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![CPPopt
As a target for therapy
TIL Sub-Category Intervention
Positioning Head elevation for ICP control
Nursed flat (180o) for CPP management
Sedation Level Sedation (low-dose as required for mechanical ventilation)
Higher-dose sedation for ICP control (not aiming for burst suppression)
Metabolic suppression for ICP control with high-dose barbiturates or propofol
NMBA Neuromuscular blockade (paralysis)
CSF Drainage CSF drainage < 120 mL/d (<5 mL/h)
CSF drainage ≤ 120 mL/d (≤5 mL/h)
Fluid/Vasopressor Therapy Fluid loading for maintenance of cerebral perfusion
Vasopressor therapy required for management of cerebral perfusion
Hyperventilation Mild hypocapnia for ICP control (PaCO2 4.6–5.3 kPa [35–40 mm Hg])
Moderate hypocapnia for ICP control (PaCO2 ≤ 4 kPa [30 mm Hg])
Intensive hypocapnia for ICP control (PaCO2 < 4 kPa [30 mm Hg])
Hyperosmolar Therapy Hyperosmolar therapy with mannitol up to 2 gm/kg/24 h
Hyperosmolar therapy with hypertonic saline up to 0.3 gm/kg/24 h
Hyperosmolar therapy with mannitol > 2 gm/kg/24 h
Hyperosmolar therapy with hypertonic saline > 0.3 gm/kg/24 h
Temperature Management Treatment of fever (>38C) or spontaneous temperature of 34.5C
Mild hypothermia for ICP control with a lower limit of 35C
Hypothermia below 35C
Surgery for ICP Control Intracranial operation for progressive mass lesion, not scheduled on admission
Decompressive craniectomy](https://image.slidesharecdn.com/cppopt-redux-230711064757-7069f5ad/75/Optimal-Cerebral-Perfusion-Pressure-40-2048.jpg)
![CPPopt
As a target for therapy
TIL Sub-Category Intervention
Positioning Head elevation for ICP control
Nursed flat (180o) for CPP management
Sedation Level Sedation (low-dose as required for mechanical ventilation)
Higher-dose sedation for ICP control (not aiming for burst suppression)
Metabolic suppression for ICP control with high-dose barbiturates or propofol
NMBA Neuromuscular blockade (paralysis)
CSF Drainage CSF drainage < 120 mL/d (<5 mL/h)
CSF drainage ≤ 120 mL/d (≤5 mL/h)
Fluid/Vasopressor Therapy Fluid loading for maintenance of cerebral perfusion
Vasopressor therapy required for management of cerebral perfusion
Hyperventilation Mild hypocapnia for ICP control (PaCO2 4.6–5.3 kPa [35–40 mm Hg])
Moderate hypocapnia for ICP control (PaCO2 ≤ 4 kPa [30 mm Hg])
Intensive hypocapnia for ICP control (PaCO2 < 4 kPa [30 mm Hg])
Hyperosmolar Therapy Hyperosmolar therapy with mannitol up to 2 gm/kg/24 h
Hyperosmolar therapy with hypertonic saline up to 0.3 gm/kg/24 h
Hyperosmolar therapy with mannitol > 2 gm/kg/24 h
Hyperosmolar therapy with hypertonic saline > 0.3 gm/kg/24 h
Temperature Management Treatment of fever (>38C) or spontaneous temperature of 34.5C
Mild hypothermia for ICP control with a lower limit of 35C
Hypothermia below 35C
Surgery for ICP Control Intracranial operation for progressive mass lesion, not scheduled on admission
Decompressive craniectomy](https://image.slidesharecdn.com/cppopt-redux-230711064757-7069f5ad/75/Optimal-Cerebral-Perfusion-Pressure-43-2048.jpg)
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Optimal Cerebral Perfusion Pressure
The document discusses key concepts regarding cerebral perfusion pressure (CPP) and intracranial pressure (ICP) management in patients with traumatic brain injury (TBI), following the Brain Trauma Foundation guidelines. It highlights the importance of maintaining specific CPP and ICP levels, the relationship between CPP and ICP, and various treatment options and monitoring techniques, including vasopressor therapy and advanced technology use. The document also emphasizes the need for further research and clinical trials to optimize treatment approaches for TBI patients.
