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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 noninvasive 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 PbtO 2, 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, PbtO 2 shows a strong positive
linear correlation with CPP (Figure 3: PbtO2 and CPP curves are shown o the left panel, while
the on-line Pearsons 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 12hour 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 semipermeable 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 patients brain extracellular fluid into
microvials and bedside analysis using manufacturers 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.
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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 (Pearsons 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.
a)
b)
c)
d)
8. The correct answer is D. The alpha-delta ratio has been shown in some studies to
predict ischemia in severe SAH patients.