Level of Consciousness: Glasgow Coma Scale

The level of consciousness is typically assessed by the Glasgow coma scale (GCS). Numerical scores are assigned for best responses in the categories of eye opening, motor response, and verbal response (Table 28.2). The GCS was originally described more than 30 years ago for the continuous assessment of patients with TBI after the initial period of stabilization (46). Because its assessment is quick, objective, and relatively reliable (47), and because the resulting score is easily documented and communicated, the GCS has gained widespread use in emergency medicine and critical care patients. It has been incorporated into the Acute Physiology and Chronic Health Evaluation (APACHE) score (48) and the World Federation of Neurosurgical Societies (WFNS) grading of subarachnoid hemorrhage (49).

The level of consciousness is a reflection of the severity of many different disease states, and can be compromised not just by diseases of the CNS, but also at the extremes of a wide variety of other organ dysfunctions common in critical care. Not surprisingly, therefore, the scores from a tool such as the GCS that assesses the level of consciousness may be associated with prognosis and outcome. For the GCS, an association of lower scores with worsened outcome has been shown for TBI (50), subarachnoid hemorrhage (51), brain abscess (52), survival after cardiac arrest (53,54), and septic encephalopathy (55). For example, in TBI, a GCS score greater than 7 suggests a 90% likelihood of an outcome of moderate disability or better, whereas a score less than 7 suggests an increased risk of death or persistent vegetative state that approaches 60% to 90% for a GCS score of 3 (50,56,57). New data suggest that, at least in children, early decompressive craniectomy significantly increases the likelihood of better outcome (only mild disability) (58). In aneurysmal subarachnoid hemorrhage, a GCS score less than 13 after initial treatment of increased ICP (i.e., WFNS grade 4 or 5) corresponds to a 60% to 90% chance of a poor functional outcome or death, whereas such outcomes only affect 14% of patients whose level of consciousness is unaffected (GCS 15, WFNS grade 1 or 2) (51).

TABLE 28.2 Glasgow Coma Scale

Despite its widespread use and appeal, the GCS has several important limitations, even if applied correctly. One is the information loss inherent in reducing a graded assessment of three responses into a single number. The second is that mechanical problems such as swelling and endotracheal intubation may prevent proper assessment of eye opening and verbal response. In this setting, some clinicians assign the lowest component score, whereas others try to infer the “true” score from related neurologic findings, and still others add the subscript “T” to indicate an intubated patient. Third, sedatives and neuromuscular-blocking agents affect the GCS score upon repeated assessment. Finally, although the degree of brainstem involvement may reflect the severity of coma, the GCS provides limited information about brainstem function.

Determination of Brain Death

The determination of brain death for purposes of organ donation or withdrawal of life support is an area that has brought both the merits and the limitations of the neurologic examination into clear focus. Because the clinical determination of brain death requires a comprehensive and methodical assessment of the patient (59), its steps may serve as a guide to the neurologic examination of a comatose patient. An algorithm for the determination of brain death is shown in Figure 28.6. Given the gravity of the “therapeutic” consequences of the diagnosis of brain death, a prerequisite to its determination is a clinical picture, typically supported by imaging studies, that is consistent with the occurrence of brain death.

TABLE 28.3 Neurologic States Resembling Brain Death

The first step in the neurologic examination for the determination of brain death is the determination of coma (i.e., lack of responsiveness to external stimuli due to unconsciousness as discussed above). Motor responses elicited by the examination need to be differentiated from spontaneous movements during the examination. The latter are typically brief, slow movements that originate from the spinal cord and do not become integrated into decerebrate or decorticate responses. Only rarely are they reproducible upon repeat testing. Reproducible partial eye opening that failed to reveal the iris has been described in response to a peripheral painful stimulus in a patient who fulfilled clinical criteria of brain death (60). Conditions that may confound the clinical diagnosis of brain death are listed in Table 28.3. In addition to considering such confounding conditions, the diagnosis of brain death should be consistent with imaging studies and/or the overall clinical picture before the formal determination of brain death is considered.

The next step in the neurologic examination is the assessment of brainstem function. As in the assessment of the level of consciousness, direct trauma to either afferent or efferent structures needs to be considered before any of the tests of brainstem function are interpreted as negative. Typical tests, their afferent and efferent pathways, and potentially interfering clinical conditions are summarized in Table 28.4.

