GENERAL THERAPY

General management of acute stroke patients

David Goldemund M.D.
Updated on 21/02/2024, published on 20/06/2023

the management of acute stroke patients includes
- diagnosis and specific stroke treatment (recanalization, surgery, etc.)
- management and prevention of general medical problems
  - similar for all types of stroke (ischemic x hemorrhagic)
  - cardiac and pulmonary care, restoration of fluid and ion balance, metabolic maintenance, and blood pressure control
  - prevention and treatment of complications (infection, VTE, intracranial hypertension, bed sores, etc.)
- evaluation of stroke etiology and initiation of individualized secondary prevention
- early initiation of rehabilitation (incl. speech therapy, ergotherapy, etc.)
- management tof stroke consequences (spasticity, depression, etc.)
proper management of general conditions and complications is equally important as the specific therapy, even though the latter may sometimes attract more attention

→ Early management of patients with suspected stroke

→ Acute stroke complications

Stroke unit care

in the acute stage of large artery occlusion (before recanalization) keep a zero-degree head-of-bed (HOB) position (ZODIAC trial)
- this position seems to enhance collateral circulation and improve prognosis after mechanical recanalization
after initial evaluation and therapy, it is recommended to admit the patient to a stroke unit (AHA/ASA 2019 I/A)
- for a minimum of 24 hours, preferably for 48-72 hours
- care is provided by a specialized multidisciplinary team
treatment in a stroke unit results in a relative reduction in mortality and dependency compared to treatment in a regular ward [Langhorne, 1997]
- treating 100 patients using this approach can result in a reduction of 5 patients who would die or remain dependent (NNT 20)
- the benefit is universal and applicable to all types of stroke and patients of varying degrees of severity

Basic monitoring

oximetry (maintain sat O₂ > 94%)
- use a finger or earlobe sensor
- oxygen should be provided to maintain oxygen saturation >94% (AHA/ASA 2019, I/C)
- do not administer oxygen in nonhypoxic patients (AHA/ASA 2019 III/B-R)
blood pressure
- check BP every 30 minutes in stabilized patient
- otherwise, proceed per specific protocols (→ Blood pressure management in acute stroke, hypertensive urgency protocols, etc.)
- hypotension and hypovolemia should be corrected to maintain necessary systemic perfusion levels
- the usefulness of drug-induced hypertension in patients with AIS is not well established (AHA/ASA 2019, IIb/B)
ECG
- record 12-lead ECG on admission, then monitor with 3-lead ECG
- especially infarctions in the right insula can lead to autonomic system failure and cardiac complications (ST depression, T wave inversion, troponin elevation in the laboratory)
- look for arrhythmias (particularly atrial fibrillation)
monitoring the state of consciousness and neurostatus (basic neurologic examination, GCS, NIHSS)
- adjust the frequency of evaluations based on the patient’s condition and underlying diagnosis (more frequent in extensive SAH, ICH, malignant edema)
- in unconscious patients, repeatedly assess brainstem reflexes
search for additional symptoms such as headache, nausea, vertigo, singultus

Extended neuromonitoring

Continuous EEG monitoring (cEEG)

recommended in patients with severe stroke (~ 24-48h); a 10-20 or 2-4 channel EEG system with adhesive electrodes is used
monitoring of SE treatment (always) and depth of anesthesia
NCSE diagnosis
- sensitivity and specificity of standard EEG is low
- clinical manifestations are none or only subtle and often escape attention (facial twitching, short eyeball deviation, autonomic signs)
DDx of non-epileptic seizures
monitoring of metabolic coma

Evoked potentials (EP)

SSEP (prognostic value in coma vigile)
BAEP (brain death diagnosis in patients with decompressive craniectomy)
ERP (event-related potential)
- detection of P300 wave in a coma is associated with a good prognosis

Direct monitoring of intracranial pressure

indications for ischemic stroke patients are ambiguous
probably advantageous in patients with GCS ≤ 8 with extensive hematoma, SAH, or hydrocephalus
intraparenchymal or intraventricular sensors are available

Ultrasound monitoring of vascular occlusion

→ TIBI criteria

Ultrasound monitoring of intracranial hypertension

doppler signs
- decrease in velocities, increase in resistance and pulsatility index (RI and PI), then disappearance of diastolic flows, and finally systolic spikes or biphasic flow curve → TCCD in the diagnosis of brain death
- ICP=(10.927* PI)-1.284
- ↓ vasomotor reactivity
B-mode signs
- optic nerve sheath enlargement or head prominence (transorbital approach)
- midline shift (transtemporal approach)

