The Lund ConceptThe Lund Concept

Does ICP really matter …. Does ICP really matter ….

(or rather who cares about ICP (or rather who cares about ICP anyway)anyway)

Approaches…Approaches…

The Lund concept for the treatment of severe head injury was introduced in 1990 to 1991 at the University Hospital of Lund, Sweden.

Conventional guidelines are based on meta-analytic surveys from clinical studies

maintenance of a relatively high CPP (the CPP-guided approach)

CPP = MAP – ICP.

Lund therapy is a theoretical physiological approach physiological and pathophysiological hemodynamic principles

of brain volume and brain perfusion regulation Tx of ICP and maintenance of cerebral perfusion

(the ICP and perfusion-guided approach).

The Lund ConceptThe Lund Concept

relatively strict recommendations regarding fluid therapy, optimal hemoglobin concentration, lung protection and temperature control, and risks and values of:

cerebrospinal fluid (CSF) drainage decompressive craniotomy

Lund therapy has also been used for the treatment of brain oedema in meningitis.

Monro-Kellie doctrine

The pressure-volume relationship between ICP, volume of CSF, blood, and brain tissue, and cerebral perfusion pressure (CPP) is known as the Monro-Kellie doctrine or the Monro-Kellie hypothesis.

cranial compartment is incompressible & volume inside the cranium is a fixed volume

Blood, CSF, and brain in equilibrium

Principal buffers for increased volumes include both CSF and, to a lesser extent, blood volume.

Compensatory mechanisms- maintains normal ICP for volume change < 100–120 mL

v.intracranial (constant) = v.brain + v.CSF + v.blood + v.mass lesion

Brain tissue (85%), cranial CSF (10%), cerebral blood (5%), spinal CSF is about 75ml - cranial CSF volume

Why do we have CSF?

Functions of CSF mechanical maintenance of a constant ionic

environment - Ca, K, Mg and HCO3 (active) and H and Cl by secondary transport.

waste removal acid/base regulation via CO2 nutritional and intracerebral transport

How’s it made CSF formation ~ 500ml/day CSF total volume 120ml- 70% from choroid plexus

- (blood vessels projecting into ventricles)

- has tight junctions which means ultrafiltration (hydrostatic pressure) and secretion are important.

CSF hydrostatic pressure is 5-15mmHg

Cilia help move CSF to the 4th ventricle and the

foramina Lushka and Magendie into the cisterna Magna then into subarachnoid space

around cerebella, then further up to basilar

cisterns Lateral/frontal cerebral cortex.

Reabsorption

Reabsorbed via 1. arachnoid villi in sagittal

and sigmoid sinuses, 90%, and 2. spinal arachnoid villi in

dural sinusoids on dorsal root nerves, 10%  reabsorption is via

pinocytosis and opening of intercellular spaces.

rate of reabsorption increases with CSF pressure.

resistance to reabsorption is normal until CSF > 22mmHg and then it decreases.

The balance

CSF formation and reabsorption is in equilibrium.

BUT if ICP increases so much that CPP is <70mmHg then CSF formation decreases.

If ICP<7mmHg then minimal reabsorption occurs

CSF reabsorption is linear from 7-70mmHg

In supine, healthy adults, normal ICP is between 7 and 15 mmHg. In supine, healthy adults, normal ICP is between 7 and 15 mmHg. Term - normal ICP 1.5-6 mmHg Term - normal ICP 1.5-6 mmHg Young children 3-7 mmHg Young children 3-7 mmHg AdultsAdults

observational studies: ICP 20-25 mmHg -> much poorer outcome from observational studies: ICP 20-25 mmHg -> much poorer outcome from TBITBI

The evidence is even more limited in children, but generally: The evidence is even more limited in children, but generally: Infants <15 mmHg Infants <15 mmHg Younger children <18 mmHg Younger children <18 mmHg Older children <20 mmHg.Older children <20 mmHg.

Some physiology….

Cerebral function is totally dependent on oxidative phosphorylation glucose -> ATP.