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Optimal Cerebral Perfusion Pressure
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- 2. CPP Key concepts • ICP •CPP = MAP - ICP • Monro-Kellie doctrine: ✴ Blood + CSF + Brain = constant ✴ CSF provides a mechanical buffer
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- 7. CPP Cerebral auto-regulation -in wakefulness • Neurovascular coupling • Tightly regulated - demand driven • Blood flow linked to function and can be visualised with fMRI, PET, XeCT - applications in psychology, functional neurosurgery, neuropsychiatry, research • Active brain draws blood
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- 10. CPP and theBTF guidelines Current TBI practice • In severe TBI intubate - GCS 3-8, protect airway, control CO2, avoid hypoxia • Evacuate mass lesions • Abnormal CT - ICP monitoring whether by monitor or EVD • Osmotherapy (HTS vs Mannitol) • Propofol, opioid • Treat seizures
- 11. Current TBI practice- don’t: • Prophylactic decompression • Prophylactic hypothermia • Steroids • Early barbituates • Allow sodium abnormalities • ? Prophylactic AED (except in some circumstances) • ? Paralysis CPP and the BTF guidelines
- 12. Current practice • MAP> 65 • ICP < 22mmHg (poor outcome is associated with level above this) • CPP > 60-70mmHg - or 50-70mmHg (BTF) • Where do we put the transducer? How we measure MAP matters! CPP and the BTF guidelines
- 13. CPP Current practice Hawryluk, G.W.J.,Aguilera, S., Buki, A. et al. A management algorithm for patients with intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC). Intensive Care Med 45, 1783–1794 (2019).
- 14. CPP Current practice Hawryluk, G.W.J.,Aguilera, S., Buki, A. et al. A management algorithm for patients with intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC). Intensive Care Med 45, 1783–1794 (2019).
- 15. CPPopt DR MARK WEEDEN STGEORGE ICU
- 16. CPPopt Clinical scenario • 33M,D4 ICU, otherwise well • MBA, GCS 4 (M2) pre intubation (BP ok) • Isolated TBI - traumatic SAH, spine ok • EVD at 10cm H2O • MAP 80, ICP 21 mmHg • CTB 1 hour ago • ICP waveform over last hours: DOI: 10.3171/2017.11.JNS171892
- 17. CPPopt ICP wave morphology4 hours ago (top) vs now (bottom)
- 18. CPPopt Clinical scenario • 33M,D4 ICU, otherwise well • MBA, GCS 4 (M2) pre intubation (BP ok) • Isolated TBI - traumatic SAH, spine ok • EVD at 10cm H2O • MAP 80, ICP 21 mmHg • What therapies would you expect? DOI: 10.3171/2017.11.JNS171892
- 19. CPPopt Clinical scenario • Propofol250mg/hr, Fentanyl 250microg/hr, Midazolam 20mg/hr • Head up 30°, temp 35.5 (actively cooled) • pCO2 35mmHg • Na 156mmol/L • Noradrenaline 17mcg/min • Nurse comes to you and wants assistance with a roll and tells you that need to suction the ETT • Anything else we should do? DOI: 10.3171/2017.11.JNS171892
- 20. CPPopt • Are ICPand MAP independent of one another? CPP = MAP - ICP • What would happen over the next half hour if we increased the noradrenaline so that the MAP increased from 80 to 86mmHg?
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- 23. CPPopt The MAP challenge •Single centre observational cohort study of all patients admitted to the ICU with TBI and ICP monitoring • Decompressive craniectomies excluded • ‘Event’: ≥100 min.mmHg in the 15-min period after increase of IV vasopressors to achieve a desired CPP (average rise of 6.7mmHg) • Changes in ICP burden measured using ICM+ DOI: 10.3171/2017.11.JNS171892
- 24. CPPopt The MAP challenge •122 ‘events’ ultimately included • 13 patients DOI: 10.3171/2017.11.JNS171892
- 25. CPPopt The MAP challenge •65% net negative ICP burden - median - 36.5min.mmHg over 15 mins • 35% had a median increase of 13.9min.mmHg in first 15min • ICP burden between 15-30min generally trended in the same direction as the first DOI: 10.3171/2017.11.JNS171892
- 26. CPPopt The MAP challenge •RAC: Moving correlation coefficient between ICP pulse amplitude and pressure CPP DOI: 10.3171/2017.11.JNS171892 • PRx: Moving correlation coefficient between ICP and MAP
- 27. CPPopt Clinical scenario • Propofol250mg/hr, Fentanyl 250microg/hr, Midazolam 20mg/hr • Head up 30°, temp 35.5 (actively cooled) • pCO2 35mmHg • Na 156mmol/L • Noradrenaline 17mcg/min • MAP 80, ICP 21mmHg • Anything else we could do? DOI: 10.3171/2017.11.JNS171892
- 28. CPPopt Clinical scenario • Wetry a MAP challenge: • Noradrenaline to 17 -> 23mcg/min • MAP increases from 80 -> 87mmHg • 15 mins later ICP 21 -> 20mmHg • 30 mins later ICP 21 -> 18mmHg • It’s Monday 8am. …Now what? DOI: 10.3171/2017.11.JNS171892
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- 30. CPPopt SIBICC guidelines Similar butnot identical to BOOST III and BONANZA TRIAL
- 31. CPPopt PRx • What ifwe did a series of MAP challenges (or even just let the MAP passively drift) and watched the ICP changes? • Then plot them against each other? • And work out a correlation coefficient
- 32. CPPopt Underlying hypothesis • CPPtoo low -> cerebral vasodilation - hyperaemia -> raised ICP • CPP too high -> cerebral oedema -> raised ICP • This relationship is likely to vary across time with the phase of illness
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- 34. CPPopt PRx - thePearson correlation co-efficient https://en.wikipedia.org/wiki/Pearson_correlation_coefficient https://en.wikipedia.org/wiki/Pearson_correlation_coefficient
- 35. CPPopt PRx • PRx isthe moving correlation co-efficient between MAP and ICP • When PRx is least - ICP is least determined by MAP • And hence maximally determined by other factors • It turns out this is how you can measure cerebral auto regulation • The CPP at which PRx is least is termed CPPopt • This is when cerebral auto regulation is most active (the least passive)
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- 38. CPPopt History • Pressure reactivityindex (PRx) described in 1997 • CPPopt in 2002 - 20 years ago! • Developed by the “brain physics” department in Cambridge, Neurosurgeons, and nascent Neurocritical Care Unit. • COGiTATE - the first (pilot) RCT published 2021
- 39. CPPopt As a targetfor therapy • PRx > 0.25 is associated in multiple cohorts with poor neurological outcomes and death • Does anything we do change it? • Is it a therapeutic target and if so does it affect outcomes?
