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    Abstract
   Introduction
    Modes of Neuromo...
    Multimodal Neuro...
    Current and Futu...
    Potential Compli...
   Conclusions
    References

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Table of Contents
REVIEW ARTICLE  
Year : 2014  |  Volume : 17  |  Issue : 1  |  Page : 25-32
Multimodal neuromonitoring in pediatric cardiac anesthesia


Department of Anesthesiology, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA

Click here for correspondence address and email

Date of Submission19-Jun-2013
Date of Acceptance13-Nov-2013
Date of Web Publication2-Jan-2014
 

   Abstract 

Despite significant improvements in overall outcome, neurological injury remains a feared complication following pediatric congenital heart surgery (CHS). Only if adverse events are detected early enough, can effective actions be initiated preventing potentially serious injury. The multifactorial etiology of neurological injury in CHS patients makes it unlikely that one single monitoring modality will be effective in capturing all possible threats. Improving current and developing new technologies and combining them according to the concept of multimodal monitoring may allow for early detection and possible intervention with the goal to further improve neurological outcome in children undergoing CHS.

Keywords: Cardiac surgery; Congenital; Monitoring; Neurological

How to cite this article:
Mittnacht AJ, Rodriguez-Diaz C. Multimodal neuromonitoring in pediatric cardiac anesthesia. Ann Card Anaesth 2014;17:25-32

How to cite this URL:
Mittnacht AJ, Rodriguez-Diaz C. Multimodal neuromonitoring in pediatric cardiac anesthesia. Ann Card Anaesth [serial online] 2014 [cited 2019 Mar 23];17:25-32. Available from: http://www.annals.in/text.asp?2014/17/1/25/124130



   Introduction Top


Despite significant improvements in overall outcome, neurological injury remains a feared complication following pediatric congenital heart surgery (CHS). Although serious neurological complications with clinical manifestation such as seizures or focal injury have been reported in 1-5% of open-heart surgery cases, [1],[2],[3] minor neurodevelopmental deficits are much more difficult to assess in infants and small children. Abnormal findings using magnetic resonance imaging (MRI) can be found in a significant number of patients with congenital heart disease (CHD) even pre-operatively, [4],[5],[6] and post-operative assessment showed new lesions or worsening of pre-existing lesions in 35-67% of patients. [7],[8] Compared with infants and older children, neonates may be particularly vulnerable to neurological injury. [9] Whereas the developing brain has a remarkable ability to compensate for injury, there is evidence that long lasting detrimental effects such as neurodevelopmental impairment are not uncommon. [10],[11] In children undergoing multiple operations, neurological deficits are even more commonly seen, suggesting a multiple impact theory. [12] Risks are not restricted to events in the operating room, but include the whole perioperative period [13] and pre-existing conditions. [14],[15] Only if adverse events are detected early enough can effective actions be initiated preventing potentially serious injury. The multifactorial etiology of neurological injury in CHS patients makes it unlikely that one single monitoring modality will be effective in capturing all possible threats. Combining the various monitoring modalities, which are currently available may allow for early detection and possible intervention with the goal to further improve neurological outcome in children undergoing surgery for CHD.


