Research Objectives: To present the broadest available evidence regarding the safety and efficacy of ketamine in traumatic brain injury (TBI) and explain the evolution of clinical guidelines. This review aims to verify historical contraindications against current knowledge and demonstrate how ketamine's role has evolved from a contraindicated drug to a potentially beneficial therapeutic option in prehospital settings. Methods: Systematic analysis of clinical studies and systematic reviews examining ketamine's effects on cerebral hemodynamics, intracranial pressure (ICP), and cerebral perfusion pressure (CPP). Evaluation of ketamine's utility as an analgesic-sedative drug in prehospital TBI care, including assessment of safety profiles and clinical outcomes across civilian and military settings. Conclusions: Ketamine's effect on cerebral hemodynamics is at least neutral and often beneficial, contrary to historical concerns about increased ICP. The drug demonstrates high utility as a prehospital analgesic-sedative agent, providing effective pain control and sedation without compromising patient safety. Historical contraindications must be regularly re-verified in light of current evidence. Clinical guidelines have evolved significantly, reflecting growing recognition that proper ventilation control and hemodynamic monitoring eliminate previous safety concerns. Current evidence supports ketamine as a safe and potentially advantageous therapeutic option in prehospital TBI management, particularly for achieving rapid sequence intubation, maintaining hemodynamic stability, and preventing secondary brain injury in emergency settings.

Cerebral autoregulation maintains stable cerebral blood flow despite fluctuations in cerebral perfusion pressure (CPP), through mechanisms that alter vascular diameter and resistance. Two commonly used indices, pressure reactivity index and mean flow index, reflect different aspects of this regulation, namely changes in cerebral blood volume and blood flow velocity. However, their interchangeability, particularly in the context of traumatic brain injury (TBI), remains questionable. This study investigates the frequency and physiological basis of discordance between these indices. Using 96 simultaneous recordings of intracranial pressure (ICP) and transcranial Doppler-derived flow velocity in TBI patients, 501 non-overlapping 20-minute segments were extracted. Each segment was classified based on autoregulatory state, and physiological parameters, including ICP, CPP, end-tidal CO₂, cerebral compliance, critical closing pressure, and vascular dynamics, were analysed. Discordance between indices occurred in 26% of segments. Statistical and machine learning models identified vessel stability metrics (e.g. wall tension, vascular resistance, time constant) and intracranial dynamics (e.g. compliance, compensatory reserve) as the most predictive features of discordance. These findings suggest that the two indices capture distinct physiological processes and should not be used interchangeably. Instead, their combined interpretation may enhance assessment of cerebrovascular autoregulation and provide a more nuanced understanding of cerebral physiology in TBI.

Cerebral autoregulation is routinely assessed through variations in intracranial pressure (ICP) and systemic hemodynamic parameters; however, its metabolic dimension remains underexplored in clinical settings. This study introduces the carbon dioxide reactivity index (CO2Rx), a novel metric derived from continuous ICP and end-tidal CO2 (ETCO2) monitoring aimed at capturing real-time cerebrovascular metabolic reactivity in patients with severe traumatic brain injury (TBI). We performed a retrospective observational analysis of patients with moderate and severe TBI admitted to a single adult and pediatric trauma center. CO2Rx was calculated as a moving Pearson correlation between ICP and ETCO2 across 60-min windows using low-frequency time-series data. Heatmaps and contour plots visualized median CO2Rx values across ICP and ETCO2 ranges. Analyses were stratified by age, decompressive craniectomy status, and 12-month outcomes. A graphical framework linked CO2Rx/ICP/ETCO2 combinations to outcome probabilities. A total of 218 patients (178 adults, 40 pediatric patients) were included. Higher CO2Rx values, indicative of preserved metabolic reactivity, were observed when ICP was ≤ 20mm Hg, and ETCO2 ranged between 30 and 40mm Hg (median: 0.27; interquartile range [IQR]: 0.20-0.37). In contrast, elevated ICP (> 20mm Hg) and reduced ETCO2 (20-30mm Hg) were associated with lower CO2Rx values (median: 0.09; IQR: - 0.02 to 0.15), suggesting impaired reactivity. A positive correlation emerged between CO2Rx and cerebral perfusion pressure, peaking at 60-75mm Hg (r = 0.31; p < 0.001). Patients with favorable outcomes displayed higher CO2Rx values, especially within optimal ICP and ETCO2 ranges, whereas lower values were associated with poorer outcomes. CO2Rx is a promising marker of cerebrovascular metabolic reactivity in TBI, offering novel insights into the dynamic relationship between ICP and ETCO2. It may aid in detecting autoregulatory dysfunction and guide individualized strategies for ventilation, CO2 control, and surgical decisions. Prospective validation is warranted to confirm its clinical relevance. ClinicalTrials.gov identifier: NCT05043545.

