Chapter 14: Multimodality Neuromonitoring

One of the most important goals of neurologic critical care is to detect secondary brain injury at a time when permanent damage can still be prevented. The clinical examination remains the gold standard for the assessment of patients with neurologic disease despite great advances in neuroimaging and other diagnostic tools. Furthermore, in medical intensive care unit (ICU) patients, daily interruption of sedation has been shown to decrease the duration of mechanical ventilation, shorten hospital stay, and, in combination with spontaneous breathing trials, lead to improved outcome.^1,2 There is some evidence suggesting that daily interruption of sedation is safe even in patients with brain injury,³ but this remains controversial.⁴ Clearly, there are a number of patients with acute brain injury in whom interruption of sedation is contraindicated such as those with ongoing status epilepticus, severe ICP crises, or respiratory failure requiring sedation. Comatose and sedated patients with brain injury are often compared to a “black box” when assessing the neurologic status. Using clinical parameters alone, it may be difficult to differentiate changes in brain physiology that warrant interventions from medication effects. Clinical examinations lack sensitivity to detect some secondary complications such as nonconvulsive status epilepticus (NCSE)⁵ or silent infarction.⁶ Interand intra-rater reliability may be a factor to consider depending on the skill of the examiner.⁷

Commonly used clinical scales may be too crude to detect secondary complications. The most widely used clinical scale in the ICU environment is the Glasgow Coma Scale (GCS),⁸ which was developed to facilitate rapid communication between first responders and specialized braininjury units to triage traumatic brain injury (TBI) patients. This widely used scale does not reliably detect secondary complications and has been shown in some studies to have poor predictive power for outcome.⁹ More recently, modifications such as the FOUR score have been proposed,¹⁰ but likely these will not be adequate monitors to detect secondary injury in brain-injured patients.¹¹ Invasive monitoring of the brain has the advantage of allowing real-time continuous assessment of brain physiology and has been shown to be safe.^12-14 Additionally, as outlined below, neuromonitoring may be used to quantify the effect of interventions and prognosticate the outcome.

The most established monitoring technique to assess ICP can be accomplished with probes placed in, for example, the ventricle, brain parenchyma, subarachnoid space, or subdural space. Most commonly, intraventricular or intraparenchymal monitoring probes are used because of safety and accuracy concerns. Measuring ICP allows calculation of cerebral perfusion pressure (CPP) using the simple formula: CPP = mean arterial pressure (MAP) – ICP. Importantly, the CPP reflects a global assessment of the pressure gradient that should not be confused with the amount of blood flow to the brain, called the cerebral blood flow (CBF), or an assessment of brain metabolism or oxygenation status (PbtO₂). Currently, no consensus exists regarding the selection of monitoring devices for specific patient groups. The selection of devices needs to be made based on the questions that the clinician wants to have answered for a specific patient and based on local experience with monitoring devices. An overview about existing monitoring devices separated by their spatial and temporal data resolution is displayed in Table 14-1. Findings from just one device may be more difficult to interpret than a more complete assessment that quantifies pressure, metabolism, and oxygenation status at the same time. Additionally, CBF monitors and intracranial electroencephalographic (EEG) monitoring are being used in some centers.^15,16 Bedside monitoring facilitates immediate detection of changing brain physiology and allows targeted treatment before obvious and often irreversible clinical deterioration occurs.¹⁷ However, the use of invasive neuromonitoring remains controversial.^13,18-20

In this patient, we selected ICP monitoring because of the high risk for intracranial hypertension (both with external ventricular drainage catheter [EVD] and parenchymal catheter). Additionally, we initiated brain oxygen tension (PbtO₂) and neurochemical monitoring (cerebral microdialysis) because of the high risk of secondary complications in this patient including ischemia from vasospasm.