   Modes of Neuromonitoring Top


Transcranial doppler

Transcranial doppler (TCD) monitoring is based on pulsed-wave ultrasound interrogation generally of the middle cerebral artery through the temporal bone. The technology has been reviewed in details elsewhere. [16] The moving blood cells cause a shift in the reflected ultrasound frequency (Doppler principle) and a blood flow velocity can be determined. Despite theoretical limitations in measuring velocity and not blood flow, several studies have shown a good relationship between cerebral blood flow and velocity in clinical use. [17],[18],[19],[20],[21] Within the individual limits of arterial blood pressure, cerebral blood flow should be autoregulated. During complex CHS, which is frequently performed under deep hypothermic circulatory arrest (DHCA) or deep hypothermia with selective cerebral perfusion, this cerebral autoregulation is lost. [22] Consequently, cerebral blood flow becomes passive and dependent on arterial blood pressure and cardiopulmonary bypass (CPB) flow. It is important to recognize and to avoid not only cerebral hypoperfusion, but also cerebral hyperperfusion, which can lead to cerebral edema especially in the vulnerable pediatric brain. The use of TCD is particularly helpful in complex CHS to help adjust CPB flow and blood pressure during various degrees of hypothermia, as well as during selective cerebral perfusion. [23] Clinical decision-making is typically based on deviation from baseline values obtained before CPB (e.g., mean middle cerebral artery blood-flow velocity). Following periods of DHCA and rewarming, cerebral blood flow may still be impaired, [24] adding further value to TCD monitoring. In addition, TCD can help with cerebral emboli detection during CPB. Despite the information gained from TCD monitoring, there are practical limitations preventing this technology from a more widespread use. For example, inconsistent Doppler signal acquisition, measurement errors due to the Doppler angle of insonation, unstable probe positioning and inadequate anatomical window for ultrasonic interrogation are frequently encountered.

Near-infrared spectroscopy

The search for less invasive monitoring devices has resulted in the introduction of near-infrared spectroscopy (NIRS), a non-invasive, optical method for the continuous real-time monitoring of tissue oxygenation into clinical practice. [25] The technological background of NIRS technology has been reviewed in detail elsewhere. [26] In brief, the main principles upon which NIRS devices rely is the fact that most biological tissues, with the exception of hemoglobin and cytochrome oxidase, are relatively transparent to infrared light (700-1000 nanometers) and that the absorbance spectrum of hemoglobin depends on its oxygenation status. Available devices emit light at wavelengths within the above-mentioned spectrum. Tissue oxygen saturation can then be derived from the change in the intensity of the reflected light, which is dependent on the oxyhemoglobin to de-oxyhemoglobin ratio. Aside from a smaller amount of arterial blood admixture, the majority of interrogated tissue contains venous blood. [27] In case of cerebral oximetry, this non-invasively measured cerebral tissue oxygenation has been validated mostly against invasively obtained jugular bulb and central venous saturation. [28],[29],[30],[31],[32] It must be noted that due to the arterial admixture cerebral oximetry readings will always have a constant bias toward higher values when compared with an invasively measured venous saturation. Importantly, cerebral oximetry does not depend on pulsatile blood flow, a particular strength of this technology during states of non-pulsatile flow such as during CPB, extracorporeal membrane oxygenation, or non-pulsatile ventricular assist devices.

The clinical value of cerebral oximetry, as well as its limitations, can be best described as a non-invasive measure of oxygen supply and demand. [33],[34] Clinical decision-making is based on trend monitoring (acute or continuous decrease from baseline values) and/or intervention based on a specific (absolute) lower threshold. [35],[36] In adults and animal models, low jugular bulb oxygen saturation measured invasively is consistently associated with clinical symptoms of neurological impairment, anaerobic metabolism and neurological damage. [37],[38] It is reasonable to assume that a similar correlation and lower threshold also exists in children. However, studies on baseline values in infants and children with various CHDs revealed a wide range of what would have to be considered normal baseline values. [39] The relevance of these low baseline cerebral oximetry readings in selected individuals and specific types of CHDs is not clear. [40],[41],[42]

The clinical utility of cerebral oximetry and correlation with various outcome measures has been published extensively. [43],[44],[45] For example, cerebral oximetry can help guide selective cerebral perfusion strategies, [46],[47] can be useful in balancing single ventricle physiology particularly before and after the first stage palliative surgery, [48] and can help with a catastrophic event detection. [49],[50],[51],[52] In a small study in infants and children cerebral oximetry responded much quicker to periods of planned apnea compared with pulse oximetry. [53] In another prospective study on 23 newborns and infants following cardiac surgery, NIRS helped to detect catastrophic events in the post-operative period in the intensive care unit (ICU). [54] Interventions based on trend or absolute thresholds usually follow intervention algorithms such as the one previously published by Denault et al. [55] There is a good evidence that prolonged periods of cerebral desaturation during CHS are associated with neurodevelopmental deficits, increased morbidity and mortality. [56],[57],[58],[59],[60],[61],[62] McQuillen et al. for example conducted pre- and post-operative brain MRI scans in 53 neonates with CHD. [63] New post-operative radiologic evidence of brain injury was seen in 35% of patients and low cerebral oximetry readings during CPB were associated with new lesions. Despite the fact that there is accumulating data that low values correlate with morbidity, there is still insufficient evidence that NIRS monitoring such as cerebral oximetry will improve patient outcome. [64],[65],[66] Some of the unique features of NIRS however, make this technology particularly suitable to be part of a multimodal monitoring approach, which is discussed later in detail.