TABLE 28.4 Clinical Examination of the Brainstem during Evaluation for Brain Death

To complete the diagnosis of brain death, an apnea test is performed to test the response to an acute decrease in the pH of CSF due to hypercarbia. Hypercarbia is induced by disconnecting mechanical ventilation while continued oxygenation is assured by both preoxygenation and apneic oxygenation. Absence of respiratory movements at an arterial PCO₂ of 60 mmHg or after an increase in PCO₂ of 20 mmHg is consistent with brain death. Apnea testing may be complicated by arterial hypotension due to loss of arterial and autonomic tone (61). While such hypotension corroborates the diagnosis of brain death, it makes the hemodynamic stability required for apnea testing difficult to attain. The apnea test may trigger movement responses, which reflect residual spinal activity (62).

Once all these criteria for brain death are met, an observation period followed by repeat assessment or a confirmatory test is used to reach a final diagnosis (see Fig. 28.6). Cerebral angiography is the gold standard among confirmatory tests. Contrast media is injected into the aortic arch and distributes to the external carotid circulation, whereas the internal carotid and vertebral arteries fill only to the level of the skull base and atlanto-occipital junction, respectively. Similar findings can be obtained with MR angiography or with single photon emission CT ^99mTc-HMPAO. Electroencephalography (EEG) and transcranial Doppler (TCD) are also frequently used as confirmatory tests. Their role will be discussed in greater detail below.

Electroencephalography

To understand how EEG can be used in the ICU, the clinician must first understand how scalp-recorded EEG is produced and what factors may affect the recordings. EEG activity is generated by neurons in the pyramidal layer of the cerebral cortex. The scalp-recorded EEG is produced by a summation of excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs), not actual cellular depolarization. EPSPs and IPSPs are produced by the spontaneous release of small packets of excitatory or inhibitory neurotransmitters from a nerve terminal that produce only very small changes in the postsynaptic membrane potential, insufficient to cause depolarization. As a result, the amplitude (voltage) of EEG electrical activity is much smaller than the electrocardiogram, ranging from less than 5 μV in the elderly to over 100 μV in the teenager. As a result, the EEG signal cannot be recorded remotely from the generator site, and practically speaking, EEG activity recorded from a single electrode only reflects cortical activity directly beneath the recording site. In addition, because the EEG signal is so small, poor electrode contact with the scalp may result in significant loss of signal.

Maintenance of ion fluxes associated with the production of the EEG is an energy-requiring process. Pharmacologic total suppression of the EEG will result in a 50% to 60% decrease in CMRO₂ (70,71). The decrease in oxygen requirement parallels the suppression of the EEG in cases of lesser suppression. An EEG that is merely slowed pharmacologically will be associated with a higher CMRO₂ than an EEG that is totally suppressed or flat.

The EEG is organized spatially and temporally, but patterns of organization are much more difficult for the clinician to recognize, primarily because few clinicians have significant experience with normal EEG patterns, pathologic EEG patterns, or drug-induced EEG patterns. EEG patterns are described primarily in terms of frequency (how fast voltage oscillations occur) and amplitude (size or voltage). Slower frequency ranges include δ (3 Hz or slower) and θ (3.5 to 7.5 Hz). These frequencies are not seen in the normal awake adult but are commonly seen in the naturally asleep adult or in the adult who is receiving therapeutic doses of sedative-hypnotic and/or analgesic drugs. Faster frequency ranges include α (8 to 13 Hz) and β (>13 Hz). Alpha frequencies (8 to 13 Hz) tend to be present on the posterior part of the head and are most prominent with the eyes closed. Alpha activity disappears with attention and concentration, replaced with faster β activity. Beta frequencies are commonly seen more toward the front of the head and are associated with increased “function” of a particular part of the brain. In the neurologically abnormal patient, θ and δ frequencies may be focal, associated with a specific loss of function, or more global, associated with generalized neurologic dysfunction. Generally, the more severe the neurologic damage/dysfunction, the slower the recorded EEG activity will be. For example, a patient with a receptive and expressive aphasia will likely demonstrate EEG slowing (θ and δ waves) over the dominant temporal lobe.

