas AIR, Murray G, Henney H III, et al. Efficacy and safety of dexanabinol in severe traumatic brain injury: results of a phase III randomised, placebo-controlled, clinical trial. Lancet Neurol (2006) 5:38–45.[CrossRef][ISI][Medline]
90 Manley G, Knudson MM, Morabito D, Damron S, Erickson V, Pitts L. Hypotension, hypoxia, and head injury: frequency, duration, and consequences. Arch Surg (2001) 136:1118–23.[Abstract/Free Full Text]
91 Marion DW, Carlier PM. Problems with initial Glasgow Coma Scale assessment caused by prehospital treatment of patients with head injuries: results of a national survey. J Trauma (1994) 36:89–95.[ISI][Medline]
92 Marion DW, Darby J, Yonas H. Acute regional cerebral blood flow changes caused by severe head injuries. J Neurosurg (1991) 74:407–14.[ISI][Medline]
93 Marmarou A, Anderson RL, Ward JD. Impact of ICP instability and hypotension on outcome in patients with severe head trauma. J Neurosurg (Suppl) (1991) 75:159–166.
94 Marshall LF, Gantille T, Klauber MR. The outcome of severe head injury. J Neurosurg (Suppl) (1991) 75:S25–36.
95 Marshall LF, Maas AI, Marshall SB, et al. A multicenter trial on the efficacy of using tirilazad mesylate in cases of head injury. J Neurosurg (1998) 89:519–25.[ISI][Medline]
96 Marshall LF, Marshall SB, Klauber MR, Clark MV. A new classification of head injury based on computerised tomography. J Neurosurg (Suppl) (1991) 75:S14–20.
97 Massagli TL, Michaud LJ, Rivara FP. Association between injury indices and outcome after severe traumatic brain injury in children. Arch Phys Med Rehabil (1996) 77:125–32.[CrossRef][ISI][Medline]
98 Maxwell WL, Bullock R, Landholt H, Fujisawa H. Massive astrocytic swelling in response to extracellular glutamate—a possible mechanism for post-traumatic brain swelling? Acta Neurochir Suppl (Wien) (1994) 60:465–7.[Medline]
99 Mendelow AD, Gillingham FJ. Extradural haematoma: effect of delayed treatment. Br Med J (1979) 2:134.[ISI][Medline]
100 Menegazzi JJ, Davis EA, Sucov AN, Paris PM. Reliability of the Glasgow Coma Scale when used by emergency physicians and paramedics. J Trauma (1993) 34:46–8.[ISI][Medline]
101 Miller JD, Sweet RC, Narayan R, Becker DP. Early insults to the injured brain. JAMA (1978) 240:439–42.[Abstract]
102 Wilson M, Montgomery H. Impact of genetic factors on outcome from brain injury. Br J Anaesth (2007) 99:43–48.[Abstract/Free Full Text]
103 Morris GF, Bullock R, Marshall SB, Marmarou A, Maas A, Marshall LF. Failure of the competitive N-methyl-D-aspartate antagonist Selfotel (CGS 19755) in the treatment of severe head injury: results of two-phase III clinical trials. The Selfotel Investigators. J Neurosurg (1999) 91:737–43.[ISI][Medline]
104 Muizelaar JP, Marmarou A, Ward JD, et al. Adverse effects of prolonged hyperventilation in patients with severe head injury: a randomized clinical trial. J Neurosurg (1991) 75:731–9.[ISI][Medline]
105 Murray GD, Teasdale GM, Braakman R, et al. The European Brain Injury Consortium survey of head injuries. Acta Neurochir (Wien) (1999) 141:223–36.[CrossRef][Medline]
106 Murray JA, Demetriades D, Berne TV, et al. Prehospital intubation in patients with severe head injury. J Trauma (2000) 49:1065–70.[ISI][Medline]
107 Nakamura N, Yamaura A, Shigemori M, et al. Final report of the Japan neurotrauma data bank project 1998–2001: 1,002 cases of traumatic brain injury. Neurol Med Chir (Tokyo) (2006) 46:567–74.[CrossRef][Medline]
108 Narayan RK, Greenberg RP, Miller JD, et al. Improved confidence of outcome prediction in severe head injury. A comparative analysis of the clinical examination, multimodality evoked potentials, CT scanning, and intracranial pressure. J Neurosurg (1981) 54:751–62.[ISI][Medline]
109 Network, Scottish Intercollegiate Guidelines. Early Management of Patients with a Head Injury (2000) Edinburgh: SIGN.
110 Ng I, Lee KK, Lim JHG, Wong HB, Yan XY. Investigating gender differences in outcome following severe traumatic brain injury in a predominantly Asian population. Br J Neurosurg (2006) 20:73–8.[CrossRef][ISI][Medline]
111 Obrist WD, Langfitt TW, Jaggi JL, Cruz J, Gennarelli TA. Cerebral blood flow and metabolism in comatose patients with acute head injury. Relationship to intracranial hypertension. J Neurosurg (1984) 61:241–53.[ISI][Medline]