Electroencephalography

Perioperative electroencephalography (EEG) changes including seizure activity are not uncommon in children undergoing CHS. [67] In a recently published study perioperative electrical seizures were seen in 30% of patients, a quarter of those showed clinical symptoms. [68] Whereas seizure activity in this study was not associated with 2-year neurodevelopmental outcome, delayed recovery of amplitude-integrated EEG was, including an increased risk of early mortality. In patients undergoing first-stage palliation for left-sided single ventricle CHD, seizures occurred in 33% of infants. In this patient cohort, seizures were associated with an increased risk of early mortality and worse motor development. [69] While some of the studies have found an association between perioperative seizures and poor neurological outcome, [70],[71] others could not confirm such a relationship. [72],[73]

The technological aspects of standard EEG monitoring as well as processed EEG have been reviewed in detail elsewhere. [74],[75] While the currently available devices using processed EEG such as the bispectral index monitoring have mainly been developed and validated in adults, a raw or unprocessed one channel EEG can still be displayed. Standard EEG with multiple channels is available for children; however, its use requires qualified personnel. Amplitude-integrated EEG, which is derived from a reduced number of EEG leads and processed before display, had been introduced to pediatrics in the early 1980s. [76] It allows for real-time continuous monitoring of the electrical activity of the brain (cerebral function) and detection of seizure activity in the perioperative period. [77] Recently, reports of its use in the perioperative period in patients with CHD or cardiac compromise have been published. [78],[79],[80] Overall, EEG signals are prone to artifacts and affected by anesthetics and low temperatures, limiting its use in CHS. Despite the inconsistency in data and above-mentioned limitations, EEG monitoring is still frequently performed as part of a multimodal approach to neurological monitoring in children undergoing CHS.


   Multimodal Neuromonitoring Top


Multimodal monitoring typically refers to combining several monitoring modalities. [81] The goal is to increase sensitivity and specificity for detecting deviations from what has been defined as normal values. For example, early detection of hypoperfusion or hypoxemia may allow for early intervention before major end-organ damage occurs. [82] In a recent meta-analysis, [83] the use of a preemptive strategy using hemodynamic monitoring guided early intervention was associated with lower surgical mortality and morbidity in moderate and high-risk adult surgical patients. A recent meta-analysis found a significant reduction in mortality and post-operative major organ dysfunction in high-risk adult surgical patients when an intervention was guided by hemodynamic monitoring. [84] In a more general sense, multimodal monitoring is already established and practiced by combining the various monitoring modalities listed in the American Society of Anesthesiology standard monitoring guidelines. [85] Multimodal neuromonitoring expands those standard monitoring modalities particularly in patients at high-risk for neurological injury. For example, earlier discussed techniques of monitoring brain function can be applied to assess the delicate balance of cerebral oxygen demand and supply. It is also reasonable to assume that monitoring multiple parameters simultaneously can be useful in the decision making process and help guide interventions aimed to improve outcome. One example could be a transfusion algorithm that includes additional parameters capable of measuring the adequacy of meeting oxygen demand of critical end-organs, instead of transfusion of red blood cells based on a particular hematocrit. [86]

