01Approach to the Critical Patient/attcp83

Immediate priorities

›Stabilization and monitoring

›Airway protection triggers

›Status epilepticus or postictal obtundation

›GCS 8 or less

›Recurrent vomiting with aspiration risk

›Breathing and oxygenation

›Oxygen saturation 94 to 98 percent

›Avoid hyperoxia once saturation adequate

›Circulation and IV access

›Two large-bore peripheral IV lines

›Continuous ECG monitoring

›Noninvasive BP every 2 to 5 minutes until infusion titrated

›Arterial line once titratable IV antihypertensive started

›Point-of-care glucose

›Hypoglycemia mimic exclusion before attributing encephalopathy to PRES

›Seizure at presentation

›Immediate abortive therapy per seizure management pathway

›Airway and oxygenation reassessment after abortive dosing

›Postictal state distinguished from ongoing nonconvulsive seizure

›Persistent altered mental status beyond 20 minutes after convulsion ends

›Imaging-first pathway

›Noncontrast CT head within minutes for new focal deficit, seizure, or depressed consciousness

›Hemorrhage excluded

›MRI brain for definitive PRES pattern once safe to obtain

›Hemorrhage identified

›Intracerebral hemorrhage pathway substituted

Definition and clinical syndrome

›Diagnostic framework

›Posterior reversible encephalopathy syndrome definition

›Clinico-radiologic syndrome of subacute headache, altered mental status, seizure, or visual disturbance

›Vasogenic edema on MRI, typically parieto-occipital and usually bilateral

›Reversible with removal or control of the precipitant in most cases

›Hypertensive encephalopathy definition

›Clinical syndrome of cerebral edema from acute breakthrough of autoregulation during severe hypertension

›Overlaps substantially with PRES and is often the same process without an MRI yet obtained

›Diagnosis of exclusion

›Requires excluding ischemic stroke, hemorrhage, and CNS infection before attributing findings to PRES

Hemodynamic targets

›Controlled blood pressure reduction strategy

›First-hour target

›Mean arterial pressure reduction of 20 to 25 percent within the first hour

›No fixed absolute BP number as the sole target

›Subsequent target

›Gradual further reduction toward normal range over the following 24 to 48 hours

›Rationale for a slower rate than other hypertensive emergencies

›Chronic hypertension shifts the cerebral autoregulation curve rightward

›A pressure read as normal on a monitor can be relatively hypotensive for that patient's autoregulated range

›Over-rapid correction risk

›Watershed cerebral ischemia from pressure-passive hypoperfusion in already-edematous tissue

›Can convert a reversible vasogenic-edema syndrome into a fixed infarct

›Contrast with acute ischemic stroke approach

›Ischemic stroke without thrombolysis tolerates permissive hypertension up to 220/120 mmHg

›PRES and hypertensive encephalopathy are treated even without a fixed threshold once target-organ cerebral injury is present

›Population-specific exceptions to the standard target

›Eclampsia or preeclampsia-associated PRES

›Treatment threshold sustained systolic BP 160 mmHg or more or diastolic BP 110 mmHg or more

›Chronic severe hypertension in older adults

›Favor the lower end of the 20 to 25 percent range and closer neuro-check monitoring

›Pediatric PRES

›BP percentile thresholds by age, sex, and height rather than adult absolute numbers

›Preferred agent class

›Titratable IV agents with predictable onset and offset

Consultation and activation triggers

›Early specialty involvement

›Neurology or neurocritical care

›Any confirmed or suspected PRES

›Refractory or recurrent seizures

›Obstetrics

›Pregnancy or recent postpartum state with severe-range BP or eclampsia concern

›Nephrology

›Concurrent acute kidney injury or dialysis dependence

›Transplant medicine or oncology

›Calcineurin inhibitor or antiangiogenic chemotherapy exposure

›Ophthalmology

›Cortical visual loss for baseline documentation and to exclude an ocular cause

›Hematology

›Suspected thrombotic microangiopathy

PEARLS

›High-yield management principles

›PRES is usually reversible when the precipitant is treated promptly

›Delayed recognition and continued exposure to the precipitant worsen outcome

›Severe hypertension is not required for the diagnosis

›Roughly a fifth to a third of cases occur with normal or only mildly elevated BP, typically drug- or disease-mediated endothelial injury

