Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5573_Библиотеки_им_академика_М_И_Перельмана.pdf
Part IV
Neurocritical Care
Chapter 16
Traumatic Brain Injury
LeslyV.JuradoHernández andTeresaA.Allison
16.1 Introduction
Traumatic brain injury (TBI) causes substantial challenges for public health
systems, leading to long-term economic burdens to patients and health systems
[1]. Globally, in 2019, there were 27.16million new TBI cases [2]. These numbers are signicantly underestimated, as they do not take into account TBIs
treated in emergency departments and primary care or those that go untreated.
In addition to the acute care requirements, these patients often need longterm care and extensive rehabilitation. Many patients are young when injured
and otherwise in good health; they can live for decades even if severely injured.
It is thought that up to 15% of patients with even a “mild TBI” will experience
a post-concussion syndrome (PCS), which consists of physical (fatigue, headaches), cognitive (difculties with concentration and memory), and emotional
(irritability, anxiety, depression) symptoms [3]. It can lead to disturbances in
personal relationships as well as the ability to return to school or work weeks to
months after injury [4]. The literature on PCS is limited due to difculty studying this population. Symptoms are not specic to PCS and may overlap with
other conditions. Additionally, it is questioned whether persistent symptoms are
driven by neurological and/or other psychological factors and how premorbid
conditions may inuence these symptoms. The severity of PCS depends on
many factors including the severity of TBI, multiple TBIs (as in contact sports),
L. V. JuradoHernández
Department of Pharmacy, Novant Health New Hanover Regional Medical Center Wilmington,
NC, USA
T. A. Allison (
Department of Pharmacy, Memorial Hermann—Texas Medical Center, Houston, TX, USA
e-mail: Teresa.Allison@memorialhermann.org
Switzerland AG 2025
Y. Alzaidi, M. A. Gebily (eds.), The Pharmacist’s Expanded Role in Critical
Care Medicine, https://doi.org/10.1007/978-3-031-77335-8_16
*)
397© The Author(s), under exclusive license to Springer Nature
398
L. V. JuradoHernández and T. A. Allison
as well as neurological and psychological factors. Patients with moderate-tosevere TBI have been shown to be twice as likely to die as similar non- braininjured people; their life expectancy is reduced by 7years [5].
16.2 Classication ofTBI
Traumatic brain injury can be described based on several different criteria.
Injuries are classied as primary or secondary. The primary injury is the event
causing the damage. It is immediate and not modiable by treatment. Secondary
injuries begin quickly after the primary injury and are thought to cause the
majority of complications following a TBI.There are many causes of secondary
injuries, with hypoxia (PaO2<60mmHg) and hypotension (SBP<95mmHg)
considered to be the leading contributing factors. One incident of either hypoxia
or hypotension has been shown to nearly double the mortality in severe
TBI [6, 7].
There are two classical types of head injury: closed head injury (CHI) or penetrating TBI. CHI (also known as non-penetrating injury or blunt TBI) is caused by
an external force strong enough to move the brain in the skull. This can be caused
by falls, motor vehicle accidents, sports injuries, being struck with an object, or a
blast injury. Penetrating TBI is caused when an object pierces the skull and enters
the brain.
Traumatic brain injury can be classied based on the effects on the brain. Focal
injuries occur at the site of the impact. The neurological decits are predominantly
conned to this area. Diffuse axonal injury is the shearing of axons in cerebral white
matter, which leads to widespread damage. Hematomas are bleeds caused by a ruptured blood vessel and are further described based on the location of the hemorrhage. Intracerebral hemorrhage is when bleeding occurs into the brain tissue.
