Continuous electroencephalographic monitoring in neurocritical care

This article reviews current and future applications of continuous electroencephalography (cEEG) to monitor brain function and physiology in the neurologic intensive care unit. In comatose patients, cEEG may provide otherwise unobtainable information and influence therapeutic management, and also help determine the prognosis of patients with acute brain injury. This technique is best used for the detection of subclinical seizures, which may frequently occur during or after treatment of convulsive status epilepticus and after many types of acute brain injury, particularly trauma. The other main application of cEEG is as a primary monitor of brain function. cEEG can detect focal cerebral ischemia, such as that caused by vasospasm after subarachnoid hemorrhage, as well as global ischemia related to intracranial pressure elevation and insufficient cerebral perfusion pressure. Other potential applications include prognostication in coma and titration of continuous infusion sedative therapy. New technologic developments include continuous digital video EEG, automated seizure-detection software, and user-friendly online quantitative EEG analysis.     

Continuous EEG monitoring in the intensive care unit

It is now feasible and desirable to continuously monitor brain function with EEG in critically ill patients. Nonconvulsive seizures are more common than previously recognized and may contribute to impaired mental status and brain injury. Alerting stimuli commonly elicit periodic or ictal-appearing EEG patterns. Cerebral ischemia can be detected at a reversible stage with continuous EEG monitoring (cEEG). With the current availability of treatments for acute ischemia, this early detection has great potential for the prevention of stroke, but is only now beginning to be utilized for this purpose. The intensive care unit poses many technical difficulties for EEG acquisition, and artifact recognition is more important than ever. Recording synchronized video with EEG is essential for maximizing the efficiency and accuracy of cEEG interpretation, and quantitative EEG analysis can be quite helpful. The role of the EEG technologist is particularly important in these patients to aid in recognizing and minimizing artifact, to enhance communication between electroencephalographers and clinicians, to assess the effect of alerting stimuli, and to note possible subtle clinical correlates of electrographic seizures.     

Advanced Monitoring of Systemic Hemodynamics in Critically Ill Patients with Acute Brain Injury

Hemodynamic monitoring is widely used in critical care; however, the impact of such intervention in patients with acute brain injury (ABI) remains unclear. Using PubMed, a systematic review was performed (1966–August 2013), and 118 studies were included. Data were extracted using the PICO approach. The evidence was classified, and recommendations were developed according to the GRADE system. Electrocardiography and invasive monitoring of arterial blood pressure should be the minimal hemodynamic monitoring required in unstable or at-risk patients in the intensive care unit. Advanced hemodynamic monitoring (i.e., assessment of preload, afterload, cardiac output, and global systemic perfusion) could help establish goals that take into account cerebral blood flow and oxygenation, which vary depending on diagnosis and disease stage. Choice of techniques for assessing preload, afterload, cardiac output, and global systemic perfusion should be guided by specific evidence and local expertise. Hemodynamic monitoring is important and has specific indications among ABI patients. Further data are necessary to understand its potential for therapeutic interventions and prognostication.     

Prognostic value of electroencephalography (EEG) for brain injury after cardiopulmonary resuscitation

Cardiac arrest (CA) patients can experience neurological sequelae or even death after successful cardiopulmonary resuscitation (CPR) due to cerebral hypoxia- and ischemia–reperfusion-mediated brain injury. Thus, it is important to perform early prognostic evaluations in CA patients. Electroencephalography (EEG) is an important tool for determining the prognosis of hypoxic–ischemic encephalopathy due to its real-time measurement of brain function. Based on EEG, burst suppression, a burst suppression ratio >0.239, periodic discharges, status epilepticus, stimulus-induced rhythmic, periodic or ictal discharges, non-reactive EEG, and the BIS value based on quantitative EEG may be associated with the prognosis of CA after successful CPR. As measures of neural network integrity, the values of small-world characteristics of the neural network derived from EEG patterns have potential applications.     

