Neurologic Multimodal Monitoring
Raphael A. Carandang
Wiley R. Hall
Donald S. Prough
Neurologic function is a major determinant of quality of life. Injury or dysfunction can have a profound effect on a patient’s ability to be alert, communicate, and interact with his or her environment meaningfully, and function as an independent human being. The brain is a highly complex organ with specialized areas of function and is exquisitely sensitive to metabolic and physical insults such as hypoxemia, acidosis, trauma, and hypoperfusion. The goal of neurocritical care is to protect the brain and preserve neurologic functions in the critically ill patient. The impetus for multimodal monitoring of brain function arises from both its importance and vulnerability and also the difficulty in obtaining a satisfactory assessment of function in the setting of numerous insults and processes including toxic and metabolic encephalopathy, sedation and chemical restraints, and primary central nervous system (CNS) processes like stroke and traumatic brain injury.
There has been rapid growth and there continues to be much interest in the field as numerous devices and modalities are developed to monitor brain function and processes including intracranial pressure (ICP) monitoring, electroencephalography, and corticography, global and regional brain tissue oxygen monitoring, cerebral blood flow measurements, and neurochemical and cellular metabolism assessment with microdialysis.
As with any diagnostic or therapeutic tool, an understanding of the indications, limitations, risks and benefits of an intervention are essential in the effective utilization, interpretation, and application of the obtained information to the management of the individual patient. Important characteristics of monitoring devices include the ability to detect important abnormalities (sensitivity), to differentiate between dissimilar disease states (specificity), and to prompt changes in care that alter long-term prognosis (Table 28.1). Limitations of techniques include risks to patients (during placement, use, and removal), variability errors in generation of data (e.g., calibration and drift), and inherent trade-offs between specificity and sensitivity. Monitors with high specificity—values fall outside of threshold levels only when a disease state is unequivocally present—are unlikely to detect less profound levels of disease, while monitors with high sensitivity (will detect any value outside of the normal range) are likely to demonstrate small deviations from normal, which may be trivial in individual patients. The advantage of multimodal monitoring is it increases the sensitivity and accuracy of our detection of physiologic and cellular changes that signal further impending clinical deterioration by using different monitoring modalities in a complementary fashion. A legitimate concern raised by some is that the vastly larger amounts of data generated by these devices requires computer-supported data analyses which is costly and time-consuming and may overwhelm the ill-prepared clinician and detract whatever benefits may be gained from the new technology [1]. Most agree that careful consideration should go into selecting the appropriate patient to monitor, the modalities to use, and that determining the most beneficial application of these technologies requires further prospective study.
The compelling theoretical importance of brain monitoring is based on the high vulnerability of the brain to hypoxic and ischemic injuries. The brain uses more oxygen and glucose per weight of tissue than any large organ, yet has no appreciable reserves of oxygen or glucose. The brain is thus completely dependent on uninterrupted cerebral blood flow (CBF) to supply metabolic substrates that are required for continued function and survival and to remove toxic byproducts. Even transient interruptions in CBF, whether local or global, can injure or kill neural cells. These perturbations may not result in immediate cell death, but can initiate metabolic or cellular processes (e.g., gene transcription, secondary injury) that may lead to cell death days, months, or years after the insult. Therefore, clinical monitoring of neuronal well-being should emphasize early detection and reversal of potentially harmful conditions. Although there is limited conclusive data to demonstrate that morbidity and mortality are reduced by the information gathered from current neurologic monitoring techniques, most clinicians caring for patients with critical neurologic illness have confidence that their use improves management. In this chapter, we review currently available techniques with emphasis on the current scientific literature and indications for utilization.
Goals of Brain Monitoring
Monitoring devices cannot independently improve outcome. Instead, they contribute physiologic data that can be integrated into a care plan that, while frequently adding risks (associated with placement, use, and removal), may lead to an overall decrease in morbidity and mortality.
Neurologic monitoring can be categorized into three main groups: (i) Monitors of neurologic function (e.g., neurologic examination, EEG, evoked potentials, functional MRI), (ii) Monitors of physiologic parameters (e.g., ICP, cerebral blood flow, transcranial Doppler), and (iii) Monitors of cellular metabolism (e.g., SjvO2, NIRS, Brain tissue oxygen tension, Microdialysis, PET, MRSPECT). Most categorizations are arbitrary and obviously overlaps and inter-relationships between modalities (e.g., blood flow and electrical activity, oxygenation, and perfusion) blur the lines of distinction. All categories provide information that may be useful in assessing the current status of the brain and nervous system and in directing therapies as well as monitoring responses to interventions, but it cannot be overemphasized that the data obtained from these monitoring devices should always be interpreted in relation to the overall clinical picture of the individual patient.