There are only few studies investigating multimodal brain monitoring and neurological outcome in pediatric CHS. Andropoulos et al. [87] for example, examined the use of TCD and cerebral oximetry in neonates undergoing aortic arch reconstruction with selective cerebral perfusion. Following cooling to 17-22°C baseline TCD and cerebral oximetry values were recorded. During selective cerebral perfusion, CPB flow was adjusted to maintain TCD velocity and cerebral oximetry values within 10% of baseline readings. The importance of multimodal monitoring was nicely demonstrated in this study. For example, the mean arterial blood pressure only poorly correlated with CPB flow requirements in this setting. In addition, the value of using cerebral oximetry to guide selective cerebral perfusion was limited in a significant number of patients due to minimal oxygen extraction under deep hypothermia. Combining the various monitoring modalities and in particular the use of TCD together with cerebral oximetry allowed the investigators to guide flow requirements during selective cerebral perfusion. This was also confirmed by Polito et al. who performed a systemic review of the literature on the role of TCD in children undergoing CHS. [88] Many of the reviewed studies have demonstrated limitations of conventional monitoring particularly in CHS performed under profound hypothermia and circulatory arrest and regional low-flow CPB perfusion techniques. Simply monitoring cerebral oxygen saturation without cerebral blood flow may not be sufficient to detect cerebral hypo- as well as hyper-perfusion particularly in CHS performed in neonates and infants. Intervention algorithms based on individual monitoring modalities, [89] as well as multimodal monitoring, [90] have been published. Perhaps the most compelling though older study regarding the utility of multimodal neuromonitoring and intervention algorithm as a tool to improve neurological outcome in CHS was conducted by Austin et al. [91] The group used cerebral oximetry, TCD and EEG in 250 children undergoing pediatric cardiac surgery. Originally planned and started as an observational study without intend to intervene, an interim analysis showed worse neurological outcome in children with observed changes in neuromonitoring parameters. An intervention protocol was then followed for the remainder of the study with the attempt to correct aberrant values back to baseline. The following values triggered an intervention: TCD velocity less than 20 cm/s and/or a decrease in velocity by more than 50% or increase by two-fold; decrease of cerebral oximetry values by at least 20% for more than 3 min; newly detected EEG changes. Overall, changes were detected in 70% of patients, 74% of those resulted in interventions. Cerebral oximetry detected most abnormalities (58%), followed by TCD (38%) and EEG (5%). When no significant changes from baseline values were detected, neurological complications were noted in 7% of the children compared with 26% when changes were noted without intervention (early phase of the study). However, when changes from baseline triggered an intervention with the attempt to correct values back to baseline, neurological changes were seen in only 6% of the cases. This is an impressive demonstration that multimodal neuromonitoring followed by an intervention can improve outcome. Since only limited data is available from the pediatric CHS setting, additional information on the value of multimodal monitoring may be gained from the adult literature. Zanatta et al., [92] performed a retrospective analysis in adult patients undergoing cardiac surgery comparing a group of patients with intraoperative multimodal brain monitoring (N = 166) to a control group without neurological monitoring (N = 1555). Multimodal neuromonitoring consisted of EEG, TCD, somatosensory-evoked potentials and continuous invasive jugular bulb saturation (jugular bulb saturation in the aortic arch surgery only). No major neurological complications were seen in patients with brain monitoring compared to 4% major neurological complications in the control group. Monitored patients spent less time on mechanical ventilation and had a shortened ICU stay. In addition, a multimodal brain protection protocol was tested in a recent investigation in adults undergoing coronary artery bypass grafting. [93] The Haga Brain Care Strategy consisted of preoperative screening for occlusive cerebrovascular and carotid disease with TCD, perioperative use of cerebral oximetry with an intervention protocol aiming to keep values within 20% of baseline and a sophisticated delirium screening assessment. Compared with a historical control group, there was no difference in stroke rate or mortality; however, the rate of delirium decreased significantly from 31% to 7.3% respectively.