  Brain is 2% of body weight, but uses 20% of body's resting oxygen

consumption.   CBF varies with metabolic rates of the areas of the brain.

CBF and cerebral metabolism are thought to be coupled.

Local metabolic factors re coupling are H+, K+, adenosine, phopholipid metabolites, glycolytic metabolites and nitric oxide.

CBF ~ 750ml/min

What’s autoregulation…

Autoregulation - phenomenon where CBF is kept constant over a MAP of 50-150mmHg.

>150mmHg, then CBF passively increases with CPP and arterial pressure.

CBF increases linerarly by 2-4% for every mmHg increase in PaCO2 (between PaCO2 of 20-80mmHg).

CO2 diffuses rapidly across BBB, increases H+ in ECF and causes vasodilation.

BUT arteriolar tone modifies this effect and hence hypotension can abolish ability of cerebral circulation to respond to PaCO2 changes.

  PaO2 - if <50mmHg then CBF will start to rise and doubles by time PaO2 is

30mmHg.  Cerebral metabolic rate decreases by 7% for each 1 degree celsius in body

temperature.

More physiology…

Cerebrovasculature - well innervated by serotonergic, adrenergic, cholinergic nerves.

Sympathetic activity can cause marked constriction of cerebral arteries - ie. in heavy exercise can stop high pressure from reaching small blood vessels and hence prevent haemorrhage.

  Hypercarbia - get vasodilation.

Cerebral steal when decreased blood flow in ischaemic area of brain result in hypercarbic induced vasodilation in non-ischaemic areas.

Conversely,  VC in normal areas of brain from hypocarbia can redistribute blood to ischaemic areas - i.e. Robin Hood or inverse steal phenomenon.

Last bit of physiology…

Starling's equation the movement of fluid depends on six

variables: Capillary hydrostatic pressure ( Pc ) Interstitial hydrostatic pressure ( Pi ) Capillary oncotic pressure ( πc ) Interstitial oncotic pressure ( πi ) Filtration coefficient ( Kf ) Reflection coefficient ( σ )

Evidence…. Or lack ofEvidence…. Or lack of

Recent Chinese studyRecent Chinese study 68 patients, GCS 3-8, severe HI68 patients, GCS 3-8, severe HI

30 had The Lund Concept….30 had The Lund Concept…. Looked at 28 day mortalityLooked at 28 day mortality

Roughly 30% vs 60% (p<0.01)Roughly 30% vs 60% (p<0.01)

Evidence… or lack ofEvidence… or lack of

Newcastle Uni – UK,… 2011 Critical Newcastle Uni – UK,… 2011 Critical carecare

MA Hamdan1, K Dizdarevic2, MA Hamdan1, K Dizdarevic2, 1Newcastle 1Newcastle University, Newcastle upon Tyne, UK; 2Clinical University, Newcastle upon Tyne, UK; 2Clinical Centre University of Sarajevo, Sarajevo, Centre University of Sarajevo, Sarajevo, Bosnia and Herzegovina, Critical Care Bosnia and Herzegovina, Critical Care 2011, 2011, 15(Suppl 1):P342 (doi: 10.1186/cc9762)15(Suppl 1):P342 (doi: 10.1186/cc9762)

60 patients – positive, p=0.0360 patients – positive, p=0.03

ConceptConcept

BBB disrupted after traumatic brain injury cerebral autoregulation is impaired

hence, the transcapillary water exchange is determined by the differences in

hydrostatic and colloid osmotic pressure between the intracapillary and extracapillary compartments.

Induce transcapillary reabsorption of interstitial fluid by controlling transcapillary osmotic and hydrostatic differences

combination pharmacotherapy b1-antagonist metoprolol a2-agonist clonidine low-dose thiopental dihydroergotamine maintenance of colloid osmotic pressure by PRBC and albumin

MxMx Alternatively, RICP ->reduction of CPP and CBF If persistent may worsen the primary brain injury and cause

cerebral ischemia

Much variability in the practice of Tx of RICP and targets for ICP and CPP

Methods focus on CPP and CBF Mx as the primary target

“CPP targeted therapy” Uses medications to increase CPP and CBF via increasing MAP

Alternatively reduce ICP as the primary target “ICP-targeted therapy” to improve cerebral perfusion Lund Concept – a specific subcategory of ICP control

involving a “volume targeted” strategy

Mx….Mx….

