Neurointensive Care

Subarachnoid Hemorrhage (SAH)

Background

• Incidence of 10 per 100,000 inhabitants/year
• Approximately 100 patients with SAH are treated annually at NIVA/SU
• ICU stay is often 7-10 days
• Slightly more women than men are affected by SAH
• The median age of onset is 50-60 years

Clinical Picture

• Sudden onset headache, “thunderclap headache”
• Nausea
• Neck stiffness
• Photophobia
• Loss of consciousness

CT/DT (the bleeding is usually clearly visible)

When the aneurysm ruptures, blood enters the subarachnoid space (SA space) –> ICP increases and CPP decreases, which can cause thunderclap headache, loss of consciousness, and global cerebral ischemia. The blood redistributes, and ICP decreases in those who wake up. Additionally, blood in the SA space can obstruct CSF outflow, leading to hydrocephalus and increased ICP. Furthermore, there is activation of inflammation, platelets, coagulation systems, endothelial damage, and excitotoxic effects of blood with its breakdown products.

Sometimes Lumbar Puncture

• Warning bleed!?

CT Image

Onset

• Aneurysm rupture – in 80% of cases
• Blood into the subarachnoid space (often also into the ventricular system and brain parenchyma)
• Increased ICP > thunderclap headache
• Decreased CPP (cerebral perfusion pressure) may cause loss of consciousness/global ischemia
• Redistribution of blood
• ICP decreases > usually improved consciousness

Blood with Breakdown Products in the Subarachnoid Space Also Causes

• Obstruction of CSF outflow, leading to hydrocephalus
• CSF production is about 500 ml/day
• Can cause ICP increase early after the bleed

Treatment Goals for SAH

• Prevent re-bleeding
• Treat the aneurysm
• Counteract and treat potential complications such as
  • Hydrocephalus
  • Vasospasm
  • Ischemia
  • Epilepsy
  • Complications related to intensive care
• Optimize conditions for recovery

Initial Management

• Secure vital functions and prevent re-bleeding
• 30% risk of re-bleeding within the first week for untreated aneurysm
• SBP < 160 mm Hg (systolic blood pressure)
• Cyklokapron (tranexamic acid) 1-2 g IV
• Calm and stress-free environment
• Analgesics
• Antiemetics
• Monitoring
• Nimotop infusion (nimodipine)

Initial Clinical Picture Varies

RLS 1

• Admitted to the neurosurgical ward/ICU for monitoring and investigation
• CT-angio and possibly conventional angiography with endovascular intervention or open neurosurgical operation

Gradually Decreasing Consciousness

• Admitted to the neurosurgical ward/ICU for monitoring
• Intubate if RLS > 3
• Possible hydrocephalus with the need for a ventricular drain (V-drain) before further investigation and aneurysm treatment

Deeply Unconscious Patient

• Sometimes kept at the local hospital to await possible improvement
• Often with hydrocephalus and given a V-drain before deciding on aneurysm treatment

Radiological Investigation of the Bleeding Source

If no source of bleeding is found, angiography is usually repeated after 1 week

CT Angiography

Treatment of the Aneurysm

Intensive care after the aneurysm is secured

Clinical neurological monitoring

• Preferably an unsedated patient who is easy to assess repeatedly
• Monitor for hydrocephalus development
• Monitor for vasospasm development

May require inotropic support and ventilator support, which requires sedation

• Inflammatory activation
• Stress cardiomyopathy/neurogenic pulmonary edema
• Altered consciousness
• No more than comfort sedation to facilitate neurological evaluation

Hydrocephalus

• Caused by cerebrospinal fluid resorption impairment
• Approximately 500 ml produced per day
• Gradual decrease in consciousness (hours)
• Sunset gaze
• Treatment: ventricular drain (V-drain)
• Drain is set to a level above which cerebrospinal fluid is drained. ICP does not exceed the set level
• Can occur acutely or later in the course
• If the drain cannot be discontinued, a shunt may be necessary

“Vasospasm” – a dreaded complication

• DCI – Delayed cerebral ischemia
• Includes everything from transient neurological symptoms to manifest strokes
• Greatest impact on the outcome in those who survived initially
• Usually develops between day 3-14 and affects 30% of patients
• The worse the patient’s condition, the greater the risk of vasospasm
• May be related to a pro-inflammatory environment
• Nimodipine (Nimotop) is the only drug shown to improve outcomes – possibly cytoprotective?

Cerebral vasospasm

• Pathophysiology not fully understood. Likely multifactorial
• Blood and its breakdown products surround the brain where the blood vessels are located
• Triggers inflammation, coagulation, and endothelial impairment
• Vasoconstriction can be observed as caliber changes in arteries
• Reduced cerebral perfusion distal to the spasm
• Can be reversible or cause permanent damage with manifest infarction

SAH – Vasospasm – diagnostics

• Clinical neurological examination is best
• Symptoms – can fluctuate
• Increasing headache
• Onset of hemiparesis (positive Grasset)
• Decreasing level of consciousness
• Increasing confusion/personality changes/aggression
• Motor agitation
• TCD (transcranial doppler) performed daily to measure flow velocities is the only monitoring tool in sedated patients

Transcranial doppler

• Measures blood flow velocity in the brain’s blood vessels
• If high velocities, it may be due to vessel constriction = smaller diameter
• Values > 2 m/sec are notable
• Many sources of error and nonspecific
• Note the effect of increased cardiac output!