Cerebrovascular autoregulation maintains stable cerebral blood flow by counteracting slow changes in cerebral perfusion pressure (termed "slow waves"). Conventional assessment involves invasive techniques using intracranial pressure (ICP) or technically challenging cerebral blood flow velocity (FV) measurements. Near-infrared spectroscopy (NIRS) has emerged as a non-invasive alternative; however, its ability to accurately capture the slow-wave oscillations fundamental to cerebrovascular autoregulation remains uncertain. 412h of simultaneous ICP, FV, NIRS, and arterial blood pressure (ABP) monitoring from 35 traumatic brain injury patients were explored. Coherence, gain, and Granger causality analyses were employed to assess whether NIRS adequately reflects slow waves in ABP, FV, or ICP to investigate whether NIRS is a suitable alternative for assessing the state of cerebrovascular autoregulation In this single-centre observational cohort study, 89 recordings from 35 moderate to severe traumatic brain injury (TBI) patients (totalling 412h of artefact-free data) were analysed. Simultaneous high-resolution recordings of NIRS, ICP, FV, and arterial blood pressure (ABP) were acquired. Coherence and gain were computed across defined frequency bands (0.001-0.5Hz), with a focus on the range most relevant to cerebrovascular autoregulation (0.005-0.05Hz). Granger causality was used to explore directional relationships between physiological inputs (ABP, FV, ICP) and NIRS outputs (rSO2 and haemoglobin metrics). Haemoglobin-based NIRS metrics (total, oxy-, deoxy-, and delta haemoglobin) demonstrated significantly higher coherence and Granger causality with FV and ICP compared to rSO2 (p < 0.001, large effect sizes) capturing the slow-wave oscillations central to cerebrovascular autoregulation. In contrast, rSO₂ exhibited poor coherence and low causality, especially with ABP, likely due to device-specific post-processing and resolution limitations. NIRS derived haemoglobin metrics reliably capture slow-wave dynamics reflective of cerebrovascular autoregulation and reactivity, offering a non-invasive alternative to traditional methods. Conversely, rSO2 lacks sufficient temporal fidelity to detect these fluctuations under routine clinical conditions, limiting its utility for cerebrovascular autoregulation assessment.

To evaluate the effects of three simple bedside challenges on cerebral oxygenation and brain activity, measured non-invasively using near-infrared spectroscopy (NIRS) and frontal single-channel electroencephalography (EEG), in comatose post-cardiac arrest patients, and to examine whether these responses differ according to cerebral autoregulation status and intensive care unit (ICU) outcome and could aid early prognostication.Three bedside physiological challenges were conducted: (1) increasing the fraction of inspired oxygen (FiO₂) to 100%, (2) lowering the head-of-bed (HOB) to 0°, and (3) elevating end-tidal carbon dioxide (etCO₂) by 1.0 kPa. Tissue oxygen saturation (StO₂) and EEG amplitude were hypothesized to increase, by enhancing oxygen delivery (FiO₂), augmenting cerebral perfusion pressure (HOB), and inducing cerebral vasodilation (etCO₂). Furthermore, we examined the associations between signal responses, cerebral autoregulation status, and ICU outcome.Of the 48 monitored patients, FiO2, HOB, and etCO₂ challenges were successfully completed in 41 (85%), 33 (69%), and 32 (67%) patients, respectively. The StO₂ increased on average by 0.3% (95%-CI 0.2-0.5, p < 0.001) for every 10% rise in FiO2, and 1.94% (95%-CI 0.9-3.0, p < 0.001) for each 15º lowering of the HOB. The etCO₂ challenge did not affect the StO₂. EEG amplitude remained unchanged during all three challenges. No significant differences were found in the responses between patients with intact versus impaired autoregulation or between the ICU outcome groups.Brief physiological challenges simulating common ICU scenarios elicited only modest increases in StO₂, and no measurable response in EEG amplitude. Response patterns were not associated with cerebral autoregulation status or ICU outcome.