TREATMENT OF ICP ? high CPP -> improves oxygenation of injured

brain “squeezing blood through the swollen brain” reduces intracranial blood volume through an

autoregulatory vasoconstrictor response.

improved oxygenation maybe transient in injured brain capillaries passively permeable to small solutes

high perfusion pressure will induce transcapillary filtration and exacerbate edema

and the autoregulatory response is weak after a brain injury.

A passive venous collapse (resistance) is developed just inside the dura

protects brain from change in PV (i.e, head elevation or by PEEP)

↑ ICP from filtration (disrupted BBB) because of ↑ Pc and ↓ Ponc This ↑ -> partly transferred to capillaries with ↑ Pc and further

filtration, etc -> new steady state

Hence ICP ↑ >> initial increase in Pc or decrease in Ponc that started the filtration.

filtration -> ↑↑ ICP than increase in Pc or decrease in Ponc, triggering the filtration.

Hence, ↓ ICP >> ↓ Pc and ↑Ponc -> triggers ↓ ICP

Passise venous resistance Passise venous resistance vesselvessel

NoteNote slow process taking several hoursslow process taking several hours Vasoconstrictors –Vasoconstrictors –

↑ ↑ BP but also SE’s like BP but also SE’s like ARDS and ARDS and ↑ ↑ leakage of plasma -> hypovolemia and general tissue leakage of plasma -> hypovolemia and general tissue

oedema; oedema; inotropes like dobutamine cause cerebral vasodilation…)inotropes like dobutamine cause cerebral vasodilation…)

(Lund patients don’t get these problems (Lund patients don’t get these problems as much…..)as much…..)

The Lund concept… ICPThe Lund concept… ICP

Accept a lower CPP than the initial recommended 70mm Hg -> avoids vasopressors.

Antihypertensive treatment b-1 blockade, a-2 agonists, and ARB’s to counteract oedema Fluid therapy given in the Lund concept -> CPP will stay acceptable

Normalization of reduced Ponc may counteract filtration in brain Hence higher CPP can be accepted without inducing transcapillary

filtration i.e. albumin as the main plasma volume expander.

Dihydroergotamine to reduce venous intracranial blood volume at significantly RICP

(no longer used due to decompressive craniotomy being more effective)

Blood volume expandersBlood volume expanders A ↓ blood volume -> ? too low for adequate cerebral perfusion, especially in penumbra zone

Emphasis on avoiding hypovolemia-induced activation of the baroreceptor reflex

Conventional guidelines have risk from concealed hypovolemia.

Crystalloids not used b/c general tissue oedema (injured brain with a disrupted BBB)

Albumin (? 20% solution) due to its more effective absorbing effect beneficial to ↓ interstitial volume for both injured brain and rest of the body.

Slow infusion rate of colloid results for longer effect

Hence relatively low arterial pressures, avoidance of vasopressors, maintenance of relatively normal Hb (transfuse upto Hb 120 for oxygenation/blood volume) physiotherapy to stimulate the lymphatic drainage system,

All reduce plasma leakage and the need for plasma volume expanders. albumin compared with saline trial ? explained by ↑ plasma leakage of albumin from

vasopressors

To improve perfusion…To improve perfusion… Perfusion depends on pressure & resistance.

Brain: a relatively low CPP can be compensated by an optimal fluid therapy.

Confirmed by a microdialysis study on TBI pts treated by Lund concept This study showed improved oxygenation, greater blood flow, and less tissue degradation,

despite reduced arterial pressure with antihypertensive therapy, by measurement of the interstitial lactate/puruvate ratio, glycerol, glucose, and glutamate in the penumbra zone.

The results can be explained by avoidance of noradrenalin-induced vasoconstriction and plasma leakage and by avoidance of low hemoglobin concentrations.