   Current and Future Trends Top


At present, patients' hemodynamic parameters are mostly managed within a range of what is considered to represent normal values. In general, those normal values were established from a pool of healthy individuals, limiting its use in many patients undergoing cardiac surgery. Recent developments have aimed at using multimodal monitoring, specifically the combination of invasive blood pressure monitoring, cerebral oximetry and TCD, to determine individual lower limits of cerebral autoregulation continuously in real time. [94] The results showed a wide range of required mean arterial pressures rather than the traditionally taught limits of cerebral autoregulation in adults undergoing cardiac surgery. The same group subsequently published a similar approach of cerebral autoregulation monitoring in pediatric patients undergoing CHS. [95] In a prospective observational study, individual autoregulation curves were determined in 54 children undergoing CHS based on a combination of cerebral oximetry index and invasive blood pressure. In this pediatric patient cohort, the mean arterial blood pressure at the lower limit of cerebral autoregulation during CPB was 42 ± 7 mmHg, and individuals spent significant time before, during and after CPB below this threshold. These preliminary findings suggest that adequate cerebral blood flow may not be guaranteed at the mean arterial blood pressure levels frequently tolerated in children undergoing cardiac surgery with CPB. A prototype monitor capable of determining individual limits of cerebral autoregulation using a combination of cerebral oximetry and blood pressure monitoring has been investigated. [96] The clinical relevance of "multimodal" autoregulation monitoring has already been studied in small patient populations. In adults undergoing cardiac surgery, mean arterial blood pressure did not differ between patients developing acute kidney injury following surgery compared to those without kidney damage. However, when not the absolute blood pressure, but the duration spent below the individual lower limits of autoregulation was compared, there was a significant difference. [97] Even though the technology behind individual real-time autoregulation monitoring is still in its early stages, the published results are promising. It is foreseeable that using a combination of multiple monitoring modalities, hemodynamic management in patients will be much more individualized, rather than assuming similar normal values across a wide range of patients.


   Potential Complications and Limitations Associated With Multimodal Neuromonitoring Top


It the often assumed that monitoring must be associated with improved outcomes. In a seminal paper by Connors et al., [98] however, monitoring patients with a pulmonary artery catheter (PAC) was found to be associated with an increased mortality. After multiple studies have failed to show potential benefits, a shift in paradigm occurred and PAC use has since dramatically decreased in most clinical settings. The search for less invasive monitoring modalities was driven also by trying to avoid complications associated with invasive monitoring. However, it must be recognized, that non-invasive monitoring does not mean that there are no associated risks. For example, if cerebral oximetry monitoring and interpretation would result in unnecessary blood transfusion this could lead to adverse events including increased long-term mortality. Increasing CPB flow in order to maintain cerebral oximetry or TCD values close to baseline values could increase embolic load and even cause cerebral edema. The concept of multimodal monitoring however, should hopefully help avoid possible threats and minimize risks by interpreting findings and individual measurements in the context of other monitoring modalities. A major concern for many institutions is the costs associated with some of these technologies, particularly in the absence of substantial evidence that monitoring actually improves outcome. It must be acknowledged though, that similar data is missing for all monitoring devices. [99] One of the problems is that monitoring per se will not change outcome unless an intervention associated with outcome benefits is initiated based on the monitored parameters. It is widely believed that studies required proving this would be ethically not feasible and the sample size required would be exceedingly large.


   Conclusions Top


Advances in CHS have allowed for more complex surgery in even smaller children. Originally, many of those surgeries were performed under deep hypothermia and hypothermic cardiac arrest. More recently, a shift towards selective cerebral perfusion techniques and even warm cardioplegia and near normothermic CPB techniques have been introduced to avoid circulatory arrest and the detrimental effects of hypothermia, but at the same time have narrowed the margins for error regarding neurological damage. Improving current and developing new technologies and combining them according to the concept of multimodal monitoring should be encouraged. The goal is to keep up with the surgical advances, to assure patient safety, and to further improve outcome in patients undergoing CHS.

 
   References Top

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Correspondence Address:
Alexander J. C. Mittnacht
Department of Anesthesiology, The Mount Sinai Medical Center, P.O. Box 1010, New York, NY 10029
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0971-9784.124130

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