Monitoring Nutrition and Glucose in Acute Brain Injury

The metabolic response to injury is well described; however, very little is understood about optimal markers to measure this response. This summary will address the current evidence about monitoring nutritional status including blood glucose after acute brain injury (ABI). An electronic literature search was conducted for English language articles describing the testing, utility, and optimal methods to measure nutritional status and blood glucose levels in the neurocritical care population. A total of 45 articles were included in this review. Providing adequate and timely nutritional support can help improve outcome after ABI. However, the optimal content and total nutrition requirements remain unclear. In addition, how best to monitor the nutritional status in ABI is still being elucidated, and at present, there is no validated optimal method to monitor the global response to nutritional support on a day-to-day basis in ABI patients. Nitrogen balance may be monitored to assess the adequacy of caloric intake as it relates to protein energy metabolism, but indirect calorimetry, anthropometric measurement, or serum biomarker requires further validation. The adverse effects of hyperglycemia in ABI are well described, and data indicate that blood glucose should be carefully controlled in critically ill patients. However, the optimal frequency or duration for blood glucose monitoring after ABI remains poorly defined. There are significant knowledge gaps about monitoring nutritional status and response to nutritional interventions in ABI; these need to be addressed and hence few recommendations can be made. The optimal frequency and duration of blood glucose monitoring need further study.     

Continuous EEG monitoring in the evaluation of non-convulsive seizures and status epilepticus

Non-convulsive seizures (NCSzs) and non-convulsive status epilepticus (NCSE) occur in a substantial proportion of patients with acute brain injury. These acute seizure disorders are often unrecognized and under-diagnosed. Seizure semiology of NCSz is too subtle clinically to be noticed. Most often, mental status impairment is the presenting feature. Changes in the functions of the thalamo-cortical system in patients with impaired consciousness can be detected by continuous EEG (cEEG) monitoring. cEEG monitoring allows detection of the changes at a reversible stage, often when there are no clinical indications of such phenomena. In addition EEG provides reasonable spatial resolution and excellent temporal resolution. This makes cEEG an excellent method for supplementing single or serial recordings in the detection of NCSzs and NCSE. Recent advances in digital EEG have made cEEG monitoring in the neurological intensive care unit (NICU) technically feasible. Current evidence suggests that the common clinical denominator associated with electrographic seizures or NCSzs is mental status impairment. In NCSE, the duration of ictal activity and the time of delay to diagnosis are independent predictors of poor outcome. It will be prudent to do cEEG monitoring in any patient with impaired consciousness either in the setting of acute brain injury or with no clear explanation to detect NCSzs/NCSE. Early recognition and timely intervention is likely to be associated with good outcomes.     

Continuous electroencephalogram monitoring in critically ill patients

The past few years have witnessed remarkable advances in continuous EEG monitoring (cEEG). The indications and applications for cEEG are broadening, including detection of nonconvulsive seizures, spell characterization, and prognostication. Seizures are common in the critically ill, are usually nonconvulsive, and can easily be missed without cEEG. Interpretation and clinical management of the complex periodic and rhythmic EEG patterns commonly identified in these patients require further study. With the use of quantitative analysis techniques, cEEG can detect cerebral ischemia very early, before permanent neuronal injury occurs. This article reviews the indications and recent advances in cEEG in critically ill patients. Continuous brain monitoring with cEEG is rapidly becoming the standard of care in critically ill patients with neurologic impairment.     

