Oxygen-Induced and pH-Induced Direct Current Artifacts on Invasive Platinum/Iridium Electrodes for Electrocorticography

Background: Spreading depolarization (SD) and the initial, still reversible phase of neuronal cytotoxic edema in the cerebral gray matter are two modalities of the same process. SD may thus serve as a real-time mechanistic biomarker for impending parenchyma damage in patients during neurocritical care. Using subdural platinum/iridium (Pt/Ir) electrodes, SD is observed as a large negative direct current (DC) shift. Besides SD, there are other causes of DC shifts that are not to be confused with SD. Here, we systematically analyzed DC artifacts in ventilated patients by observing changes in the fraction of inspired oxygen. For the same change in blood oxygenation, we found that negative and positive DC shifts can simultaneously occur at adjacent Pt/Ir electrodes. Methods: Nurses and intensivists typically increase blood oxygenation by increasing the fraction of inspired oxygen at the ventilator before performing manipulations on the patient. We retrospectively identified 20 such episodes in six patients via tissue partial pressure of oxygen (p(ti)O(2)) measurements with an intracortical O-2 sensor and analyzed the associated DC shifts. In vitro, we compared Pt/Ir with silver/silver chloride (Ag/AgCl) to assess DC responses to changes in pO(2), pH, or 5-min square voltage pulses and investigated the effect of electrode polarization on pO(2)-induced DC artifacts. Results: Hyperoxygenation episodes started from a p(ti)O(2) of 37 (30-40) mmHg (median and interquartile range) reaching 71 (50-97) mmHg. During a total of 20 episodes on each of six subdural Pt/Ir electrodes in six patients, we observed 95 predominantly negative responses in six patients, 25 predominantly positive responses in four patients, and no brain activity changes. Adjacent electrodes could show positive and negative responses simultaneously. In vitro, Pt/Ir in contrast with Ag/AgCl responded to changes in either pO(2) or pH with large DC shifts. In response to square voltage pulses, Pt/Ir falsely showed smaller DC shifts than Ag/AgCl, with the worst performance under anoxia. In response to pO(2) increase, Pt/Ir showed DC positivity when positively polarized and DC negativity when negatively polarized. Conclusions: The magnitude of pO(2)-induced subdural DC shifts by approximately 6 mV was similar to that of SDs, but they did not show a sequential onset at adjacent recording sites, could be either predominantly negative or positive in contrast with the always negative DC shifts of SD, and were not accompanied by brain activity depression. Opposing polarities of pO(2)-induced DC artifacts may result from differences in baseline electrode polarization or subdural p(ti)O(2) inhomogeneities relative to subdermal p(ti)O(2) at the quasi-reference

Unveiling age-independent spectral markers of propofol-induced loss of consciousness by decomposing the electroencephalographic spectrum into its periodic and aperiodic components

Background: Induction of general anesthesia with propofol induces radical changes in cortical network organization, leading to unconsciousness. While perioperative frontal electroencephalography (EEG) has been widely implemented in the past decades, validated and age-independent EEG markers for the timepoint of loss of consciousness (LOC) are lacking. Especially the appearance of spatially coherent frontal alpha oscillations (8-12 Hz) marks the transition to unconsciousness.Here we explored whether decomposing the EEG spectrum into its periodic and aperiodic components unveiled markers of LOC and investigated their age-dependency. We further characterized the LOC-associated alpha oscillations by parametrizing the adjusted power over the aperiodic component, the center frequency, and the bandwidth of the peak in the alpha range. Methods: In this prospective observational trial, EEG were recorded in a young (18-30 years) and an elderly age-cohort (>= 70 years) over the transition to propofol-induced unconsciousness. An event marker was set in the EEG recordings at the timepoint of LOC, defined with the suppression of the lid closure reflex. Spectral analysis was conducted with the multitaper method. Aperiodic and periodic components were parametrized with the FOOOF toolbox. Aperiodic parametrization comprised the exponent and the offset. The periodic parametrization consisted in the characterization of the peak in the alpha range with its adjusted power, center frequency and bandwidth. Three time-segments were defined: preLOC (105 - 75 s before LOC), LOC (15 s before to 15 s after LOC), postLOC (190 - 220 s after LOC). Statistical significance was determined with a repeated-measures ANOVA. Results: Loss of consciousness was associated with an increase in the aperiodic exponent (young: p = 0.004, elderly: p = 0.007) and offset (young: p = 0.020, elderly: p = 0.004) as well as an increase in the adjusted power (young: p < 0.001, elderly p = 0.011) and center frequency (young: p = 0.008, elderly: p < 0.001) of the periodic alpha peak. We saw age-related differences in the aperiodic exponent and offset after LOC as well as in the power and bandwidth of the periodic alpha peak during LOC. Conclusion: Decomposing the EEG spectrum over induction of anesthesia into its periodic and aperiodic components unveiled novel age-independent EEG markers of propofol-induced LOC: the aperiodic exponent and offset as well as the center frequency and adjusted power of the power peak in the alpha range

