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© 2013 Neurocritical Care Society Practice Update

Multimodality Neuromonitoring

Mauro Oddo, MD Department of Intensive Care Medicine

Centre Hospitalier Universitaire Vaudois (CHUV) Lausanne University Hospital

CH-1011 Lausanne, Switzerland DEFINITION Monitor (from the latin verb monere = to warn) has, since the beginning, be an essential, constitutive, focus of critical care. Multimodality neuromonitoring has evolved in parallel with the introduction and constant development of modern neurocritical care. It defines the number of neuromonitoring tools – including intracranial pressure (ICP), brain tissue oxygen tension (PbtO2), cerebral microdialysis (CMD) and quantitative electroencephalography (qEEG) – that assist ICU physicians in the management of brain-injured patients. PATHOPHYSIOLOGY Multimodality neuromonitoring consists in the integration of cerebral physiological data derived from different devices (ICP, PbtO2, cerebral microdialysis, qEEG) [1]. It provides a comprehensive scrutiny of the injured human brain and allows an individualized management of secondary cerebral damage, targeted to patient-specific pathophysiology. As summarized in Table 1, secondary cerebral damage consists of a series of pathological events that occur in the early hours following the primary brain insult. Additional secondary systemic insults that can add further injury include

- hyperglycemia - hyperthermia - hypoxemia - hypocapnia - hypercapnia

Secondary cerebral and systemic insults compromise cerebral blood flow (CBF) and the delivery of oxygen and energy supply to the injured brain [2]. INDICATIONS Multimodality neuromonitoring has been mostly studied in patients with severe brain injury (mainly, TBI, SAH, intracerebral hemorrhage, stroke) with a GCS <9 and an abnormal brain CT scan (intra-parenchymal contusions/hemorrhages) in whom clinical examination is not reliable and who are at high risk for secondary cerebral damage, particularly elevated ICP, cerebral ischemia/hypoxia, energy dysfunction, non-convulsive seizures. Although still not supported by any randomized clinical trial these patients with severe brain injury may potentially benefit most from multimodality neuromonitoring. The objective of this review is to illustrate with practical clinical examples how the use of neuromonitoring tools might


help to prevent secondary cerebral damage and to identify optimal brain physiologic targets to provide adequate CBF, oxygen and energy supply in individual patients (individualized therapy) at the bedside in a timely way. DIAGNOSIS AND THERAPY The practical use of multimodality neuromonitoring is illustrated through a series of three cases which demonstrate various monitoring methods and how they may influence clinical care. CLINICAL CASE 1 The value of combined ICP/PbtO2 monitoring for the management of intracranial hypertension. The brain CT represented on the left panel of Figure 1 is obtained in a 24 year old man, at about 24 hours following a traumatic brain injury (TBI) secondary to a motor vehicle accident. The patient has a post-resuscitation Glasgow Coma Scale (GCS) of 6, bilaterally reactive pupils, no major extra-cranial injuries, and the CT-scan shows a right fronto-parietal hemorrhagic contusion. The diagnosis is that of a severe (GCS <9) with an abnormal brain CT (contusion). According to the Brain Trauma Foundation (BTF) guidelines [3], an ICP probe is inserted. A PbtO2 probe is also inserted at the same time [4]. Both probes are located into brain parenchyma, right side, around the contusion (visually normal brain). The CT scan on the left is performed at 5 PM, while ICP and PbtO2 are into normal ranges (ICP <20 mmHg, PbtO2>20 mmHg). In the following hours, sustained increased ICP >25 mmHg is observed, accompanied by simultaneous reductions of PbtO2 <15 mmHg. The ICP curve also shows reduced brain elastance (Figure 2, showing on the left an ICP curve of a patient with normal brain compliance [P1>P2] and on the right an ICP curve with pathologically reduced brain elastance [P1=/<P2] [5]). Therapy is initiated with deep sedation-analgesia, and mannitol is rapidly instituted, which improves ICP/PbtO2 only temporarily. A second brain CT is performed at 12PM (Figure 1, right panel) that shows a net increase of the hemorrhagic contusion. The diagnosis is that of a refractory elevated ICP secondary to a post-TBI contusion. Further surgical therapy (decompressive craniectomy) is decided which successfully reduces ICP and increase PbtO2 to normal ranges. The patient is discharged from ICU on day 6 and the final outcome at 6 months is a Glasgow Outcome Scale of 5 (complete recovery). Monitoring of ICP remains a cornerstone for patients with severe TBI, particularly if brain CT scan is abnormal (i.e. edema, midline shift, compressed basal cisterns, parenchymal lesions such as hemorrhagic contusions). Increased volumes could produce brain herniation and reduction of CBF and high ICP is related to increased disability and mortality [6]. Even if non-invasive evaluation, not monitoring, of high ICP is possible using transcranial doppler or optic nerve sonography, the only way for on-line continuous monitoring of ICP is invasive. Intra-ventricular and intra-parenchymal devices provide equivalent pressure measurements. Intra-ventricular probes allow cerebrospinal fluid drainage. ICP monitors are cost-effective and have an acceptably low complication rate, particularly if inserted in the brain parenchyma.