112 Patel HC, Menon DK, Tebbs S, Hawker R, Hutchinson PJ, Kirkpatrick PJ. Specialist neurocritical care and outcome from head injury. Intensive Care Med (2002) 28:547–53.[CrossRef][ISI][Medline]
113 Peek-Asa C, McArthur D, Hovda D, Kraus J. Early predictors of mortality in penetrating compared with closed brain injury. Brain Inj (2001) 15:801–10.[ISI][Medline]
114 Pfenninger E, Ahnefeld FW, Kilian J, Dell U. Behavior of blood gases in patients with craniocerebral trauma at the accident site and at the time of admission to the clinic. Anaesthesist (1987) 36:570–6.[ISI][Medline]
115 Phonprasert C, Suwanwela C, Hongsaprabhas C, Prichayudh P, O'Charoen S. Extradural hematoma: analysis of 138 cases. J Trauma (1980) 20:679–83.[ISI][Medline]
116 Phuenpathom N, Choomuang M, Ratanalert S. Outcome and outcome prediction in acute subdural hematoma. Surg Neurol (1993) 40:22–5.[CrossRef][ISI][Medline]
117 Pietropaoli JA, Rogers FB, Shackford SR, Wald SL, Schmoker JD, Zhuang J. The deleterious effects of intraoperative hypotension on outcome in patients with severe head injuries. J Trauma (1992) 33:403–7.[ISI][Medline]
118 Pigula FA, Wald SL, Shackford SR, Vane DW. The effect of hypotension and hypoxia on children with severe head injuries. J Pediatr Surg (1993) 28:310–4.[CrossRef][ISI][Medline]
119 Povlishock JT. Traumatically induced axonal injury: pathogenesis and pathobiological implications. Brain Pathol (1992) 2:1–12.[ISI][Medline]
120 Ransom GH, Mann FA, Vavilala MS, Haruff R, Rivara FP. Cerebral infarct in head injury: relationship to child abuse. Child Abuse Negl (2003) 27:381–92.[CrossRef][ISI][Medline]
121 Reilly PL. Brain injury: the pathophysiology of the first hours. Talk and Die revisited. J Clin Neurosci (2001) 8:398–403.[CrossRef][ISI][Medline]
122 Reilly PL, Simpson DA, Sprod R, Thomas L. Assessing the conscious level in infants and young children: a paediatric version of the Glasgow Coma Scale. Childs Nerv Syst (1988) 4:30–3.[ISI][Medline]
123 Rivas JJ, Lobato RD, Sarabia R, Cordobes F, Cabrera A, Gomez P. Extradural hematoma: analysis of factors influencing the courses of 161 patients. Neurosurgery (1988) 23:44–51.[ISI][Medline]
124 Roberts I. Aminosteroids for acute traumatic brain injury. Cochrane Database Syst Rev (1999) 3. doi:10.1002/14651858. CD001527.
125 Roberts I, Smith R, Evans S. Doubts over head injury studies. Br Med J (2007) 334:292–4.[Free Full Text]
126 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) 364:1321–8.[CrossRef][ISI][Medline]
127 Rosner MJ, Newsome HH, Becker DP. Mechanical brain injury: the sympathoadrenal response. J Neurosurg (1984) 61:76–86.[ISI][Medline]
128 Rutledge R, Lentz CW, Fakhry S, Hunt J. Appropriate use of the Glasgow Coma Scale in intubated patients: a linear regression prediction of the Glasgow verbal score from the Glasgow eye and motor scores. J Trauma (1996) 41:514–22.[ISI][Medline]
129 Sakas DE, Bullock MR, Teasdale GM. One-year outcome following craniotomy for traumatic hematoma in patients with fixed dilated pupils. J Neurosurg (1995) 82:961–5.[ISI][Medline]
130 Sarrafzadeh AS, Peltonen EE, Kaisers U, Kuchler I, Lanksch WR, Unterberg AW. Secondary insults in severe head injury–do multiply injured patients do worse? Crit Care Med (2001) 29:1116–23.[CrossRef][ISI][Medline]
131 Schierhout G, Roberts I. Anti-epileptic drugs for preventing seizures following acute traumatic brain injury. Cochrane Database Syst Rev (2001) 4. doi:10.1002/14651858. CD000173.
132 Seelig JM, Becker DP, Miller JD, Greenberg RP, Ward JD, Choi SC. Traumatic acute subdural hematoma: major mortality reduction in comatose patients treated within four hours. N Engl J Med (1981) 304:1511–8.[Abstract]
133 Selladurai BM, Jayakumar R, Tan YY, Low HC. Outcome prediction in early management of severe head injury: an experience in Malaysia. Br J Neurosurg (1992) 6:549–57.[ISI][Medline]
134 Servadei F, Murray GD, Penny K, et al. The value of the worst computed tomographic scan in clinical studies of moderate and severe head injury. European Brain Injury Consortium. Neurosurgery (2000) 46:70–5.[CrossRef][ISI][Medline]
135 Servadei F, Nasi MT, Cremonini AM, Giuliani G, Cenni P, Nanni A. Importance of a reliable admission Glasgow Coma Scale score for determining the need for evacuation of posttraumatic subdural hematomas: a prospective study of 65 patients. J Trauma (1998) 44:868–73.[ISI][Medline]