Epidural hematomas occur in the area between the skull and the dura mater, the top
layer of the meninges. Subdural hematomas occur in the area between the dura
mater and arachnoid mater. Subarachnoid hemorrhages (SAHs) occur in the area
between the arachnoid mater and pia mater. Traumatic SAHs are treated as a TBI
per TBI guidelines, while aneurysmal SAH is considered a subset of stroke and is
treated according to aneurysmal SAH guidelines [8]. Further discussion of aneurysmal SAH is outside the scope of this chapter. Contusions are a bruising or swelling
when very small blood vessels bleed into the brain. Contusions are further classied
as coup and contrecoup injuries. A coup injury occurs directly under the impact site,
while the contrecoup injury occurs on the opposite side of the impact. Coup and
contrecoup injuries often happen when the brain is bounced back and forth within
the skull, such as in high-speed motor vehicle collisions or in shaken baby syndrome. Concussions are considered a mild TBI and a temporary injury. However, it
can take the brain months to heal.
Traumatic brain injury is classied based on the severity of injury as mild, moderate, or severe. Table16.1 describes the severity of injury.
raumatic Brain Injury
16
T
Table 16.1 Classication of severity of traumatic brain injury [9, 10]
Mild Moderate Severe
GCS 13–15 9–12 3–8
Loss of
consciousness
Post-traumatic
amnesia
Structural imaging Normal Normal or abnormal Normal or abnormal
Interventions No Imaging and monitoring, possible
GCS Glasgow Coma Scale
<30min 30min–24h >24h
0–1days >1–7days >7days
treatment
Imaging, monitoring, and
treatment
399
16.3 Hemodynamics
The skull is a rigid compartment comprised of brain matter, blood, and cerebrospinal uid (CSF). The Monro-Kellie hypothesis states that the sum of the volumes of brain tissue, intracranial blood, and CSF is constant. An increase in the
volume of one component should cause a proportional decrease in one or both
remaining components, or it will result in an increase in intracranial pressure
(ICP) [11]. Intracranial blood (primarily venous) and CSF are the two components where the volume can adapt most easily to accommodate an increase in
volume of intracranial contents. Once these compensatory mechanisms are
exhausted, volume increases in any of the three components (e.g., hematoma,
cerebral edema, space-occupying lesions, hemorrhage) will lead to increases in
pressure, resulting in elevated ICP [11].
Intracranial pressure is the pressure within the cranial vault; the relationship
between volume and pressure within the cranium is nonlinear. Cerebral perfusion
pressure (CPP) is the mean arterial pressure (MAP) minus ICP and is used as a surrogate for cerebral blood ow (CBF). Mathematically, this is shown as CPP =
MAP—ICP. Normally, CBF is maintained constant over a CPP range by cerebral
autoregulation. Once autoregulation is impaired, changes in MAP or ICP can have
direct effects on CBF [11].
The Brain Trauma Foundation Guidelines for the Management of Severe
Traumatic Brain Injury fourth Edition (BTF Guidelines) recommend a CPP target
between 60 and 70mm Hg and ICP below 22mm Hg, which has demonstrated to
reduce 2-week mortality in traumatic brain injury [12, 13]. The goals of ICP management are to preserve adequate brain oxygen delivery, avoid secondary injury,
and prevent herniation. Brain herniation syndrome results in an extreme elevation of
ICP accompanied by Cushing’s triad consisting of irregular respirations, bradycardia, and hypertension, followed by normalization of ICP [11]. Elevated ICP and
cerebral herniation are life-threatening neurologic emergencies. Intracranial hypertension is dened as a sustained (>5min) elevation of ICP to >22mm Hg [13].
Additionally, the systolic blood pressure goal is >100mm Hg for patients aged
50–69years and >110mm Hg for patients aged 15–49 and >70years [13].
400
L. V. JuradoHernández and T. A. Allison
16.4 Neurological Evaluation andImaging
Admission to a neurologic intensive care unit is associated with reduced morbidity
and mortality in patients with TBI [14, 15]. After initial assessment in the emergency room, patients with severe TBI should be admitted to the ICU, a specialized
neuro ICU if one is present. However, utilization of other services may be required
depending on the extent of injuries.