Acute brain injuries-including traumatic brain injury, subarachnoid hemorrhage, and intracerebral hemorrhage-exhibit profound pathophysiological heterogeneity, yet are often managed using standardized treatment protocols. While evidence-based guidelines have improved outcomes at a population level, they frequently overlook patient-specific variations in cerebral compliance, autoregulation, and metabolic reserve. This review explores the evolving paradigm of personalized neurocritical care, which integrates dynamic multimodal monitoring, individualized intracranial pressure management strategies, and real-time physiological indices such as pressure reactivity index, cerebral perfusion pressure optimization, and waveform analytics. We highlight the role of noninvasive modalities including quantitative pupillometry, transcranial Doppler, optic nerve sheath diameter ultrasound, near-infrared spectroscopy, and electroencephalography as adjuncts when invasive monitoring is limited or contraindicated. Furthermore, we examine tissue-level monitoring using brain oxygen tension and cerebral microdialysis and emerging blood-based biomarkers such as glial fibrillary acidic protein and neurofilament light. These tools provide granular insight into evolving secondary injury processes. In parallel, advances in artificial intelligence (AI) and machine learning enable deep phenotyping, predictive modeling, and integration of high-dimensional data including imaging, physiology, and omics-based profiles. The development of digital twin models further supports individualized simulation and therapeutic planning. While challenges remain in implementation, data harmonization, and resource availability, the convergence of physiologic monitoring, molecular profiling, and computational modeling offers a transformative pathway toward precision medicine in neurocritical care.

Background: Maintaining an adequate mean arterial pressure (MAP) and cerebral perfusion pressure to ensure proper perfusion and oxygen delivery to all major organs is crucial—especially for neurosurgical patients after subarachnoid hemorrhage or traumatic brain injury—for preventing secondary brain damage or delayed cerebral ischemia. Currently, most neurosurgical intensive care units rely on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) values to guide therapy. Fluid resuscitation and norepinephrine are standard treatments for achieving a CPP between 60 and 70 mmHg; however, patients sometimes experience norepinephrine-refractory hypotension. In such cases, vasopressin is often the preferred medication; it is widely utilized and has gained interest in treating septic shock or refractory hypotension following cardiac surgery or hypovolemic shock. Recent studies have also shown the significant impact of vasopressin on resuscitation after traumatic brain injury (TBI) and its effect on CPP during ICU care. Nevertheless, little is known about how vasopressin affects cerebral perfusion and oxygenation, especially in patients with subarachnoid hemorrhage. Methods: This preliminary retrospective single-arm study examined how vasopressin affects PbtO2 and cerebral blood flow using the non-invasive QuantixND® device. After administering vasopressin for treating catecholamine-refractory hypotension, MAP, CPP, ICP, PbtO2, and cerebral blood flow were measured over a 20-min period. Results: In this small cohort, vasopressin sufficiently improved MAP and CPP over a 20 min period following AVP bolus administration with a slight decline at later time points. The ICP decreased throughout this period, indicating some level of autoregulation. In contrast, cerebral blood flow did not improve despite the rise in CPP, and PbtO2 levels remained below 20 mmHg. Conclusions: We conclude that vasopressin could be a viable option for maintaining MAP and CPP, but caution should be exercised in patients with already impaired cerebral perfusion. Furthermore, relying solely on CPP as the therapeutic guide in subarachnoid hemorrhage patients appears to be at least questionable.