When suspected vasospasm

• CT-angiography – shows caliber changes in vessels
• Perfusion CT – can identify if perfusion is reduced
• Conventional angiography. Angiography of the brain’s vessels, shows vasospasm. Simultaneous treatment possible.

Vasospasm in ICU – time to step up!!

Before spasm

• Nimotop (nimodipine)
• Normovolemia
• No prophylactic fluids beyond basic needs
• Negative fluid balance to prevent weight gain, guideline -500 ml/day
• Normonatremia 137-146 mmol/L

Spasm

• Increased Nimotop dose
• Normovolemia
• Induced hypertension, SBP > 140 mmHg
• Monitoring of global hemodynamics with filling targets and cardiac index in the upper reference range
• If needed, use Ringer’s acetate and albumin
• Avoid vasopressors
• Avoid hyponatremia
• Avoid continued edema development = high ELWI
• Treat rarely for high blood pressure

Goal-directed circulation optimization during cerebral vasospasm

Systemic complications – SAH is not just a brain disease…

Increased sympathetic activity

• Cardiac involvement with risk of failure
• Acute lung injury
• Pulmonary edema

Systemic inflammatory response syndrome (SIRS) with elevated levels of inflammatory cytokines in the blood

• Fever
• Tachypnea
• Tachycardia
• Leukocytosis

Circulation and respiration

• About 15% develop heart failure
• So-called stress cardiomyopathy/Takotsubo cardiomyopathy
• Occurs due to the catecholamine surge during the hemorrhage
• More common in women (about 85%)
• Elevated troponin or NT-proBNP
• ECG changes
• Low blood pressure/significant norepinephrine use
• SAH can also cause so-called neurogenic pulmonary edema (5-10%)

Fluid and electrolyte balance disorders

• Monitor fluid balance and weight development
• Normovolemia is the goal
• Avoid prophylactic fluid administration!
• Avoid weight gain during the first days (fluid balance goal: – 500 ml/day)
• Give crystalloids combined with colloids (albumin)
• Many sodium disturbances have an iatrogenic component, but SIADH, CSWS, DI, and other endocrine disorders occur
• Diagnose, investigate, and analyze first – treat later!

General intensive care principles

• As little sedation as possible to allow thorough neurological evaluation
• Supported ventilation – no hyperventilation here!
• Thromboprophylaxis, including mechanical leg pumps
• Ulcer prophylaxis
• Antibiotics as indicated and treatment for fever > 38°C
• Mobilization as tolerated after aneurysm is secured
• Bed rest if vasospasm

Different phases during ICU/NIMA time

• Acute phase before the aneurysm is secured
  • Rebleeding is the biggest threat > calm and quiet! Cyklokapron!
  • Cardiorespiratory failure may be pronounced
• Spasm phase day 3-14
  • Focus on preventing and early treatment of possible vasospasm. Nimotop!
  • Hydrocephalus development
  • Problems secondary to ICU care; infections
• Recovery
  • Discontinuation of V-drain if possible
  • Restoration of normal fluid status
  • Mobilization and oral nutrition and Nimotop tablets

How it goes for patients with SAH

• About 10% of patients die before reaching the hospital.
• Mortality 20-25%
• 15% experience severe neurological deficits
• 55% become independent

Cognitive dysfunction is common, as is persistent mental fatigue even in those with a good outcome.

The scientific support behind SAH care (AHA guidelines 2012)

To prevent rebleeding

• Control blood pressure if high with short-acting agents (IB)
• Lower blood pressure SBP < 160 mmHg
• Administer tranexamic acid (Cyklokapron) within 72 hours

To prevent DCI (Delayed cerebral ischemia)

• Normovolemia (IB)
• Prophylactic hypervolemia should be avoided
• Nimodipine (IA)
• Monitoring TCD is reasonable
• Treat fever

For those with DCI symptoms

• Induce hypertension in those who do not have it (IB)
• Treat anemia if there is a risk of ischemia, Hgb threshold?
• Perform perfusion CT
• Cerebral intra-arterial vasodilation if not reversible with hypertension

Other complications

• Correct hyponatremia
• Monitor volume status and global hemodynamics in selected patients
• Normothermia
• Glucose control
• Identify and treat HIT and DVT (IB)

Traumatic Brain Injury

The sequelae a patient experiences after a head injury result from the primary injury at the time of impact and secondary injury mechanisms that develop in the first hours and days following the primary injury. The primary goal of neuro-intensive care is to limit secondary injuries.