→ neurosonology in intensive care

Jugular oximetry

a special catheter is inserted into the bulb of the internal jugular vein to monitor venous blood O₂ saturation
global information is provided, and therefore may not reflect localized issues; take into account body temperature and the effect of medication)
normal values: 55-80%
- SjO2 < 50% with normal arterial O₂ saturation indicates either ↓ CBF (e.g., when cerebrovascular resistance is increased) or increased consumption (↑CMRO₂)
- SjO2 > 85% indicates either hyperemia with ↑CBF or ↓CMRO₂

Near-InfraRed Spectroscopy (NIRS)

2 sensors are placed on the forehead; emitted beams penetrate to about 4 cm
from the reflected light, the oxygenation of the brain tissue is derived

Tissue oximetry

direct measurement of parenchymal oxygenation near the sensor
standard 20-45 mm Hg
ischemic threshold (depending on the type of sensor < 15-20 mm Hg)

Microdialysis

measurement of extracellular metabolite levels in the CNS ( glucose, lactate, pyruvate, lactate/pyruvate ratio, glutamate, glycerol)

Intravascular access

Peripheral venous system

ensure intravascular access via a venous cannula in every acute stroke patient (bilaterally if thrombolysis is planned)
- uncomplicated insertion and management
- prefer disinfection with 0.5% chlorhexidine in alcohol during insertion
- can not be used for certain drugs and concentrated solutions (limit < 600 mosm/l)
- insertion time: 72-96 h
- remove if not used > 24h or no further use is probable
- replace the cannula in case of local (e.g., pain, swelling, skin discoloration, skin temperature change, hardening, resistance to flushing) or systemic (fever) complications
for long-term use, prefer the midline catheter (approx. 14 days – 3 months)
- can be used for blood sampling
- drugs with osmolarity < 600 mOsm/l and nutrition < 800 mOsm/l can be administered
when peripheral IV access is required for > 3 months, prefer PICC catheter
- it is placed under ultrasound guidance in the cavoatrial junction (when maximum P wave is seen in ECG)
- may be retained for several months

Central venous system

central venous catheters (lines) are commonly placed in the internal jugular, subclavian, or femoral veins (usually using a 2 or 3-way cannula)
- order chest X-ray to exclude pneumothorax 3 hours after subclavian vein cannulation
central catheter enables:
- administration of all types of drugs and concentrated solutions
- measuring central venous pressure (CVP)
  - normally 5-12 cm H₂O; subtract PEEP in ventilated patients
adhere to aseptic treatment – use sterile cover and perform daily checks
complications:
- during insertion: pneumothorax, artery puncture
- late complications: venous thrombosis, catheter sepsis
insertion time: 1-3 weeks
- risk of infection increases from day 7 [Öncü, 2003]
use PICC or tunneled catheters when prolonged central venous access is required

Major indications for the use of central venous catheters

difficult peripheral venous access
delivery of certain medications or fluids
- medications such as vasopressors, chemotherapeutic agents, or hypertonic solutions that can damage peripheral veins
- additionally, catheters with multiple lumens enable the delivery of several parenteral medications simultaneously
prolonged intravenous therapies that require a more stable and reliable access point
specialized treatment
- hemodialysis, plasmapheresis, transvenous cardiac pacing, and invasive hemodynamic monitoring

Classification of intravascular access according to the expected time of insertion

Classification of intravascular access according to the expected time of insertion

► Short-term

peripheral cannula – 3-4 days
central venous catheter – 1-3 weeks

► Mid-term (→ care)

midline catheter – 1-3 months
PICC (Peripherally Inserted Central Catheter) – 3 -12 months

► Long-term

tunneled catheters with cuff – years
ports – years

Ventilation and respiration

ensure adequate oxygenation (O₂ saturation > 94%)
- SO2S trial showed no benefit from routine O₂ administration ⇒ O₂ administration is not recommended in nonhypoxic patients
test breathing reflexes and regularly assess the risk of aspiration (many patients have bulbar or pseudobulbar syndrome) → see water swallow test below
- a common cause of acute respiratory insufficiency is aspiration and/or accumulation of mucus and saliva in the airways due to inadequate expectoration
in cases of respiratory infection, administer antibiotics empirically after collecting sputum and swabs. Adjust the therapy according to cultures and sensitivity results
in case of respiratory failure, initiate early intubation and mechanical ventilation
- before intubation, consider the patient´s prior wishes, general condition, and prognosis
Hyperbaric Oxygen Therapy (HBOT) is not recommended, except for stroke caused by air embolization (Murphy, 2019) (AHA/ASA 2019 III/B)
- the limited data show no benefit
- HBO should thus be offered only in the context of a clinical trial or for individuals with cerebral air embolism