Sedative-hypnotic drugs produce a change in neurologic function that is likewise paralleled by EEG changes. The EEG changes associated with sedative-hypnotic drugs are predictable, related both to the drug used and the dosage of drug given. The vast majority of sedative-hypnotic drugs used in the ICU will produce identical, dose-related changes in the EEG. Table 28.5 shows EEG pattern changes associated with most drugs that would be used in the ICU environment. Dexmedetomidine sedation produces EEG patterns indicating that patients are more sedated than they actually are. Even a low-dose infusion produces a combination of slow delta oscillations with bursting 9- to 15-Hz spindles (72). Combinations of drugs, of course, will have different effects than when either drug is used alone. Specific data regarding the effect of combinations of drugs is limited and beyond the scope of this chapter. However, in general, both sedative and analgesic drugs will increase the primary effect of the drug being used in the higher dose as well as add effects of their own.

In summary, the scalp-recorded EEG reflects the function of closely underlying neuronal tissue. These functions may be altered by neurologic damage, pharmacologic means, normal changes in function associated with changes in alertness or sleep, or any combination of these factors. Thus, whether the EEG is used as a monitor or a diagnostic/prognostic tool, interpretation of data without a thorough knowledge of all factors that could influence recordings is not possible.

Diagnostic Electroencephalography in the Intensive Care Unit

Diagnostic EEG studies or EEG monitoring in the ICU is done primarily for one of three purposes: Brain death determination, monitoring for evidence of seizure activity or cerebral ischemia, and determination of drug effect for the purposes of titrating sedative and analgesic drugs or control of ICP.

Criteria for brain death vary from state to state, but in most states, a 16- to 32-channel isoelectric EEG on two consecutive recordings at least 24 hours apart can provide strong corroborating evidence for cessation of brain function (see Fig. 28.6). Because other factors affecting the EEG can produce an isoelectric EEG in the absence of brain death, the EEG cannot be used as the sole evaluation for brain death. Although it is likely that drug levels (see Table 28.5) will decline significantly over a 24-hour period, patients with massive drug overdose or impaired metabolic pathways may show an isoelectric EEG for much longer than 24 or 48 hours. In these cases, the neurologic examination may also not be useful because high drug levels may suppress even the most resistant reflex responses. Fortunately, other diagnostic testing methods, including other electrophysiologic and nonelectrophysiologic methods, may be helpful. EPs (see below), for example, are more resistant to drug effects than the EEG and can frequently be used to demonstrate brainstem and cortical function, even in the face of an isoelectric EEG (73,74). In addition, an EEG recorded immediately after cardiac arrest may show an isoelectric pattern that subsequently recovers (75). Cortical EPs have also been demonstrated to be more reliable in assessing neurologic function immediately after an ischemic/anoxic insult (75). In summary, a scalp-recorded, 16- to 32-channel EEG is a helpful adjunct to the diagnosis of brain death, provided all other factors influencing the EEG are understood and controlled.

TABLE 28.5 Sedative-Hypnotic and Analgesic Drugs and the Electroencephalogram (EEG)

Continuous EEG monitoring in the ICU or, alternatively, sequential diagnostic EEG studies, have been described for detection of nonconvulsive seizure (NCS) activity (or seizure activity in the pharmacologically paralyzed patient) and for detection of cerebral ischemia (67–69,76–78). This type of monitoring requires multiple channels of information to obtain adequate monitoring coverage of the entire brain. A highly trained technologist observes the patient simultaneously with the EEG recording and operates the equipment and maintains recording electrodes during nursing care that will commonly dislodge them. The technologist also provides real-time neurophysiologic data to the clinicians caring for the patient. Processed EEG algorithms have been developed to facilitate detection of ischemia epileptiform and frank seizure activity during continuous EEG monitoring (79,80). Although the technology shows promise even in the hands of nonneurophysiologists (81), this technique has not yet evolved enough to eliminate the need for an on-site technologist with monitoring experience.

Continuous EEG monitoring in the ICU has demonstrated that NCSs are much more common than previously thought (77,78,82). NCSs have been reported following neurosurgical procedures, subarachnoid hemorrhage, CNS infection, head injury, and other conditions. In addition, there is evidence using neuron-specific enolase as a marker of neurologic injury that NCSs may produce neurologic damage and that seizure duration and time to diagnosis are significantly related to the extent of damage and long-term outcome. Without continuous EEG monitoring, NCSs cannot be detected, as they are not consistently and specifically associated with other findings such as hypertension and tachycardia (82).