In the acute phase of ICU management, hemodynamic and neurological assessments are performed on TBI patients every hour. As the patient’s condition stabilizes, neurological assessment periods may be extended. Neurological evaluations
are most commonly performed with a Glasgow Coma Scale (GCS), which objectively describes the extent of impaired consciousness [16]. The scale assesses three
components of responsiveness, including eye-opening, verbal, and motor responses.
The total score is a sum of each of these three components; see Table16.2. A patient
who is completely awake and intact will receive a score of 15, while patients in a
coma will have a score of 8 or less. A completely unresponsive patient will receive
a score of 3, which is the lowest possible score.
Neuroimaging with a non-contrast-enhanced computed tomography (CT) scan
should be performed immediately in the emergency department in order to determine if neurosurgical interventions are possible [9]. If the injury is amenable to
surgery, the patient should be taken to the operating room (OR) immediately. If the
injury is not amenable to surgery, the patient should be taken immediately to
the ICU.
The BTF Guidelines recommend monitoring ICP in all salvageable patients with
a severe TBI and an abnormal CT scan with either hematomas, contusions, swelling, herniation, or compressed basal cisterns [13]. ICP monitoring is indicated in
patients with severe TBI with a normal CT scan if two or more of the following
features are noted at admission: age >40 years, unilateral or bilateral motor
Table 16.2 Glasgow Coma Scale [16]
Response Score
Eye opening Spontaneous
To speech
To pain
No response
Best verbal response Oriented to person, place, and time
Confused
Inappropriate words
Incomprehensible sounds
No response
Best motor response Obeys commands
Moves to localized pain
Flexion withdrawal from pain
Abnormal exion (decorticate)
Abnormal extension (decerebrate)
No response
4
3
2
1
5
4
3
2
1
6
5
4
3
2
1
16 Traumatic Brain Injury
posturing, or an SBP <90mmHg. Typically, ICP and MAP are monitored, and CPP
is calculated hourly in patients with an ICP monitor. There are two basic types of
ICP monitors. The external ventricular drainage catheter is placed inside a ventricle;
it can measure ICP and drain CSF.The ICP monitor known as a “bolt” is placed in
the subarachnoid space, epidural space, or parenchyma. The bolt is only able to
monitor the ICP.
Advanced cerebral monitoring techniques for blood ow and oxygen include
transcranial Doppler (TCD)/duplex sonography, differences between arterial and
arterio-jugular venous oxygen (AVDO2), and measurements of local tissue oxygen.
Arterio-jugular AVDO2 globally measures cerebral oxygen extraction. Microdialysis
measures brain metabolism, and electrocorticography determines cortical spreading
depression. Currently, use of these monitoring techniques in clinical practice is limited due to insufcient evidence demonstrating a benet as well as questions regarding how to use the data provided by these advanced cerebral monitors.
401
16.5 Pharmacological Management
Pharmacological management can be divided into management of CPP, management of ICP, and adjunct therapies. Management of CPP entails maintaining a MAP
to balance the ICP. MAP is increased with uids, blood products, and vasopressors.
ICP is managed with pharmacological agents including hyperosmolar therapy,
sedation and analgesia, and anesthetics. Nonpharmacological methods include
decompressive craniectomy, prophylactic hypothermia, cerebrospinal uid drainage, and ventilation strategies. Because uids and vasopressors are covered elsewhere, the focus of this chapter will be the management of ICP.
16.5.1 Hyperosmolar Therapy
The administration of hyperosmolar agents is one of the principal strategies in treating cerebral edema and lowering elevated ICP. Hyperosmolar therapy primarily
consists of mannitol and hypertonic saline (HTS). Current literature suggests that
both agents are effective for managing acute intracranial hypertension in the setting
of TBI; however, Class I evidence for this therapy is meager, and most evidence is
derived from retrospective analyses or case series [13]. See Table16.3 for comparisons of the two agents. The optimal agent, method of administration, and precise
mechanism of action for this class continue to be examined.
Hyperosmolar agents have two main mechanisms of action. An immediate
ICP reduction is observed through changes in blood uid dynamics or rheology.