Cerebrovascular pressure autoregulation is the physiological mechanism that maintains cerebral blood flow (CBF) relatively constant across changes in cerebral perfusion pressure. It is a vital protective mechanism of the brain during fluctuations in arterial blood pressure that is particularly volatile in newborn infants. Yet, much remains unknown of the mechanisms underlying CBF autoregulation in the infant brain. Time-dated pregnant Sprague-Dawley rats were randomly divided into the normoxic control group and continuous hypoxic exposure group (10.5% oxygen) from day 15 to 21 of gestation. Rat pups were raised in normoxic conditions after birth. We tested the hypothesis that TRPC6 (transient receptor potential canonical channel 6) plays a key role in CBF autoregulation in the neonatal brain using postnatal days 12 to 14 rat pups. Blood pressure and CBF were measured. TRPC6 and CaV1.2 expression and activity were assessed. We demonstrated that TRPC6 functions as a mechanosensor to stretch the cell membrane and modulates CaV1.2 activity of the middle cerebral artery in the neonatal rat brain. Fetal hypoxia downregulated TRPC6 expression/activity, TRPC6-CaV1.2 coupling, and CBF autoregulation in the neonate. The loss-of-function approach using TRPC6 knockdown by siRNA and pharmacological TRPC6 inhibition recapitulated the effect of fetal hypoxia on the impairments of CBF autoregulation in neonatal pups. Our findings provide novel insights into the mechanism of CBF autoregulation in newborn brains and highlight a critical role of TRPC6 dysfunction in impaired cerebral autoregulation and heightened vulnerability to brain injury that is observed in the infant exposed to fetal hypoxia.

To review the current knowledge on mechanical ventilation after cardiac arrest, carefully balancing the protection of both the brain and the lungs. Although lung-protective ventilation (LPV) strategies are often considered in the general population and widely studied in acute respiratory distress syndrome (ARDS) patients, current knowledge focused on patients after cardiac arrest is unclear. Mechanical ventilation in this unique population should prevent potential brain injury while also avoiding ventilation-induced lung injury. This includes optimizing ventilation parameters, such as tidal volume ( VT ), positive end-expiratory pressure (PEEP), and gas exchange targets, while also considering the impact on cerebral perfusion and intracranial pressure. The role of LPV in patients without ARDS and after cardiac arrest is still uncertain. In this review, we updated the strategy to optimize mechanical ventilation after cardiac arrest with the primary aim of protecting the lungs and brain, improving the patients' outcomes.

BackgroundWhite matter hyperintensities (WMHs), visible as bright regions on T2‐weighted FLAIR MRI, are frequent with age and elevated in Alzheimer’s disease (AD). Representing axonal damage, demyelination, and edema, WMHs are driven by vascular mechanisms, including endothelial dysfunction and impaired cerebrovascular autoregulation. WMHs also exhibit strong heritability (55–73%), with overlapping genetic pathways shared with AD. Emerging evidence suggests systemic factors across the brain‐body axis influence WMHs, yet these contributions and their genetic overlap with AD remain underexplored. Our study investigated genetic underpinnings specific to WMHs and those shared with AD by assessing partitioned heritability of WMHs and AD across the brain‐body axis with SNP level tissue‐ and cell‐specific annotations; identifying genes associated with WMHs and AD through integration of gene expression data, establishing causal links between SNP‐level findings and imaging‐derived phenotypes (IDPs), particularly structural variations in regional brain volumes.MethodPartitioned heritability was assessed using stratified‐linkage disequilibrium score regression (sLDSC) on GWAS summary statistics (N = 3 WMH studies; N = 6 AD studies) using human A1) tissue level annotations (N = 10) and A2) continuous cell‐specific annotations (N = 64). MAGMA and FUSION analyses highlighted genes associated with WMH and AD for further bioinformatics analysis (using human protein atlas (HPA) and STRING database). MACAW (Vigneshwaran et al, 2024) modeled causal relationships between WMH‐associated SNPs (from FUMA analysis) and IDPs (N = 172), leveraging directed acyclic graphs to evaluate genetic effects while controlling for confounders (Figure 2).ResultTissue‐specific analysis revealed significant enrichment of WMH‐associated SNPs in the CNS, liver, cardiovascular system, and kidneys, while AD‐associated SNPs were enriched in the CNS, connective bone, liver, and immune tissues. (Figure 1). Cell‐specific analysis identified vascular endothelial cells as enriched across WMH‐enriched tissues. MAGMA analysis, combined with HPA analysis, corroborated sLDSC tissue‐level findings. MAGMA and FUSION analyses highlighted genes associated with WMHs (N = 39 and 69) and AD (N = 291 and 193). MACAW linked WMH‐associated SNP to 172 IDPs, consistently impacting WM hypointensities and regional brain volumes (e.g., left inferior temporal volume).ConclusionOur findings highlight systemic multi‐tissue contributions (CNS, liver, cardiovascular system, and kidneys) to WMHs, driven by vascular endothelial dysfunction and shared AD genetics, with SNPs across the body also affecting brain imaging derived phenotypes.