The overarching goal in treating patients with traumatic brain injury is to prevent the development of secondary injuries by establishing the best possible physiological conditions for the brain, which, after a primary injury, is highly vulnerable. Key requirements include adequate neurological and physiological monitoring. Treatment involves both neurosurgical interventions and neuro-intensive care to achieve treatment goals. The treatment is ICP-guided and primarily aims to lower elevated ICP. Measures to reduce capillary hydrostatic pressure, thus reducing transcapillary filtration across a damaged blood-brain barrier, are central.

• Incidence: 200-450/100,000 population per year in Sweden
• Traffic accidents dominate
• 75% men
• About 50% are over 50 years old
• TBI is the most common cause of death for people < 40 years old

If the patient has a pre-hospital blood pressure < 90 mm Hg and oxygen saturation below 90%, this results in worse outcomes.

Injury types – primary brain injury

• Epidural hematoma
• Subdural hematoma
• Cerebral contusions
• Diffuse axonal injury (DAI)

The acute management is determined by

• Level of consciousness
• Neurological status
• Radiological image
• Other injuries
• Clinical course
• ABCDE applies!!

Prevent secondary brain injury

• Reduce ICP by counteracting edema development
• Reduce the stress response/sympathetic activity
• Decrease oxygen demand by lowering metabolism
• Ensure sufficient oxygen delivery to the brain
• Adequate O₂ supply to the brain
• Hgb ≥ 12 g/dL
• pO₂ ≥ 12 kPa
• Controlled ventilation
• pCO₂  4.5 – 5 kPa , VC, “optimal” PEEP

You can intervene and control

• O₂ demand
• Lower metabolism through sedation and temperature regulation
• Reduce brain edema development
• Suppress sympathetic activity with β-blockade, α-blockade (metoprolol, clonidine)
• Optimize electrolyte and fluid balance
• Normalize blood pressure (age-dependent)

Prevent complications from intensive care

• Ventilator treatment; VILI, VAP, tracheostomy
• Immobilization; Venous thromboembolism
• Infections; catheter-related infections, VAP
• Toxic effects of drugs; Propofol, Pentothal

In a closed space, there is only room for a certain volume

What shares the space inside the skull is…

• Brain parenchyma
• Cerebrospinal fluid
• Arterial blood
• Venous blood

Any additional expansion

• Tumor
• Bleeding

Factors affecting intracranial dynamics

What can we influence/what matters?

Volume regulation of brain tissue

• Blood-brain barrier
• Transcapillary hydrostatic pressure
• Crystalloid osmotic pressure
• Plasma oncotic pressure
• Intracellular edema due to, for example, ischemia

Volume regulation of CSF

• CSF drainage

Cerebral blood volume

• Position change, elevated head of bed
• Obstruction of outflow; head rotation, high intrathoracic pressure > ICP

Cerebral blood flow

• Autoregulation
• PCO₂
• Metabolism
• Sedation
• Body temperature

Blood-brain barrier

• The most important factor for regulating brain volume
• Normally only permeable to H₂O
• Fluid transport is governed by differences in:
  • Hydrostatic pressure
  • Crystalloid and colloid osmotic pressure

Therefore we correct

• Hyponatremia
• Hypoalbuminemia
• Anemia

Normally, only H₂O passes freely between the bloodstream and the interstitial space. The permeability for albumin, NaCl, and mannitol is low. Hydrostatic pressure (MAP) pushes water out of the bloodstream. It dilutes the small and large osmotically active substances in the interstitium while concentrating them in the bloodstream, creating a concentration gradient that draws water back into the bloodstream.

Damaged blood-brain barrier

• Can occur in parts of the brain
• Permeability increases for small molecules
• Later, also for large molecules
• Then crystalloid and colloid osmotic pressure becomes less significant

Spontaneous Intracerebral Hemorrhage – ICH

Acute Diagnosis in Intracerebral Hematoma (ICH)

Several factors influence whether a brain CT should be supplemented with CT angiography:

• CT angiography is usually indicated acutely in younger patients or for atypical bleeding (e.g., lobar hematomas)
• CT angiography is generally not indicated acutely for deep intracerebral bleeding (basal ganglia, thalamus, pons, central cerebellum, or deep white matter near the basal ganglia) in older patients with hypertension. It is also not indicated in elderly patients with low functional grade/short expected survival.
• CT angiography in venous phase if sinus thrombosis is suspected
• Radiologist measures the hemorrhage in cm in three planes x*y*z. (volume is approximately x*y*z/2 in ml)

Urgent Contact with ICU On-Call for Intubation or Help with Blood Pressure Reduction if

• Patient is experiencing reduced consciousness (RLS >3)
• Airway obstruction
• Rapid deterioration in level of consciousness
• Initially high blood pressure (approx. >220 systolic) or difficult-to-control blood pressure
• Biologically young patient – be liberal with ICU contact if blood pressure >200 mmHg systolic

Urgent Contact with Neurosurgery On-Call for

• Cerebellar hematoma >15 ml (approx. >3 cm)
• Hemorrhage in the ventricular system with hydrocephalus development/tendency
• Lobar hematomas 60–110 ml
• Visible surgical bleeding source on CT angiography
• Biologically young – individually more liberal with neurosurgery contact
• Older, multi-morbid – individually less liberal with neurosurgery contact

Blood Pressure Targets

ICH can expand in the acute phase (hematoma expansion), often occurring within the first few hours/day after symptom onset. Studies typically do not include larger hematomas (>60 ml) or patients scheduled for surgery. A large randomized controlled trial (RCT), INTERACT2, showed an effect of early blood pressure reduction <140 mmHg on functional outcome (modified Rankin Scale) at 3 months, while another large RCT, ATACH-II, did not find such an effect. A meta-analysis of RCTs shows that intensive blood pressure reduction within 6 hours reduces the risk of hematoma expansion.