The mechanisms underlying these rheological modications include lowering
of blood viscosity and increasing MAP, which lead to reduced cerebral blood
volume and a compensatory cerebral vasoconstriction [17, 18]. Additionally,
402
Table 16.3 Comparison of mannitol and hypertonic saline [18, 20, 22, 23, 26, 27, 33, 37, 43, 46,
48–51, 55, 56]
Mannitol Hypertonic saline
Mechanism of
action
Additional
proposed
benets
Onset of action 20min 20min
Duration of
effect
Administration
access
Infusion Infused via boluses Infused via boluses or continuous
Dose Typically 20% solution at 0.5–1g/kgDependent on sodium level, goal sodium
Intravascular
volume effects
Electrolyte
disturbances
Acute kidney
injury
Neurological
complications
ICP intracranial pressure
Decreases blood viscosity and
improves microcirculatory blood
ow
Free radical scavenger and
inhibits programed cell death
90min to 6h 90min to 4h
May be administered via
peripheral line
Produces diuresis; benecial in
hypervolemic patients
Risk of sodium and potassium
abnormalities; hyper- or hypodepending on the time of lab draw
in relation to administration of
mannitol
Risk of acute kidney injury
(theoretically when osmolar gap
>20mOsm/kg)
Administration of continuous
infusions can lead to
accumulation, worsening cerebral
edema, and rebound ICP elevation
L. V. JuradoHernández and T. A. Allison
Decreases blood viscosity and improves
microcirculatory blood ow
Anti-inammatory processes
Traditionally administered via central
line; newer literature suggests that it is
safe to administer via peripheral line.
Institutional polices will dictate
peripheral or central administration
infusion
level, and uid status
Increases intravascular volume;
benecial in hypovolemic patients.
However, can lead to hypervolemia and
complications
Risk of electrolyte abnormalities:
Hypernatremia and hyperchloremia. Risk
of metabolic acidosis due to
hyperchloremia
Risk of acute kidney injury due to
hypernatremia and hyperchloremia
Risk of osmotic demyelination,
especially in hyponatremic patients
these agents have osmotic properties, which take effect in approximately 20min
after dosing. These osmotic properties produce a reduction in brain water content and a reduction in cerebrospinal uid pressure. When administered in clinical doses, mannitol reduces brain water by approximately 2% [18]. Other
features of mannitol that have been proposed to contribute to its therapeutic
effects include that it is a free radical scavenger and it inhibits programmed cell
death [19–21]. It has been proposed that hypertonic saline has additional vasoregulatory, immunomodulatory, and neurochemical effects that provide benet
in this patient population [22].
16 Traumatic Brain Injury
403
Both agents do appear to be effective at lowering ICP, but the literature has not
demonstrated a superior agent. Additionally, neither agent has shown to improve
neurological outcomes [23]. As such, guidelines have differing recommendations.
The BTF Guidelines recommend mannitol at 0.25–1 g/kg, in one-time or asneeded doses.
Currently, there is insufcient evidence from comparative studies to support a
formal recommendation regarding hypertonic saline [13]. However, the 2019 Seattle
International Severe Traumatic Brain Injury Consensus Conference (SIBICC) recommends either hypertonic saline or mannitol boluses as initial (Tier 1) treatment
for an elevated ICP and considers treatments within a tier to be equivalent [24]. The
2020 Neurocritical Care Society (NCS) Guidelines for the Acute Treatment of
Cerebral Edema in Neurocritical Care Patients recommend hypertonic saline over
mannitol for initial management of elevated ICP and cerebral edema in patients
with TBI.The panel acknowledged that the quality of evidence was low; however,
hypertonic saline was at least as safe and effective as mannitol. Additionally, the
panel agreed that the purposed advantages of hypertonic saline over mannitol for
uid resuscitation and cerebral perfusion supported this recommendation [23]. The
Western Trauma Association (WTA) management recommendations state that it is
generally accepted that both agents are effective in reducing elevated ICP, though
they suggest HTS in the polytrauma patient who requires vascular volume expansion in addition to lowering of the ICP [25].