The personnel and fiscal costs of continuous EEG monitoring have made it unfeasible except in the larger neurologic and neurosurgical ICUs, where many patients with conditions amenable to continuous monitoring require care (76). In addition, very little outcome data exist to demonstrate that such monitoring is overall cost effective. When considering real-time neurologic monitoring in the patient whose neurologic examination cannot be assessed, much work needs to be done to determine how continuous EEG monitoring will mesh with other neurologic monitoring modalities such as ICP, CBF, brain tissue pO₂ monitoring, TCD, and microdialysis monitoring. Theoretically and based on limited clinical data (76–81), there is much promise for continuous EEG monitoring when used as a part of a multimodality neurologic monitoring program.

Monitoring of Sedation by Processed Electroencephalogy

The use of the EEG to monitor the depth of sedation in patients in the ICU has been described extensively in the literature, and nearly all techniques utilize processed EEG rather than the unprocessed analog signal. Drug effect monitoring is generally accomplished using one or two channels of EEG information, generally recorded over the frontopolar region of the cerebral cortex. This location is chosen because application of surface recording electrodes is easy in this location (no hair) and most devices designed for this purpose have been validated using frontopolar recording locations. Usage of this smaller number of channels is based on the assumption that the drug effect will be similar in all areas of the brain. This assumption is generally valid except in the case of a patient with focal brain damage. In areas of damage, the drug effect will generally be greater than usual and must be interpreted in light of the abnormal baseline recording. None of the commercially available devices for monitoring drug effects on the EEG has been calibrated or validated appropriately for monitoring drug effects in the patient with the abnormal EEG, and relatively limited information is available on the use of EEG to monitor drug effects in neurologically damaged patients (83–86).

EEG drug effect monitoring is used most commonly for titrating sedative drugs, particularly in the pharmacologically paralyzed patient, but also for titration of barbiturate drugs or propofol used to control ICP (67–69,87,88). Devices used to monitor the drug effect utilize unprocessed, raw analog EEG in a fashion similar to ECG monitoring in the ICU or utilize one of three signal processing techniques: Power spectrum analysis, bispectral analysis (BIS), or EEG entropy analysis. Examples of commercial monitors include the BIS, the patient state index, SEDline, and entropy. Although the BIS monitor has been used and studied most widely among these monitors, the concepts discussed below should apply to other EEG-based monitors of sedation as well.

BIS (Aspect Medical Systems, Inc., Natick, MA) monitoring has been used in the intensive care setting to guide dosing of sedatives and reassure clinicians that paralyzed or agitated patients are amnestic but not excessively sedated (89). The BIS monitor processes EEG signals that are recorded from a self-adhesive electrode strip placed on the forehead. It calculates and displays a BIS value, a dimensionless number ranging from 0 to 100 that is derived from highly processed EEG data that includes EEG power, frequency, and bicoherence (90). Low BIS numbers indicate strong relationships among the EEG frequencies and reflect a condition consistent with a deep hypnotic state (Table 28.6). This relationship is valid despite the effects of age and infirmity on sensitivity to sedation (91,92).

Despite its obvious clinical utility, the aspects of imperfect performance of the BIS monitor are well known. For example, the BIS can decrease to numbers (20 to 50) consistent with deep general anesthesia during natural sleep without sedation (93). Moreover, although memory is less likely to form at lower BIS values, memory has been demonstrated even at a BIS in a range (40 to 60) associated with general anesthesia (94). Additionally, artifact from electromyographic, electro-oculographic (95), or pacemaker generators (96) can produce significant but spurious BIS increases (from 50s to 80s), although the algorithm has been improved in the last decade to reduce the effects of such artifacts. This finding raises the possibility of overdosing nonrelaxed or paced patients when attempting to maintain a given BIS range. BIS values can also be driven higher by medications that are CNS stimulants, such as ketamine or methylphenidate (97). Dexmedetomidine, as discussed earlier, may produce EEG patterns that will result in lower BIS values at a comparable level of sedation (71,95). In such cases, the BIS may not reflect the level of hypnosis or sedation experienced by the patient. Therefore, when the sedative dosages required to achieve a desired BIS range exceed normal expectations, the possibility of an artifactual interference deserves consideration.

TABLE 28.6 Clinical Condition Expected with Bispectral Index Values

Perhaps the most significant issue with BIS or other monitors of cortical anesthetic drug effect are their inability to differentiate deep sedation from cerebral ischemia. Both conditions cause loss of higher frequency EEG waves (α and β slowing and δ and θ wave intrusion) and, in extreme states, both can produce burst suppression or isoelectric EEG patterns with a low BIS. When O₂ delivery decreases below a level sufficient to meet the CMRO₂, electrical function fails and BIS decreases. This may partly explain improved ICU outcomes when the BIS is maintained above 60 (98). Therefore, the determination that sedation is adequate based on having achieved a target BIS value should only be made when one is confident that cerebral perfusion is adequate.