Signs of respiratory failure

dyspnoea, involvement of auxiliary respiratory muscles
tachycardia
respiratory rate > 35/min
hypoxemia < 60 mm Hg (7.59 kPa) (at FiO₂ 0.4 by mask)
hypercapnia > 55 mm Hg (7.3 kPa) (except in patients with chronic hypercapnia)

ECG monitoring, arrhythmias

acute stroke is associated with an increased risk of cardiac arrhythmias, affecting up to 25% of hospitalized stroke patients
- the incidence is greatest within the first 24 hours
- tachycardia is more common than bradycardia
- arrhythmias are more prevalent in patients with hemispheric lesions
while some arrhythmias are benign (such as ventricular/atrial extrasystoles), persistent tachyarrhythmias may lead to hypotension or cardiac failure, potentially contributing to stroke progression
atrial fibrillation should be excluded as a potential cause of the stroke
ECG monitoring is recommended for ≥ 24 hours (AHA/ASA 2019 I/B-NR)

ECG changes are common in acute stroke
- the ST segment is most commonly affected; these changes may mimic myocardial infarction (ST elevation can be present, but not depression) ⇒ exclude myocardial infarction in such cases
the situation is further complicated by frequent elevation in troponin levels, which is usually attributable to cerebral infarction rather than myocardial infarction

Fluids and minerals, glycemia

monitor fluid balance every 6-24h and aim to maintain normovolemia or mild hypervolemia
- measure central venous pressure (CVP) if needed
- avoid fluid restriction as it increases the risk of ischemic deficit (especially in subarachnoid hemorrhage)
- hypervolemic hemodilution and vasodilator therapy are not recommended
monitor biochemical parameters (ion levels, urea, creatinine, C-reactive protein, hepatic enzymes, and osmolality) as well as complete blood count (CBC) +coagulation profile
- adjust the frequency of sampling based on the patient’s condition and any detected abnormalities
check acid–base balance
- acutely to detect conditions such as hypoxemia, hypercapnia, acidosis/alkalosis
- stable ventilated patients should be checked twice daily

Glycemia

glucose serves as the primary energy source for the brain, with over 90% of the brain’s energy derived from the oxidation of glucose. Even during hypoglycemia, glucose remains the most important substrate for brain metabolism
the brain/serum glucose ratio (typically 0.6-0.7) drops to 0.2-0.4 in cases of brain injury (resulting in increased sensitivity to hypoglycemia)

hyperglycemia (stress hyperglycemia, stress diabetes) is present in up to 2/3 of stroke patients, worsening the outcome of all types of stroke and traumatic brain injuries (TBI)
- a meta-analysis focus on in-hospital mortality in critically with hyperglycemia showed that even mild hyperglycemia (6.1-8.0 mmol/l) in non-diabetics is associated with a 3.9-fold higher risk of death compared to completely normoglycemic individuals [Capes, 2000]
according to the NICE-SUGAR study, the optimal target glycemia in intensive care is < 10 mmol/L; hypercorrection to levels < 6 mmol/L increases mortality
- maintain glycemia around 7.8-10 mmol/L (140-180 mg/dL) (AHA/ASA 2019 IIa/C-LD)
- closely monitor and treat hypoglycemia when levels drop below 3.3 mmol (60mg/dL) (AHA/ASA 2019 I/C-LD)
  - intensive glycemic control can lead to hypoglycemia
  - microdialysis studies indicate that intensive insulin therapy may lead to brain glucose deprivation and and elevated levels of lactate and glutamate [Vespa, 2006]
check glycemia every 6h (glycemic profile); monitor more frequently during continuous insulin administration
use repeated boluses of subcutaneous insulin or continuous IV infusion → per insulin protocol

Fever

maintain normothermia
identify and treat sources of hyperthermia (body temperature >38°C)
administer antipyretic medication to hyperthermic patients (AHA/ASA 219 I/C)
the benefit of induced hypothermia is uncertain

Nausea and vomiting

most commonly occurs in ICH, SAH, and brainstem ischemia

Prevention and management of GI complications

gastrointestinal (GI) complications are common and significantly worsen morbidity and mortality
most common complications:
- stress ulcer
- gastroesophageal reflux (GER)
- gastroparesis
- intestinal paralysis (paralytic ileus)
  - ⇒ X-ray, abdominal SONO or CT
  - endoscopic desufflation
- constipation/diarrhea
- singultus

