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_5783_Библиотеки_им_академика_М_И_Перельмана.pdf
78
INTENSIVE CARE UNITE (ICU)
Algorithm
Clinical Status of the Patient
ABCD
Level of consciousness (Glasgow)
Bilateral Pupillary reactivity
Hemodynamic stability?
Oxygenation?
DIAGNOSIS
Suspicion of Brain Death
V. Zisimopoulou and P. N. Varelas
Confirm Death
by
Neurological Criteria
(DNC)
Hormonal Replacement Therapy
Diabetes Insipidus (DI)
Dilute Urine Output
(2.5-3 ml/Kg/h) Hypovolemia
Hyperosmolality (Na
Hypothyroidism (Less frequent)
Hypocortisolism (Less frequent)
Check - Absence
Mannitol administration
IV Hormonal Replacement
IV Antidiuretic Hormone (AVP)
[ 1 U IV bolus infusion] +
[IV Continuous infusion
0.01-0.04 U/min]
Monitor vascular resistance Monitor
800-1200 dynes-sec/m
[consider with hypotension]
IV Desmopressin (DDA)
[1-2 µg IV c/6 or 12 hs]
[Dose titulated by Urine output]
UO Goal: < 4 ml/Kg/h
Hyperglycemia
+
p > 145)
a) Detection of an irreversible coma
b) Prerequisites that have to be met before a patient is evaluated for BD
c) Thorough clinical examination by a physician who has expertise on
assessing brain function
d) Apnea testing to exclude any spontaneous respirations
e) Ancillary testing in specific situations, where parts of 3 and 4 are not certain
or cannot completely be assessed
f) Precise documentation of all the above and the time of death of the individual
ORGAN MAINTENANCE/ ORGAN DONOR
Hemodynamic Management
CVP / HR / Rythm / ABP / CO
Urine output/PAOP/CI
1. Normovolemia
2. Control of ABP
MAP > 60 mmHg
Urine Output > 1 ml/Kg/h
LV ejection > 45%(TTE)
Lower vasopressor dose
Cristaloids (Lactate Ringer) IV
HES (500-1000 ml/dose) IV
Albumin 5% IV
Packed RBCs (Hb < 7 g/dl or Bleed)
5
Vasopressors
IV Dopamine (10 µg/Kg/min)
IV Vasopressin
IV Norepinephrine
IV Fluids
Respiratory Management
Optimize function of Lungs
Euvolemia
Inducing diuresis
Treat the infections
Recruit maneuvers
Low FiO
PEEP
Mechanical Ventilation
Protective Protocol
[Tidal volume 6-8 ml/Kg]
[PEEP 8-10]
Closed circuit to suctioning
Positive airway pressure
[Apnea Test]
Thermodilution T3
[EVLW / EVLWI]
[PVPI] < 3
Cardiac Output (CO)
(as possible)
2
Corticosteroids
Optimize donor lung quality
[Methylprednisolone 15mg/Kg IV
Infusion] or [250 mg IV Bolus +
100 mg/h IV Infusion]
Thyroid Hormone
T4
[20 µg IV bolus + 10 µg/h
IV Infusion]
Or
[4µg IV bolus + 3 µg/h
IV Infusion]
Na+p plasmatic sodium, IV Intravenous, EVLW extravascular lung water, EVLWI extravascular
lung water index, PVPI permeability vascular, MAP mean artery pressure, ABP arterial blood pressure, TTE transthoracic echocardio, BD brain death, LV left ventricule, CVP central venous pressure, HR heart rate, CO cardiac output, CI cardiac index, PAO P pulmonary artery occlusion
pressure, HES hydroxyetilstarch, RBC red blood cells
References
1. Mollaret P, Goulon M.The depassed coma (preliminary memoir). Rev Neurol. 1959;101:3–15.
2. Wahlster S, Wijdicks EF, Patel PV, etal. Brain death declaration: practices and perceptions
worldwide. Neurology. 2015;84:1870–9.
4 Organ Maintenance After Death by Neurological Criteria (DNC) in Neuro-ICU…
3. Greer DM, Wang HH, Robinson JD, Varelas PN, Henderson GV, Wijdicks EF.Variability of
brain death policies in the United States. JAMA Neurol. 2015;73:213–8.
4. Practice parameters for determining brain death in adults (summary statement). The Quality
Standards Subcommittee of the American Academy of Neurology. Neurology. 1995;45:1012–4.