Predictors of nonconvulsive seizures among critically ill children

Purpose: Continuous electroencephalography (EEG) monitoring is a valuable tool for the detection of seizures among critically ill children, in particular when these seizures occur without clinical signs: termed nonconvulsive seizures. Continuous EEG monitoring is a limited resource in many centers. We sought to identify which critically ill children most frequently experience nonconvulsive seizures, and thus may particularly benefit from continuous EEG monitoring. Methods: Single‐center review was undertaken of consecutive diagnostic continuous EEG (cEEG) recordings performed in our pediatric and neonatal intensive care units (ICUs). We examined the indications for monitoring, the clinical characteristics of monitored patients, the occurrence and timing of seizures, and clinical and EEG characteristics associated with nonconvulsive seizures. Key Findings: One hundred twenty‐one patients underwent diagnostic continuous EEG monitoring, for a mean duration of 26 h. Seizures were detected in 32% of these patients, of which 90% experienced some nonconvulsive seizures, and 72% experienced exclusively nonconvulsive seizures. Patients with nonconvulsive seizures had significantly greater odds of having acute epilepsy, acute structural brain injury, prior in‐hospital convulsive seizures, and the presence of interictal epileptiform abnormalities on EEG. Significance: Seizures are common among critically ill children undergoing diagnostic cEEG monitoring. The great majority of these seizures are nonconvulsive, requiring EEG for their detection. Predictors of nonconvulsive seizures include acute epilepsy, acute structural brain injury, prior in‐hospital convulsive seizures, and interictal epileptiform abnormalities on EEG. These findings can help inform future allocation of limited cEEG monitoring resources to those patients at greatest risk for nonconvulsive seizures.     

Neurophysiological assessment of brain dysfunction in critically ill patients: an update

The aim of this review was to provide up-to-date information about the usefulness of clinical neurophysiology testing in the management of critically ill patients. Evoked potentials (EPs) and electroencephalogram (EEG) are non-invasive clinical neurophysiology tools that allow an objective assessment of the central nervous system’s function at the bedside in intensive care unit (ICU). These tests are quite useful in diagnosing cerebral complications, and establishing the vital and functional prognosis in ICU. EEG keeps a particularly privileged importance in detecting seizures phenomena such as subclinical seizures and non-convulsive status epilepticus. Quantitative EEG (QEEG) analysis techniques commonly called EEG Brain mapping can provide obvious topographic displays of digital EEG signals characteristics, showing the potential distribution over the entire scalp including filtering, frequency, and amplitude analysis and color mapping. Evidences of usefulness of QEEG for seizures detection in ICU are provided by several recent studies. Furthermore, beyond detection of epileptic phenomena, changes of some QEEG panels are early warning indicators of sedation level as well as brain damage or dysfunction in ICU. EPs offer the opportunity for assessing brainstem’s functional integrity, as well as subcortical and cortical brain areas. A multimodal use, combining EEG and various modalities of EPs is recommended since this allows a more accurate functional exploration of the brain and helps caregivers to tailor therapeutic measures according to neurological worsening trends and to anticipate the prognosis in ICU.     

Perfusion CT to evaluate the effect of transluminal angioplasty on cerebral perfusion in the treatment of vasospasm after subarachnoid hemorrhage

Introduction  

Splanchnic ischemia (SI) and increased gut permeability (GP) have been described in acute brain injury (ABI), although their incidence and relation to the type and severity of injury are uncertain. The aim of this study was to evaluate the incidence of both abnormalities in a series of patients with severe ABI secondary to intracranial hemorrhage (ICH) managed with a resuscitation protocol pursuing adequate cerebral and systemic hemodynamics.     

Emergency EEG and continuous EEG monitoring in acute ischemic stroke.

There is physiologic coupling of EEG morphology, frequencies, and amplitudes with cerebral blood flow. Intraoperative continuous electroencephalographic monitoring (CEEG) is an established modality that has been used for 30 years to detect cerebral ischemia during carotid surgery. These facts have generated interest in applying EEG/CEEG in the intensive care unit to monitor cerebral ischemia. However, its use in acute ischemic stroke (AIS) has been limited, and its value has been questioned in comparison with modern MRI imaging techniques and the clinical neurologic examination. This review presents evidence that EEG/CEEG adds value to early diagnosis, outcome prediction, patient selection for treatment, clinical management, and seizure detection in AIS. Research studies correlating EEG/CEEG and advanced imaging techniques in AIS are encouraged. Improvements in real-time ischemia detection systems are needed for EEG/CEEG to have wider application in AIS.     