Table 28.1 Glossary of Neurologic Monitor Characteristics | ||||||||||||||||||
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Cerebral Ischemia
Given the brain’s dependence and sensitivity to perturbations in oxygenation many if not all monitors are concerned with the detection of cerebral ischemia defined as cerebral delivery of oxygen (CDO2) insufficient to meet metabolic needs. Cerebral ischemia is traditionally characterized as global or focal, and complete or incomplete (Table 28.2). Systemic monitors readily detect most global cerebral insults, such as hypotension, hypoxemia, or cardiac arrest. Brain-specific monitors can provide additional information primarily in situations, such as stroke, SAH with vasospasm, and TBI, in which systemic oxygenation and perfusion appear to be adequate but focal cerebral oxygenation may be impaired.
The severity of ischemic brain damage has traditionally been thought to be proportional to the magnitude and duration of reduced CDO2. For monitoring to influence long-term patient morbidity and mortality, prompt recognition of reversible cerebral hypoxia/ischemia is essential. Numerous animal studies and human studies using different imaging techniques such as PET, MRI, and SPECT have concluded that the ischemic threshold for reversible injury or penumbra is a cerebral blood flow of 20 mL per 100 g per minute below which tissue is at risk for irreversible damage [2,3]. The tolerable duration of more profound ischemia is inversely proportional to the severity of CBF reduction (Fig. 28.1). Ischemia and hypoxemia initiate a cascade of cellular reactions that involve multiple pathways including energy failure from anaerobic glycolysis with accumulation of lactic acid and increase in lactate/pyruvate ratios, loss of ion homeostasis and failure of ATP-dependent ion pumps to maintain ion gradients. This leads to sodium and calcium influx into the cell and activation of enzymes such as phospholipases that result in further membrane and cytoskeletal damage, glutamate release and excitotoxicity, lipoperoxidases and free fatty acid breakdown, and free-radical formation and inflammation with microvascular changes. Endonucleases which alter gene regulation and protein synthesis and activate the caspase pathways that trigger apoptosis are also released [4,5]. Other proteins synthesized in response to altered oxygen delivery, such as hypoxia inducible factors (HIF), have been identified as adaptive mechanisms that respond to variations in oxygen partial pressure [6] and may be protective. These multiple pathways and cellular mediators and their interactions are potential areas for therapeutic intervention. Byproducts of these reactions provide potential biomarkers for secondary injury that can be used for monitoring. Our current understanding of the utility of this data is still evolving and currently when a cerebral monitor detects ischemia, the results must be carefully interpreted. Often, all that is known is that cerebral oxygenation in the region of the brain that is assessed by that monitor has fallen below a critical threshold. Such information neither definitively implies
that ischemia will necessarily progress to infarction nor does it clearly define what biochemical or genetic transcriptional changes may subsequently occur. Also, because more severe ischemia produces neurologic injury more quickly than less severe ischemia, time and dose effects must be considered. More important, if regional ischemia involves structures that are not components of the monitored variable, then infarction could develop without warning.
that ischemia will necessarily progress to infarction nor does it clearly define what biochemical or genetic transcriptional changes may subsequently occur. Also, because more severe ischemia produces neurologic injury more quickly than less severe ischemia, time and dose effects must be considered. More important, if regional ischemia involves structures that are not components of the monitored variable, then infarction could develop without warning.