The recent BEST TRIP randomized control trial demonstrated equipoise in terms of major outcome endpoints (mortality and functional recovery) between an ICP monitoring-based management and a strategy based on clinical examination and repeated CT imaging without ICP monitoring. Another important result of the trial was that ICP monitoring was more efficient in guiding ICP therapy, since it reduced by 50% the number of ICP treatments administered per patient as well as the number of ICU days during which patients received TBI interventions [7]. There are numerous causes of elevated ICP [8] and different approaches to therapy [9]. The response to ICP therapy is an important determinant of final outcome: as in the case of the patient illustrated here, the effective reduction of ICP translated into good recovery. However, a subset of patients fails to respond to aggressive therapy and eventually has a poor outcome [10]. Careful evaluation of the effectiveness in reducing ICP allows better individual titration of therapy. The value of combining ICP with PbtO2 monitoring is underlined in this case. On-line measurement of PbtO2 is generally obtained via the insertion through multiple-lumen bolts of specialized probes in the sub-cortical white matter, adjacent to ICP monitors. Using ad hoc catheters for brain tunneling, PbtO2 can also be measured in penumbral tissue, such as around hemorrhagic contusions or in areas at risk for secondary delayed vasospasm/ischemia. The study by Rosenthal and colleagues demonstrates that PbtO2, or the partial pressure of oxygen in brain tissue, is a complex variable that reflects the product of CBF and cerebral arterio-venous oxygen tension difference [11]. The combination of elevated ICP with PbtO2 decrease <15 mmHg suggests reduced CBF and low CPP, and therefore secondary ischemia. It has been shown the combination of high ICP/low PbtO2 has a major impact on outcome, while at the contrary mildly elevated ICP (20-25 mmHg) with normal PbtO2 levels seems better tolerated and may not necessarily require aggressive therapy [12]. PbtO2 is useful to guide the management of intracranial hypertension, to select the time and the type of treatment and to monitor the effects of therapeutic interventions. CLINICAL CASE 2 The role of PbtO2 monitoring for the individualized management of CPP and cerebral ischemia. A 59 year old woman is admitted to the neuro ICU following a subarachnoid hemorrhage (SAH) due to a ruptured communicating artery aneurysm. She is Hunt&Hess 4 and the brain CT scan shows a Fisher grade IV. The aneurysm is clipped and a combined ICP-PbtO2 monitoring is placed in the right frontal brain parenchyma. On day 4 the patient still requires ICU and mechanical ventilation due to reduced GCS, and the clinical examination is unreliable due to sedation. ICP is normal. Since the beginning, PbtO2 shows a strong positive linear correlation with CPP (Figure 3: PbtO2 and CPP curves are shown o the left panel, while the on-line Pearson’s linear correlation coefficient R=0.74 between PbtO2and CPP is shown on the right panel). In this patient, CPP was maintained between >80 mmHg to avoid PbtO2<20 mmHg. Starting on day 4, “optimal” CPP (i.e. CPP level to maintain PbtO2>20