Unveiling age-independent spectral markers of propofol-induced loss of consciousness by decomposing the electroencephalographic spectrum into its periodic and aperiodic components

BackgroundInduction of general anesthesia with propofol induces radical changes in cortical network organization, leading to unconsciousness. While perioperative frontal electroencephalography (EEG) has been widely implemented in the past decades, validated and age-independent EEG markers for the timepoint of loss of consciousness (LOC) are lacking. Especially the appearance of spatially coherent frontal alpha oscillations (8–12 Hz) marks the transition to unconsciousness.Here we explored whether decomposing the EEG spectrum into its periodic and aperiodic components unveiled markers of LOC and investigated their age-dependency. We further characterized the LOC-associated alpha oscillations by parametrizing the adjusted power over the aperiodic component, the center frequency, and the bandwidth of the peak in the alpha range.MethodsIn this prospective observational trial, EEG were recorded in a young (18–30 years) and an elderly age-cohort (≥ 70 years) over the transition to propofol-induced unconsciousness. An event marker was set in the EEG recordings at the timepoint of LOC, defined with the suppression of the lid closure reflex. Spectral analysis was conducted with the multitaper method. Aperiodic and periodic components were parametrized with the FOOOF toolbox. Aperiodic parametrization comprised the exponent and the offset. The periodic parametrization consisted in the characterization of the peak in the alpha range with its adjusted power, center frequency and bandwidth. Three time-segments were defined: preLOC (105 – 75 s before LOC), LOC (15 s before to 15 s after LOC), postLOC (190 – 220 s after LOC). Statistical significance was determined with a repeated-measures ANOVA.ResultsLoss of consciousness was associated with an increase in the aperiodic exponent (young: p = 0.004, elderly: p = 0.007) and offset (young: p = 0.020, elderly: p = 0.004) as well as an increase in the adjusted power (young: p &lt; 0.001, elderly p = 0.011) and center frequency (young: p = 0.008, elderly: p &lt; 0.001) of the periodic alpha peak. We saw age-related differences in the aperiodic exponent and offset after LOC as well as in the power and bandwidth of the periodic alpha peak during LOC.ConclusionDecomposing the EEG spectrum over induction of anesthesia into its periodic and aperiodic components unveiled novel age-independent EEG markers of propofol-induced LOC: the aperiodic exponent and offset as well as the center frequency and adjusted power of the power peak in the alpha range

Enhanced recovery (ERAS) protocol in patients undergoing laparoscopic total gastrectomy

INTRODUCTION: Laparoscopic technique combined with the ERAS (Enhanced Recovery after Surgery) protocol enables a shorter hospital stay and a lower complication rate. Although it has been widely used in many patients undergoing elective abdominal surgery, especially in patients with colorectal cancer, there are only a few papers describing laparoscopic total gastrectomy and the enhanced recovery protocol in patients with gastric cancer. Minimally invasive gastrectomy is still an uncommon procedure, mostly because of its difficulty. AIM: To present the preliminary results of treatment of patients with gastric neoplasms who underwent laparoscopic gastrectomy D2 with perioperative care according to ERAS principles. MATERIAL AND METHODS: Eleven patients (5 male and 6 female, age 52–77 years) underwent laparoscopic D2 gastrectomy with intracorporeal esophagojejunal anastomosis. In all patients the ERAS protocol was implemented. We analyzed operation time, complications and hospital stay. Additionally we focused on operative technique as well as the perioperative care protocol. RESULTS: The mean duration of the procedure was 245 min. There was 1 conversion due to unclear tumor infiltration. Mean hospital stay was 4.6 days. One postoperative complication (central venous catheter sepsis) was reported. Histological analysis confirmed the tentative diagnosis (R0 resection) in 10/11 patients. There were no readmissions. CONCLUSIONS: Laparoscopic gastrectomy is a valuable alternative to the classical approach and combined with the ERAS protocol can result in reduced hospital stay. However, due to the small group of patients it is difficult to adequately assess the incidence of early and late complications of the laparoscopic procedures; therefore further research is needed

Migraine Aura, Transient Ischemic Attacks, Stroke, and Dying of the Brain Share the Same Key Pathophysiological Process in Neurons Driven by Gibbs–Donnan Forces, Namely Spreading Depolarization