136 Sharples PM, Storey A, Aynsley-Green A, Eyre JA. Causes of fatal childhood accidents involving head injury in northern region, 1979–86. Br Med J (1990) 301:1193–7.[ISI][Medline]
137 Sheinberg M, Kanter MJ, Robertson CS, Contant CF, Narayan RK, Grossman RG. Continuous monitoring of jugular venous oxygen saturation in head-injured patients. J Neurosurg (1992) 76:212–7.[ISI][Medline]
138 Shohami E, Novikov M, Bass R. Long-term effect of HU-211, a novel non-competitive NMDA antagonist, on motor and memory functions after closed head injury in the rat. Brain Res (1995) 674:55–62.[CrossRef][ISI][Medline]
139 Simpson DA. Clinical examination and grading. In: Head Injury: Pathophysiology and Management of Severe Closed Head Injury—Reilly PL, Bullock MR, eds. (1997) London: Chapman and Hall Medical. 145–65.
140 Simpson DA, Cockington RA, Hanieh A, Raftos J, Reilly PL. Head injuries in infants and young children: the value of the Paediatric Coma Scale. Review of literature and report on a study. Childs Nerv Syst (1991) 7:183–90.[ISI][Medline]
141 Starmark JE, Stalhammar D, Holmgren E. The Reaction Level Scale (RLS85). Manual and guidelines. Acta Neurochir (Wien) (1988) 91:12–20.[CrossRef][Medline]
142 Starmark JE, Stalhammar D, Holmgren E, Rosander B. A comparison of the Glasgow Coma Scale and the Reaction Level Scale (RLS85). J Neurosurg (1988) 69:699–706.[ISI][Medline]
143 Stiefel MF, Tomita Y, Marmarou A. Secondary ischemia impairing the restoration of ion homeostasis following traumatic brain injury. J Neurosurg (2005) 103:707–14.[ISI][Medline]
144 Stiell IG, Wells GA, Vandemheen K, et al. The Canadian CT Head Rule for patients with minor head injury. Lancet (2001) 357:1391–6.[CrossRef][ISI][Medline]
145 Stocchetti N, Croci M, Spagnoli D, Gilardoni F, Resta F, Colombo A. Mass volume measurement in severe head injury: accuracy and feasibility of two pragmatic methods. J Neurol Neurosurg Psychiatry (2000) 68:14–7.[Abstract/Free Full Text]
146 Sultan HY, Boyle A, Pereira M, Antoun N, Maimaris C. Application of the Canadian CT head rules in managing minor head injuries in a UK emergency department: implications for the implementation of the NICE guidelines. Emerg Med J (2004) 21:420–25.[Abstract/Free Full Text]
147 Tatman A, Warren A, Williams A, Powell JE, Whitehouse W. Development of a modified paediatric coma scale in intensive care clinical practice. Arch Dis Child (1997) 77:519–21.[Abstract/Free Full Text]
148 Teasdale G, Bailey I, Bell A, et al. The effect of nimodipine on outcome after head injury: a prospective randomised control trial. The British/Finnish Co-operative Head Injury Trial Group. Acta Neurochir Suppl (Wien) (1990) 51:315–6.[Medline]
149 Teasdale G, Jennett B. Assessment and prognosis of coma after head injury. Acta Neurochir (Wien) (1976) 34:45–55.[CrossRef][Medline]
150 Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet (1974) 2:81–4.[CrossRef][ISI][Medline]
151 Teasdale G, Knill-Jones R, van der Sande J. Observer variability in assessing impaired consciousness and coma. J Neurol Neurosurg Psychiatry (1978) 41:603–10.[Abstract]
152 Temkin NR, Dikmen SS, Wilensky AJ, Keihm J, Chabal S, Winn HR. A randomized, double-blind study of phenytoin for the prevention of post-traumatic seizures. N Engl J Med (1990) 323:497–502.[Abstract]
153 Tennant A. Admission to hospital following head injury in England: incidence and socio-economic associations. BMC Public Health (2005) 5:21.[CrossRef][Medline]
154 Tennant A. The epidemiology of head injury. In: Traumatic Brain Injury Rehabilitation: Services, Treatments and Outcomes—Chamberlain MA, Neumann V, Tennant A, eds. (1996) London: Chapman Hall.
155 The Association of Anaesthetists of Great Britain and Ireland. Recommendations for the Safe Transfer of Patients with Brain Injury (2006) London: The Association of Anaesthetists of Great Britain and Ireland.
156 Thornhill S, Teasdale GM, Murray GD, McEwen J, Roy CW, Penny KI. Disability in young people and adults one year after head injury: prospective cohort study. Br Med J (2000) 320:1631–5.[Abstract/Free Full Text]
157 Tolias CM, Bullock MR. Critical appraisal of neuroprotection trials in head injury: what have we learned? NeuroRx (2004) 1:71–9.[CrossRef][Medline]