Currently, the choice of agent is based on perceived advantages and disadvantages as well as pharmacokinetic and pharmacodynamic properties. Mannitol is a
sugar alcohol that is excreted unchanged in the urine. The half-life is affected by
glomerular ltration rate and averages 39–103min [18, 26]. Mannitol is removed
via hemodialysis and peritoneal dialysis [27]. The peak ICP-lowering effect occurs
within 30–45 min and lasts around 6 h. Mannitol becomes less effective with
repeated doses. Mannitol is most frequently administered as a 20% (1098mOsm/L)
or 25% (1375mOsm/L) solution when given for ICP control. The dose can range
from 0.25 to 2g/kg, while most clinicians will use doses of 0.5–1g/kg. Doses may
be repeated every 4–6h based on clinical need. Mannitol should be infused through
an in-line ≤5micron lter due to the risk of precipitation. The infusion length is
typically 10–30min, with the faster infusion rate of 10min reserved for impending
cerebral herniation.
The acute effect of mannitol on systemic arterial pressure is variable. A slight
increase in pulse pressure and MAP is commonly observed. However, transient
decreases in blood pressure secondary to decreases in systemic vascular resistance
have been reported in the literature [28]. Hypotension is most likely to occur in
patients who are relatively volume depleted. Acute mannitol-induced hypotension is
rarely a serious problem. However, it can present a challenge when attempting to
maintain CPP.
The potential complication of mannitol accumulating in damaged brain tissue
and worsening uid shifts appears to be more of an issue when the drug is not
cleared from the blood between doses. A theoretical risk of mannitol is “rebound”
intracranial pressure, which is most often attributed to continuous infusions or
404
L. V. JuradoHernández and T. A. Allison
repeated high doses. In either case, it is proposed that prolonged therapy leads to
penetration of osmotically active particles into brain tissue, especially in areas of a
disrupted blood-brain barrier (BBB). Accumulation of mannitol leads to the creation of an osmotic gradient favoring water movement into the tissue, leading to
edema [29]. Whether this actually occurs is unclear; several studies in animals and
humans have reported no clinical evidence of rebound intracranial pressure [30–34].
Alternate proposed mechanisms include rapid volume depletion from administration of mannitol without adequate uid administration as well as the administration
of uids that are hypotonic relative to the osmolarity of the patient combined with a
rise in the number of intracellular osmotic particles induces movement of water
back into regions with disrupted BBB and increased water permeability [20, 35].
Until the actual mechanism of rebound intracranial pressure can be determined, it is
recommended not to administer mannitol as continuous infusions or more often
than every 4–6h.
Mannitol-induced acute kidney injury (AKI) has been extensively discussed in
the literature; however, the mechanism remains unclear. Suggested mechanisms
include renal vasoconstriction produced by a high dose/concentration of mannitol;
profound diuresis and natriuresis, and osmotic nephropathy, which is isomeric tubular vacuolization or tubular cell swelling [36–38]. Furthermore, patients with preexisting risk factors including advanced age, underlying kidney disease, and
concomitant use of nephrotoxic agents have been shown to be susceptible to the
development of mannitol-induced AKI [36, 39, 40].
The risk of AKI is suggested to increase with a serum osmolality greater than
320mOsm/kg [18]. Hence, many institutions continue to monitor serum osmolality
when administering mannitol therapy with an upper allowable limit of 320mOsm/
kg [24]. While monitoring serum osmolality in patients who have received multiple
doses of mannitol may be useful for associated toxicities, it does not predict mannitol concentrations [41]. The 2020 NCS Guidelines for the Acute Treatment of
Cerebral Edema in Neurocritical Care Patients recommend using serum osmolar
gap (measured serum osmolality—calculated osmolality) over serum osmolality to
monitor for increased risk of AKI [23]. The osmolar gap has been shown to correlate better with mannitol serum concentrations than serum osmolality. Additionally,
a normal osmolar gap concentration indicates that sufcient clearance of mannitol
has occurred for additional dosing [42]. Retrospective analyses suggest that AKI
with an osmolar gap <55mOsm/kg is extremely rare and is more likely to occur
once it exceeds 60–75mOsm/kg [26, 43, 44]. The guidelines acknowledge that an
upper limit of 20mOsm/kg is often used as the threshold for AKI risk, although this
number is not clearly supported by literature [23]. Mannitol-induced AKI is often
reversible with cessation of the drug and will respond to hemodialysis, if required
[44, 45].