Increased vulnerability of the mildly traumatized rat brain to cerebral ischemia: the use of controlled secondary ischemia as a research tool to identify common or different mechanisms contributing to mechanical and ischemic brain injury

Fasted Wistar rats were subjected to either a mild mechanical injury, 6 min of transient forebrain ischemia, or a mild mechanical injury followed 1 h later by 6 min of forebrain ischemia. EEG and evoked potentials were assessed intermittently and morphological analyses were performed after 7 days postinjury survival. In all groups complete qualitative recovery of electrical activity and general behavior was observed with 7-day survival. However, rats subjected to combined concussion and ischemia displayed EEG spike activity and a delayed return of EEG and evoked potentials during acute recovery not evident in other groups. No overt neuronal cell loss was seen in trauma alone and was minimal or absent in ischemia alone. However, extensive bilateral CA1 and subicular pyramidal cell loss was found in the septal and mid-dorsal hippocampi in the combined trauma and ischemia group. In contrast, no overt axonal injury was found in any group. We conclude that even mild mechanical injury can potentiate selective ischemic hippocampal neuronal necrosis in the absence of overt axonal injury. This potentiation also occurs in conjunction with more generalized electrophysiological disturbances such as EEG evidence of postischemic neuronal hyperactivity suggesting that mild concussion may also decrease the threshold for post-ischemic neuronal excitation. These results suggest the potential of this model for examining common or different injury mechanisms in mechanical and ischemic brain injury.     

Ellen R. Grass Lecture: Rapid EEG analysis for intensive care decisions in status epilepticus

Nonconvulsive status epilepticus in intensive care units (ICUs) is common and increases the risk of death. Nonconvulsive status epilepticus treatment delays are associated with poor patient outcomes. Continuous EEG or EEG-video monitoring is used in ICU settings to diagnose subtle seizures and nonconvulsive status epilepticus among at-risk populations including patients with closed head injuries and altered consciousness, stroke, subarachnoid hemorrhage, neonates at-risk for sepsis or hypoxic-ischemic encephalopathy, and children who have undergone surgery for congenital heart disease. However expert EEG interpretation, currently required for accurate diagnosis, often lags behind the real-time recordings by hours or even longer. At most hospitals the numbers of at-risk patients in intensive care units far exceeds the capacity of the available EEG equipment and personnel to perform and interpret EEGs. Seizure-detection software, compressed EEG spectral arrays, and near real-time remote EEG interpretation have brought us closer to the goal of real-time analysis of EEG for intensive care decisions, but even at major tertiary referral centers the vast majority of at-risk ICU patients do not undergo EEG monitoring. Additional technological advances, innovative use of EEG technologists and ICU personnel, and clinical trials of new EEG monitoring technology and associated clinical outcomes are needed to achieve the goal of optimal use of EEG data for intensive care decisions.     

Hemispheric asymmetry and temporal profiles of cerebral pressure autoregulation in head injury

A moving correlation index (Mx-ABP) between arterial blood pressure (ABP) and mean middle cerebral artery blood flow velocity (CBFV) can be used to monitor dynamic cerebrovascular autoregulation (CA) after traumatic brain injury (TBI). In this study we examined hemispheric CA asymmetry and temporal CA profiles, their relationship with ABP and CBFV, and their prognostic relevance. Mx-ABP was calculated for each hemisphere in 25 TBI patients second-daily for as long as they were receiving sedation and analgesia. Forty-nine recordings were obtained, between one and six per patient. Four time periods were defined: immediate - postinjury days (PID) 0 and 1; early - PID 2 and 3; intermediate - PID 4 and 5, and late - PID 6 and later. GOS was estimated at discharge, GOS 4 and 5 were considered favorable (15 patients) and GOS 1-3 unfavorable outcome (10 patients). A Mx difference >0.2 was classified as hemispheric asymmetry (HA). HA was observed at least once in 12 of the 25 patients (48%) and in 18 of 49 recordings (37%). It was observed during all time periods: 35%, 43%, 25%, 43%, respectively, and was not related to outcome. There was no difference in mean CBFV or ABP between patients with and without HA. HA was not related to interhemispheric CBFV differences. A significant improvement in Mx was seen over time. Hemispheric CA asymmetry is common after traumatic brain injury. It does not bear significant clinical or predictive relevance, and it is unrelated to CBFV or ABP. CA is most profoundly disturbed during the immediate postinjury phase and improves gradually during the ICU course. Further studies are needed to investigate CA during post ICU recovery and rehabilitation.     

