Transcript The-Lund-Concept

The Lund Concept
Does ICP really matter ….
(or rather who cares about ICP anyway)
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 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.
Term - normal ICP 1.5-6 mmHg
Young children 3-7 mmHg
Adults
 observational studies: ICP 20-25 mmHg -> much poorer outcome from TBI
The evidence is even more limited in children, but generally:
 Infants <15 mmHg
 Younger children <18 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 50150mmHg.

>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 of

Recent Chinese study

68 patients, GCS 3-8, severe HI
30 had The Lund Concept….
 Looked at 28 day mortality


Roughly 30% vs 60% (p<0.01)
Evidence… or lack of

Newcastle Uni – UK,… 2011 Critical care

MA Hamdan1, K Dizdarevic2, 1Newcastle University,
Newcastle upon Tyne, UK; 2Clinical Centre University
of Sarajevo, Sarajevo, Bosnia and Herzegovina,
Critical Care 2011, 15(Suppl 1):P342 (doi:
10.1186/cc9762)

60 patients – positive, p=0.03
Concept

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
Mx



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….


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 vessel

Note


slow process taking several hours
Vasoconstrictors –

↑ BP but also SE’s like




ARDS and
↑ leakage of plasma -> hypovolemia and general tissue
oedema;
inotropes like dobutamine cause cerebral vasodilation…)
(Lund patients don’t get these problems
as much…..)
The Lund concept… ICP

Accept a lower CPP than the initial recommended 70mm Hg -> avoids
vasopressors.

Antihypertensive treatment



Normalization of reduced Ponc may counteract filtration in brain



b-1 blockade, a-2 agonists, and ARB’s to counteract oedema
Fluid therapy given in the Lund concept -> CPP will stay acceptable
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 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…

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.
Osmotherapy

Not used



ICP-reducing effect is transient



lack of scientific and physiological support
documented side effects.
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 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 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.
Temperature


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 CSF/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 controversies

Prostacyclin to improve microcirculation has been recently added

General quality of care has improved



Local variations in tissue pressure and hence perfusion pressure
 Maybe the injured areas needs a higher CPP, but achieving this
results in oedema….
Reducing catecholamines may prevent their escape across BBB
which increased cerebral metabolism and O2 consumption
Is oncotic pressure as important as Lund therapy emphasises
Summary:

Basic concept is normalisation of various
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)
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 3035 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…


Physiologically, it makes sense
But without adequate evidence and
general lack of use elsewhere…