158 Trauma Committee of the American College of Surgeons. Advanced Trauma Life Support Program for Physicians (2004) 7th Edn. Chicago: American College of Surgeons.
159 Udekwu P, Kromhout-Schiro S, Vaslef S, Baker C, Oller D. Glasgow Coma Scale score, mortality, and functional outcome in head-injured patients. J Trauma (2004) 56:1084–9.[ISI][Medline]
160 Van den Berghe G, Schoonheydt K, Becx P, Bruyninckx F, Wouters PJ. Insulin therapy protects the central and peripheral nervous system of intensive care patients. Neurology (2005) 64:1348–53.[Abstract/Free Full Text]
161 Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in the critically ill patients. N Engl J Med (2001) 345:1359–67.[Abstract/Free Full Text]
162 Van der Naalt J, Van Zomeren AH, Sluiter WJ, Minderhoud JM. One year outcome in mild to moderate head injury: the predictive value of acute injury characteristics related to complaints and return to work. J Neurol Neurosurg Psychiatry (1999) 66:207–13.[Abstract/Free Full Text]
163 Van Dongen KJ, Braakman R, Gelpke GJ. The prognostic value of computerized tomography in comatose head-injured patients. J Neurosurg (1983) 59:951–7.[ISI][Medline]
164 Van Putten HP, Bouwhuis MG, Muizelaar JP, Lyeth BG, Berman RF. Diffusion-weighted imaging of edema following traumatic brain injury in rats: effects of secondary hypoxia. J Neurotrauma (2005) 22:857–72.[CrossRef][ISI][Medline]
165 Vassar MJ, Fischer RP, O'Brien PE, et al. A multicenter trial for resuscitation of injured patients with 7.5% sodium chloride. The effect of added dextran 70. The multicenter group for the study of hypertonic saline in trauma patients. Arch Surg (1993) 128:1003–11.[Abstract]
166 Vassar MJ, Perry CA, Gannaway WL, Holcroft JW. 7.5% sodium chloride/dextran for resuscitation of trauma patients undergoing helicopter transport. Arch Surg (1991) 126:1065–72.[Abstract]
167 Vassar MJ, Perry CA, Holcroft JW. Analysis of potential risks associated with 7.5% sodium chloride resuscitation of traumatic shock. Arch Surg (1990) 125:1309–15.[Abstract]
168 Vassar MJ, Perry CA, Holcroft JW. Prehospital resuscitation of hypotensive trauma patients with 7.5% NaCl versus 7.5% NaCl with added dextran: a controlled trial. J Trauma (1993) 34:622–32.[ISI][Medline]
169 Vespa P, Boonyaputthikul R, McArthur DL, et al. Intensive insulin therapy reduces microdialysis glucose values without altering glucose utilization or improving the lactate/pyruvate ratio after traumatic brain injury. Crit Care Med (2006) 34:850–6.[CrossRef][ISI][Medline]
170 Vollmer DG, Torner JC, Jane JA. Age and outcome following traumatic coma: why do older patients fare worse? J Neurosurg (Suppl) (1991) 75:S37–49.
171 Vos PE, Battistin L, Birbamer G, et al. EFNS guideline on mild traumatic brain injury: report of an EFNS task force. Eur J Neurol (2002) 9:207–19.[CrossRef][ISI][Medline]
172 Vos PE, van Voskuilen AC, Beems T, Krabbe PF, Vogels OJ. Evaluation of the traumatic coma data bank computed tomography classification for severe head injury. J Neurotrauma (2001) 18:649–55.[CrossRef][ISI][Medline]
173 Wakai A, Roberts I, Schierhout G. Mannitol for acute traumatic brain injury. Cochrane Database Syst Rev (2007) 1. doi:10.1002/14651858. CD001049.pub4.
174 Wardlaw JM, Easton VJ, Statham P. Which CT features help predict outcome after head injury? J Neurol Neurosurg Psychiatry (2002) 72:188–92.[Abstract/Free Full Text]
175 Waters RJ, Nicoll JAR. Genetic influences on outcome following acute neurological insults. Curr Opin Crit Care (2005) 11:105–10.[CrossRef][ISI][Medline]
176 Werner C, Engelhard K. Pathophysiology of traumatic brain injury. Br J Anaesth (2007) 99:4–9.[Abstract/Free Full Text]
177 Winchell RJ, Hoyt DB. Endotracheal intubation in the field improves survival in patients with severe head injury. Trauma Research and Education Foundation of San Diego. Arch Surg (1997) 132:592–7.[Abstract]
178 Yates PJ, Williams WH, Harris A, Round A, Jenkins R. An epidemiological study of head injuries in a UK population attending an emergency department. J Neurol Neurosurg Psychiatry (2006) 77:699–701.[Abstract/Free Full Text]
179 Young B, Ott L, Dempsey R, Haack D, Tibbs P. Relationship between admission hyperglycemia and neurologic outcome of severely brain-injured patients. Ann Surg (1989) 210:466–72.[ISI][Medline]}
 