Invasive mechanical ventilation (MV) is often a lifesaving intervention in patients with traumatic brain injury (TBI) to optimize gas exchange and prevent secondary brain injury, thereby avoiding the deleterious effects of both hypoxia and hyperoxia, as well as hypocapnia and hypercapnia. However, MV in these patients represents a unique clinical challenge, as it must take into account multiple parameters, including cerebral autoregulation and autoregulatory reserves, brain compliance, cerebral dynamics such as intracranial pressure (ICP), cerebral perfusion pressure (CPP), and cerebral blood flow (CBF), as well as systemic hemodynamics and respiratory system mechanics. Moreover, the detrimental effects of MV on extracranial organs and systems are well established, with the lungs being the most vulnerable, particularly when non-protective ventilation strategies involving high tidal volumes (TV) and inspiratory pressures are applied. Currently, the optimal ventilation approach in patients with TBI, with or without LI, remains incompletely defined. While protective ventilation practices are recommended for a large number of critically ill patients, their application in individuals with acute brain injury (ABI) may adversely affect cerebral and systemic hemodynamics, as well as brain physiology, potentially leading to secondary damage and poor clinical outcomes. Because the consequences of TBI, such as secondary brain damage and lung complications, begin shortly after the primary event, the role of prehospital MV in these patients is crucial. However, existing data from the out-of-hospital setting are scarce. Thus, in the present review, we aim to summarize the available evidence on MV in patients with TBI, with an emphasis on the prehospital setting.

IntroductionIsotonic crystalloids are commonly used for maintaining fluid balance and cerebral perfusion pressure in critical care patients with aneurysmal subarachnoid hemorrhage (aSAH). However, the relatively high concentration of chloride in normal saline (NS) might lead to hyperchloremia or acute kidney injury, comparing with multi-electrolyte solutions (BMES). The aim of the study is to compare the incidence of hyperchloremia in aSAH patients and provide feasibility and safety research for further study.MethodsThis is a pilot study of a single center, randomized, controlled trail. Patients were enrolled randomly to receive BMES or NS for 3 days of ICU stay.ResultsOverall, 87 patients were randomized to receive BMES or NS, 60 patients (30 in each group) were enrolled for final analysis. Within 3 days of randomization, hyperchloremia occurred in 18/30 (60%) patients in the BMES group and 23/30 (76.7%) in the NS group (p = 0.165, relative risk 0.58, 95% CI 0.27–1.28). Incidence of hyperchloremia (BMES 36.7% vs. NS 63.3%, p = 0.039) and hyperchloremic acidosis (BMES 36.7% vs. NS 63.3%, p = 0.039) were decreased on trial day 1. There were no differences on bicarbonate, anion gap, serum creatinine, incidence of acute kidney injury, or length of hospital stay between groups.DiscussionFor patients with aSAH, the use of BMES did not result in a lower risk of hyperchloremia, and also did not increase the incidence of hyponatremia or intracranial hypertension over NS, which warrants further research.

Traumatic brain injury in morbidly obese patients (body mass index ⩾ 35 kg/m²) presents complex perioperative challenges due to compounded respiratory, cardiovascular, and metabolic dysfunctions. Reduced functional residual capacity, obstructive sleep apnoea, and increased thoracoabdominal pressures impair oxygenation and elevate intracranial pressure. Cardiovascular comorbidities such as hypertension and arrhythmias further compromise cerebral perfusion. Altered pharmacokinetics in obesity demand weight-adjusted anaesthetic dosing to avoid over- or under-sedation. This narrative review highlights the need for a structured, evidence-based approach involving preoperative optimisation, advanced airway planning, lung-protective ventilation, and invasive haemodynamic monitoring to maintain cerebral perfusion pressure. Postoperative strategies should include cautious extubation, continuous positive airway pressure or high-flow nasal oxygen, multimodal analgesia, and close neurological monitoring. Dexmedetomidine offers neuroprotective advantages with minimal respiratory depression. Multidisciplinary collaboration among anaesthesia, neurosurgery, and intensive care teams is critical to minimising perioperative risks and improving outcomes in this high-risk population.