All monitoring devices discussed above measure local brain physiology. Knowledge about catheter location is crucial for the treating neurointensivist in order to correctly interpret the collected data. Currently, no consensus exists regarding the desired placement of devices in relation to injured brain tissue. Generally, most practitioners recommend placement in tissue at highest risk for secondary complications. In patients with spontaneous SAH, the tissue at highest risk for vasospasm and delayed cerebral ischemia (DCI) are those in the area perfused by the ruptured artery.²¹ However, vasospasm is a diffuse pathology and delayed ischemia may occur in a distant area. Therefore, local invasive neuromonitoring may miss the onset of DCI. In patients with focal brain injury such as intracranial hemorrhage (ICH), cerebral contusion, or a well-demarcated area of hypodensity in a vascular distribution consistent with an infarct, a perilesional placement is generally attempted. Currently used placement techniques at the bedside through a burr hole are not very accurate in reaching this goal. Placement of neuromonitoring devices inside the lesion, that is, within an infarct or hemorrhage, will not yield any meaningful data.¹² Using a CT-guided neuronavigated approach may allow for more accurate perilesional catheter placement. In patients with a diffuse or nonfocal injury (diffuse SAH, multifocal bilateral injuries, global cerebral edema, confined IVH), the neuromonitoring devices are generally placed in the frontal lobe of the nondominant hemisphere. A CT scan after neuromonitoring device placement is recommended to determine probe location and to detect procedure-related complications such as bleeding.

In the absence of large multicenter trials, no exact numbers are known but the most significant complications include intracerebral, subdural, or epidural bleeding; encephalitis or meningitis; and device malfunctioning or misplacement.^22,23 A major bleeding risk is higher in patients who receive an antiplatelet agent such as clopidogrel or aspirin. Caution is warranted in those receiving antiplatelet agents and those with a low platelet count or dysfunctional platelets (ie, during uremia). Most series report an infection risk of 5% or lower,^23,24 while antibiotic prophylaxis remains controversial.^23-25

Based on very little data, there are recommendations for PbtO₂ monitoring in patients with TBI. Guidelines from the Brain Trauma Foundation recommend monitoring of brain tissue oxygen tension (PbtO₂) or jugular venous oxygen saturation (SvjO₂) if hyperventilation is used (level III).²⁶ Further, it is advised to address brain tissue oxygen tension levels below 15 mm Hg with appropriate treatment strategies (level III).²⁷ For other diagnoses there are no recommendations to be found. SAH guidelines published in 2009 by the American Heart Association do not address the issue of PbtO₂ measurement.²⁸

PbtO₂ is a marker of the balance between oxygen delivery and oxygen consumption in brain cells. PbtO₂ is assessed using a Clark electrode that samples the tension of oxygen in the extracellular fluid, reflecting a small volume of brain (17 mm³) at the distal end of the probe. The health of the brain tissue that is monitored with the probe significantly correlates with the behavior of the brain oxygen measurements.^29,30 In healthy normal brain, PbtO₂ is 25 to 35 mm Hg at all times, and there is a good correlation between CPP and PbtO₂ when PbtO₂ is low, suggesting intact autoregulation. In dead brain tissue, PbtO₂ levels are generally less than 5 mm Hg and no correlation with CPP is observed. If the probe is placed in the penumbra, PbtO₂ may be low and there is a general correlation with CPP, suggesting disturbed autoregulation.^29,30

A number of studies found a good correlation between a low PbtO₂ (less than 15 mm Hg) and poor outcome after SAH³¹ and in TBI patients.^13,30,32-36 However, from these data, it is not clear if the low PbtO₂ is just a surrogate marker for the extent of brain injury. The idea behind cerebral oxygen monitoring is to address these changes to hypoxic values with appropriate treatment strategies. PbtO₂-guided therapy to prevent hypoxic brain injury has been associated with improved outcome in uncontrolled, single-center trials.^20,37,38 Based on this finding, a multicenter randomized controlled trial in patients with severe TBI (GCS 8 or less) is under way (National Institute of Neurological Disease and Stroke [NINDS]–funded phase II trial entitled Randomized Controlled Trial of Brain Tissue Oxygenation Monitoring).

What we measure with PbtO₂ is the balance between oxygen delivery and oxygen consumption in brain cells. PbtO₂ may be influenced by a whole host of different local factors including oxygen consumption of neurons and glia, oxygen diffusion conditions and gradients in the sampled brain tissue, the number of perfused capillaries per tissue volume, the length and diameter of perfused capillaries, the capillary perfusion rate and microflow pattern, and the hemoglobin oxygen release in the microcirculation. Systemic factors that may influence PbtO₂ measurements include arterial blood pressure, ICP, PaO₂, PacO₂, pH, temperature, the blood Hgb content, blood viscosity, and the hematocrit.