Table 28.2 Characteristics of Types of Cerebral Ischemic Insults | ||||||||
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 Figure 28.1. Schematic representation of ischemic thresholds in awake monkeys. The threshold for reversible paralysis occurs at local cerebral blood flow (local CBF) of approximately 23 mL/100 m/min. Irreversible injury (infarction) is a function of the magnitude of blood flow reduction and the duration of that reduction. Relatively severe ischemia is potentially reversible if the duration is sufficiently short. (From Jones TH, Morawetz RB, Crowell RM, et al: Thresholds of focal cerebral ischemia in awake monkeys. J Neurosurg 54:773–782, 1981, with permission.) |
 Figure 28.2. A: The normal relationship between the cerebral metabolic rate of oxygen consumption (CMRO2) and cerebral blood flow (CBF) is characterized by closely couple changes in both variables. Normally, CBF is 50 mL per 100 g per minute in adults (open triangle). As CMRO2 increases of decreases, CBF changes in a parallel fashion (solid line). B: Effect of mean arterial pressure (MAP) on CBF. Note that changes in MAP produce little change in CBF over a broad range of pressures. If intracranial pressure (ICP) exceeds normal limits, substitute cerebral perfusion pressure on the horizontal axis. C: Effect of PaCO2 on CBF. Changes in PaCO2 exert powerful effects on cerebral vascular resistance across the entire clinically applicable range of values. |
In healthy persons, CBF is tightly regulated through multiple pathways such that CDO2 is adjusted to meet the metabolic requirements of the brain. In the normal, “coupled” relationship, CBF is dependent on the cerebral metabolic rate for oxygen (CMRO2), which varies directly with body temperature and with the level of brain activation (Fig. 28.2A). As CMRO2 increases or decreases, CBF increases or decreases to match oxygen requirements with oxygen delivery. Pressure autoregulation maintains CBF at a constant rate (assuming unchanged metabolic needs) over a wide range of systemic blood pressures (Fig. 28.2B). If pressure autoregulation is intact, changes of cerebral perfusion pressure (CPP) do not alter CBF over a range of pressures of 50 to 130 mm Hg. CPP can be described by the equation CPP = MAP – ICP, where MAP equals mean arterial pressure. After neurologic insults (e.g., TBI), autoregulation of the cerebral vasculature may be impaired such that CBF may not increase sufficiently in response to decreasing CPP [7]. This failure to maintain adequate CDO2 can lead to ischemia and add to preexisting brain injury, a process termed secondary injury, at blood pressures that would not normally be associated with cerebral ischemia/injury. Normally, arterial partial pressure of carbon dioxide, (PaCO2) significantly regulates cerebral vascular resistance over a range of PaCO2 of 20 to 80 mm Hg (Fig. 28.2C). CBF is acutely halved if PaCO2 is halved, and doubled if PaCO2 is doubled. This reduction in CBF (via arteriolar vasoconstriction) results in a decrease in cerebral blood volume and a decrease in ICP. Conceptually, decreasing PaCO2 to decrease ICP may appear to be desirable. Hyperventilation as a clinical tool was described by Lundberg et al. [8] in 1959 as a treatment for increased ICP and was a mainstay of treatment for over 40 years. However, in healthy brain, there are limits to maximal cerebral vasoconstriction with falling PaCO2 (as well as vasodilation with increasing PaCO2), such that, as CBF decreases to the point of producing inadequate CDO2, local vasodilatory mechanisms tend to restore CBF and CDO2. As a consequence, in healthy brain, hyperventilation does not produce severe cerebral ischemia; however, after TBI, hypocapnia can generate cerebral ischemia as reflected in decreased PbtO2 and SjvO2 [9,10]. For this reason, hyperventilation has fallen out of favor as a treatment modality for intracranial hypertension. If hyperventilation is required to acutely reduce ICP to bridge a patient to emergent surgery for example, administration of an increased inspired oxygen concentration can markedly increase SjvO2 (Fig. 28.3). In response to decreasing arterial oxygen content (CaO2), whether the reduction is secondary to a decrease of hemoglobin (Hgb) concentration or of arterial oxygen saturation (SaO2), CBF normally increases, although injured brain tissue has impaired ability to increase CBF [11].
Techniques of Neurologic Monitoring
Neurologic Examination
Frequent and accurately recorded neurologic examinations are an essential aspect of medical care, but are often limited in patients with moderate-to-severe neurologic compromise. Neurologic examination quantifies three key characteristics: level of consciousness, focal brain dysfunction, and trends in neurologic function. Recognition of changing consciousness or new focal deficits may warn of a variety of treatable conditions, such as progression of intracranial hypertension, new mass lesions such as expansion of intraparenchymal contusions or subdural hematoma and systemic complications of intracranial pathology, such as hyponatremia.