mmHg) increased to 80-90 mmHg, which was coupled with signs of symptomatic vasospasm on transcranial Doppler (TCD from day 4 to 5: increase in CBF velocities in the right middle cerebral artery from 95 to 135 cm/sec with increase in the Lindegaard ratio from 2.5 to 3.9). This prompted angio-CT and perfusion confirming severe vasospasm in the right middle cerebral artery. Therapy with euvolemic hemodynamic augmentation (with fluids and norepinephrine) and angioplasty was performed with eventually a good result (no infarcts on brain CT scan, patient had moderate disability). PbtO2 monitoring is useful to guide the management of CPP individually over time, particularly in comatose brain-injured patients at high risk for secondary cerebral ischemia and in whom clinical examination may not be reliable. Assessing the response or reactivity of PbtO2 to CPP/MAP increase allows tailoring the individual CPP threshold to avoid secondary cerebral ischemia, both in patients with poor grade SAH [13] and severe TBI [14], where optimal CPP can be found in up to 70% of patients. Also, using the moving linear correlation coefficient between PbtO2 and CPP (the so-called oxygen pressure reactivity index, ORx) allows to identify patients at particularly higher risk of developing delayed cerebral ischemia/infarcts after SAH [15], as illustrated by the case presented here, and can be helpful to target therapy (hemodynamic augmentation) at the bedside [16]. It is important to remind that although MAP/CPP are important determinants of PbtO2, other physiologic variables might affect PbtO2, including PaO2 [17], PaCO2 [18] and hemoglobin concentration [19,20]. As with ICP therapy, a stepwise management approach is also used for PbtO2 augmentation, MAP/CPP increase, respiratory manipulations and blood transfusions [21]. Given the large number of studies showing its safety and clinical utility, PbtO2 monitoring appears ready for implementation and to become part of routine multimodality neuromonitoring. However, practical issues are to be kept in mind. Particularly, significant differences in measured PbtO2 values can be observed when comparing the two main devices for routine monitoring (Licox®, Integra Neurosciences and Neurovent®, Raumedic), so these systems may not be used interchangeably. Although PbtO2 may be a good marker of CBF, it is influenced by other parameters and does not provide a direct measurement of CBF [11]. Recent advancement in technology allows direct measure of regional CBF (rCBF) via a Thermal Diffusion Probe (TDP Hemedex® Cambridge, Massachusetts) that can be inserted into brain parenchyma, generally next to ICP/PbtO2 probes. This technique is still not widely used, therefore will not be treated in details here. For further reading please consult our recent review on multimodality neuromonitoring [1]. Electroencephalography (EEG) is also emerging as a non-invasive tool to detect cerebral ischemia. The EEG or electroencephalogram has long been used to study the electrical activity of the cerebral cortex. In this standard approach, EEG shows brain electrical activity in the form of a line with repetitive wave-like activity. The classical indication of EEG is the detection of seizures and the prognostication of coma. A recent extensive review of the utility of EEG in the ICU has been published in Intensive Care Medicine journal [22]. This review summarizes current recommendations of EEG to detect non-convulsive seizures in patients with acute brain injury. All patients with protracted unexplained coma should undergo urgent EEG to rule out non-convulsive seizures.


In the last decade, a more advanced form of EEG has been developed, called quantitative EEG (qEEG), in which the raw EEG signal is converted to digital form using compressed