5. Wijdicks EF, Varelas PN, Gronseth GS, Greer DM, American Academy of N. Evidence-
based guideline update: determining brain death in adults: report of the Quality Standards
Subcommittee of the American Academy of Neurology. Neurology. 2010;74:1911–8.
6. Singbartl K, Murugan R, Kaynar AM, etal. Intensivist-led management of brain-dead donors
is associated with an increase in organ recovery for transplantation. Am J Transplant Off J Am
Soc Transplant Am Soc Transplant Surg. 2011;11:1517–21.
7. Kotloff RM, Blosser S, Fulda GJ, et al. Management of the Potential Organ Donor in the
ICU: Society of Critical Care Medicine/American College of Chest Physicians/Association of
Organ Procurement Organizations Consensus Statement. Crit Care Med. 2015;43:1291–325.
8. Watts RP, Thom O, Fraser JF.Inammatory signalling associated with brain dead organ dona-
tion: from brain injury to brain stem death and posttransplant ischaemia reperfusion injury. J
Transpl. 2013;2013:521369.
9. Wood KE, Becker BN, McCartney JG, D’Alessandro AM, Coursin DB.Care of the potential
organ donor. N Engl J Med. 2004;351:2730–9.
10. Reyes KG, Mason DP, Thuita L, etal. Guidelines for donor lung selection: time for revision?
Ann Thorac Surg. 2010;89:1756–64. discussion 64–5.
11. Mascia L, Pasero D, Slutsky AS, etal. Effect of a lung protective strategy for organ donors
on eligibility and availability of lungs for transplantation: a randomized controlled trial.
JAMA. 2010;304:2620–7.
12. Hanna K, Seder CW, Weinberger JB, Sills PA, Hagan M, Janczyk RJ.Airway pressure release
ventilation and successful lung donation. Arch Surg. 2011;146:325–8.
13. Lustbader D, O'Hara D, Wijdicks EF, et al. Second brain death examination may negatively
affect organ donation. Neurology. 2011;76:119–24.
14. Dalle Ave AL, Gardiner D, Shaw DM.Cardio-pulmonary resuscitation of brain-dead organ
donors: a literature review and suggestions for practice. Transpl Int. 2016;29:12–9.
79
Chapter 5
Neuropharmacology intheICU:
Monitoring theTherapeutic Response
andNeurological Hemodynamic Impact
ofOur Therapeutic Decisions inReal Time
RyanFillmore andGretchenM.Brophy
Key Points
1. Vasoactive drugs impact both systemic and cerebral hemodynamic parameters.
2. Impaired cerebral autoregulation (CA) may cause an unwanted effect of a drug
on central nervous system (CNS) vasculature.
3. Avoid abrupt hemodynamic changes that may lead to unwanted increases in
intracranial pressure.
4. Optimization of mean arterial pressure (MAP) and cerebral perfusion pressure
(CPP) needs to be considered when selecting certain drugs due to their potential
side effects.
5. Comorbid disease states, organ dysfunction, and temperature must be consid-
ered when administering medications that may alter cerebrovascular
hemodynamics.
6. The use of noninvasive techniques, such as transcranial Doppler (TCD/TCCS),
can serve as a tool for determining the therapeutic response of pharmacological
treatments in neurocritical care patients.
R. Fillmore
Department of Neurology-Neurocritical Care, The University of California, Irvine,
Orange, CA, USA
G. M. Brophy (
Virginia Commonwealth University, Medical College of Virginia Campus,
Richmond, VA, USA
e-mail: gbrophy@vcu.edu
C. N. Rodríguez et al. (eds.), Neurosonology in Critical Care,
https://doi.org/10.1007/978-3-030-81419-9_5
*)
81© Springer Nature Switzerland AG 2022
82
R. Fillmore and G. M. Brophy
5.1 Introduction
It is essential to understand the systemic and central effects of different medications
when managing patients with acute, life-threatening neurological injuries. Patients
with a severe acute brain injury, secondary to ischemic/hemorrhagic strokes, anoxic
injury after cardiac arrest, status epilepticus, or traumatic brain injury, may have
impaired cerebral autoregulation. Therefore, changes in systemic blood pressure
can have a profound effect on central nervous system (CNS) hemodynamics [1].