Stress ulcer

the most common cause of GI bleeding is either a preexisting lesion or a newly developed “stress ulcer”
- disruption of the integrity of the upper GI mucosa due to extreme physiological stress, typically in critically ill patients
- often develops within a few hours after the initial insult
- can result in bleeding or perforation ⇒ ↑ mortality and intensive care stay
- incidence approx. 3% when on prophylactic medication
risk factors for GI bleeding
- coagulopathies, including iatrogenic
- history of GI bleeding/peptic ulcer
- mechanical ventilation > 48h
- traumatic brain/spinal cord injury
- sepsis
- corticosteroids use
- renal and hepatic impairment
- malignancy
- severe stroke

initiate enteral nutrition as soon as possible!

prophylaxis should be administered only to patients at increased risk and discontinued in a timely manner (due to the increased risk of nosocomial pneumonia, Clostridium difficile infection, drug interactions, or hepatotoxicity); routine use of PPIs does not reduce mortality

proton pump inhibitors (PPIs)

PANTOPRAZOLE OMEPRAZOLE

PPIs are more expensive and significantly more effective than H₂-blockers [Buendgens, 2016]

use H2 blockers if PPIs are contraindicated

FAMOTIDINE

40 mg once daily, or 20 mg twice daily PO

SUCRALFATE
- 1g PO or via nasogastric tube every 6-8 hours
- used in peptic ulcer prevention and treatment or to reduce hyperphosphatemia

Singultus

caused by a clonic contraction of the diaphragm with simultaneous closure of the glottis
short-term hiccups are mostly benign and can be attributed to factors such as:
- distention of the esophagus and stomach, intake of carbonated fluids, irritation of the digestive tract with spices
- emotions, excitement
- sudden change in temperature: drinks (hot/cold), shower, air, etc.
more serious underlying causes:
- pulmonary and mediastinal diseases (pneumonia, lung tumors, mediastinitis, and mediastinal tumors)
- abdominal cavity diseases (direct irritation of the diaphragm – ileus, peritonitis, stomach and liver tumors and metastases, liver abscess, pancreatitis, and pancreatic tumors, etc.)
- heart diseases (pericarditis, myocardial infarction)
- esophageal diseases (oesophageal obstruction by solid food or tumor, or esophagitis)
- metabolic causes (uremia, diabetes decompensation), acid-base disorders, mineral imbalances (hyponatremia)
- central causes (direct or indirect brainstem lesions) – tumors, stroke, trauma
- alcohol and drugs (dexamethasone, methyldopa, sulfonamides, antiseizure medications)
severe forms of hiccups are frequently resistant to symptomatic treatment

treat potential causes
pharmacotherapy (see table) – combination therapy may be effective (e.g., omeprazole + baclofen + gabapentin)
psychotherapy (cognitive-behavioral therapy or other psychological interventions may be beneficial for stress-induced hiccups)
acupuncture (may provide symptomatic relief, particularly for hiccups resistant to pharmacotherapy)

→ overview of treatment options see here

*BACLOFEN* (has a peripheral and central effect)	initial dose: 5-10 mg PO every 8 hours maintenance dose: 10-20 mg PO every 8 hours max dose 60-80 mg per day abrupt discontinuation should be avoided to prevent withdrawal symptoms
Anticonvulsive drugs
gabapentin (NEURONTIN)	initial dose: 300 mg PO every 8 hours the dose may be titrated up based on patient response and tolerance. Commonly used regimens include 300 mg every 8 hours or 600 mg twice a day
valproate *(ORFIRIL, DEPAKINE)*	initial dose: 250 mg PO every 12 hours maintenance dose: 500-1000 mg divided into 2 or 3 doses
Neuroleptics (central effect)
*HALOPERIDOL*	initial dose: 0.5-2 mg PO every 8 hours titrate gradually (sometimes 1-2 mg per night is enough); fewer AEs occur at this dose maintenance dose: 1-4 mg every 8 hours
chlorpromazine (PLEGOMAZIN)	initial dose: 25-50 mg PO or IM every 8 hours after 3 days, the dose may be increased to 25-50mg every 4h chlorpromazine may cause extrapyramidal symptoms, QT prolongation, or other serious side effects and may interact with other medications. Monitoring for adverse effects is recommended.
Prokinetic drugs
metoclopramide	PO 10 mg every 6-8 hours (max 40 mg/d)
PPI (use if GER is suspected)
omeprazole pantoprazole	PO 20-40 mg once daily