 

---

Concerns Raised Over Head Injury Studies

Information from Industry

NEW YORK (Reuters Health) Feb 22 - Using high-dose mannitol to treat head injuries may not be a sound strategy as the three main studies supporting this practice may not have even taken place, according to a report in British Medical Journal for February 24.

Between 2001 and 2004, a research group led by Brazilian neurosurgeon Dr. Julio Cruz published three trials showing that high-dose mannitol is preferable to the conventional dose in treating head injury. In particular, a reduction in death and disability was noted at 6 months by using high- rather than standard-dose mannitol.

However, concerns over the data began to surface. In an editorial accompanying one of the studies, the validity and reliability of the findings were called into question, largely because the research was conducted "at only one institution." A later investigation by the Cochrane Collaboration was unable to verify that any of the studies had actually occurred.

In the present report, appearing in the British Medical Journal for February 24, Dr. Ian Roberts, coordinating editor of the Cochrane Injuries Group, and colleagues describe the numerous unsuccessful efforts they took to verify the data from Cruz's studies.

One major problem in confirming the data was that Dr. Cruz committed suicide in 2005. Another problem was that Dr. Roberts' team could not determine where the patients included in the studies had come from. The Federal University of Sao Paulo, which was listed as Dr. Cruz's affiliation on the papers, later told the investigators that it had never employed Dr. Cruz.

Dr. Roberts' team contacted the living co-authors in an effort to retract the reports. These authors declined to seek retraction and supported Dr. Cruz, commenting that "he would never have been able to do something false."

After considerable efforts to confirm the data, Dr. Roberts and colleagues conclude, "We are left with serious doubt about important studies but with no way of determining with confidence whether the results are fabricated or real. The main author is dead. There is no institution to investigate. The implications for patients are serious."

BMJ 2007;334:392-394.

 

 

---

Hypotension and Head Inj

Neurogenic hypotension in patients with severe head injuries.