Studies have also shown that hematoma expansion is associated with neurological deterioration, mortality, and increased functional dependence. However, pronounced blood pressure reduction (>60 mmHg) within the first hour may be associated with death. Furthermore, systolic blood pressure (SBP) should be maintained >110 mmHg to reduce the risk of hypoperfusion with organ damage (e.g., kidneys). Extreme blood pressure fluctuations should also be avoided.

Swedish guidelines (Person-Centered Cohesive Care Pathway Stroke and TIA 2020, National Board of Health and Welfare National Guidelines for Stroke Care 2018) recommend early blood pressure reduction to between 140 and 180 mmHg, using IV medication. European Guidelines (ESO 2021) recommend that in individuals arriving within 6 hours, blood pressure should be reduced to SBP <140 mmHg (but >110 mmHg) to reduce the risk of hematoma expansion. Blood pressure should not be reduced by more than 90 mmHg from the arrival pressure. This blood pressure level should be maintained for 24-72 hours.

Meanwhile, it is noted that intensive blood pressure reduction to SBP <140 mmHg within 24 hours has not shown an effect on functional outcome at 3 months. American guidelines recommend a target SBP of 140 mmHg with a range of 130-150. In this routine, we aim to avoid hypotension by recommending active blood pressure reduction at SBP ≥150 mmHg.

Summary of Blood Pressure Targets

• Target SBP 120–140 mm Hg as soon as possible
• Treat with IV medication if SBP ≥150 mm Hg
• Reduce blood pressure by a maximum of 60 mm Hg in the first hour
• Do not reduce blood pressure by more than a maximum of 90 mm Hg from the initial pressure within the first 24 hours
• Avoid SBP <110 mm Hg (risk of worse outcome)
• Avoid blood pressure fluctuations and peaks
• If the patient is scheduled for neurosurgery or is being cared for in an ICU, consult the ICU/neurosurgery on-call regarding blood pressure targets
• Blood pressure targets can be individualized (e.g., SBP ><180 mmHg in frail elderly patients with short expected survival, or SBP ><180 mm Hg if the patient has long-standing untreated hypertension, is multi-morbid, or a tailored blood pressure target, e.g., SBP <160 mmHg for bleeding >60 ml)

Acute Blood Pressure Management in Practice

There is no evidence regarding the best blood pressure-lowering treatment for ICH. Always continue with the usual oral treatment (use a tube if necessary). Introduce oral treatment early as a complement. Treat with labetalol as first choice, clonidine or nepresol if insufficient effect. After each dose, recheck blood pressure after 10–15 minutes; if the target blood pressure has not been reached, give additional antihypertensive treatment. Repeat until the patient reaches the target blood pressure. Typically, start with 10 mg labetalol, as ICH often requires 2-4 ml of labetalol as needed. Treating nausea (IV ondansetron 4–8 mg), pain (IV morphine 2-3 mg), or emptying the bladder often also helps lower blood pressure.

Labetalol (Trandate®)

Mechanism of action:

• Blocks peripheral alpha-adrenoceptors in arterioles
• Cardiac beta-blockade reduces reflex sympathetic feedback

Dosage:

• IV (5)-10-20 mg (-40) mg/dose
• Max 200 mg per day

• Avoid if AV block, pulse <50/min, or ongoing asthma
• Side effect bradycardia (administer atropine 1–2 mg IV if needed)
• Higher doses often needed for blood pressure reduction in ICH than in ischemic stroke; needing 20 mg or more repeatedly is not unusual
• Max effect within 10–15 min, pharmacodynamics: t½ <4h, but effect sometimes lasts only 60 min

Clonidine (Catapresan)

• Mechanism of action:
• Central alpha-adrenoceptor agonist
• Effect on the renin-angiotensin system

• Dosage: 75-150 µg/dose IV
• Max approx. 600 µg/day
• Avoid if severe renal failure or pulse <50/min
• Side effects: sedation (higher doses)
• Especially effective in motor agitation, pain
• Max effect within 20–30 min, effect duration in renal-healthy patients approx. 5 hours, 72% renal excretion, t½ up to 41 hours in severe renal failure

Nepresol (License Prep, Dihydralazine)

• Mechanism of action:
• Dilates peripheral resistance vessels (arterioles, not venous system)

• Dosage: 3.125-6.25 mg IV (0.25-0.5 ml IV)
• Max approx. 75 mg per day
• Avoid if severe renal failure, SLE, or ongoing heart attack
• Side effects: high heart rate, headache, nausea
• Effect within 5-10 min, max effect within 30 (60) min, effect duration 1-4 hours