One study suggests that local brain tissue oxygen tension is more closely related to CBF and the diffusion of dissolved plasma oxygen rather than total oxygen delivery to the brain and oxygen metabolism of the brain cell.³⁹ Strategies to influence low PbtO₂ are multiple and should be decided on an individual basis (Figure 14-3). While PbtO₂ may increase in one patient after CPP optimization or improvement of cardiac function, other patients may benefit from an increase in oxygen transport capacity (blood transfusion). Additional monitoring devices (CBF, brain temperature, EEG) may be helpful for the clinician to narrow down the differential diagnosis of a low PbtO₂.

Low PbtO₂ values may be observed without changes in brain metabolism as this strongly depends on the duration of brain hypoxia. Basic strategies to minimize oxygen consumption of the brain include aggressive fever management, treatment of shivering,^40,41 management of pain and agitation (sedation and adequate analgesia), and optimization of positioning of the upper part of the body (30 degrees or more).

The following text questions use a correlational data analysis approach to better understand brain physiology in the acute brain injury setting. This approach may help clinicians to understand complex physiologic relationships and identify optimal physiologic targets in real time. Additionally, the behavior of physiologic parameters in relation to interventions (eg, increasing MAP/CPP, optimizing cardiac output, decreasing ICP, blood transfusion, ventilator strategies) may identify individualized thresholds such as MAP goals and assess cerebral autoregulation.

In general there is a close relationship between PbtO₂ and PacO₂ as well as end-tidal CO₂ (Figure 14-4). Hyperventilation leads to cerebral vasoconstriction and may cause infarction. In TBI patients, hyperventilation is only recommended as a temporizing measure for increased ICP (level III) and should not be used in the first 24 hours after head injury (Level III).²⁶ Prophylactic hyperventilation is not recommended (level II), and if hyperventilation is used, jugular venous oxygen saturation (SvjO₂) or brain tissue oxygen tension (PbtO₂) measurements are recommended to monitor oxygen delivery (level III).²⁶

Figure 14-5 illustrates the tight correlation between CPP and PbtO₂ in our patient during a 24-hour monitoring period. Brain tissue hypoxia (PbtO₂ less than 15 mm Hg) is observed at CPP values of 90 mm Hg and lower. There are several treatment options to optimize CPP in this patient. As a first step, the intravascular volume status should be optimized, which may be estimated using a clinical assessment or monitored parameters such as the stroke volume variation, the global end-diastolic index (GEDI), or the pulmonary artery wedge pressure. If optimizing volume status does not result in improved CPP and PbtO₂ numbers, MAP may be titrated up to achieve PbtO₂ improvements greater than 20 mm Hg. Depending on cardiac performance (which can be estimated using the cardiac index or the ejection fraction), this can be achieved using pressors including norepinephrine, phenylephrine, milrinone, dobutamine, or dopamine.

This case illustrates how PbtO₂-guided therapy may lead to more aggressive management. Additionally, hypoxic and ischemic events can also be observed despite maintaining a CPP of greater than 70 mm Hg in patients with severe brain injury. Lowering CPP may improve brain oxygenation; however, once the CPP reaches the lower threshold of the autoregulatory breakthrough zone, hyperemia and a secondary increase in ICP may result (Figure 14-7).⁴⁵

Increasing FiO₂ effectively increases local brain oxygen partial pressure. However, this does not necessarily lead to an improvement in brain metabolism. What has been described is a simultaneous decrease in lactate and pyruvate, leaving the lactate-to-pyruvate ratio overall unchanged. This would suggest that hyperoxia may lead to retardation of the metabolism rather than stimulation.⁴⁶ Another study showed that hyperoxia may decrease brain lactate levels.⁴⁷ Contrarily, hyperbaric hyperoxygenation may have a positive effect on PbtO₂ and brain metabolism.⁴⁸