The GCS score, originally developed as a tool for the assessment of impaired consciousness [12], has also been used as a prognostic tool for patients with TBI [13]. The GCS score at the time of initial hospitalization is used to characterize the severity of TBI, with severe TBI defined as a GCS score less than or equal to 8, moderate TBI as a GCS score of 9 to 12, and mild TBI as that associated with a GCS score greater than 12. Lower GCS scores are generally associated with poorer long-term outcomes, although correlation to individual patients with TBI is difficult because of the significant variations in mortality rates and functional outcome [14]. Significant concern has arisen regarding the validity of the initial GCS score on presentation given the aggressive prehospital management of these patients over the last decade or so, that includes sedation and intubation in the field or the administration of paralytics and sedatives in
the emergency room. Some authors have reported a loss of predictive value of the GCS score from 1997 onwards and call for a critical reconsideration of its use [15]. Other studies done have looked at GCS in the field versus GCS upon arrival and have found good correlation and prognostic value in predicting outcome and have even found the changes in scores from field GCS to arrival GCS to be highly predictive of outcome in patients with moderate to severe TBI [16]. Many centers use the best GCS or postresuscitation GCS in the first 24 hours or just the motor component of the GCS instead of initial GCS given these issues. Nevertheless, the GCS score is popular as a quick, reproducible estimate of level of consciousness (Table 28.3), has become a common tool for the serial monitoring of consciousness, and has been incorporated into various outcome models, such as the Trauma score, APACHE II, and the Trauma-Injury Severity score. The GCS score, which includes eye opening, motor responses in the best functioning limb, and verbal responses is limited and by no means replaces a thoughtful and focused neurologic examination. It should be supplemented by recording pupillary size and reactivity, cranial nerve examination and more detailed neurologic testing depending on the relevant neuroanatomy involved in the disease process. Even so, the use of serial GCS determinations remains a common tool in the management of patients with neurologic dysfunction.
the emergency room. Some authors have reported a loss of predictive value of the GCS score from 1997 onwards and call for a critical reconsideration of its use [15]. Other studies done have looked at GCS in the field versus GCS upon arrival and have found good correlation and prognostic value in predicting outcome and have even found the changes in scores from field GCS to arrival GCS to be highly predictive of outcome in patients with moderate to severe TBI [16]. Many centers use the best GCS or postresuscitation GCS in the first 24 hours or just the motor component of the GCS instead of initial GCS given these issues. Nevertheless, the GCS score is popular as a quick, reproducible estimate of level of consciousness (Table 28.3), has become a common tool for the serial monitoring of consciousness, and has been incorporated into various outcome models, such as the Trauma score, APACHE II, and the Trauma-Injury Severity score. The GCS score, which includes eye opening, motor responses in the best functioning limb, and verbal responses is limited and by no means replaces a thoughtful and focused neurologic examination. It should be supplemented by recording pupillary size and reactivity, cranial nerve examination and more detailed neurologic testing depending on the relevant neuroanatomy involved in the disease process. Even so, the use of serial GCS determinations remains a common tool in the management of patients with neurologic dysfunction.
 Figure 28.3. The effect of hyperoxia on percentage of oxygen saturation of jugular venous blood (SjvO2) at two levels of PaCO2. * p < 0.001 for SjvO2 at PaCO2 25–30 mm Hg at each PaO2. †p < 0.001 for SjvO2 between PaO2 at each PaCO2 level. (From Thiagarajan A, Goverdhan PD, Chari P, et al: The effect of hyperventilation and hyperoxia on cerebral venous oxygen saturation in patients with traumatic brain injury. Anesth Analg 87:850–853, 1998, with permission.) |
Systemic Monitoring
Although not specific to neurologic monitoring, systemic parameters, including blood pressure, arterial oxygen saturation (SaO2), PaCO2, serum glucose concentration, and temperature, have clinical relevance in the management of patients with neurologic dysfunction or injury. The relationships between these systemic variables and long-term outcome after neurologic insults are closely linked and are subject to continuing research.
Perhaps the most important systemic monitor is blood pressure, as CBF is dependent on the relationship between CPP and cerebral vascular resistance (CVR), and can be modeled generally by the equation: CBF = CPP/CVR. As previously discussed, CBF is maintained relatively constant over a wide range of blood pressures (pressure autoregulation) through arteriolar changes in resistance (assuming no change in brain metabolism) in healthy individuals. After brain injury, autoregulation may become impaired, especially in traumatically brain-injured patients. Chesnut et al. [17,18] reported that even brief periods of hypotension (systolic blood pressure less than 90 mm Hg) worsened outcome after TBI, and recommended that systolic blood pressure be maintained greater than 90 mm Hg (with possible benefit from higher pressures). These recommendations have also been promoted by the Brain Trauma Foundation for patients with severe TBI [19]. To achieve this goal, the use of vasoactive substances, such as norepinephrine, may be required [20]. Nevertheless, optimal blood pressure management
for patients with TBI has yet to be defined. Some clinical data suggest that the influence of hypotension on outcome after TBI is equivalent to the influence of hypotension on outcome after non-neurologic trauma [21]. Proposed treatment protocols include CPP greater than 70 mm Hg [22], greater than 60 mm Hg [23], or greater than 50 mm Hg [24]. The augmentation of CPP above 70 mm Hg with fluids and vasopressors has, however, been associated with increased risk of acute respiratory distress syndrome and is not universally recommended [23].
for patients with TBI has yet to be defined. Some clinical data suggest that the influence of hypotension on outcome after TBI is equivalent to the influence of hypotension on outcome after non-neurologic trauma [21]. Proposed treatment protocols include CPP greater than 70 mm Hg [22], greater than 60 mm Hg [23], or greater than 50 mm Hg [24]. The augmentation of CPP above 70 mm Hg with fluids and vasopressors has, however, been associated with increased risk of acute respiratory distress syndrome and is not universally recommended [23].