spectral array. Using the analysis of the variability in and power, it is possible to use qEEG for the prediction of delayed cerebral ischemia [23]. EEG-derived indices such as the alpha power or the alpha/delta ratio can be used to detect delayed cerebral ischemia in poor grade SAH and severe stroke patients. CLINICAL CASE 3 Monitoring of cerebral energy metabolism and supply in brain-injured patients. A young 24 year old woman is admitted to the ICU because of TBI following a fall from a horse. She has isolated TBI, with a post-resuscitation GCS of 6, bilaterally reactive pupils. The admission brain CT-scan shows a small epidural hematoma and two small frontal contusions. Monitoring with ICP, PbtO2 and cerebral microdialysis (CMD) is inserted (see 12-hour control brain CT scan, Figure 4) in the right frontal lobe. At 12 hours following TBI, ICP and PbtO2 are within normal ranges, but CMD shows reduced brain glucose <1 mmol/L (0.7 mmol/L). Arterial blood glucose concentration is 5.6 mmol/L, and the relationship between brain and blood glucose is shown in Figure 5. Enteral nutrition is rapidly instituted together with a slow infusion of hypertonic (10%) glucose. Blood glucose target is set at 7-8 mmol/L to avoid CMD glucose <0.8 mmol/L, and insulin infusion is withhold. At 48 hours, brain glucose shows progressive increase >1 mmol/L and the blood glucose target is set at >6 mmol/L. Sedation is withdrawn and the patient develops elevated ICP (20-25 mmHg) with no PbtO2 decrease (PbtO2 remains stable at 30 mmHg). Brain CT scan is repeated showing no lesion progression and absence of cerebral edema. In this case, elevated ICP was due to agitation and in the absence of PbtO2 decrease and pathological brain CT scan signs, no aggressive treatment of elevated ICP was considered. Progressive weaning of sedation coupled with clonidine and haloperidol to treat post-TBI agitation was introduced and the patient was eventually extubated on day 5. This patient well illustrates the value of multimodal neuromonitoring for individualized therapy of secondary cerebral damage. It also shows the potential importance of monitoring cerebral metabolism and the adequacy of energy supply in patients with severe brain injury. Cerebral microdialysis consists in the insertion of a specialized catheter tipped with a semi-permeable dialysis membrane, usually with a 20kDa cut-off, in the brain parenchyma. The CMD catheter is constantly perfused with a cerebrospinal fluid-like solution, thereby allowing regular (usually every 60 min) sampling of patient’s brain extracellular fluid into microvials and bedside analysis using manufacturer’s device [24]. Using CMD technology allows on-line monitoring of dynamic changes in patients’ neurochemistry. Neurochemical markers that demonstrated clinical utility for the management of secondary cerebral damage are glucose, lactate/pyruvate ratio (LPR), and glutamate. Thresholds of abnormalities are CMD glucose <(0.7)-1 mmol/L and LPR> 35-40. Increased glycolysis and glucose utilization is frequently observed in these patients [25], potentially leading to reduced availability of the main brain substrate, i.e. glucose [26].


Combined monitoring of CMD and blood glucose is particularly helpful for the management of insulin infusion in neurocritical care and allows individualization of optimal glucose targets [27,28]. Increase in LPR and glutamate has been used as a warning sign of delayed cerebral ischemia in patients with poor grade SAH [29,30]. The CMD technology can be used in combination with PbtO2 for the detection of delayed ischemia and to target blood pressure and transfusion requirement in patients with SAH [20,31,32]. In patients with TBI, elevated LPR was associated with poor neurological recovery in a large cohort study [33]. Although these studies show considerable advancement in terms of feasibility, implementation of CMD still requires some time and effort. CMD catheters can be inserted together with ICP and PbtO2 probes using a triple-lumen bolt. This option has some advantage, including reduced risk of catheter displacement. Alternatively, using the tunneling technique, the CMD catheter can be placed in selected areas, which is of particular value when therapy is aimed to attenuate secondary insults around tissue at risk. Catheter displacement or injury to catheter membrane however is more frequent. DOES MONITORING IMPROVE OUTCOME? By definition, a monitoring technique is not a therapeutic intervention and without interventions the natural course of an illness cannot be modified. Consequently, to provide benefit for monitoring, appropriate therapy should derive from the information acquired by the monitoring itself. Stein [6] reviewed four decade trials and case series in which patients were treated for severe closed TBI. Aggressive ICP monitoring and treatment of patients with severe TBI is associated with a statistically significant improvement in outcome. However, Chesnut and colleagues in a recent randomized multicenter trial showed that ICP monitoring did not change the outcome of patients with severe TBI [7]. Although PbtO2-directed therapy in some historical-control single-center studies was associated with better outcome [34], the issue remains controversial and no randomized studies have been confirmed this association so far. As demonstrated by past trials performed in the general ICU setting, monitoring per se may be insufficient to change patient prognosis substantially [35]. The same is likely to apply to brain multimodality monitoring. Monitoring does not mean effective therapy. Rather, monitoring, if appropriately interpreted and assisted by clinical experience, may help ICU physicians to provide adequate interventions and timely therapy. Recent clinical investigations by several independent groups show feasibility and utility of brain multimodality monitoring. The appropriate interpretation of brain physiological variables and the worldwide implementation of standardized management protocols driven by multimodal monitoring might offer optimal individualized therapy to brain-injured patients and may further improve overall prognosis and quality of care. REFERENCES 1. Oddo M, Villa F, Citerio G. Brain multimodality monitoring: an update. Curr Opin Crit

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2. Bouzat P, Sala N, Payen JF, Oddo M. Beyond intracranial pressure: optimization of cerebral blood flow, oxygen, and substrate delivery after traumatic brain injury. Ann Intensive Care. 2013;3:23.