Furosemide (Furix)

• Dosage: (40) -80 mg/dose IV
• Usually effective only with concurrent heart failure/overhydration
• Rapid but often transient effect

Initiation of Oral Antihypertensive Treatment with Rapid Effect (via Tube)

T. Amlodipine 5–10 mg
T. Enalapril 5–10 mg

Autoregulation

Cerebral blood flow remains constant across normal blood pressure ranges. Cerebral autoregulation aims to maintain cerebral blood flow at an optimal level, preventing both hypoperfusion with a risk of ischemia and hyperperfusion with a risk of edema development. Within a relatively broad blood pressure range (MAP 50-150 in a normotensive adult), CBF is kept constant through varying degrees of vascular constriction. In all cases of brain injury, the capacity for autoregulation may be impaired to varying degrees or completely lost. For these patients, determining an optimal CPP range can be challenging.

A CPP above 60 is generally recommended unless otherwise indicated, though this is not always sufficient. A higher CPP, when cerebral autoregulation is preserved, may lower ICP through vascular constriction to maintain constant cerebral blood flow. This can be investigated under very controlled conditions.

If not specified, the following applies to traumatic brain injury patients in neurointensive care

• ICP < 20 mm Hg
• CPP > 60 mm Hg
• MAP > 70 mm Hg
• pO₂ 12-16 kPa
• Normovolemia with negative fluid balance
• pCO₂ within normal range
• Hb > 100 g/L
• S-Na within normal range
• S-Alb within normal range
• B-Glucose 6-10
• Normothermia
• Head of bed elevated 10-30 degrees – note the actual perfusion pressure!!

Surgical Treatment

Rapid evacuation of focal expansive intracranial hemorrhages/contusions. Surgery is generally indicated for contusions/hematomas causing > 5 mm midline shift. However, the decision for surgery is based on analysis of several factors, such as clinical course, timing after injury, current level of consciousness, focal neurological symptoms, ICP, and other CT findings.

Tranexamic Acid

Tranexamic acid should be administered within 3 hours after traumatic brain injury in adult patients, following the CRASH-3 study guidelines, without delaying other care. 1g Tranexamic acid (Cyklokapron/Strataxen) is given intravenously as a bolus over approximately 10 minutes, if not already administered pre-hospital. Followed by an additional 1g Tranexamic acid (Cyklokapron) as an infusion over 8 hours.

Body Position

Initially, the patient is managed with a slight head elevation of about 10°, which can be increased to a maximum of 30° if ICP is elevated. It is important to note that effective CPP decreases with head elevation, and the effect of head elevation on venous outflow is debated. The patient should lie without head rotation, and regular body position changes should be made if there are no contraindications, such as increased ICP. Special consideration is required for craniectomized patients. To prevent lung complications, patients in this group, like all ICU patients, should regularly undergo body position changes. If the patient, with stable ICP, can lie on the craniectomized side, this should be done with attention to neck position to support venous outflow. The craniectomy site should be handled carefully, avoiding direct pressure. In cases of uncertainty, consult the responsible physicians for individual assessment.

Sedation

Initial sedation is typically with Propofol (max 4 mg/kg/h for up to 48 hours) and Fentanyl, with early addition of Midazolam (typically 0.05-0.2 mg/kg/h) to allow reduction and potential discontinuation of Propofol. Propofol remains useful when clinical assessment after sedation is desired, adhering to maximum dose limits. Doses should be based on the patient’s ideal weight, with precise pump settings. Barbiturate (Thiopental) sedation is considered as a Step 3 intervention when other medical measures are exhausted, and any surgical evacuation of hematoma or contusions has been completed. The goal is to reduce ICP, not to deepen sedation. Continuous EEG monitoring should begin as soon as possible to avoid excessive sedation. The minimum effective dose of Thiopental is pursued due to dose-dependent complication risks. Key complications include hypotension from myocardial depression, kidney failure, lung issues, liver effects, and infections. Hypokalemia and arrhythmias from intracellular potassium shifts may occur with Thiopental initiation, with rebound hyperkalemia possible upon discontinuation. This treatment carries a high risk of multi-organ failure.

Ventilation

Controlled ventilation with tidal volume 6 (-8) ml/kg ideal body weight (IBW). Adequate individualized PEEP, typically around 10 cmH2O. FiO2 adjusted to pO2 12-16 kPa. Respiratory rate adjusted for normoventilation in patients with normal ICP. For elevated ICP, ventilation is increased to target a pCO2 range of 4.5-5.0 kPa. When ICP control is challenging, temporary pCO2 levels of 4.0-4.5 kPa are acceptable. Hyperventilation down to pCO2 3.5 kPa is allowed temporarily, such as before urgent surgery, but prolonged hyperventilation is not recommended as it can cause cerebral vasoconstriction and ischemia risk. Ventilator-associated pneumonia (VAP) is common in brain injury patients, increasing risks of prolonged ventilation time, fever, hypoxia, hypotension, and elevated ICP. Preventive measures are crucial. In severely ill patients who are unlikely to be extubated successfully, tracheostomy is often necessary once ICP is stable, given that sedation weaning can be prolonged.