- 40. CPPopt As a targetfor therapy TIL Sub-Category Intervention Positioning Head elevation for ICP control Nursed flat (180o) for CPP management Sedation Level Sedation (low-dose as required for mechanical ventilation) Higher-dose sedation for ICP control (not aiming for burst suppression) Metabolic suppression for ICP control with high-dose barbiturates or propofol NMBA Neuromuscular blockade (paralysis) CSF Drainage CSF drainage < 120 mL/d (<5 mL/h) CSF drainage ≤ 120 mL/d (≤5 mL/h) Fluid/Vasopressor Therapy Fluid loading for maintenance of cerebral perfusion Vasopressor therapy required for management of cerebral perfusion Hyperventilation Mild hypocapnia for ICP control (PaCO2 4.6–5.3 kPa [35–40 mm Hg]) Moderate hypocapnia for ICP control (PaCO2 ≤ 4 kPa [30 mm Hg]) Intensive hypocapnia for ICP control (PaCO2 < 4 kPa [30 mm Hg]) Hyperosmolar Therapy Hyperosmolar therapy with mannitol up to 2 gm/kg/24 h Hyperosmolar therapy with hypertonic saline up to 0.3 gm/kg/24 h Hyperosmolar therapy with mannitol > 2 gm/kg/24 h Hyperosmolar therapy with hypertonic saline > 0.3 gm/kg/24 h Temperature Management Treatment of fever (>38C) or spontaneous temperature of 34.5C Mild hypothermia for ICP control with a lower limit of 35C Hypothermia below 35C Surgery for ICP Control Intracranial operation for progressive mass lesion, not scheduled on admission Decompressive craniectomy
- 41. CPPopt As a targetfor therapy
- 42. CPPopt Underlying hypothesis • CENTER-TBIstudy: Prospective observational cohort study • PRx mapped against semi-quantitative “treatment intensity” • 249 patients • Assocated with small improvements in PRx: • Mild hyperventilation, • Mild hypothermia, • High levels of sedation for ICP control, • Vasopressor use for CPP target
- 43. CPPopt As a targetfor therapy TIL Sub-Category Intervention Positioning Head elevation for ICP control Nursed flat (180o) for CPP management Sedation Level Sedation (low-dose as required for mechanical ventilation) Higher-dose sedation for ICP control (not aiming for burst suppression) Metabolic suppression for ICP control with high-dose barbiturates or propofol NMBA Neuromuscular blockade (paralysis) CSF Drainage CSF drainage < 120 mL/d (<5 mL/h) CSF drainage ≤ 120 mL/d (≤5 mL/h) Fluid/Vasopressor Therapy Fluid loading for maintenance of cerebral perfusion Vasopressor therapy required for management of cerebral perfusion Hyperventilation Mild hypocapnia for ICP control (PaCO2 4.6–5.3 kPa [35–40 mm Hg]) Moderate hypocapnia for ICP control (PaCO2 ≤ 4 kPa [30 mm Hg]) Intensive hypocapnia for ICP control (PaCO2 < 4 kPa [30 mm Hg]) Hyperosmolar Therapy Hyperosmolar therapy with mannitol up to 2 gm/kg/24 h Hyperosmolar therapy with hypertonic saline up to 0.3 gm/kg/24 h Hyperosmolar therapy with mannitol > 2 gm/kg/24 h Hyperosmolar therapy with hypertonic saline > 0.3 gm/kg/24 h Temperature Management Treatment of fever (>38C) or spontaneous temperature of 34.5C Mild hypothermia for ICP control with a lower limit of 35C Hypothermia below 35C Surgery for ICP Control Intracranial operation for progressive mass lesion, not scheduled on admission Decompressive craniectomy
- 44. CPPopt PRx as atarget for therapy • What about differential effects of vasopressors on PRx/CPPopt? Vasopressin, Angiotensin II, adrenaline, dexmedetomidine… • How about ketamine? • Other agents like glibenclamide, neurokinin 1 receptor antagonists, remimazolam…?