3. Bratton SL, Chestnut RM, Ghajar J, et al. Guidelines for the management of severe traumatic brain injury. VI. Indications for intracranial pressure monitoring. J Neurotrauma. 2007;24 Suppl 1:S37-44.

4. Bratton SL, Chestnut RM, Ghajar J, et al. Guidelines for the management of severe traumatic brain injury. X. Brain oxygen monitoring and thresholds. J Neurotrauma. 2007;24 Suppl 1:S65-70.

5. Czosnyka M, Pickard JD. Monitoring and interpretation of intracranial pressure. J Neurol Neurosurg Psychiatry. 2004;75:813-21.

6. Stein SC, Georgoff P, Meghan S, Mirza KL, El Falaky OM. Relationship of aggressive monitoring and treatment to improved outcomes in severe traumatic brain injury. J Neurosurg. 2010;112:1105-12.

7. Chesnut RM, Temkin N, Carney N, et al. A trial of intracranial-pressure monitoring in traumatic brain injury. N Engl J Med. 2012;367:2471-81.

8. Li LM, Timofeev I, Czosnyka M, Hutchinson PJ. Review article: the surgical approach to the management of increased intracranial pressure after traumatic brain injury. Anesth Analg. 2010;111:736-48.

9. Schreckinger M, Marion DW. Contemporary management of traumatic intracranial hypertension: is there a role for therapeutic hypothermia? Neurocritical care. 2009;11:427-36.

10. Treggiari MM, Schutz N, Yanez ND, Romand JA. Role of intracranial pressure values and patterns in predicting outcome in traumatic brain injury: a systematic review. Neurocritical care. 2007;6:104-12.

11. Rosenthal G, Hemphill JC, 3rd, Sorani M, et al. Brain tissue oxygen tension is more indicative of oxygen diffusion than oxygen delivery and metabolism in patients with traumatic brain injury. Crit Care Med. 2008;36:1917-24.

12. Oddo M, Levine JM, Mackenzie L, et al. Brain hypoxia is associated with short-term outcome after severe traumatic brain injury independent of intracranial hypertension and low cerebral perfusion pressure. Neurosurgery. 2011.

13. Jaeger M, Schuhmann MU, Soehle M, Nagel C, Meixensberger J. Continuous monitoring of cerebrovascular autoregulation after subarachnoid hemorrhage by brain tissue oxygen pressure reactivity and its relation to delayed cerebral infarction. Stroke. 2007;38:981-6.

14. Jaeger M, Dengl M, Meixensberger J, Schuhmann MU. Effects of cerebrovascular pressure reactivity-guided optimization of cerebral perfusion pressure on brain tissue oxygenation after traumatic brain injury. Critical care medicine. 2010;38:1343-7.

15. Jaeger M, Soehle M, Schuhmann MU, Meixensberger J. Clinical significance of impaired cerebrovascular autoregulation after severe aneurysmal subarachnoid hemorrhage. Stroke. 2012;43:2097-101.

16. Muench E, Horn P, Bauhuf C, et al. Effects of hypervolemia and hypertension on regional cerebral blood flow, intracranial pressure, and brain tissue oxygenation after subarachnoid hemorrhage. Crit Care Med. 2007;35:1844-51; quiz 52.

17. Oddo M, Nduom E, Frangos S, et al. Acute lung injury is an independent risk factor for brain hypoxia after severe traumatic brain injury. Neurosurgery. 2010;67:338-44.


18. Rangel-Castilla L, Lara LR, Gopinath S, Swank PR, Valadka A, Robertson C. Cerebral hemodynamic effects of acute hyperoxia and hyperventilation after severe traumatic brain injury. J Neurotrauma. 2010;27:1853-63.