These data support the view that adequate blood volume is more important for oxygenation of the penumbra zone than high CPP.

CPP stays in the range of 60 to 70mm Hg in most adult patients treated with the Lund therapy

Can accept a minimum CPP of 50mmHg if otherwise optimal fluid therapy CPP values down to 38-40mm Hg are accepted in small children.

OsmotherapyOsmotherapy

Not used lack of scientific and physiological support documented side effects.

ICP-reducing effect is transient mannitol and urea often has rebound increase in

ICP some hours after the infusion aggravating the brain edema.

Mannitol may also be associated with renal insufficiency and severe electrolyte disturbances.

Exception: Osmotherapy, especially HTS maybe for acute

control (ED/ambulance)

Lung functionLung function The Lund concept includes some specific lung-protective measures

Vasoconstrictors and high-dose barbiturate therapy are associated with pulmonary complications in terms of ARDS, pneumonia, and high fever - better

Positive end expiratory pressure (PEEP) is used extensively reduce atelectasis controversial in head-injured patients due to the potential risk of increasing ICP by an

increase in venous pressure. Experimentally shown that brain in rigid shell- variable passive venous outflow

resistance, provided that the tissue pressure is above the venous pressure outside the shell

hence moderate PEEP (5 to 8 cm H2O) is safe. Inhalations and moderate bagging (under ICP control) are other lung protecting

measures recommended in the Lund therapy.

Avoid crystalloids - plasma volume expanders may ↓ risk of lung oedema.

Severe ARDS is very rare in patients with an isolated head injury who are treated according to the Lund concept.

Hyperventilation is not used due to aggravation of hypoxia in the penumbra zone

Anti stress therapyAnti stress therapy

Barbituates decrease ICP by decreasing cerebral metabolism, CMRO2 and hence CBF and CBV

Wake-up tests are not used due to stress effects (results in ↑ICP) and release of catecholamines (may reduce brain perfusion)

Heavy sedation midazolam and analgetics in combination with clonidine sometimes short-term treatment with a low dose of pentobarbital

Sedatives continued until ICP stabilized at a normal level and until weaning from the ventilator will be successful.

A beneficial effect of this sedation regime is the lack of epileptic seizures, which means that there is no indication of prophylactic anticonvulsary treatment.

TemperatureTemperature

Fever stimulates cerebral metabolism and induces vasodilation

Active cooling not used potential side effects inherent in the significant stress and

catecholamine release risk of reducing cerebral circulation of the penumbra zone. The Lund therapy involves treatment of high fever

pharmacologically Steroids (methylprednisolone)

Controversial due to SE’s (adrenal suppression, effects on catecholamine synthesis, decrease NO production->?vasoconstriction)

CRASH trial showed adverse outcome with high dose steroids

Drainage of Drainage of CSF/decompressive craniotomyCSF/decompressive craniotomy Drainage of CSF ↑ transcapillary pressure in the brain due to ↓ tissue pressure

inducing filtration.

Loss of CSF volume ->replaced by more oedema with risk of ventricular collapse.

The risk can be reduced if the drainage is performed from a relatively high pressure level and if ventricular volumes are evaluated by computed tomography controls.

Under such circumstances, CSF drainage is accepted in the Lund concept to control a raised ICP (only through ventricular drainage), especially if there are signs of hydrocephalus.

Decompressive surgery in terms of craniotomy and evacuation of hematomas and available contusions are options in the Lund therapy.

lack of studies -> decompressive craniotomy is controversial SE of craniotomy is strangulation in the cranial opening due to herniation. As the protuberance at least partly can be explained by transcapillary filtration

due to loss of counter pressure in the cranial opening, antihypertensive treatment, and a relatively low CPP, in combination with normal plasma oncotic pressure, as favored in the Lund concept, may reduce adverse effects of craniotomy.