Circulation

The relationship between systolic blood pressure (SBP), mean arterial pressure (MAP), and cerebral perfusion pressure (CPP) is essential. MAP should never be below 70 mmHg, and before ICP monitoring, MAP should be kept >80 mmHg. Different limits apply for children. Acute hypertension should be managed cautiously, only treated if SBP >200 mmHg or MAP >120 mmHg, initially by increasing sedation. If further blood pressure reduction is needed, short-acting Labetalol (Trandate®) 5 mg/ml, 1-2 ml IV may be used, often needing repetition. Persistent hypertension at a later stage should be managed with antihypertensive treatment and stress reduction using Clonidine (Catapresan®) or Metoprolol (Seloken®). For hypotension requiring vasopressors, discontinue these medications, optimize volume status, and initiate invasive circulatory monitoring (PiCCO), complemented by UCG. CPP goals should primarily be achieved by lowering ICP. Volume optimization and cardiac output optimization are secondary, with Noradrenaline as a vasopressor as a last resort.

Fluid Therapy, Electrolytes, and Transfusion Thresholds

Normovolemia with normal electrolytes and colloid osmotic pressure is the target, with S-Na 137-145 mmol/L, S-Albumin 36-48 g/L, and Hb usually >90 g/L. For pronounced ICP issues, aim for the upper end of the reference range. A slight negative fluid balance, achieved with diuretics if needed, is required to prevent weight gain. Hyperosmotic therapy is always administered in consultation with a neurosurgeon. Before emergency surgery, 200-300 ml of Mannitol is typically given.

For neuro-ICU patients with critically high ICP, osmotic therapy with hypertonic saline may be considered. If no ready solution is available, mix 80 mmol Na in 250 ml NaCl (approx. 3% solution) and administer over 20 minutes. Possible side effects include acid/base imbalances, electrolyte disturbances, coagulation effects, and renal failure. S-Na should be kept below 155 mmol/L and S-Osmolarity below 365 mOsm/L, thus monitored regularly.

Nutrition and Blood Glucose

During the first few days, administer glucose 50 mg/ml with added sodium to cover basic fluid requirements. Early initiation of enteral nutrition is recommended. If basic caloric needs are not met within 5-7 days, supplement enteral nutrition with TPN to provide 15-20(-25) kcal/kg daily. Energy supply should be tailored to the individual, sedation level, and mobilization level; indirect calorimetry may be used as a guide. The “nutrition calculator” takes caloric drugs like Propofol into account. Under deep sedation with Thiopental, gastrointestinal atony often develops, possibly requiring suspension of enteral nutrition. Barbiturates decrease overall metabolism, which should be considered in daily energy calculations and orders. See also “Nutrition during intensive care” protocol. Precise blood glucose control is essential, with target values of 6-10 mmol/L. See protocol for insulin infusion. Ulcer prophylaxis with IV omeprazole is given until full enteral nutrition is achieved, then usually switched to an oral or NG tube H2-receptor blocker.

Body Temperature

Normothermia is the target, and temperatures >38°C should be treated. Paracetamol is administered for fever. Active cooling with an external cooling device is only for deeply sedated patients. There is no support for hypothermia treatment. High-dose steroids are contraindicated. Early infection investigation and treatment are essential.

Antiepileptic Treatment

There is no support for prophylactic seizure treatment; however, epileptic seizures should be treated promptly as they increase brain oxygen demand. If a seizure is not controlled with single doses of Midazolam or if recurrent seizures occur, intravenous Levetiracetam 500 mg x 2 may be administered. For persistent issues, consult a neurologist on duty. EEG is performed during the day.

Thromboprophylaxis

Patients with brain injuries have an elevated risk of deep vein thrombosis. For most patients, low-dose Fragmin® (2500 E x 1 sc) is indicated, in consultation with neurosurgery. Fragmin® should be combined with pneumatic compression if available; compression stockings are an alternative. In patients where Fragmin® is contraindicated, pneumatic compression should always be used.

Traumatic brain injury care – Step 1

• Aim for basic treatment goals
• For patients > RLS 3 , secure the airway and provide ”comfort sedation”
• ICP monitoring is initiated. Until then, the patient is assessed through regular sedation stops and
  
  /or CT scans
• Normal physiological parameters apply to ventilation, circulation, fluids, Hb, electrolytes, etc.
• If ICP control is not achieved with Step 1, proceed to Step 2 after assessing whether hematomas or contusions should/can be evacuated

Traumatic brain injury care – Step 2

• Sedation is therapeutic (RASS -4) to reduce metabolism, decrease stress, and control ICP:
  • Propofol + Fentanyl + Midazolam
• Ventricular drain is considered for CSF drainage/tapping.
• Specific stress reduction to counter sympathetic activation:
  • β-blockade and α-agonist (clonidine) in continuous infusion
• Osmotic therapy
• Hypertonic NaCl
• Electrolytes, ventilation, and Hb are monitored even more closely
• If ICP control is not achieved, consider Step 3 after assessing possible evacuation of hematomas/contusions