19. Oddo M, Levine JM, Kumar M, et al. Anemia and brain oxygen after severe traumatic brain injury. Intensive Care Med. 2012;38:1497-504.

20. Oddo M, Milby A, Chen I, et al. Hemoglobin Concentration and Cerebral Metabolism in Patients With Aneurysmal Subarachnoid Hemorrhage. Stroke. 2009.

21. Bohman LE, Heuer GG, Macyszyn L, et al. Medical management of compromised brain oxygen in patients with severe traumatic brain injury. Neurocritical care. 2011;14:361-9.

22. Claassen J, Taccone FS, Horn P, Holtkamp M, Stocchetti N, Oddo M. Recommendations on the use of EEG monitoring in critically ill patients: consensus statement from the neurointensive care section of the ESICM. Intensive Care Med. 2013;39:1337-51.

23. Foreman B, Claassen J. Quantitative EEG for the detection of brain ischemia. Crit Care. 2012;16:216.

24. Hillered L, Vespa PM, Hovda DA. Translational neurochemical research in acute human brain injury: the current status and potential future for cerebral microdialysis. J Neurotrauma. 2005;22:3-41.

25. Glenn TC, Kelly DF, Boscardin WJ, et al. Energy dysfunction as a predictor of outcome after moderate or severe head injury: indices of oxygen, glucose, and lactate metabolism. J Cereb Blood Flow Metab. 2003;23:1239-50.

26. Vespa PM, McArthur D, O'Phelan K, et al. Persistently low extracellular glucose correlates with poor outcome 6 months after human traumatic brain injury despite a lack of increased lactate: a microdialysis study. J Cereb Blood Flow Metab. 2003;23:865-77.

27. Oddo M, Schmidt JM, Carrera E, et al. Impact of tight glycemic control on cerebral glucose metabolism after severe brain injury: a microdialysis study. Crit Care Med. 2008;36:3233-8.

28. Vespa P, McArthur DL, Stein N, et al. Tight glycemic control increases metabolic distress in traumatic brain injury: a randomized controlled within-subjects trial. Crit Care Med. 2012;40:1923-9.

29. Sarrafzadeh A, Haux D, Sakowitz O, et al. Acute focal neurological deficits in aneurysmal subarachnoid hemorrhage: relation of clinical course, CT findings, and metabolite abnormalities monitored with bedside microdialysis. Stroke. 2003;34:1382-8.

30. Sarrafzadeh AS, Haux D, Ludemann L, et al. Cerebral ischemia in aneurysmal subarachnoid hemorrhage: a correlative microdialysis-PET study. Stroke. 2004;35:638-43.

31. Ko SB, Choi HA, Parikh G, et al. Multimodality monitoring for cerebral perfusion pressure optimization in comatose patients with intracerebral hemorrhage. Stroke. 2011;42:3087-92.

32. Schmidt JM, Ko SB, Helbok R, et al. Cerebral perfusion pressure thresholds for brain tissue hypoxia and metabolic crisis after poor-grade subarachnoid hemorrhage. Stroke. 2011;42:1351-6.

33. Timofeev I, Carpenter KL, Nortje J, et al. Cerebral extracellular chemistry and outcome following traumatic brain injury: a microdialysis study of 223 patients. Brain. 2011;134:484-94.

34. Nangunoori R, Maloney-Wilensky E, Stiefel M, et al. Brain tissue oxygen-based therapy and outcome after severe traumatic brain injury: a systematic literature review. Neurocritical care. 2012;17:131-8.


35. Ospina-Tascon GA, Cordioli RL, Vincent JL. What type of monitoring has been shown to improve outcomes in acutely ill patients? Intensive Care Med. 2008;34:800-20.


Table 1. Pathophysiology of secondary cerebral damage.