Blood transfusions increase oxygen transport capacity to the brain and have been shown to increase PbtO₂ after severe head injury without improving brain metabolism.⁴⁹ In a randomized controlled trial, a transfusion threshold of less than 7 mg/dL was not associated with increased 30-day mortality rate in critically ill patients.⁵⁰ For neurologic ICU (NeuroICU, NICU) patients, there is conflicting evidence about the optimal transfusion threshold. Decisions regarding blood transfusions in patients with SAH must be individualized because optimal transfusion triggers are not known (level III).⁵¹ Currently, there are a number of trials underway to compare different transfusion thresholds for SAH patients.^51-56 Subpopulations of SAH patients such as those with ongoing DCI from vasospasm may benefit from higher transfusion thresholds (ie, keeping hemoglobin greater than 10 mg/dL).^55,57 Patients with moderate-to-severe TBI do not benefit from a “liberal” transfusion strategy (level II).⁵¹ Recent reports on multimodal neuromonitoring and hemoglobin suggest that low hemoglobin is associated with brain metabolic distress (LPR greater than 40) and low cerebral glucose concentration (less than 0.7 mmol/L).^49,58 Currently, data are too preliminary to define optimal transfusion thresholds. However, the assessment of brain physiology using invasive multimodality monitoring may support decisions for transfusion threshold in selected individuals.

For patients with ICP elevation, an aggressive stepwise approach to lower ICP is indicated. Lowering ICP is usually performed in a stepwise fashion, and while a protocol is useful and warranted, interventions may be started simultaneously and may need to be individualized in certain scenarios. Some of the measures used include cerebrospinal fluid (CSF) diversion by EVD, sedation and analgesia, surgical decompression, short-term hyperventilation, osmotic agents, therapeutic hypothermia, and EEG-guided barbiturate coma.

Osmotherapeutic agents include mannitol (1.0 to 1.5 g/kg IV bag infused over 30 minutes, every 6 hours; avoid serum osmolarity greater than 360 mOsm/L, osmolarity gap greater than 10) and hypertonic saline 23.4% (30 mL over 5 minutes IV, every 4 to 6 hours, avoid serum Na greater than 160 mg/dL). Both osmotherapeutics effectively decrease ICP. Recent studies suggest that hypertonic saline, but not mannitol, may increase PbtO₂^59,60 (Figures 14-8 and 14-9), mostly through improvement of cardiac function and secondary increase of CPP; however, mannitol may improve brain metabolism.⁶¹ So far, no treatment can specifically be recommended unless one drug is relatively contraindicated (Figure 14-10).

Yes, it may. As shown in Figure 14-11, cerebral oxygenation, as measured by PbtO₂, may improve with increased cardiac output. Carbon dioxide can be optimized with the use of inotropic agents in volume-resuscitated patients with inadequate cardiac output or through the infusion of fluids in preload-responsive patients. In patients with inadequate oxygen delivery to the brain despite normal ICP and CPP, the improvement in cardiac performance may further optimize cerebral blood flow and potentially improve aerobic metabolism.

Yes. It has been known for more than a decade that there is a relationship between the autoregulatory status of a patient and the arterial blood pressure (BP) versus ICP correlation.⁶² This has been termed the pressure reactivity index (PRx) and is calculated as a moving correlation between BP and ICP. A negative correlation is seen in patients with vasoreactivity, whereas a positive correlation indicates a passive pressure response system and is seen in absent vasoreactivity (Figure 14-12).

Yes, the oxygen reactivity index (ORx), which is calculated as the moving correlation coefficient between CPP and PbtO₂,^63-65 provides further information into the patient's cerebrovascular response to changes in pressure. In a patient with intact reactivity, variations in CPP should not be reflected in changes in PbtO₂ since vasodilation and vasoconstriction of the cerebral arterioles should prevent passive variations in CBF and thus oxygen delivery and PbtO₂ (Figure 14-13). In this case, PbtO₂ variation is most likely reflecting CBF changes, and the passive dependence between CPP and PbtO₂ is associated with a more severe brain injury.^63-65

Cerebral microdialysis (MD) allows a neurochemical assessment of the extracellular space. Values of various substrates including cerebral glucose (= substrate), lactate, pyruvate (metabolites), glycerol, or glutamate (= substrate) can be obtained at the bedside at intervals between 20 minutes and usually 1 hour (routine parameters) (Figure 14-14).⁶⁶