The use of vasoactive drugs in this population may have variable and possibly
unwanted results due to this impaired cerebral autoregulation. The impact of these
agents on the cerebrovasculature may ultimately result in decreased cerebral tissue
oxygenation and poor outcomes. In addition, acute/chronic comorbidities (e.g.,
chronic hypertension, renal insufciency, or hepatic failure), hyperthermia/hypothermia, alterations in acid/base status, and even volume status can alter the pharmacokinetics of these drugs [2]. In patients with aneurysmal SAH, tailoring therapy
can be challenging as cerebral vasospasm along with other pathophysiologic mechanisms are thought to contribute to morbidity and mortality in these patients [3–6].
There is a paucity of data describing the effects of medications on the cerebrovasculature when using multimodality monitoring devices, such as transcranial Doppler
(TCD/TCCS). Therefore, this chapter will review the available evidence in
this regard.
5.2 Systemic andCerebral Vasculature: Drug Effects
Select medications are given to directly inuence system hemodynamic characteristics (e.g., vasodilation and vasoconstriction) through varying mechanisms.
However, there can be secondary effects of these medications on cerebrovascular
hemodynamics, such as increased or decreased ICP, which must be taken into
account when optimizing cerebral perfusion pressure and oxygenation in patients
within the neurocritical care setting [7, 8].
5.2.1 Vasoactive Agents
5.2.1.1 Vasodilators (Table 5.1)
Calcium Channel Blockers
Dihydropyridine calcium channel blockers (CCB) act on L-type slow-conducting
calcium channels in vascular smooth muscle causing vasodilation. Potential adverse
effects of these agents are reex tachycardia and systemic hypotension.
↑
5 Neuropharmacology in the ICU: Monitoring the Therapeutic Response…
83
Table 5.1 Vasodilator drugs
Drug/Drug
Class:
Calcium
Channel
Blockers
Magnesium Possible
StatinsHMG-COA reductase
Nitroprusside ↓ ABP ↑ICP with large
Clazosentan ↓ ABP ↑cerebral
Hydralazine Not fully understood. Causes
Sildenafil
citrate
Papavarine Inhibits cyclic cAMP, cGMP,
Act on L-type slow-conducting
Ca
muscle
Calcium ion antagonist in
smooth muscle
inhibitors, induction of NO
pathway.
Metabolized to
NO→cGMP→vasodilation in
smooth muscle of arterioles
and venules
Endothelin-1 antagonist
smooth muscle relaxation and
peripheral vasodilation
Phosphodiesterase-5Inhibitor→decrease
cGMP→vasodilation
and calcium ion channels in
smooth muscle
MOA Systemic
2+
channels in smooth
Vascular
Effects
↓ ABPNo significant effect
↓ ABP
No significant
effect
↓ ABPPossible ↑CBF
↓ ABPObserved
↓ ABP ↑ICP/velocityIntra-arterial administration for the
Cerebrovascular
Effects/TCD
findings
on ICP
Possible ↑CBF. No
significant effect on
ICP
Possible ↑CBF
and therefore ↑ICP
dosage
adjustments or
toxicity
vasospasm, no
significant effect on
ICP
and therefore
↑ICP/velocity
Vasodilatory effect
in normal and
spastic vessels
Clinical Pearls
Avoid rapid titration: systemic
hypotension, reflex tachycardia
(esp. IV nicardipine)
Continuous infusions can lead to
high concentrations and
cardiac/systemic adverse effects
Caution in hepatic dysfunction
Small titrations recommended,
monitor for thiocyanate toxicity,
Expensive
Not FDA approved, pulmonary
complications, anemia
Reflex tachycardia, headache,
flushing, hypotension
Headache
Main use: pulmonary hypertension
and erectile dysfunction
treatment of vasospasm
MOA mechanism of action, ABP arterial blood pressure, TCD transcranial Doppler, CPP cerebral
perfusion pressure, CBF cerebral blood ow, ICP intracranial pressure;
Decrease, ↓ Increase
Nimodipine
It is the only CCB indicated for reducing the incidence and severity of ischemic
decits following aneurysmal SAH [4]. Unfortunately, nimodipine is not available
as an intravenous (IV) formulation in the United States, which increases the
unwanted systemic hypotensive effects with immediate-release capsule oral administration. It can be very problematic and sometimes warrants the administration of a
vasoconstrictor to counter these effects to decrease the risk of lowering cerebral
perfusion and oxygenation. Other countermeasures include lower dosages given
every 2hours orally or via feeding tube by extracting the gel from the capsule.