Neuronal cytotoxic edema is the morphological correlate of the near-complete neuronal battery breakdown called spreading depolarization, or conversely, spreading depolarization is the electrophysiological correlate of the initial, still reversible phase of neuronal cytotoxic edema. Cytotoxic edema and spreading depolarization are thus different modalities of the same process, which represents a metastable universal reference state in the gray matter of the brain close to Gibbs-Donnan equilibrium. Different but merging sections of the spreading-depolarization continuum from short duration waves to intermediate duration waves to terminal waves occur in a plethora of clinical conditions, including migraine aura, ischemic stroke, traumatic brain injury, aneurysmal subarachnoid hemorrhage (aSAH) and delayed cerebral ischemia (DCI), spontaneous intracerebral hemorrhage, subdural hematoma, development of brain death, and the dying process during cardio circulatory arrest. Thus, spreading depolarization represents a prime and simultaneously the most neglected pathophysiological process in acute neurology. Aristides Leao postulated as early as the 1940s that the pathophysiological process in neurons underlying migraine aura is of the same nature as the pathophysiological process in neurons that occurs in response to cerebral circulatory arrest, because he assumed that spreading depolarization occurs in both conditions. With this in mind, it is not surprising that patients with migraine with aura have about a twofold increased risk of stroke, as some spreading depolarizations leading to the patient percept of migraine aura could be caused by cerebral ischemia. However, it is in the nature of spreading depolarization that it can have different etiologies and not all spreading depolarizations arise because of ischemia. Spreading depolarization is observed as a negative direct current (DC) shift and associated with different changes in spontaneous brain activity in the alternating current (AC) band of the electrocorticogram. These are non-spreading depression and spreading activity depression and epileptiform activity. The same spreading depolarization wave may be associated with different activity changes in adjacent brain regions. Here, we review the basal mechanism underlying spreading depolarization and the associated activity changes. Using original recordings in animals and patients, we illustrate that the associated changes in spontaneous activity are by no means trivial, but pose unsolved mechanistic puzzles and require proper scientific analysis

Correlates of Spreading Depolarization, Spreading Depression, and Negative Ultraslow Potential in Epidural Versus Subdural Electrocorticography

Spreading depolarizations (SDs) are characterized by near-complete breakdown of the transmembrane ion gradients, neuronal oedema and activity loss (=depression). The SD extreme in ischemic tissue, termed 'terminal SD,' shows prolonged depolarization, in addition to a slow baseline variation called 'negative ultraslow potential' (NUP). The NUP is the largest bioelectrical signal ever recorded from the human brain and is thought to reflect the progressive recruitment of neurons into death in the wake of SD. However, it is unclear whether the NUP is a field potential or results from contaminating sensitivities of platinum electrodes. In contrast to Ag/AgCl-based electrodes in animals, platinum/iridium electrodes are the gold standard for intracranial direct current (DC) recordings in humans. Here, we investigated the full continuum including short-lasting SDs under normoxia, long-lasting SDs under systemic hypoxia, and terminal SD under severe global ischemia using platinum/iridium electrodes in rats to better understand their recording characteristics. Sensitivities for detecting SDs or NUPs were 100% for both electrode types. Nonetheless, the platinum/iridium-recorded NUP was 10 times smaller in rats than humans. The SD continuum was then further investigated by comparing subdural platinum/iridium and epidural titanium peg electrodes in patients. In seven patients with either aneurysmal subarachnoid hemorrhage or malignant hemispheric stroke, two epidural peg electrodes were placed 10 mm from a subdural strip. We found that 31/67 SDs (46%) on the subdural strip were also detected epidurally. SDs that had longer negative DC shifts and spread more widely across the subdural strip were more likely to be observed in epidural recordings. One patient displayed an SD-initiated NUP while undergoing brain death despite continued circulatory function. The NUP's amplitude was -150 mV subdurally and -67 mV epidurally. This suggests that the human NUP is a bioelectrical field potential rather than an artifact of electrode sensitivity to other factors, since the dura separates the epidural from the subdural compartment and the epidural microenvironment was unlikely changed, given that ventilation, arterial pressure and peripheral oxygen saturation remained constant during the NUP. Our data provide further evidence for the clinical value of invasive electrocorticographic monitoring, highlighting important possibilities as well as limitations of less invasive recording techniques

Correlates of Spreading Depolarization, Spreading Depression, and Negative Ultraslow Potential in Epidural Versus Subdural Electrocorticography