Critically ill benign EEG variants: Is there such a thing?

Despite growing use of critical care electroencephalography (ccEEG) to detect seizures and status epilepticus in the intensive care unit (ICU), integrating ccEEG findings with traditionally described benign EEG variants (BEVs) is a relatively new concept. BEV-like waveforms are now increasingly encountered in the ICU, and have also been explicitly included in proposed definitions of brief potentially ictal rhythmic discharges (BIRDs) in the ICU, bringing to the fore the question of if and which EEG patterns in critically ill patients can be safely deemed “benign”. Though well-characterized as benign in healthy outpatients at low pre-test risk for neurologic disease, the significance of BEVs in the ICU remains largely unknown. Simultaneously, there has been mounting evidence to suggest that certain BEVs can arise from heterogeneous intracranial sources, including some pathologic generators. We conducted an extensive literature review on all known BEVs to assess what is known of BEVs in the ICU. Here we discuss critically ill BEVs and how to interpret them.     

Continuous Renal Replacement Therapy for Refractory Intracranial Hypertension

Introduction  Little is known about the effects of hemodialysis on the injured brain, however; concern exists over the use of intermittent hemodialysis in patients with acute brain injury (ABI) due to its hemodynamic effects and increased intracranial pressure (ICP) associated with therapy. Continuous renal replacement therapy (CRRT) has become the preferred method of renal support in these patients though there is limited data to support its safety. Furthermore, exacerbations of cerebral edema have been reported. CRRT is an option for the treatment of hypervolemia and in theory may improve intracranial compliance. We report the case of a poly-trauma patient with severe traumatic brain injury (TBI) in which CRRT was implemented solely for refractory intracranial hypertension. Methods  A 28-year-old male was involved in a high-speed motor vehicle collision suffering a severe TBI and polytrauma. He required significant volume resuscitation. Intensive care unit course was complicated by shock, acute respiratory distress syndrome, ventilator associated pneumonia, and development of intracranial hypertension (IH). Data were collected by retrospective chart review. Results  Continuous hemofiltration was initiated for IH refractory to medical therapy. Within hours of initiation increase, ICP improved and normalized. Hemofiltration was safely discontinued after 48 h. Modified Rankin Score was 2 at 90 days. Conclusion  Though unproven, CRRT may be beneficial in patients with IH due to gentle removal of fluid, solutes, and inflammatory cytokines. Given the limited data on safety of CRRT in patients with ABI, we encourage further reports.     

Plenary Session II: Neurophysiological Monitoring of the Critically Ill 8:15 a.m.–10:15 a.m.

¹ Ronald Emerson (   ¹ Neurology, Columbia University, New York, NY )
Until recently, functional neurological assessment of neurologically critically ill patients has been limited largely to periodic physical examinations, often compromised by medication effects, along with occasional, brief EEG's. This is changing with the availability of continuous/EEG monitoring, made practical by recent advances in computer and network technology. Indeed, in some centers, continuous EEG monitoring, with or without concurrent video, has become part of routine neuro-critical care. Its greatest initial impact has been on the recognition and management of non-convulsive seizures. The use of EEG monitoring for real-time detection of cerebral ischemia will likely become compelling as effective treatments for acute stroke emerge. Practical implementation of EEG-based cerebral ischemia detection in the ICU, however, awaits development of reliable, robust automated detection algorithms capable of triggering bedside alarms. Concurrent monitoring of other physiological parameters, including blood pressures, intracranial pressure and brain tissue oxygenation along with EEG-derived parameters may provide the basis for development of better treatment models incorporating multivariable feedback systems. Evoked potentials can provide useful prognostic information, with long latency evoked potentials attracting recent attention as possible predictors of recovery of consciousness in comatose patients.     