It is important to closely monitor electrolytes while patients are receiving hyperosmolar therapy [23]. With mannitol, it is important to note the subacute phase in
which electrolytes and the uid status are being monitored. For example, hyponatremia may be observed immediately after the dose of mannitol secondary to dilution. However, hypernatremia may be observed in the diuresis period as it causes a
16 Traumatic Brain Injury
405
net clearance of “free water.” In addition to water and sodium chloride, abundant
urine loss of potassium, phosphate, and magnesium can occur in patients receiving
mannitol. Though exceedingly rare, mannitol can lead to volume overload with subsequent pulmonary edema or heart failure immediately following administration [26].
The ratio of urine diuresed to the volume of mannitol 25% solution administered
can be as high as 5:1 [20]. For example, if 125mL of mannitol is administered, the
patient may diurese 625mL. As such, patients can become severely dehydrated.
Often, uids and sodium will need to be replaced after a mannitol infusion using
normal saline (0.9%), one-half normal saline (0.45%), or one-quarter normal saline
(0.22%) depending on the sodium concentration. The volume replaced is dependent
on the perceived volume status of the patient and may require ½ to 1mL per mL
diuresed.
A theoretical advantage of HTS to mannitol is that an intact BBB is less permeable to saline than to mannitol. The reection coefcient, which is a measure of the
ability of a membrane to prevent the passage of solutes, is 1 for sodium chloride vs.
0.9 for mannitol. Animal studies show that with an intact BBB, sodium administration increases CSF sodium concentrations but lags behind plasma levels by 1–4h,
creating an effective osmotic gradient.
Therapeutic HTS dosing regimens are more varied compared to mannitol.
Regimens include concentrations ranging from 2% to 23.4%, which are administered as bolus doses or continuous infusions. There is no evidence to suggest that
one regimen is superior to another. Currently, clear guidelines and specic sodium
targets are lacking. Because of this, a 2011 survey of Neurocritical Care Society
members showed that administration patterns varied considerably [46]. One-third of
respondents used prophylactic continuous infusions, one-fourth reported using
symptom-based bolus dosing, and one-fth reported using a combination of the two
strategies. Additionally, a small number reported using scheduled bolus dosing.
Traditionally, it has been recommended that concentrations of hypertonic saline
solutions of 3% or greater be infused through a central catheter to avoid extravasation, thrombophlebitis, and tissue necrosis. It is thought that this recommendation
was extrapolated from studies on peripheral administration of osmolar loads of total
parenteral nutrition, which determined maximum osmolarity of peripherally infused
solutions be limited to 900 mOsml/L.Currently, there is still concern for thrombophlebitis and extravasation; however, there is growing support in the literature for
the peripheral administration of HTS [47–52]. Additionally, there are practical reasons for peripheral line administration. First, central venous access is not immediately available in the acute setting in all patients. This recommendation can lead to
a delay in therapy and potentially worsen outcomes. Second, central catheters are
associated with complications including infection, symptomatic thrombosis, and
pneumothorax. Catheter-related complications are estimated to occur with up to
15–20% of catheters, depending on the site of placement [53]. Prior to a facility or
ICU adopting peripheral administration of HTS, a protocol for administration and
monitoring should be implemented. It should include the following: (a) infusing
HTS only through large veins (18–20 gauge) in an upper extremity that are not in an