In general, all molecules below the cutoff size of the semipermeable membrane (either less than 20 kDa or less than 100 kDa) in the extracellular space can be measured (cytokines, antibiotics, anticonvulsants, and other agents). The interstitial biomarkers obtained with MD reflect the net effect of several processes: energy supply, diffusion, and consumption. A simplistic approach on changes in routine parameters obtained by cerebral MD is given in Table 14-2. A typical ischemic pattern includes a marked decrease in brain glucose, increase in LPR and LGR (lactate-to-glucose ratio), and a moderate increase in brain lactate and a decrease in brain pyruvate.²¹

Many other metabolites, including adenosine, inosine, hypoxanthine urate, glutathione, cysteine, glycine, and gamma-aminobutyric acid (GABA) have been studied and others such as taurine, interleukins, and a number of amino acids are under investigation.²¹ The clinical role that these metabolites may play remains to be determined.

Prolonged episodes (more than 25 minutes) of profound brain tissue hypoxia (PbtO₂ less than 10 mm Hg) are associated with marked metabolic changes (including increasing MD-LPR and decreasing MD-glucose; see Figure 14-16).^67-69 MD-glucose, MD-lactate, MD-pyruvate, or lactate-to-pyruvate ratio may be indicators for the detection of secondary complications involving hypoxia or ischemia. Brain biochemistry may predict neurologic deterioration secondary to cerebral vasospasm even hours before the symptoms occur.¹⁷ Poor outcome has been associated with elevated lactate, lactate-to-pyruvate ratio, and glutamate and low glucose in SAH ^31,70-74 and TBI^75-77 patients.

A typical ischemic MD pattern of the human brain is a marked increase in LPR combined with a very low MD-glucose level.⁷⁹ Other biochemical changes observed in the setting of acutely brain-injured patients are summarized in Table 14-3, including the nonischemic glycolysis.⁸⁰

Metabolic distress is commonly defined as LPR greater than 40, whereas metabolic crisis comprises the combination of LPR greater than 40 and brain glucose less than 0.7 mmol/L.^21,79-81 Metabolic distress/crisis, therefore, is a composite value that reflects, in the direct measurement of brain glucose and its anaerobic and aerobic metabolites (lactate/pyruvate), the difference between energy supply and demand.^21,81 A reduction in energy supply can be caused by reduced CBF, which decreases the oxygen and glucose supply, resulting in a shift to anaerobic metabolism with increased brain lactate.⁷⁹ Alternatively, low glucose availability can lead to a decrease in brain pyruvate without an increase in lactate.^76,80 Elevated LPR with and without low MD-glucose, high brain-serum glucose variability, high MD-lactate, and high MD-glutamate concentration, measured in the interstitial space by MD, have been linked with poor outcome in patients with acute brain injury (including TBI and SAH patients).^70-76,82-84 The etiology of MC is diverse, including low CPP, elevated ICP, spreading depolarizations, and others.^83-86

IA calcium channel blockers are a treatment option in severe vasospasm (papaverine, verapamil, nicardipine, nimodipine).^87-93 Awareness of side effects, depending on the half-life of the drug, and the total dose given is warranted. Cerebral vasodilation may cause intracranial hypertension, which lasted for 3 hours after high-dose IA verapamil in a small series of SAH patients (Figure 14-18).^22,87,88,94 Furthermore, CPP may decrease secondary to a drop in MAP as a systemic side effect. Close hemodynamic monitoring up to 12 hours following treatment is necessary. Preliminary data suggest that brain metabolism is not affected by this intervention; however, an increased brain perfusion may result in increase of substrate delivery (glucose) to the brain.⁹⁴

There is generally a close correlation between serum and brain glucose, which renders the central nervous system vulnerable to episodes of hypoglycemia (Figure 14-19). A critical threshold for MD-glucose is generally believed to be 0.7 mmol/L. Tight glucose control (4.4 to 6.2 mmol/L) with intravenous insulin was implemented in a large number of ICUs after 2001, when a randomized controlled trial showed the survival benefit of surgical ICU patients.⁹⁵ However, the results could not be replicated in mixed populations of critically ill patients, mostly because of hypoglycemic episodes in the tight glycemic controlled group,⁹⁶ and a recent study actually favored a more liberal glucose regimen (less than 180 mg/dL).⁹⁷ Multimodal neuromonitoring studies showed that tight glycemic control may be associated with MC in severely brain-injured patients (Figure 14-20).^98,99 Insulin therapy may decrease brain glucose despite serum normoglycemia.^99,100 As a treatment strategy, invasive monitoring can be used to ensure that the energy supply to the brain (serum glucose and oxygen) should be adjusted to meet the individual demand of the brain tissue to prevent cerebral hypoglycemic episodes.