Traumatic brain injury care – Step 3

• All steps have been exhausted, and the patient is pharmacologically, physiologically, and surgically optimized
• Continuous sedation with intravenous barbiturates – ”Pentocoma” inducing metabolically induced vasoconstriction
• Associated with high risk of complications and not suitable for all patients
• Requires continuous EEG monitoring
• Pentothal is given until ICP control is achieved, not to a specific depth of sleep, but with maximum burst suppression for the shortest possible time
• 0.5-1 g pentothal is administered over 2-4 hours
• Then continuous pentothal infusion at 2-4 mg/kg/h
• Additionally, midazolam at 0.15 mg/kg/h
• Decompressive craniectomy may be considered in rare cases of treatment failure, but its value is uncertain and up to the responsible neurosurgeon to assess.

Decompressive craniectomy

Prophylactic hypothermia

Normothermia is optimal

• Treat fever > 38°C
• Paracetamol may be administered
• Active infection investigation and treatment if indicated
• In deeply sedated patients, active normothermia at 36-37°C can be considered
• No steroids are given for this indication!

Hyperosmolar therapy

Options are

• Mannitol 200 – 300 ml before surgery
• Hypertonic saline can be administered as a bolus over 20 minutes
• 80 mmol Na in 250 ml NaCl – provides nearly 120 mmol extra Na

CSF drainage

• Open ventricular drain with intermittent measurement
• Closed ventricular drain with intermittent drainage/”drip” as needed
• Closed ventricular drain

How do we do it?

• The ventricular drain setting is prescribed by the neurosurgeon, but changes should always be communicated to the intensive care physician

Ventilation

• Tidal volume: 6 ml/kg IBW
• PEEP: 10 cm H₂O or as needed
• PaO₂: 12-16 kPa
• PaCO₂: normoventilation is the basic rule (4.6-6.0 kPa)
• In case of ICP issues: PaCO₂ in the lower normal range (4.0-4.5-5.0)
• Short-term hyperventilation en route to surgery to PaCO₂ 3.5 – no lower

Sedation / Analgesia

• Sedation on three levels:
• Comfort: propofol, fentanyl
• Therapeutic: (propofol,) fentanyl, midazolam
• Barbiturate-based: (propofol), fentanyl, midazolam, pentothal

Steroids

• Not recommended in traumatic brain injury

Nutrition

• Use the nutrition calculator and adjust the nutritional level according to need and sedation depth; 15-20-25 kcal/kg
• Use glucose 5% only for a maximum of 7 days
• Enteral nutrition as far as possible

Infection prophylaxis

• Tracheostomy when ICP is stabilized for patients suspected to need prolonged ventilation or slow neurological recovery.

Thrombosis prophylaxis

• Fragmin (LMWH) 2500 IU x 1 sc for almost everyone
• Compression stockings
• Mechanical leg pumps

Epilepsy prophylaxis

• No prophylactic treatment
• If epilepsy is suspected, administer benzodiazepines
• If seizures recur, perform EEG and start Keppra

ICP monitoring

• ICP monitoring is initiated for patients with RLS ≥ 4 and who remain sedated

CPP monitoring

• When ICP monitoring is available, CPP is calculated as MAP-ICP

Advanced cerebral monitoring

• Jugular bulb monitoring – not routinely used
• Jugular venous saturation below 50% should be avoided

Recommended blood pressure limits

• MAP > 70 mmHg
• Alternatively, the MAP required for CPP > 60 mmHg
• Before ICP measurement, it is reasonable to maintain MAP > 80 mmHg

ICP limit

• ICP target < 20 mmHg
• If ICP exceeds 22 mmHg, active treatment is recommended
• CPP target > 60 mmHg

CSF Analysis

If meningitis, ventriculitis, or encephalitis is suspected, lumbar puncture is often performed with cell analysis. During lumbar puncture, a small needle hemorrhage may occur, which can be mistaken for subarachnoid hemorrhage. In needle hemorrhage, there are abundant red blood cells (absence of xanthochromia (yellow-red discoloration) after centrifugation early after LP indicates needle hemorrhage and against subarachnoid hemorrhage).

Suspicion of infection in the CSF exists if more than 1 white blood cell (granulocyte)/1000 red blood cells (erythrocytes) is present. If the patient has undergone surgery or has a confirmed subarachnoid hemorrhage, infection is suspected if more than 1-10 white blood cells per 200 red blood cells are found.

Typical signs in CSF of fulminant bacterial meningitis with barrier damage are:

• High lactate, about 10 mmol/l
• High albumin, significantly elevated around 800 mg/l. Normal < 320 mg/l
• Leukocytes, high neutrophils, more than 500 x 10⁶/l
• Low glucose, about 60% of B-glucose. Normally more than 2/3 of B-glucose.

In bacterial meningitis, there is often a sharp increase in leukocytes (> 500-1000 x 10⁶/l) dominated by neutrophils, though the leukocyte count may be lower early in the process.