Main pathogenic mechanisms Potential clinical consequences

Brain edema Elevation of ICP Cerebral perfusion pressure (CPP) decrease Increased barriers to O2 diffusion brain tissue hypoxia

Impaired cerebro-vascular reactivity Increased susceptibility to secondary cerebral ischemia, limited tolerance to reduced CPP

Energy dysfunction, increased glucose utilization

Limited brain glucose availability, increased risk of cerebral glycopenia and metabolic distress

Non-convulsive seizures Increased ICP, increased cerebral metabolic distress


Figure 1. Brain CT-scan of a young adult at 12 hours after severe TBI. Neuroimaging shows the rapid progression of a post-traumatic right fronto-parietal contusion and illustrates clearly the role of ICP monitoring in detecting early intracranial hypertension and directing timely therapy (decompressive craniectomy in this case).

Figure 2. ICP curve showing normal brain compliance (left, P1 > P2) vs. impaired brain

compliance (right, P2 > P1). Not only the absolute value of ICP is important, but also the configuration of the ICP curve: on the right panel, the increase in the second component of the invasive ICP curve (P2=cerebral venous return) is a warning sign that the brain has poor compliance, and must prompt aggressive therapy of intracranial hypertension.


Figure 3. Continuous monitoring of PbtO2 and CPP in a patient at day 4 after poor grade aneurysmal SAH. On the left, the two PbtO2 and CPP curves evolve in parallel over time: “optimal” CPP to avoid brain tissue hypoxia (PbtO2<20 mmHg) here is >80 mmHg. On the right, we see a strong positive linear correlation between the two variables (Pearson’s R oxygen pressure correlation coefficient, ORx, 0.74), indicating a high risk for secondary delayed cerebral ischemia.

Figure 4. Brain CT-scan of a patient with severe TBI, showing the localization of

multimodal neuromonitoring (ICP, PbtO2, cerebral microdialysis) in the right frontal lobe.


Figure 5. Continuous monitoring of arterial blood and extracellular brain (using cerebral microdialysis) glucose at the bedside. Adequate supply of the main energy substrate (glucose) is essential for the injured brain: cerebral microdialysis (CMD) monitoring can help to optimize glucose control and insulin therapy in patients with acute brain injury, thereby avoiding unwanted critical reductions of cerebral glucose. Here, infusion of 10% iv glucose allowed normalization of CMD glucose (ICP and PbtO2 remained in normal ranges) and prevention of sustained neuroglucopenia and cerebral metabolic distress.


MULTIMODALITY NEUROMONITORING QUESTIONS 1. The recent BEST TRIP randomized controlled trial from Chesnut and colleagues

compared clinical examination plus repeated brain CT scan with or without ICP monitoring in patients with severe TBI (New England Journal of Medicine, Dec 2012). Which one of the following sentence about this study is true?

a) ICP monitoring was effective in improving outcome b) ICP monitoring was associated with a worse outcome c) ICP monitoring was associated with reduced number of days in the ICU d) ICP monitoring was effective in guiding therapy of intracranial hypertension e) ICP monitoring had no benefit

2. The ICP curve of a young adult patient at day 2 following severe TBI is depicted, showing

elevated ICP up to 30 mmHg. Which of the following sentence is wrong?

a) The ICP threshold alone should be used to guide ICP therapy b) P2 > P1 is a sign of poor intracranial compliance c) P1 > P2 is normally seen and is a sign of normal brain compliance d) The ICP curve is useful to diagnose brain compliance and identify patients at

higher risk of intracranial hypertension that may benefit form aggressive ICP therapy

e) P2 reflects cerebral venous return 3. What are the main physiologic determinants of brain tissue oxygen tension (PbtO2)?

(More than one answer may apply). a) PaO2 b) Temperature c) MAP d) ICP e) CPP

4. What is the potential clinical utility of PbtO2 monitoring? (More than one answer may apply).

a) Management of CPP b) Management of elevated ICP c) Management of mechanical ventilation d) Management of blood transfusion e) Management of sedation


5. Which one is not an indication for EEG monitoring? a) Detection of cerebral ischemia b) Detection of non-convulsive seizures c) Detection of elevated ICP d) Prognostication of coma e) Management of barbiturate coma