- 45. CPPopt SIBICC guidelines • LiCOXprobe + temperature • NIRS Cerebral oximetry • Cerebral microdialysis • Cerebral thermal diffusion • Continuous (spectrographic) EEG monitoring • Jugular venous saturations • MMM monitoring • AI prediction
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- 48. CPPopt & Brain tissue oxygen •A multi-centre retrospective cohort study using the Canadian TBI registry • Inclusion criteria were TBI with ICP and PbtO2 probe • 77 patients, 260 days of data • Collected 2011-2021
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- 50. CPPopt & Brain tissue oxygen PRx:> 0.25 vs < 0.25
- 51. CPPopt & Brain tissue oxygen PRx:> 0.25 vs < 0.25
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- 54. CPPopt & Brain tissue oxygen Doestargeting CPPopt, at least partially obviate the tier 1 & 2 therapies?
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- 56. CPPopt • Enrolled/Randomised within24 hours of ICU admission • Excluded - decompression + expected to die • Pilot study - enrolled 60 patients • Powered for 20% increase in time spent within 5mmHg of CPPopt COGiTATE
- 57. CPPopt • Control: 60-70mmHg •Intervention: ICM+ guided CPP - adjusted 4 hourly • CPP achieved as per clinician preference • Enrolled for up to 5 days COGiTATE
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- 63. CPPopt COGiTATE • Favourable outcome: OR2.35 (95%-CI 0.9 – 6.12), p=0.08) • A larger trial is warranted!
- 64. CPPopt COGiTATE • Is theputative difference due to differences in CPP? • Where does the arterial transducer go? • Should we aim at the upper end of the CPP target range?
- 65. CPPopt Guidelines • 4th edition(2016) of brain trauma foundation guidelines - insufficient evidence to make a reccomendation • COGiTATE subsequently released • Worth acknowledging that there are considerable knowledge gaps in this field
Editor's Notes
- #3 ICP - what is normal? 5-15 - varies wildly with posture and straining? how can we measure? idiopathic intracranial hypertension - 60
- #4 Monro-Kellie - Monro 1783 - Kellie Scottish Neurosurgeons from Edinburgh Doesn’t work in infants -> How do we measure ICP, MAP, CPP?
- #5 MAP - where do we put the transducer? BTF: RA/Phlebostatic axis - European: Tragus - 10mmHg at 30 deg head up.
- #6 MAP - where do we put the transducer? BTF: RA/Phlebostatic axis - European: Tragus - 10mmHg at 30 deg head up.
- #13 What MAP is required for CPP 70 if is ICP 22?
- #14 What MAP is required for CPP 70 if is ICP 22?
- #15 What MAP is required for CPP 70 if is ICP 22?
- #16 Questions?
- #17 Tight head \\
- #18 Tight head \\
- #19 Tight head \\
- #21 Two questions for the room
- #27 Lets return to our case
- #47 Which brings us to a brief excursion
- #59 Absence of slow arterial blood pressure waves (odds ratio, 2.7; p <0.001), higher pressure reactivity index values (odds ratio, 2.9; p <0.001), lower amount of sedative-analgesic drugs (odds ratio, 1.9; p = 0.03), higher vasoactive medication dose (odds ratio, 3.2; p = 0.02), no administration of maintenance neuromuscular blockers (odds ratio, 1.7; p <0.01), and following decompressive craniectomy (odds ratio, 1.8; p <0.01) were independently associated with optimal cerebral perfusion pressure curve absence.
- #60 Absence of slow arterial blood pressure waves (odds ratio, 2.7; p <0.001), higher pressure reactivity index values (odds ratio, 2.9; p <0.001), lower amount of sedative-analgesic drugs (odds ratio, 1.9; p = 0.03), higher vasoactive medication dose (odds ratio, 3.2; p = 0.02), no administration of maintenance neuromuscular blockers (odds ratio, 1.7; p <0.01), and following decompressive craniectomy (odds ratio, 1.8; p <0.01) were independently associated with optimal cerebral perfusion pressure curve absence.
- #64 moderate disability (GOS=4) and good recovery (GOS=5)
- #65 moderate disability (GOS=4) and good recovery (GOS=5)
- #66 Gaps: Optimal CPP, dysregulation of cerebral blood flow,