›Atypical imaging patterns are common and do not exclude the diagnosis

›Frontal, brainstem, cerebellar, and basal ganglia involvement described

›Restricted diffusion on MRI is a poor prognostic sign

›Suggests evolving infarction rather than reversible vasogenic edema

02History/hx51

Presenting symptom pattern

›Symptom characterization

›Headache

›Subacute onset over hours, not thunderclap

›Altered mental status

›Confusion

›Somnolence progressing to obtundation

›Seizure

›Generalized tonic-clonic most common

›Focal seizure activity

›Visual disturbance

›Blurred vision

›Visual field cut

›Cortical blindness with preserved pupillary reflexes

›Focal neurologic complaint

›Less common presentation, raises stroke mimic concern

›Timing

›Symptom onset over hours to a few days rather than sudden

Risk factors and precipitants

›Etiology categories

›Severe or rapidly rising hypertension

›Known chronic hypertension with medication nonadherence

›De novo severe hypertension

›Preeclampsia or eclampsia

›Current pregnancy or within 4 weeks postpartum

›Renal disease

›Acute glomerulonephritis

›Nephrotic syndrome

03Physical Exam/exam42

Vital signs and global appearance

›Severity markers

›BP confirmation

›Correct cuff size

›Bilateral arm measurement

›Mental status trajectory

›Serial GCS to detect decline

›Fever

›Raises sepsis-associated PRES or CNS infection concern

Neurologic and visual exam

›Neurologic injury screening

›Mental status

›Attention and orientation

›Level of consciousness

›Visual fields

›Homonymous hemianopia

›Cortical blindness with intact pupillary light reflex

›Focal motor or language deficit

›Atypical for PRES, raises stroke concern

›Seizure activity or postictal Todd paralysis

›Cerebellar and brainstem signs

›Ataxia

›Dysarthria

Fundoscopic exam

›Hypertensive retinopathy grading

›Arteriolar narrowing

›Arteriovenous nicking

›Flame hemorrhages or cotton-wool spots

04Differential Diagnosis/ddx35

PRES mimics and alternative diagnoses

›Acute neurologic presentations

›Posterior circulation ischemic stroke

›Restricted diffusion rather than vasogenic edema on MRI

›Cerebral venous sinus thrombosis

›Papilledema and hemorrhagic venous infarct pattern

›Subarachnoid hemorrhage

›Thunderclap headache onset

›CNS infection

›Encephalitis

›Bacterial meningitis

›Acute demyelinating encephalomyelitis

›Recent viral illness or vaccination

›CNS vasculitis

›Multifocal ischemic pattern rather than symmetric posterior edema

›Hypoglycemia

›Toxic-metabolic encephalopathy

›Hepatic encephalopathy

›Uremic encephalopathy

Underlying etiology categories

›Precipitant classification for treatment planning

›Hypertensive emergency without a separate identified trigger

›Obstetric

›Preeclampsia with severe features

›Eclampsia

›Drug- or therapy-induced

›Calcineurin inhibitor toxicity

›Chemotherapy-associated

05Laboratory Tests/lt40

Core evaluation for etiology and target-organ injury

›Baseline labs

›Electrolytes and renal function

›Sodium mmol/l

›Potassium mmol/l

›Creatinine umol/l

›Complete blood count

›Platelets for thrombotic microangiopathy concern

›Hemoglobin for hemolysis concern

›Liver function tests

›AST and ALT for HELLP concern

›Urinalysis

›Proteinuria

›Urine protein-to-creatinine ratio if preeclampsia suspected

›Pregnancy test in any patient of reproductive potential

›Coagulation profile

›Baseline before procedures or anticoagulant decisions

Etiology-specific testing

›Phenotype-driven labs

›Calcineurin inhibitor exposure

›Tacrolimus or cyclosporine trough level

›Suspected thrombotic microangiopathy

›Peripheral smear for schistocytes

›LDH elevation

›Haptoglobin reduction