Sodium and fluid balance disorders in brain injury

SIADH (syndrome of inappropriate secretion of ADH)

Causes water retention and hyponatremia. Results in euvolemic hyponatremia. It is due to excessive antidiuretic hormone (ADH) relative to serum osmolality. Seen in CNS injury and as a paraneoplastic phenomenon.

Symptoms of SIADH:

• Hyponatremia
• Fluid retention
• Weight gain or lack of weight loss
• S-Osm < 270 mOsm/kg
• U-Na > 20
• U-Osmolarity 300-1400

Treatment

• Fluid restriction
• Diuretics
• Hypertonic saline
• Possibly dialysis

Diabetes insipidus

Water loss occurs, resulting in hypernatremia, sometimes severe.

• Hypernatremia (> 150 mmol/l)
• Fluid loss
• S-Osm > 270 mOsm/kg
• U-Na < 20
• U-Osmolarity significantly reduced

Treatment of diabetes insipidus

• Can be treated with minirin 0.4 mcg/ml in small repeated doses of 0.25 ml = 1 mcg.
• Hypotonic fluid intravenously.

CSWS (Cerebral salt wasting syndrome)

The patient loses sodium and water. Becomes hypovolemic and hyponatremic or requires significant sodium supplementation.

• Hyponatremia
• Dehydration
• Weight loss
• U-Osmolality is higher than S-Osmolality
• U-Sodium > 100 mOsm/kg

Treatment

• Follow diuresis with Ringer’s acetate or Plasmalyte
• Tablet Florinef 0.1 mg/tablet x 1-2. An aldosterone agonist that retains sodium and eliminates potassium.

Iatrogenic fluid balance disorder

• Hyponatremia
• Hypotonic solutions/fluid intake
• Patients beyond their spasm risk must be allowed to reduce fluid balance if they have excess fluid – often seen as lack of weight loss during hospitalization.
• Common methods of calculating fluid balance are VERY crude!
• +/- 0 in fluid balance over time means the patient accumulates fluid

Thiopentone (Pentocur/Pentothal) “Pento”

Ultrashort-acting intravenous anesthetic that is a barbiturate derivative. Thiopenthone induces sleep rapidly when given intravenously. It induces hypnosis and anesthesia, but not analgesia. Primarily used for anesthesia induction for surgery but also for short medical procedures where brief sleep is desired. Typically administered by manual syringe injection (25 mg/ml) with the speed and dose adjusted based on the patient’s condition and procedure type. Thiopenthone can be given as a continuous infusion in the treatment of status epilepticus and elevated intracranial pressure due to brain edema. For decades, Thiopenthone was the standard anesthetic for induction, but it has been replaced by propofol and other anesthetics in recent years. It causes dose-dependent respiratory and circulatory depression. Thiopenthone is only a hypnotic and not a true analgesic, but pain relief follows to some extent with anesthetic depth. For surgical anesthesia, Thiopenthone is typically combined with strong opioids such as fentanyl in a balanced anesthesia. Compared to propofol, Thiopenthone does not provide the same relaxation of the upper airways, which can result in rigidity and difficulties during manual ventilation. A small dose of Thiopenthone can be given to prevent or treat laryngospasm.

Concentration: 25 mg/ml

Thiopenthone is supplied and stored as a powder and is typically diluted to a daily concentration of 25 mg/ml. The diluted solution has a shelf life of only 24 hours and should be stored in the refrigerator.

Dosage

• Anesthesia induction: 4-6 mg/kg.
• Typical dose for a 70 kg patient is approximately 14 ml (± 4 ml) = 350 mg.

Use in neurological patients with increased intracranial pressure

Intermittent bolus injection of 1.5 – 3 mg/kg body weight may be given to reduce increased intracranial pressure during controlled ventilation. In continuous infusion 2-4 mg/kg/hour. A maximum dose of 5 mg/kg/hour should not be exceeded.

A typical induction dose for adults is 4-6 mg/kg body weight, but the individual response is so variable that no fixed dosage can be stated. Typically, 200 to 400 mg is given as an induction dose (8 – 16 ml at 25 mg/ml), with a normal starting dose of 14 ml. In patients with poor general condition, the dose is usually reduced and carefully titrated. After intravenous administration, unconsciousness occurs within 30 seconds and lasts for 20-30 minutes after a single dose. It is rapidly absorbed in most vascular areas of the brain, followed by redistribution to other tissues. It is rarely justified to administer more than 500 mg intravenously. Thiopenthone has a distribution half-life of 2-4 hours after an intravenous single dose, and for elimination, the half-life is 9-11 hours. Plasma protein binding is 80-90% at therapeutic concentration.

Cave

Porphyria, upper airway obstruction, asthma attack, extravasal and intra-arterial injection. Pentothal is histamine-releasing, and a transient skin flush (usually over the chest and neck) can be observed after intravenous injection.

Caution

Caution in cases of severe obesity, hypovolemia, hypotension, or severe shock.

Trade name

Pentocur, Thiopenthone (discontinued).