There is a new liquid formulation of nimodine available, but it is very expensive and
is not available at all institutions. The most recent randomized, controlled trial,
Nimodipine Microparticles to Enhance Recovery While Reducing Toxicity After
Subarachnoid Hemorrhage (NEWTON), evaluated nimodipine gel administered
intraventricularly and slowly released over 21days [8]. Although animal studies of
this formulation showed promise, the NEWTON trial did not show clinical benet
in aSAH patients.
Nicardipine
It is ideal for system blood pressure control in patients who require continuous IV
administration and has been shown to reduce the incidence of symptomatic vasospasm in patients with aSAH. However, it was not shown to improve overall
84
R. Fillmore and G. M. Brophy
outcome after 3months [9]. Exercise caution with nicardipine due to potential systemic hypotension if titrated too rapidly, prolonged effects as treatment duration
increases, and volume overload due to low concentrations required for peripheral
administration [4]. There have been some reports of headache as an adverse effect
with IV nicardipine administration, especially in studies for the treatment of symptomatic vasospasm after aSAH [10]. More recently, IV nicardipine was shown to
paradoxically increase intracerebral arterial contractility based on an elevated pulsatile index (PI) calculated from TCD measurements in a small group of patients
with aSAH [11]. However, it is still unclear if IV nicardipine ultimately increases
ICP. Other formulations have been studied for use in aSAH, such as nicardipine
prolonged-release implants (NPRIs), and intraarterial administration (IA). The
NPRIs were shown in one study to decrease the incidence of delayed ischemic neurologic decit (DIND) in patients with thick subarachnoid clots (Fisher grade 3) if
implanted adjacent to arteries located within the clots [12, 13]. IA nicardipine
administration was shown in one prospective study to reverse vasospasm without
any sustained effect on ICP or on systemic hemodynamics in patients who required
interventional treatment for vasospasm [14].
The newest CCB available for IV administration is clevidipine. This is a shortacting CCB administered as a continuous infusion for rapid control of hypertension.
One study has evaluated the cerebrovascular effects of clevidipine and it was not
found to signicantly increase cerebral blood ow velocity (CBFV) or CO2 responsiveness [15]. The key to reducing adverse effects from CCB agents is to avoid
abrupt changes in dosage and maintaining euvolemia throughout the duration of
treatment.
Other Vasodilators
Magnesium
Calcium has been shown to play a role in vasoconstriction via its action on smooth
muscle within the arterial walls. Intravenous magnesium antagonizes calcium,
which can increase cerebral blood ow via decreasing cerebral vasoconstriction.
Several studies have evaluated the use of continuous IV magnesium infusions in
patents with aSAH, but the most recent prospective study (MASH-II trial) showed
no benet in reducing ischemic decits. Currently, no data exist to support continuous intravenous infusions of magnesium for improving clinical outcomes in patients
with aSAH [16].
3-Hydroxy-3-Methyl-Glutaryl-CoA (HMG-CoA) Reductase Inhibitors (Statins)
HMG-CoA reductase enzyme inhibitors, often called statins, are thought to induce
the nitric oxide (NO) pathway (via inhibition of Rho protein) resulting in increased
NO production and dilation of cerebral blood vessels improving cerebral blood ow
5 Neuropharmacology in the ICU: Monitoring the Therapeutic Response…
85
(CBF). Some studies report that both simvastatin and pravastatin can reduce the
incidence of angiographically proven vasospasm and delayed ischemic neurological
decit (DIND) in patients treated with statins for management of aSAH [17, 18].
One randomized prospective study showed simvastatin reduced the highest mean
velocities within the middle cerebral artery (using TCDs), postulating that it inhibited biochemical inammatory markers that are thought to cause vasospasm [18].
The most recent study evaluating statins for prevention of ischemic decits following aSAH (STASH trial) was unable to show benet with these agents [19]. However,
if a patient is on a statin prior to admission, the statin should not be stopped as this
has been associated with rebound vasoconstriction and worse outcomes [20, 21].