Acute antiepileptic drug use in intensive care units

Background

In intensive care units (ICUs), antiepileptic drugs (AEDs) are used for manifold indications. This is the first study to assess the prevalence of acute AED use in ICUs and to identify associated clinical variables.

Methods

All patients in seven adult ICUs of a German university hospital in 2016 were retrospectively evaluated. Data were extracted from the computerized critical care information system and manually reviewed. Acute AED treatments were defined as initiated during ICU treatment or ≤?6 h before ICU admission, excluding benzodiazepines and sedatives.

Results

Among 2335 patients evaluated, 8.8% received acutely started AEDs: 5.1% due to epileptic seizures, mostly acute symptomatic, and 3.7% for other indications like pain, post-hypoxic myoclonus, and singultus. Following multivariable analyses, acute AED use was independently associated with intracranial reasons for ICU admission and long durations of ICU stay, but not with increased disease severity scores or mortality. Levetiracetam was the substance most frequently used to treat epileptic seizures (88%) as was pregabalin for other conditions (49%). Among surviving patients, acute AEDs were continued beyond ICU discharge in 86% if seizure-related and in 78% if not seizure-related, even if there was no evident need for long-term AED treatment.

Conclusions

One out of eleven ICU patients receives acute AEDs, in almost half of cases for non-seizure indications. Acute AED use is a marker for intracranial ICU indications and prolonged ICU treatments. Usually, newer-generation AEDs are employed with favourable pharmacokinetic and safety profiles. However, whenever possible, acutely started AED should be discontinued before discharge from ICU.

     

Inducing ketogenesis via an enteral formulation in patients with acute brain injury:a phase II study

ABSTRACT

Objective: Although extensively studied in children, the safety and tolerability of ketone supplementation in adults is unclear, particularly in the acute brain injury population. The purpose of this study was to examine the feasibility and safety of inducing ketosis using an enteric ketogenic formulation and determine its impact on intracranial and cerebral perfusion pressures and metabolic parameters.

Methods: Prospective interventional Phase II trial of ventilated critically ill patients with acute brain injury administered a ketogenic feed over a 6 day period.

Results: 20 patients were recruited, 5 females and 15 males, 3 with stroke, 2 with subarachnoid haemorrhage and 15 with traumatic brain injury. Feeds were well tolerated with 19 patients completing study. There was a significant increase in both plasma beta-hydroxybutyrate and acetoacetate from 0.24± 0.31 mmol/l and 0.19 ± 0.16 mmol/l to 0.61 ± 0.53 mmol/l (p =0.0005) and 0.52 ± 0.40 mmol/l (p<0.0001) respectively over the 6 day period. Total daily Ketocal® caloric intake was positively correlated with plasma beta-hydroxybutyrate concentrations (p=0.0011). There was no significant correlation between the cerebral hypertension and cerebral hypoperfusion indices and plasma ketone concentrations. In 95% of patients there were no clinically significant changes in acid/base status over the 6 days with pH remaining within normal range.

Conclusion: In patients with acute brain injury, an enterally administered ketogenic formulation increased plasma ketone concentrations, was well tolerated, did not impact on cerebral hemodynamics and can be safely administered.

Clinical trial registered at the Australian New Zealand Clinical Trials Registry (ACTRN12616000332426)

Abbreviations: BHB: betahydroxybutyrate; AcAc: acetoacetate; ABI: acute brain injury; TBI: traumatic brain injury; CSF: cerebrospinal fluid; SAH: subarachnoid injury; CVA: cerebrovascular accidents; ICP: intracranial pressure; CPP: cerebral perfusion pressure; ICU: intensive care unit; EVD: external ventricular device; CHI: cerebral hypoperfusion index; IHI: intracranial hypertension index; GCS: Glasgow Coma Scale