The Lund Concept

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The Lund Concept

• Does ICP really matter .
• (or rather who cares about ICP anyway)

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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).

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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.

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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 lt 100120 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

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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

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Hows 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.

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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 gt
  22mmHg and then it decreases.

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The balance

• CSF formation and reabsorption is in equilibrium.
• BUT if ICP increases so much that CPP is lt70mmHg
  then CSF formation decreases.
• If ICPlt7mmHg then minimal reabsorption occurs
• CSF reabsorption is linear from 7-70mmHg

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• 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 -gt much
  poorer outcome from TBI
• The evidence is even more limited in children,
  but generally
• Infants lt15 mmHg
• Younger children lt18 mmHg
• Older children lt20 mmHg.

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Some physiology.

• Cerebral function is totally dependent on
  oxidative phosphorylation
• glucose -gt 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

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Whats autoregulation

• Autoregulation - phenomenon where CBF is kept
  constant over a MAP of 50-150mmHg.
• gt150mmHg, 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 lt50mmHg 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.

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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.

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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 ( pc )
• Interstitial oncotic pressure ( pi )
• Filtration coefficient ( Kf )
• Reflection coefficient ( s )

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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 (plt0.01)

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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, p0.03

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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

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Mx

• Alternatively,
• RICP -gtreduction 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

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Mx.

• TREATMENT OF ICP
• ? high CPP -gt 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.

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• 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 ? -gt partly transferred to capillaries with
  ? Pc and further filtration, etc
• -gt new steady state
• Hence ICP ? gtgt initial increase in Pc or decrease
  in Ponc that started the filtration.
• filtration -gt ?? ICP than increase in Pc or
  decrease in Ponc, triggering the filtration.
• Hence, ? ICP gtgt ? Pc and ?Ponc -gt triggers ? ICP

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Passise venous resistance vessel

• Note
• slow process taking several hours
• Vasoconstrictors
• ? BP but also SEs like
• ARDS and
• ? leakage of plasma -gt hypovolemia and general
  tissue oedema
• inotropes like dobutamine cause cerebral
  vasodilation)
• (Lund patients dont get these problems as
  much..)

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The Lund concept ICP

• Accept a lower CPP than the initial recommended
  70mm Hg -gt avoids vasopressors.
• Antihypertensive treatment
• b-1 blockade, a-2 agonists, and ARBs to
  counteract oedema
• Fluid therapy given in the Lund concept -gt 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)

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Blood volume expanders

• A ? blood volume -gt ? 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,

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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.

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Osmotherapy

• 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)

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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

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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.

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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 SEs (adrenal suppression,
  effects on catecholamine synthesis, decrease NO
  production-gt?vasoconstriction)
• CRASH trial showed adverse outcome with high dose
  steroids

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Drainage of CSF/decompressive craniotomy

• Drainage of CSF ? transcapillary pressure in the
  brain due to ? tissue pressure inducing
  filtration.
• Loss of CSF volume -gtreplaced 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 -gt 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

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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

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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

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From APIC volume 2, (Antonino Gullo)
Goal Target Intervention
Decreased capillary hydrostatic pressure CPP 60-70mmHg Metoprolol, clonidine, dihydroergotamine
Reduce cerebral blood volume ICP lt25mmHg 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 lt25mmHg EVD
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Our current protocol

• Maintain cerebral perfusion pressure (CPP) gt 60
  mmHg using noradrenaline regardless of ICP.
• Ensure normovolaemia eg. CVP 8-12 mmHg and/or
  ?down lt 5 mmHg
• Maintain Hb close to 100g/l.
• Maintain pO2 gt 100 mmHg (check ABG if SpO2 lt 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 MM 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 gt 37.5oC
• More aggressive maintenance of normothermia with
  ice can be used at the discretion of the duty
  intensivist
• Saline or Hartmanns should be used as
  maintenance fluid aiming for Na gt 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,

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Our current protocol

• Intracranial hypertension needs to be treated
  when ICP gt 20-25mmHg for greater than 5 minutes.
  Aim to control ICP lt 20 mmHg ideally.
• ALL PATIENTS-
• Ensure basic management measures are in place as
  above.
• Ensure that CPP is maintained gt 60 mmHg with
  noradrenaline.
• Optimise sedation.
• morphine/midazolam.
• Bolus of muscle relaxant
• Ensure normothermia.
• Osmotherapy
• Mannitol If Na lt 155 mmol/l and CVP gt 12 mmHg
• HTS If Na lt 155 mmol/l and CVP lt 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.

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Would I recommend it

• Physiologically, it makes sense
• But without adequate evidence and general lack of
  use elsewhere