›ADAMTS13 activity if TTP suspected

›Suspected lupus or autoimmune process

›ANA and complement levels

06Diagnostic Tests/dt46

Scoring Systems

›Structured decision support

›No validated PRES-specific severity score

›Diagnosis and severity anchored in clinical trajectory and MRI pattern

›GCS for serial mental status tracking

›NIHSS if a stroke mimic is being actively considered

MRI

›MRI brain with FLAIR, DWI, and ADC

›Classic pattern

›Bilateral parieto-occipital vasogenic edema

›FLAIR and T2 hyperintensity

›Atypical patterns

›Frontal lobe predominant

›Brainstem or cerebellar predominant

›Basal ganglia predominant

›Asymmetric or unilateral distribution

›Diffusion-weighted interpretation

›Vasogenic edema shows elevated ADC and is reversible

›Restricted diffusion with low ADC suggests evolving infarction

›Associated with worse functional outcome

›Gradient echo or susceptibility-weighted sequence

›Microhemorrhage identification

›Timing and logistics

›Obtain once the patient is stable enough to transport

›Unstable patient with active infusion titration may require CT-based diagnosis until transportable

CT

›CT head noncontrast

›First-line imaging to exclude hemorrhage

07Disposition/dispo18

Level of care decisions

›Admission criteria

›ICU or monitored setting with titratable IV antihypertensive therapy

›Any confirmed or strongly suspected PRES or hypertensive encephalopathy

›Frequent neurologic reassessment

›Every 15 minutes during initial BP titration

›Extending to hourly once stable and improving

Transfer and escalation

›Higher-level care triggers

›Need for neurocritical care or continuous arterial-line titration unavailable locally

›Eclampsia or severe preeclampsia requiring labor and delivery unit with obstetric ICU capability

›Transplant-specific management decisions requiring the transplant center

›Refractory BP despite two IV agents

›Critical care consultation

Discharge criteria when appropriate

›Safe discharge framework

›Full neurologic recovery and no ongoing seizure risk

›Precipitant identified and controlled

›Reliable follow-up imaging arranged

›Admission is typical

›Direct discharge from the ED is rare given the need for BP titration and monitoring

08Treatment/t140

General strategy

›Treatment architecture

›Identify and remove or treat the precipitant

›Discontinue or reduce the offending drug

›Deliver if eclampsia is the driver

›Controlled BP reduction per the hemodynamic targets above

›Seizure control

›Monitoring during BP lowering

›Serial neuro checks

›Urine output tracking

›Frequent electrolytes for prolonged infusions

Blood pressure reduction protocol

›Titration monitoring cadence

›Arterial line for beat-to-beat pressure once available

›Neuro checks and BP every 15 minutes during the first hour of titration

›Extending to every 30 to 60 minutes once the first-hour target is reached

›Preferred IV agents

›Nicardipine IV infusion

›Initiate 5 mg/hour

›Titrate 2.5 mg/hour every 5 to 15 minutes

›Maximum 15 mg/hour

›Preferred phenotype

›Neurologic hypertensive emergencies including PRES

›Clevidipine IV infusion

›Initiate 1 to 2 mg/hour

›Double dose every 90 seconds early as needed

›Typical maintenance 4 to 6 mg/hour

›Maximum 21 mg/hour

›Contraindications

›Egg or soy allergy

›Disordered lipid metabolism

›Labetalol IV bolus

›Initiate 10 to 20 mg IV over 2 minutes

›Repeat or double every 10 minutes as needed

›Maximum 300 mg total

›Contraindications

›Asthma with active bronchospasm

›Severe bradycardia or high-grade AV block

›Avoided agent

›Nitroprusside IV infusion

›Would be initiated at 0.3 mcg/kg/min, titrated 0.5 mcg/kg/min every 5 minutes, maximum 10 mcg/kg/min