OBJECTIVE: To examine the occurrence of hypotensive episodes in patients with severe traumatic brain injuries that are not of hypovolemic origin and to investigate possible neurogenic or iatrogenic causes of such episodes. METHODS: We reviewed Traumatic Coma Data Bank (TCDB) records of the 248 patients with early hypotension. We attempted to eliminate episodes related to hemorrhagic hypovolemia by excluding patients with (1) extracranial injuries of Abbreviated Injury Scale scores > 3 (n = 99, 40%); (2) postresuscitation hematocrit levels < 35% (n = 76, 30.6%); (3) hematocrit levels decreasing to < 35% during the first 24 hours after injury (n = 47, 19%); and (4) patients with conflicting data (n = 5, 2%). This left 21 patients (8.5%) without discernible extracranial causes for their hypotension. RESULTS: Of these 21 patients, 4 had no extracranial injuries and 4 had only a single injury with Abbreviated Injury Scale score = 1. Hypotensive episodes were not associated with terminal or unsalvageable status. Mortality was 43%. Of the multiple factors investigated, the only two that were strongly associated with these "unexplained" hypotensive episodes were the presence of a diffuse injury pattern on computed tomography (n = 15, 71%) and the early use of mannitol or furosemide (n = 16, 76%) (It was policy at TCDB centers that hypotensive patients not receive diuretics until they were resuscitated.) CONCLUSIONS: (1) Some episodes of severe traumatic brain injury-related hypotension may be of neurogenic origin. (2) The risk/benefit ratio of early diuretic use in patients with severe traumatic brain injuries may be too high to support liberal use. These data strongly support the need for a study involving prospective collection of data describing the early blood pressure courses in such patients. (J Trauma. 1998 Jun;44(6):958-63)

 

Isolated brain injury as a cause of hypotension in the blunt trauma patient.

BACKGROUND: Emerging evidence suggests that, contrary to standard teaching, isolated brain injury may be associated with hypotension. This study sought to determine the frequency of isolated brain injury-induced hypotension in blunt trauma victims. METHODS: Hypotensive adult trauma patients were categorized according to the cause of hypotension: hemorrhagic (hemoglobin < 11.0), neurogenic, isolated brain, or other. Their clinical data and outcomes were compared. RESULTS: The cause of hypotension was hemorrhagic in 113 (49%), isolated brain injury in 30 (13%), neurogenic in 14 (6%), and other causes in 24 (10%). Fifty (22%) were indeterminate. Hemorrhagic, isolated brain, and neurogenic groups were similar in age, Injury Severity Score, and systolic blood pressure. The Glasgow Coma Scale score of the isolated brain group was lower than in the hemorrhagic group (4.4 vs. 8.4, p < 0.05). Mortality was higher in the isolated brain group compared with the hemorrhagic group (80% vs. 50%, p < 0.05) and in the subgroup of hemorrhagic patients with versus without associated brain injury (57% vs. 39%, p < 0.05). CONCLUSION: Isolated brain injuries account for 13% of hypotensive events after blunt trauma and are associated with an increased mortality compared with hemorrhage-induced hypotension. In hypotensive brain-injured patients, hemorrhagic sources should be excluded rapidly, and the focus should be on resuscitation. (J Trauma. 2003 Dec;55(6):1065-9)

 

---

  (J Trauma Volume 63(2), August 2007, pp 370)Results: There were 122 lesions <=1 cm and 82 lesions >1 cm. In the first group, 115 were managed nonoperatively, with 111 good outcomes (minimal deficit with a Rancho Los Amigos score [RLAS] >=3), two poor outcomes (severely disabled with RLAS <3), and two deaths. Twenty-eight patients with lesions greater than 1 cm had concomitant cerebral edema (CE) with an 89% mortality rate. The mortality rate in this group without CE was 20%, demonstrating the presence of CE in this group may have adversely affected the mortality rate, regardless of intervention.
 

Conclusions: This data suggests that EDH or SDH <1 cm thick can be safely managed nonoperatively unless there is concomitant CE.

---

 

ICP Monitoring

ICP changes in a limited number of patterns after TBI 9:

In 1965, Nils Lundberg et al. characterized ICP slow waves.51 “A” waves or “plateau” waves are steep increases in ICP from baseline to peaks of 50-80 mm Hg that persist for 5-20 min. These waves are always pathologic and may be associated with early signs of brain herniation, such as bradycardia and hypertension. They occur in patients with intact autoregulation and reduced intracranial compliance and represent reflex, phasic vasodilatation in response to reduced cerebral perfusion.52,53 The development of plateau waves leads to a vicious cycle, with reductions in CPP predisposing to the development of more plateau waves, further reductions in CPP and irreversible cerebral ischemia. “B” waves are rhythmic oscillations occurring at 0.5-2 waves/min with peak ICP increasing to around 20-30 mm Hg above baseline. They are related to changes in vascular tone, probably due to vasomotor instability