Pain management

pain is typically present in SAH, less commonly in ICH and ischemic stroke
untreated pain may contribute to elevated blood pressure, tachycardia, or patient agitation
rule out fractures or dislocations, which are often caused by falls due to sudden paresis

Dysphagia screening, oral hygiene

Nutrition

catabolic state is common in the acute phase of stroke
the total energy demand depends on the basic metabolic rate (BMR) and other factors
early initiation of nutrition (within 24 hours) reduces the risk of various complications (malnutrition increases the risk of infection, muscle loss, etc.)
enteral nutrition is preferred; if parenteral nutrition is necessary, use it for the shortest possible duration
in patients with significant dysphagia, insert a nasogastric tube (NGS) for the prevention of aspiration bronchopneumonia
follow oral hygiene protocols (AHA/ASA 2018 IIb/B-NR)

Basic metabolic rate (BMR) calculation

Harris-Benedict formula – basal metabolic rate (BMR) [kcal/day]
- men = 66,47 + 13,75 x weight [kg] + 5 x height [cm] – 6,67 x age [years]
- women = 65,10 + 9,56 x weight [kg] + 1,85 x height[cm] – 4,68 x age [years]
- total energy demand = BMR x A factor x T factor (kcal/day)
- kJ = 4.18 * kcal

for obese people (with a BMI > 30) prefer the Mifflin−St. Jeor (MSJ) equation → calculator
- men(kcal/day) = 5 + 10× weight (kg) + 6.25× height (cm) − 5× age (years)
- women(kcal/day) = −161 + 10× weight (kg) + 6.25× height (cm) − 5× age (years)

*A factor* (activity)	immobile patient 1.2
*A factor* (activity)	mobile patient 1.3
*T factor* (trauma)	surgery	minor-moderate 1.0-1.1 major 1.1-1.2
	infection	light 1.0-1.2 moderate 1.2-1.4 severe 1.4-1.8
	trauma	1.2-1.35
	polytrauma	1.6
	burn injury	< 20% 1.0-1.5 20-40% 1.,5-1.85 > 40% 1.85-1.95

Prevention of infection

adhere to barrier measures when in contact with the patient, ensure careful hand washing by staff
follow protocols for the prevention of aspiration and early detection of impaired airway hygiene
regularly evaluate the necessity of each invasive access, and replace them regularly
- risk of complications increases significantly:
  - from day 3 for cannula
  - from day 5 for urinary catheter
  - from day 7 for central venous catheter (CVC)
conduct microbiological screening
- repeated sputum (throat and nasal swab) and urine cultures twice a week in the ICU
- take cultures after the patient’s transfer from another department
- isolate the patient if necessary (especially after transfers from another ICU, neurosurgery, etc.)
prophylactic administration of antibiotics is not indicated (AHA/ASA 2018 III/B-R)

Early rehabilitation and speech therapy

start rehabilitation and ergotherapy ASAP, including early verticalization
- however, overly aggressive therapy in the first 24h is not beneficial (AVERT study) (AHA/ASA 2019 III/B-R)
mechanical aids have a positive effect
- ReStore exosuit was approved by FDA in 2019
the effect of fluoxetine on improving motor function is not proven
the timing and intensity of rehabilitation in SAH and ICH must be individualized

Delirium, anxiety, depression

search for signs of delirium, depression, or anxiety and treat them properly
in patients without depression, fluoxetine therapy is not effective in enhancing poststroke functional status

→ Delirium

→ Poststroke depression

anxiolytics: DIAZEPAM ALPRAZOLAM BROMAZEPAM

Preventing pressure ulcers

preventing pressure ulcers is crucial, especially since paralysis can lead to extended periods of bedrest, increasing the chance of pressure sore development
pressure sores typically develop on the back of the head, shoulders, elbows, sacrum and buttocks, hips, and heels
preventive measures include:
- regular repositioning of the patient (every 2h), physiotherapy, massages
- skincare
- adequate hydration and nutrition (monitor protein and albumin levels)
- early mobilization
- use of prevention devices:
  - anti-decubitus mattress
  - anti-decubitus fleece
- minimize pharmacological sedation for agitated patients

Brain edema, intracranial hypertension

→ Intracranial hypertension
→ Malignant cerebral infarction

Prevention of venous thromboembolism (VTE)

deep vein thrombosis is detected in the first 2 weeks in up to 50% of immobile patients [Brandstater, 1992]

→ VTE prevention

Prophylaxis and management of acute symptomatic seizures

→ see Acute symptomatic seizures