Nitroprusside
Nitric oxide activates guanylate cyclase in vascular smooth muscle and increases
the intracellular production of cyclic guanosine monophosphate (cGMP) causing
vascular smooth muscle relaxation and vasodilation. Nitroprusside, a potent vasodilator, breaks down in the systemic circulation to release NO causing vasodilation of
arterioles (and venules). Caution should be used with prolonged high-dose infusions, especially in patients with renal dysfunction, due to potential cyanide/thiocyanate toxicity. This toxicity manifests as systemic hypotension, massive
vasodilation, increased cerebral blood ow (shunted from systemic autoregulation),
and increased ICP [22, 23]. Large dosage adjustments should also be avoided as this
can result in decreased systemic blood pressure and increased ICP.
Endothelin-1 Antagonists
The interaction between endothelin-1 (ET-1) and NO is essential for maintaining
adequate cerebral blood ow (via cerebral vasodilatation) in patients with aSAH
[3]. Clazosentan, an ET-1 antagonist, has been found to reduce cerebral vasospasm
in a dose-dependent fashion in patients undergoing endovascular coiling, but it did
not change the overall clinical outcome (CONSCIOUS-III TRIAL). Additionally,
adverse effects observed were pulmonary complications, hypotension, and anemia
with the use of clazosentan [24].
Hydralazine
It directly acts on peripheral vasculature causing relaxation of smooth muscle and
vasodilation. In rodent animal models, dihydralazine caused increased CBF if autoregulation was intact. The extent and duration of systemic vasodilatory effects are
highly variable and caution should be used due to potential reex tachycardia, headache, ushing, and systemic hypotension [25].
86
↑ ICP/velocities
refractory hypotension
↑
R. Fillmore and G. M. Brophy
Phosphodiesterase Inhibitors
Cyclic guanosine monophosphate (cGMP) is an important nucleotide involved in
endovascular smooth muscle contraction. The phosphodiesterase isoenzyme type V
(PDE-V) hydrolyzes cGMP, which lowers its intracellular concentration subsequently causing vasoconstriction. Sildenal citrate (PDE-V inhibitor), commonly
used for erectile dysfunction and pulmonary hypertension, has been shown in animal models to have a vasodilatory effect in normal and spastic cerebral vessels [3,
26]. These cerebrovascular changes may result in headache, which is reported to
occur in up to 46% of patients [27].
Papaverine
It is a benzylisoquinoline alkaloid derived from opium, and acts as a nonselective
vasodilator via its inhibition of cyclic adenosine monophosphate (cAMP), cGMP,
and calcium ion channels in smooth muscle. Intraarterial administration has been
shown in some studies to reduce cerebral vasospasm angiographically (TCD proven)
and clinically [28]. Papaverine can increase ICP, and its use has fallen out of favor
with the availability of safer and more effective vasodilatory agents [29].
5.2.1.2 Vasoconstrictors (Table5.2)
Generally, an increase in systemic vasoconstriction can cause an increase in cerebral blood volume (CBV) and CBF, which may increase ICP.Remember, however,
that in patients with impaired cerebral autoregulation, the secondary effect of vasoconstrictive drugs can change [30, 31].
Table 5.2 Vasoconstrictors
Drug:
Norepinephrine α-adrenergic and β-1
Epinephrine α-1, β-1, and β-2 agonist ↑ ABP No significant impact on
Dopamine α-adrenergic, β-1, and
Phenylephrine α-adrenergic agonist ↑ ABP ↑ CPP, ↑ CBF, possible
VasopressinV1-endothelium receptor ↑ ABP ↑ CPP, ↑CBF, possible
MOA Systemic
adrenergic agonist
dopamine receptor agonist
Vascular
Effects
↑ ABP No significant impact on
↑ ABP ↑ CBF and ICP: may see
MOA mechanism of action, ABP arterial blood pressure, TCD transcranial Doppler, CPP cerebral
perfusion pressure, CBF cerebral blood ow, ICP intracranial pressure,
Cerebrovascular
Effects/TCD Findings
CBF or ICP
CBF or ICP
↑ velocities
↑ ICP/velocities
Clinical Pearls
Can cause tachyarrythmias
Can cause tachyarrythmias
Likely to cause
tachyarrythmias at high doses
Caution: reflex bradycardia
Adjunctive therapy for
Increase, ↓ Decrease
5 Neuropharmacology in the ICU: Monitoring the Therapeutic Response…
87
Norepinephrine
It is an alpha adrenergic and beta-1 adrenergic agonist that can cause systemic
hypertension and increased cardiac output, respectively [30]. No signicant impact
on CBF or ICP has been observed [32].