Table 28.3 Glasgow Coma Scale | ||||||||||||||||||||||||||||||||||||||||||||
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Another essential step in insuring adequate CDO2 is the maintenance of adequate CaO2, which in turn is dependent on Hgb and SaO2; therefore, anemia and hypoxemia can reduce CDO2, which would normally result in compensatory increases in CBF. However, these compensatory mechanisms are limited. As SaO2 (or PaO2) decreases below the compensatory threshold, SjvO2 and jugular venous oxygen content (CjvO2), which reflect the ability of CDO2 to supply CMRO2, also decrease. The correlation is most evident below a PaO2 of approximately 60 mm Hg, the PaO2 at which SaO2 is 90% and below which SaO2 rapidly decreases. In contrast, as Hgb is reduced by normovolemic hemodilution, SjvO2 remains relatively constant unless severe anemia is produced [25].
The management of arterial CO2 in patients with neurologic injury has changed dramatically in the past 10 years. Although hyperventilation as a management strategy for increased ICP was routine in the 1990s, it is now reserved for acute or life-threatening increases in the intensive care unit (ICU) and is no longer recommended for routine use. Having been associated with cerebral ischemia in children and adults [9,10] with severe TBI, hyperventilation is least likely to be harmful when combined with monitoring, such as SjvO2 or PbtO2, that can identify cerebral ischemia.
Hyperglycemia increased injury in experimental TBI [26] and was associated with worse outcome in clinical TBI [27,28], although it is difficult to distinguish between elevated glucose causing worsened outcome versus increased severity of TBI inducing more elevated glucose levels [29]. In critically ill patients requiring mechanical ventilation, elevated glucose levels were associated with worsened outcomes [30], and current recommendations are to tightly control serum glucose in critically ill patients in the medical and surgical ICU [31]. Caution must be exercised in the brain injured patient as there is also evidence to suggest that hypoglycemia can be more detrimental than hyperglycemia and microdialysis studies in traumatic brain injury patients found that extracellular glucose concentration is low after TBI and is associated with markers for tissue distress and poor outcome [32].
The monitoring and management of body temperature remains an important aspect of care for critically ill patients. Hypothermia and hyperthermia should be considered separately in this context. The use of hypothermia as a treatment for brain injury, while demonstrating benefit in animals [33] and in some phase II human studies, has not shown consistent benefit in larger studies [34] and is not recommended for general use in TBI [35,36]. Although the largest clinical trials (NABISH-1 and Hypothermia Pediatric Head Injury Trial Investigators and the Canadian Critical Care Trials Group) were negative [37,38], there were numerous smaller human trials and meta-analyses that suggested improved neurologic outcomes with hypothermia in TBI. Some authors suggest that the failure of these trials was because of poor protocol design and lack of proper management of the side effects of hypothermia [39,40]. In contrast, induced hypothermia after resuscitation from cardiac arrest (secondary to ventricular tachycardia or fibrillation) has improved outcome in some trials [41,42]. Research into this complex area is ongoing, and clinical practice is likely to undergo further refinement.
Hyperthermia is common in critically ill patients, occurring in up to 90% of patients with neurologic disease, related to both diagnosis and length of stay [43,44]. Hyperthermia is generally associated with poorer outcome when associated with neurologic injury in adults and children [45], but a causal link with adverse outcome (as with serum glucose levels) is lacking. It is unclear whether increased temperatures result in worsened long-term neurologic outcome, or whether a greater severity of brain injury is associated with more frequent or severe increases in systemic temperature.
The method of temperature monitoring is important. Thermal gradients exist throughout the body, and the site of measurement influences the diagnosis of hypothermia, normothermia, or hyperthermia. Measurements of systemic temperature may underestimate brain temperature. In studies of temperature monitoring by site, variations of up to 3°C have been identified between the brain and other routinely used monitoring sites, emphasizing the importance of monitoring site selection in patients with neurologic injury and the need to appreciate the difference between brain temperature and the active site of measurement used clinically for a given patient.