Interpretation of BIS or, for that matter, any EEG-based monitor of sedation is best accomplished when the patient’s pharmacologic support remains stable in the face of changing CPP or, conversely, the CPP remains adequate and stable during pharmacologic adjustments and BIS changes. As a corollary, the BIS can assist with guiding therapy when the adequacy of O₂ supply to the CNS is in question (99).

In summary, other than for drug effect monitoring, use of the EEG in the ICU remains relatively limited, primarily because of personnel costs and difficulty in maintaining stable technical conditions for monitoring multiple channels of information. As our understanding of underlying mechanisms for neurologic injury improves, we may be able to learn which monitoring modalities are most useful for a given clinical scenario and which can more specifically target EEG monitoring to a smaller area of the brain. In addition, as computing power continues to improve, signal processing technology will likewise improve, and EEG monitoring equipment that recognizes artifact and self-corrects technical problems may reduce the need for the continuous presence of highly trained personnel to operate the EEG in the ICU environment.

Peripheral Nerve Stimulation

The rate of recovery from neuromuscular-blocking agents depends upon the neuromuscular-blocking agent chosen, its dosing pattern (intermittent or continuous infusion), and numerous patient factors (e.g., pseudocholinesterase deficiency, hepatic or renal dysfunction, induced cytochrome P450 enzyme, organophosphate toxicity, among many others) (100). The suitability for extubation following prolonged neuromuscular blockade has traditionally relied upon functional strength testing, such as an ability to produce a negative inspiratory force or to sustain a head lift. Incomplete patient cooperation caused by sedation or confusion, among other reasons, can adversely affect these tests. Peripheral nerve stimulation (PNS), used for “muscle twitch” testing, or acceleromyography, complements such functional assessments by objectively revealing the condition of the neuromuscular junction, independent of patient participation.

Reliable interpretation of nerve stimulation requires uniform stimulation and placement parameters. Conventional PNS delivers current—adjustable up to 80 mA—in a train-of-four (TOF) series at 2 Hz as double-burst stimulation, as single shocks at 1.0 or 0.1 Hz, or by tetanic stimuli of 50 or 100 Hz. When tolerated, maximal current settings assure the best chance of delivering supra-threshold stimuli and activation of the greatest percentage of motor fibers despite changes of impedance or proximity, as can occur with electrode separation or desiccation, skin cooling, or peripheral edema. TOF and double-burst stimulation patterns do not require comparison to earlier responses for interpretation, and are therefore well suited for use in the ICU setting where recovery of neuromuscular function may take hours to days and may involve assessments by multiple providers.

Muscle twitch testing measures the force of muscle contractions in response to PNS. The ratio of the force between the last and first stimuli in a series (TOF or double-burst stimulation) best defines the percentage of acetylcholine receptors occupied by nondepolarizing neuromuscular-blocking agents in the neuromuscular junction, but is cumbersome to perform (101). Counting the loss of twitches in a TOF is a simpler method for assessing the level of block and has greater bedside utility (Table 28.7). In contrast, the TOF ratio does not change following the administration of a depolarizing neuromuscular-blocking agent such as succinylcholine. When depolarizing neuromuscular-blocking agents are used, the force of contraction diminishes equally across all stimuli and disappears altogether with sufficient dose. If an excessive depolarizing neuromuscular-blocking agent is administered, a prolonged phase II block emerges. TOF responses during a phase II block behave similarly to responses obtained following nondepolarizing neuromuscular-blocking agents.

The peripheral nerve stimulator is attached to a patient using two pre-gelled electrocardiogram electrodes, although needle electrodes can also be used. The electrodes should be placed closely (without the gels touching) to one another over a site where a nerve with motor function lies relatively superficial to the skin. Antegrade nerve conduction is improved if the positive lead is applied to the proximal electrode. The current path between electrodes should not contain the muscle whose movement is being monitored. Separation of electrodes beyond several centimeters increases the probability that the PNS current may depolarize muscle directly, causing movement unrelated to conduction through the neuromuscular junction and thus, misinterpretation of the level of neuromuscular blockade.

TABLE 28.7 Percentage of Neuromuscular Junction Blockade with Nondepolarizing Neuromuscular-Blocking Agents and Corresponding Train-of-Four and Clinical Responses

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