Epinephrine
Acts on alpha, beta-1, and beta-2 adrenergic receptors, but has no signicant impact
on CBF or ICP [32].
Dopamine (DA)
It is an alpha adrenergic, beta-1 adrenergic, and dopamine receptor agonist that has
been shown to directly increase CBF and ICP [32].
Phenylephrine
It is an alpha-adrenergic receptor agonist that causes vasoconstriction of peripheral
blood vessels. It has been shown to cause an increase in CPP (cerebral perfusion
pressure), which then increases CBF [33]. Caution should be used due to the potential for reex bradycardia [30].
Vasopressin
Acts on the V1 endothelium receptor, and is often used in refractory hypotension
due to sepsis as adjunctive therapy. It has also been shown to be effective in maintaining CPP in TBI swine models without a signicant increase in ICP [34].
Neuromonitoring
Can be extremely helpful when using vasoconstrictive agents in patients with neurological injury and impaired autoregulation in order to optimize therapeutic
strategies.
88
antagonist
hallucinations,
↑
R. Fillmore and G. M. Brophy
5.2.2 Anesthetics/Sedative Agents (Table5.3)
We know from prior studies that IV sedatives generally cause a dose-dependent
decrease in CBF as well decrease the cerebral metabolic rate for oxygen (CMRO2),
ultimately causing a reduction in ICP [35–37]. However, the reduction in CBF can
be variable between drugs, and there may be compensatory cerebral vasodilation
which can increase ICP in the setting of preserved autoregulation [37]. In addition
to the coupled reduction of both CBF/CMRO
vasodilation, therefore leading to a reduction in the systemic mean arterial blood
pressure (MAP). In patients with impaired cerebral autoregulation, lowering the
MAP can cause a decrease in CPP and brain tissue ischemia/hypoxia [35, 38]. Keep
this in mind when selecting agents for sedation and/or pain control by avoiding
hypotension, therefore maintaining MAP and CPP in patients with impaired cerebral autoregulation [38].
5.2.2.1 Benzodiazepines
Benzodiazepines (e.g., diazepam, lorazepam, midazolam, and clonazepam) are
GABAA receptor agonists. The amount of reduction in CBF as a result of benzodiazepines administration can be variable. Common adverse reactions are
, sedatives can also cause peripheral
2
Table 5.3 Anesthetics/sedatives
Drug/Drug Class
Benzodiazepines
Barbiturates
Anticonvulsants
Opioids
Propofol
Dexmedetomidine
Clonidine
Ketamine
a
Cause sedation, however primary indication is for seizure control
a
MOA Systemic Effects CNS effects/TCD
receptor
GABA
A
agonists
GABA
agonists ↓ ABP Directly ↓ ICP/possible
A
Depends on drug
class
Mu receptor
agonists
Not completely
understood;
probable GABA
agonist activity
α-2 agonist Bradycardia and
α-2 agonist Bradycardia and
Non-competitive
NMDA
A
↓ ABP Indirectly ↑ ICP
Can cause
↓ ABP
↓ ABP Can ↑ ICP/velocities,
↓ ABP Possible
↓ ABP
↓ ABP
↑ ABP,
preservation of MAP
(hypercarbia)/possible
↑ velocities
↓ velocities
May cause ↑ or ↓ICP
(Topiramate observed
to ↑ICP, causes
metabolic acidosis).
and cause hypercarbia
(respiratory depression)
↓ ICP/↓velocities
No significant effect on
ICP
No significant effect on
ICP
No significant effect on
ICP
findings
Clinical Pearls
Respiratory
depression. IV LZP
and DZP contain
propylene glycol
Phenobarbital has
longest half-life. IV
contains propylene
glycol
IV phenytoin contains
propylene glycol
Caution in renal and
hepatic failure
Systemic
hypotension,
Propofol-related
infusion syndrome
(PRIS)
Does not cause
significant respiratory
depression
Dissociative
symptoms;
MOA mechanism of action, ABP arterial blood pressure, TCD transcranial Doppler, CPP cerebral
perfusion pressure, CBF cerebral blood ow, ICP intracranial pressure, LZP lorazepam, DZP diaz-
epam,
Decrease, ↓ Increase