›Avoided in PRES and hypertensive encephalopathy

›Cerebral vasodilation risk raising intracranial pressure

›Cyanide and thiocyanate toxicity risk with prolonged use

›Immediate-release oral nifedipine

›Avoided for rapid lowering due to unpredictable, precipitous BP drop

›Deceleration and overshoot precautions

›Slow the titration step size once within 20 to 25 percent of baseline

›Do not continue escalating to a fixed absolute target

›If overshoot hypotension occurs

›Stop or reduce the infusion immediately

›Reassess neuro exam for new deficit suggesting watershed ischemia

›Troubleshooting refractory hypertension

›BP not at target despite two titrated IV agents

›Add a third agent from a different class

›Reassess for undiagnosed secondary cause

›Pheochromocytoma

›Renal artery stenosis

›Escalate to ICU and critical care consultation

Seizure management

›Abortive therapy

›Lorazepam 0.1 mg/kg IV

›Maximum 4 mg per dose

›Repeat once if seizure continues

›Maintenance antiseizure therapy

›Levetiracetam

›Initiate 1000 to 1500 mg IV load

›Maintenance 500 to 1500 mg twice daily

›Renal dose adjustment

›Prophylaxis and duration

›No routine long-term antiseizure prophylaxis once PRES resolves

›Seizures typically resolve as the syndrome resolves

›Troubleshooting recurrent or refractory seizures despite escalating therapy

›EEG to exclude nonconvulsive status epilepticus

›Reconsider the diagnosis

›Cerebral venous thrombosis

›CNS infection

Etiology-directed therapy

›Eclampsia-associated PRES

›Magnesium sulfate

›Initiate 4 to 6 g IV loading dose over 15 to 20 minutes

›Continue 1 to 2 g/hour infusion

›ECG and clinical toxicity monitoring

›Loss of deep tendon reflexes near serum magnesium 4 to 6 mmol/l

›Respiratory depression risk near serum magnesium 6 to 9 mmol/l

›Cardiac arrest risk above approximately 12 mmol/l

›ECG changes with hypermagnesemia

›PR interval prolongation

›QRS widening

›Reversal for toxicity

›Calcium gluconate 1 g IV over 5 to 10 minutes

›Delivery

›Definitive treatment once maternal stabilization achieved

›Guideline alignment

›Class I recommendation for magnesium sulfate in eclampsia prevention and treatment

›Calcineurin inhibitor toxicity

›Discontinue or substantially reduce the dose in coordination with transplant medicine

›Alternative immunosuppression per transplant protocol

›Thrombotic microangiopathy

›Plasma exchange for suspected TTP

›Hematology-directed initiation

›Renal failure driving hypertension

›Nephrology-directed volume and dialysis management

Iatrogenic harms from routine ED interventions

›Intervention-by-intervention review

›Intubation and RSI

›Induction agent choice affects cerebral perfusion

›Propofol can drop BP precipitously in an already autoregulation-impaired brain

›Ketamine raises BP and heart rate, undesirable when the goal is controlled lowering

›Verify pediatric RSI doses against current pediatric guideline before use

›Sedation

›Oversedation masks the neuro exam that guides BP titration decisions

›Sedative agents with hypotensive effect can cause overshoot when combined with an antihypertensive infusion

›Fluid loading

›Aggressive crystalloid worsens cerebral and pulmonary edema in eclampsia and renal-failure phenotypes

›Hypovolemia during BP lowering worsens overshoot hypotension risk

›Oxygen

›Routine supplemental oxygen without hypoxemia offers no benefit and is not required

›Vasopressors

›Contraindicated as routine therapy

›Would raise BP further, directly opposing the treatment goal

›Mechanical circulatory support including intra-aortic balloon pump

›Not indicated

›PRES is not a primary cardiac output or structural cardiac problem

›Anticoagulation

›Not indicated empirically

›Withhold until ischemic stroke or venous thrombosis is confirmed on imaging

›Fibrinolysis

›The single highest-risk error in this topic

›Giving tissue plasminogen activator for a presumed acute ischemic stroke when the true process is PRES risks catastrophic intracranial hemorrhage into vasogenic edema

›MRI with DWI and ADC before thrombolysis whenever the presentation is atypical for vascular-territory stroke

›Analgesia

›Opioids can cause hypotension and further blunt the neuro exam

›Acetaminophen 650 to 1000 mg PO or IV every 6 hours, maximum 4 g per day, preferred first line for pain or fever

›Maximum 3 g per day with hepatic impairment

Oral step-down therapy

›Transition criteria

›Neurologic recovery and BP approaching target on the IV infusion

›Oral options

›Amlodipine 5 mg PO daily

›Maximum 10 mg PO daily

›Labetalol 100 mg PO twice daily

›Maximum 2400 mg per day divided

›Avoided as monotherapy substitute for a nondihydropyridine rate-control need when bradycardia is already present

›ACE inhibitor or ARB

›Avoided in pregnancy and in the immediate postpartum period while breastfeeding safety is confirmed