Spreading depolarizations (SDs) are characterized by near-complete breakdown of the transmembrane ion gradients, neuronal oedema and activity loss (=depression). The SD extreme in ischemic tissue, termed ‘terminal SD,’ shows prolonged depolarization, in addition to a slow baseline variation called ‘negative ultraslow potential’ (NUP). The NUP is the largest bioelectrical signal ever recorded from the human brain and is thought to reflect the progressive recruitment of neurons into death in the wake of SD. However, it is unclear whether the NUP is a field potential or results from contaminating sensitivities of platinum electrodes. In contrast to Ag/AgCl-based electrodes in animals, platinum/iridium electrodes are the gold standard for intracranial direct current (DC) recordings in humans. Here, we investigated the full continuum including short-lasting SDs under normoxia, long-lasting SDs under systemic hypoxia, and terminal SD under severe global ischemia using platinum/iridium electrodes in rats to better understand their recording characteristics. Sensitivities for detecting SDs or NUPs were 100% for both electrode types. Nonetheless, the platinum/iridium-recorded NUP was 10 times smaller in rats than humans. The SD continuum was then further investigated by comparing subdural platinum/iridium and epidural titanium peg electrodes in patients. In seven patients with either aneurysmal subarachnoid hemorrhage or malignant hemispheric stroke, two epidural peg electrodes were placed 10 mm from a subdural strip. We found that 31/67 SDs (46%) on the subdural strip were also detected epidurally. SDs that had longer negative DC shifts and spread more widely across the subdural strip were more likely to be observed in epidural recordings. One patient displayed an SD-initiated NUP while undergoing brain death despite continued circulatory function. The NUP’s amplitude was -150 mV subdurally and -67 mV epidurally. This suggests that the human NUP is a bioelectrical field potential rather than an artifact of electrode sensitivity to other factors, since the dura separates the epidural from the subdural compartment and the epidural microenvironment was unlikely changed, given that ventilation, arterial pressure and peripheral oxygen saturation remained constant during the NUP. Our data provide further evidence for the clinical value of invasive electrocorticographic monitoring, highlighting important possibilities as well as limitations of less invasive recording techniques

Terminal spreading depolarization and electrical silence in death of human cerebral cortex

Objective: Restoring the circulation is the primary goal in emergency treatment of cerebral ischemia. However, better understanding of how the brain responds to energy depletion could help predict the time available for resuscitation until irreversible damage and advance development of interventions that prolong this span. Experimentally, injury to central neurons begins only with anoxic depolarization. This potentially reversible, spreading wave typically starts 2 to 5 minutes after the onset of severe ischemia, marking the onset of a toxic intraneuronal change that eventually results in irreversible injury. Methods: To investigate this in the human brain, we performed recordings with either subdural electrode strips (n = 4) or intraparenchymal electrode arrays (n = 5) in patients with devastating brain injury that resulted in activation of a Do Not Resuscitate–Comfort Care order followed by terminal extubation. Results: Withdrawal of life‐sustaining therapies produced a decline in brain tissue partial pressure of oxygen (ptiO2) and circulatory arrest. Silencing of spontaneous electrical activity developed simultaneously across regional electrode arrays in 8 patients. This silencing, termed “nonspreading depression,” developed during the steep falling phase of ptiO2 (intraparenchymal sensor, n = 6) at 11 (interquartile range [IQR] = 7–14) mmHg. Terminal spreading depolarizations started to propagate between electrodes 3.9 (IQR = 2.6–6.3) minutes after onset of the final drop in perfusion and 13 to 266 seconds after nonspreading depression. In 1 patient, terminal spreading depolarization induced the initial electrocerebral silence in a spreading depression pattern; circulatory arrest developed thereafter. Interpretation: These results provide fundamental insight into the neurobiology of dying and have important implications for survivable cerebral ischemic insults. Ann Neurol 2018;83:295–31

Correlation of velocity and susceptibility in patients with aneurysmal subarachnoid hemorrhage

In many cerebral grey matter structures including the neocortex, spreading depolarization (SD) is the principal mechanism of the near-complete breakdown of the transcellular ion gradients with abrupt water influx into neurons. Accordingly, SDs are abundantly recorded in patients with traumatic brain injury, spontaneous intracerebral hemorrhage, aneurysmal subarachnoid hemorrhage (aSAH) and malignant hemispheric stroke using subdural electrode strips. SD is observed as a large slow potential change, spreading in the cortex at velocities between 2 and 9 mm/min. Velocity and SD susceptibility typically correlate positively in various animal models. In patients monitored in neurocritical care, the Co-Operative Studies on Brain Injury Depolarizations (COSBID) recommends several variables to quantify SD occurrence and susceptibility, although accurate measures of SD velocity have not been possible. Therefore, we developed an algorithm to estimate SD velocities based on reconstructing SD trajectories of the wave-front's curvature center from magnetic resonance imaging scans and time-of-SD-arrival- differences between subdural electrode pairs. We then correlated variables indicating SD susceptibility with algorithm-estimated SD velocities in twelve aSAH patients. Highly significant correlations supported the algorithm's validity. The trajectory search failed significantly more often for SDs recorded directly over emerging focal brain lesions suggesting in humans similar to animals that the complexity of SD propagation paths increase in tissue undergoing injury