Yes. A decrease in brain glucose concentration can be triggered by several primary and secondary complications in patients with severe brain injury such as ischemia, hypoxia, intracranial hypertension, seizures, vasospasm, and others.^101,102 Beyond delivery and consumption, impaired glucose transportation through GLUT-1 transporters may limit the passage of glucose through the blood-brain barrier and decrease its brain tissue concentration.^103,104 Thus, ineffective upregulation or dysfunction of GLUT-1 transporters can potentially limit glucose utilization by the neuron and astrocyte. In a high-energy- demand environment, this may lead to energy failure.^71,105 Another potential cause of low brain tissue glucose is the hyperglycolysis observed in the acute phase after severe brain injury (TBI and SAH). If the overstimulated glycolytic pathway is not supplied with enough substrate, tissue concentrations of glucose may be decreased. A recent study using ¹³C-labeled acetate and lactate nuclear magnetic resonance (NMR) spectra of microdialysate fluid confirmed that we only have an incomplete understanding of brain metabolism in the acute brain injury state.¹⁰⁶ These investigators found that the brain may be able to utilize lactate as a fuel, and they proposed the mechanism shown in Figure 14-21.

Patients with severe brain injury will often present parallel fluctuations of lactate and pyruvate that do not affect LPR. Usually, increases in the concentrations of both metabolites reflect increased metabolic activity, such as that seen during rewarming from hypothermia (Figure 14-22). On the other hand, decreased metabolic activity, such as what is observed during sedation, is reflected by reductions of pyruvate and lactate tissue concentrations. If enough substrate delivery and oxygenation are available, variations of metabolic activity should not lead to energy failure and increased LPR. However, if increased metabolic demand (eg, interruption of sedation, rewarming) leads to unbalanced delivery and consumption of substrate and oxygen, LPR will likely increase.

Continuous monitoring of rCBF is possible through a thermal diffusion (TD) microprobe inserted into the brain parenchyma.¹⁰⁷ The microprobe consists of a thermistor in the distal tip and a temperature sensor 5 mm proximal. The thermistor is heated to 2^°C above tissue temperature and rCBF is calculated by a mathematical model using the tissue's ability to transport heat, which depends on tissue perfusion.¹⁰⁸ The sample volume is approximately 27 mm³. The microprobe should be inserted in the vascular region of interest 20 to 25 mm deep, thus reflecting white matter perfusion, and secured with a metal bolt. TD-rCBF should be integrated into other modalities of neuromonitoring, such as MD and tissue oxygenation. Anaerobic metabolism and PbtO₂ reductions in patients with severe SAH, combined with dynamic changes in rCBF, clearly point to an ischemic injury due to vasospasm.^109-111 On the other hand, metabolic distress with stable rCBF may indicate hypoxic hypoxia or mitochondrial dysfunction. rCBF has been shown to correlate fairly with PbtO₂ and reflect perfusion changes due to systemic parameters such as CPP (Figure 14-23).¹¹² Thus, it can aid in goal-directed management of CPP and cardiac output management. Although it makes physiologic sense to incorporate rCBF to multimodality monitoring of patients with severe SAH and TBI, there are very little data to support its role in diagnosis and management of cerebral hypoperfusion.

Jugular venous oxygen saturation (SvjO₂) has been extensively used in patients with severe TBI and is currently included in the TBI management guidelines published by the Brain Trauma Foundation.²⁷ Measurement of SvjO₂ and the arterial-jugular difference of oxygen content (AJDO₂) offers a global estimate of the balance between oxygen delivery and extraction by the brain.^113,114 Both parameters have been associated with secondary brain injury and outcome after severe TBI.¹¹³ Patients with low (less than 50% to 55%) and high (greater than 80%) SvjO₂ have worse outcomes than those with values in the middle range. Critically low values of SvjO₂ reflect cerebral hypoperfusion with increased oxygen extraction. Exhaustion of this compensatory mechanism results in secondary ischemic injury to the brain. After TBI, high SvjO₂ is usually associated with hyperemia, which may lead to intracranial hypertension. Patients with low AJDO₂ have also been shown to have worse outcomes than the ones with normal values. This may be the result of an inability to compensate for increased oxygen extraction in a context of high metabolic demand, reflecting more severe brain injury.¹¹³