6. Regarding ICP monitoring, which of the following sentence is true?

a) Non-invasive tools (optic sound ultrasound, transcranial Doppler) can be used to monitor ICP

b) ICP monitoring improves outcome in patients with severe TBI c) ICP monitoring reduces the length of ICU stay d) Based on randomized controlled trials, ICP monitoring is effective in guiding

the treatment of intracranial hypertension e) ICP monitoring should be abandoned

7. What is the oxygen pressure reactivity index (ORx)?

a) On-line linear correlation coefficient between ICP and PbtO2 b) On-line linear correlation coefficient between ICP and MAP c) An index that quantifies the response of PbtO2 to CPP

d) An index that quantifies the response of PbtO2 to FiO2

e) On-line linear correlation coefficient between CPP and PbtO2 8. The alpha/delta ratio on the EEG can be used to detect:

a) The depth of sedation b) Cellular hypoxia c) Burst-suppression d) Delayed cerebral ischemia e) Elevated ICP

9. Based on the 2007 Brain Trauma Foundation guidelines, which of the following one is not

an indication of ICP monitoring? a) Moderate TBI b) Severe TBI with abnormal brain CT scan c) Severe TBI with polytrauma and ARDS d) Severe TBI with compressed basal cisterns on brain CT scan

10. What sentence about multimodal neuromonitoring is true ?

a) It has been shown to improve outcome in randomized controlled trials b) It has been shown to improve outcome in retrospective studies c) It is still a research tool d) Its feasibility and safety has not been demonstrated yet e) The appropriate interpretation of brain physiological variables and the of

standardized management protocols driven by multimodal neuromonitoring might offer optimal individualized therapy to brain-injured patients


MULTIMODALITY NEUROMONITORING ANSWERS

1. The correct answer is D. Compared to the control group (repeated clinical examination + brain CT without ICP monitoring) the intervention group (clinical examination + CT with ICP monitoring) had comparable outcome (lack of efficacy in improving outcome) and spent more days in the ICU. However the trial showed that ICP monitoring reduced by 50% the number of treatments for ICP per patient and reduced the number of ICU days during which patients received brain-specific treatments: therefore ICP monitoring was effective in guiding therapy of intracranial hypertension.

2. The correct answer is A. Not only the ICP threshold per se (generally >20 mmHg) is

important, but also, and similarly important, the shape of the ICP curve. Increased P2 (= or above P1) suggests poor cerebral compliance and thus should prompt aggressive ICP therapy. On the other hand, values at 20-25 mmHg with an ICP curve showing good compliance may not necessarily need treatment escalation.

3. The correct answers are A, B, C, D, E. PbtO2 can be expressed by the formula: CBF x

(PaO2-PvO2). PaO2 is a major determinant of PbtO2, as well as all variables that may influence CBF (i.e. MAP, ICP, CPP). PbtO2 has to be adapted to temperature, ideally brain temperature.

4. The correct answers are A, B, C, D, E. Several independent single-center clinical

studies showed that PbtO2 monitoring might help in the management of all previously listed interventions.

5. The correct answer is C. Clinical studies have shown a potential utility of EEG

monitoring for the detection of delayed cerebral ischemia after SAH, to detect non-convulsive seizures, to improve coma prognostication and to titrate barbiturate coma.

6. The correct answer is D. Non-invasive tools can only estimate ICP, but invasive ICP

monitoring remains the only way to measure ICP. In the Chesnut trial (NEJM 2012), compared to the control group (repeated clinical examination + brain CT without ICP monitoring) the intervention group (clinical examination + CT with ICP monitoring) had comparable outcome (lack of efficacy in improving outcome) and spent more days in the ICU. However the trial showed that ICP monitoring reduced by 50% the number of treatments for ICP per patient and reduced the number of ICU days during which patients received brain-specific treatments: therefore ICP monitoring was effective in guiding therapy of intracranial hypertension.

7. The correct answer is E. The oxygen pressure reactivity index measures the linear

correlation between PbtO2 and allows the assessment of cerebral autoregulation and of optimal CPP.


8. The correct answer is D. The alpha-delta ratio has been shown in some studies to predict ischemia in severe SAH patients.

9. The correct answer is A. ICP monitoring is not recommended in patients with moderate TBI.

10. The correct answer is E. Multimodal neuromonitoring might help ICU clinicians with

the management of secondary cerebral damage. Incorporation of multimodal neuromonitoring into standardized algorithms is essential.

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