Decompressive craniotomy is the last therapeutic measure to prevent brain stem herniation in Lund therapy

Other controversiesOther controversies

Prostacyclin to improve microcirculation has been recently addedProstacyclin to improve microcirculation has been recently added

General quality of care has improvedGeneral quality of care has improved

Local variations in tissue pressure and hence perfusion pressureLocal variations in tissue pressure and hence perfusion pressure Maybe the injured areas needs a higher CPP, but achieving this Maybe the injured areas needs a higher CPP, but achieving this

results in oedema….results in oedema….

Reducing catecholamines may prevent their escape across BBB Reducing catecholamines may prevent their escape across BBB which increased cerebral metabolism and O2 consumptionwhich increased cerebral metabolism and O2 consumption

Is oncotic pressure as important as Lund therapy emphasisesIs oncotic pressure as important as Lund therapy emphasises

Summary:Summary:

Basic concept is normalisation of Basic concept is normalisation of various parametersvarious parameters fluid therapy, Hb lung protection temperature control Potentially:

cerebrospinal fluid (CSF) drainage decompressive craniotomy

Other Normalisation of PaO2, PaCO2, enteral nutrition, avoidance

of overnutrition

From APIC volume 2, (Antonino Gullo)From APIC volume 2, (Antonino Gullo)

Goal Target Intervention

Decreased capillary hydrostatic pressure

CPP 60-70mmHg Metoprolol, clonidine, dihydroergotamine

Reduce cerebral blood volume

ICP <25mmHg Thiopentone, dihydroergtamine

Reduce CMRO2 and stress response

Sedation and analgesia

BDZ, fentanyl, thiopentone

Maintain blood volume and colloid osmotic pressure

Normal Hb, albumin, equal fluid balance

Albumin, frusemide, blood, nutrition

Intermittent CSF drainage

ICP <25mmHg EVD

Our current protocol…

Maintain cerebral perfusion pressure (CPP) > 60 mmHg using noradrenaline regardless of ICP. Ensure normovolaemia eg. CVP 8-12 mmHg and/or Δdown < 5 mmHg Maintain Hb close to 100g/l. Maintain pO2 > 100 mmHg (check ABG if SpO2 < 98%) &Maintain pCO2 36-40 mmHg. Monitor ETCO2. continuously if an Evita ventilator with capnography is available. Aim for

ETCO2 30-35 mmHg Sedation 7-14 mls/hr of standard M&M for a 70kg patient. Nurse 20-30o head up – tilt the whole bed if the spine has not been cleared. Ensure that ETT tapes are not causing jugular venous obstruction. Control BSL as per unit protocol. Monitor temperature continuously aiming for normothermia. Give paracetamol if T >

37.5oC More aggressive maintenance of normothermia with ice can be used at the discretion of

the duty intensivist Saline or Hartmann’s should be used as maintenance fluid aiming for Na+ > 140 mmol/l. Do not use dextrose solutions.

General Early enteral nutrition as per ICU protocol. Stress ulcer prophylaxis – ranitidine 50mg tds IV. DVT prophylaxis as per ICU protocol. TEDs and calf compressors initially, Frequent position changes and chest physiotherapy. Bowel care as per unit protocol.

Our current protocol

Intracranial hypertension needs to be treated when ICP > 20-25mmHg for greater than 5 minutes. Aim to “control” ICP < 20 mmHg ideally.

ALL PATIENTS:- Ensure basic management measures are in place as above. Ensure that CPP is maintained > 60 mmHg with noradrenaline.

Optimise sedation. morphine/midazolam. Bolus of muscle relaxant Ensure normothermia.

Osmotherapy: Mannitol: If Na+ < 155 mmol/l and CVP > 12 mmHg HTS: If Na+ < 155 mmol/l and CVP < 12 mmHg, give 30ml of 23.4% saline Expect a decrease in ICP within 20-30 minutes. Repeat CT scan to exclude a surgically remediable lesion and generally

follow the evolution of the injury.

Would I recommend it…Would I recommend it…

Physiologically, it makes sensePhysiologically, it makes sense But without adequate evidence and But without adequate evidence and

general lack of use elsewhere…general lack of use elsewhere…