There is a paucity of data on the use of SvjO₂ monitoring for patients with poor-grade SAH. A few small studies have shown that SvjO₂ decreases prior to the development of symptomatic vasospasm.¹¹⁴ The physiologic rationale of SvjO₂ monitoring extensively applied to TBI patients (balance between oxygen delivery and consumption) should remain valid for patients with severe brain injury with other etiologies and justify its use in some selected patients.

Fever is common after subarachnoid hemorrhage¹¹⁵ and can effectively be controlled by intravascular or surface-cooling devices.^116,117 Treatment of fever is nowadays routine in neurocritical care and may improve outcome.¹¹⁶ Besides infections, fever has been linked to severity of injury, hemorrhage load, occurrence of vasospasm, and elevated ICP.^118-120 Recently, fever has been associated with high LPR¹²¹ (Figure 14-24). These data furthermore suggest that fever control may improve brain metabolism. Although these results have to be confirmed in larger studies, beneficial effects of fever control on brain homeostasis may be explained by a reduction in ICP and a decrease in metabolic need.¹²⁰

The answer is not entirely clear, but multimodality monitoring may in select cases help clarify questionable EEG patterns.¹²² At times that the patient's EEG had these ictal/interictal patterns she had a rise in LPR, glycerol, and glutamate (Figure 14-26). Her glucose initially rose and then dropped. This led to further investigation and she was found to have developed ACA strokes in the territory of the neuromonitoring bundle secondary to vasospasm.

The scalp EEG demonstrates diffuse background slowing (top 12 tracings) and the depth EEG shows highly epileptiform discharges (bottom 4 tracings).

The ICE shows an evolution from the highly epileptiform initial baseline EEG (see Figure 14-28) to a burst-suppression pattern and ultimately nearly complete attenuation, whereas the overlying scalp coverage did not demonstrate an obvious concerning change. Quantitative EEG analysis of a 6-hour period surrounding the identification of ICE-specific changes is shown. The top two rows are derived from scalp EEG, and the bottom two rows from the intracortical electrode. After a period of slow decrease, a significant and permanent decline in EEG total power was seen in isolation from the intracortical electrode (arrow) with a similarly obvious and dramatic change in the ICE spectrogram. A similar trend could not be appreciated from the scalp-derived quantitative EEG trends. This event was associated with a period of progressive decrease in CPP (purple line), as well as a delayed and significant increase in ICP (blue line); the corresponding time interval is marked with dotted lines.

Owing to decreasing CPP, the patient developed diffuse widespread infarction of her brain (Figure 14-30).

Cortical spreading depression (CSD) is a 1- to 5-mm per minute wave of depolarization in the gray matter. CSDs are recorded by subdural electrocorticography electrode strips and occur both in healthy cortical tissue (reversible) and the diseased brain¹⁶ under conditions of energy compromise (ischemia, hypoxia, hypoglycemia). CSDs are associated with neuronal injury.¹²³ CSDs in the peri-ischemic brain tissue are referred as “peri-infarct depolarization” (PID).¹²⁴ CSDs and PID indicate compromised metabolism and are commonly observed after TBI, malignant MCA infarction, and SAH.^16,125-127 It has been suggested that the vasodilatory response of CSD indicates progressive ischemia, whereas the following vasoconstrictive response—also referred to as cortical spreading ischemia—may contribute to progression of ischemic lesions.¹²⁵ This novel technology may have potential to monitor for ongoing ischemia in severe brain injury.

This has not been adequately studied and all studies so far were underpowered to investigate this question. This may be the wrong question to ask. In patients with cEEG monitoring, this technique was helpful in decision making: “decisive” 54%, “contributing” 32%, “noncontributing” 14% (retrospective, depends on cooperation with ICU physicians).¹²⁸ Currently, clinical trials are under way to test if multimodality-targeted management strategies impact on outcome.