09Special Populations/sp43

Pregnancy

›Pregnancy-specific considerations

›Eclampsia-associated PRES

›MRI pattern present in the large majority of eclampsia patients imaged

›Magnesium sulfate per the etiology-directed protocol above

›Medication safety

›Preferred agents

›Labetalol

›Nicardipine

›Hydralazine

›Avoided agents

›ACE inhibitors

›ARBs

›Nitroprusside when alternatives available

›Postpartum window

›PRES risk persists up to 4 weeks postpartum without visible pregnancy cues

›Obstetric coordination

›Fetal monitoring based on gestational age

›Delivery planning only after maternal stabilization

Geriatric

›Older adult considerations

›Autoregulation shift from chronic hypertension

›Higher watershed-ischemia risk with over-rapid correction

›Favor the low end of the 20 to 25 percent first-hour reduction

›Comorbidity burden

›Chronic kidney disease prevalence affecting agent choice

›Polypharmacy interaction review

›Medication sensitivity

10Background/b27

Epidemiology

›Population patterns

›Reported in up to 90 percent of eclampsia patients undergoing MRI

›Estimated 0.4 to 6 percent of solid organ and hematopoietic stem cell transplant recipients on calcineurin inhibitor therapy

›Overall mortality approximately 3 to 5 percent when recognized and treated

›Full clinical and radiologic recovery in the majority of cases within days to weeks

Pathophysiology

›Competing mechanistic theories

›Hyperperfusion or autoregulation-breakthrough theory

›Severe or rapidly rising BP exceeds the upper limit of cerebral autoregulation

›Forced vasodilation, endothelial disruption, and blood-brain barrier breakdown

›Posterior circulation relative vulnerability

›Sparser sympathetic innervation of the vertebrobasilar territory limits protective vasoconstriction

›Endothelial toxicity theory

›Circulating toxins, cytokines, or cytotoxic drugs injure the endothelium directly

›Explains PRES occurring with normal or only mildly elevated BP

›Relevant in eclampsia, sepsis, and calcineurin inhibitor toxicity

›Common downstream pathway

›Vasogenic edema from blood-brain barrier disruption, typically reversible if the precipitant resolves

Therapeutic Considerations

›Why controlled reduction matters

›Autoregulatory curve shift in chronic hypertension

›Hypoperfusion risk with abrupt BP drop into what appears to be a normal range

›Agent selection principles

›Titratable, short half-life IV agents for predictable, reversible effect

›Evidence framing

›Management is extrapolated largely from hypertensive emergency and eclampsia trial data

›No dedicated randomized trial defines an optimal BP target specific to PRES

11Patient Discharge Instructions/pdi24

copy discharge instructions

›Discharge instructions

›Diagnosis summary

›Brain swelling related to severe blood pressure or another treatable trigger, expected to improve with treatment

›Medications

›Take all prescribed blood pressure medicines exactly as directed

›Do not stop or change an immunosuppressant medicine without talking to the transplant team first

›Home monitoring

›BP log twice daily for 7 days

›Proper cuff size and seated rest 5 minutes before checks

›Activity guidance

›No driving until cleared by a physician, following local licensing requirements after a seizure

›Follow-up

›Neurology or stroke clinic follow-up within 1 to 2 weeks

›Repeat MRI as scheduled to confirm resolution

›Return to ED now for

›Severe headache

›New vision loss

›Seizure

›Worsening confusion

›New weakness or trouble speaking

›Blood pressure above the specific number given at discharge

›Fever

›Decreased urination

›Pregnancy or recent delivery with headache, vision changes, or abdominal pain

12References/r16

Clinical guidelines and consensus

›Guideline sources

›ACC and AHA guidance on hypertensive crises and acute BP management

›Framework for controlled reduction in neurologic hypertensive emergencies

›ACOG guidance for hypertensive disorders of pregnancy

›Magnesium sulfate and severe-range BP treatment thresholds

›AHA and ASA acute ischemic stroke guidelines

›Permissive hypertension thresholds used as the contrast case for PRES BP strategy

Evidence-based sources

›Key evidence themes

›Hinchey and colleagues original description of reversible posterior leukoencephalopathy syndrome, New England Journal of Medicine 1996

›First systematic clinical-radiologic characterization of the syndrome

›Fugate and Rabinstein review of posterior reversible encephalopathy syndrome, Lancet Neurology 2015

›Synthesis of mechanism, imaging patterns, and outcome data

›Case series on calcineurin inhibitor and transplant-associated PRES

›Basis for trough-level and dose-adjustment guidance

›Magnesium sulfate trial evidence in eclampsia

›Basis for Class I recommendation in seizure prevention and treatment

Evidence & Review

Evidence & Review