Background/Objectives: An increasing number of older individuals require general anaesthesia for major non-cardiac surgery, with 20% displaying postoperative complications. Regional cerebral oxygen saturation (rSO2) correlates with the gold standard of mixed venous oxygen saturation, indicating global perfusion. We hypothesised that rSO2-based anaesthesia reduces organ dysfunction and morbidity after major non-cardiac surgery. Methods: In Singapore and Toronto, we conducted a prospective, double-blind, randomised controlled trial in elderly patients undergoing major non-cardiac surgery, after obtaining research ethics board permission and informed consent. This RCT followed the CONSORT guidelines. Patients received bilateral cerebral oximetry sensors, and the control group received standard care. In the intervention group, an algorithm restored rSO2 if it dropped 10% below baseline for >15 s by adjusting cerebral perfusion pressure, inspired oxygen concentration, end-tidal carbon dioxide, depth of anaesthesia, haemoglobin, and cardiac index. Postoperative complications and outcomes were noted. Categorical data were analysed using Chi-square or Fisher's exact tests and continuous data using a t-test or a Mann-Whitney U test. The study was powered for 394 patients, but due to the COVID-19 pandemic and funding constraints, this study was terminated at 101 patients. Results: Of 101 patients, 49 were randomised to the control and 52 to the intervention group. A total of 31 (63%) patients in the control group and 30 (58%) in the interventional exhibited bilateral cerebral desaturation. Time of cumulative cerebral desaturation was longer in the control group (23 ± 48 min vs. 9 ± 15 min, respectively, p = 0.01). A total of 142 algorithm-based treatments were employed, restoring rSO2 in 29 (86%) patients. Both groups displayed equal postoperative outcomes. Conclusions: In major non-cardiac surgery, cerebral desaturation is prevalent in over 85% of patients. Although algorithm-guided therapy restored rSO2 in the majority of patients, it did not result in reduced postoperative morbidity.

Abstract Background and Aims Patients with chronic heart failure in the terminal stage suffer from chronic organ hypoperfusion, which also affects the brain, despite the activation of adaptation mechanisms. This results in impaired autoregulation of cerebral circulation, expressed as a deterioration in cerebrovascular reactivity (CVR) as well as cognitive function (1,2). Orthotopic heart transplantation (OHT) is followed by a rapid and sudden restoration of cardiac output along with subsequent improvement in cerebral perfusion and cognitive function (3-5). A sudden rise in cerebral perfusion pressure can simultaneously lead to neurological complications in the early postoperative period, specifically the potential development of cerebral hyperperfusion syndrome (CHS). An important risk factor for the development of CHS is impairment of cerebrovascular reactivity in the preoperative period (6). The primary aim of presented study was to evaluate cerebrovascular reactivity in patients indicated for heart transplantation compared to subjects from a control group, and also to monitor CVR development 1 month and 6 months after heart transplantation. The secondary aim of the study was to evaluate other haemodynamic parameters before OHT as well as 24-48 hours, 1 month, and 6 months after OHT. We presented first results of the study previously (7). Now we have complete results to be presented and published. Methods Monitored parameters were evaluated by transcranial colour-coded duplex sonography (TCCS). An apnoea test was performed to determine the breath-holding index (BHI) as a parameter of cerebrovascular reactivity. The measurement was performed in the M1 segment of the middle cerebral artery. CVR was evaluated in all patients before transplantation (group A, n=10) and 1 month and 6 months after transplantation (group B, n=9). Other haemodynamic parameters (secondary endpoints of follow-up) were evaluated before OHT as well as 24-48 hours, 1 month, and 6 months after OHT. The control group consisted of 16 healthy volunteers. Results (primary endpoint) Cerebrovascular reactivity was reduced preoperatively in all but one heart transplantation candidates; it was normal in all control subjects. There was a significant difference in BHI between the OHT candidate group and the control group (0.29 vs. 0.96, p&amp;lt;0,0001), indicating a significant impairment of CVR in OHT candidates. Six months after OHT, there was a significant increase in the BHI value compared to the preoperative value (0.29 vs. 1.06, p=0.009), pointing to CVR restoration. Contrary to our preliminary results, there were significant increase of BHI also one month after OHT (0.29 vs. 0.04, p=0.04), pointing to an early post OHT restoration of CVR. Conclusions Cerebrovascular reactivity was significantly reduced in heart transplant candidates. However, this impairment proved reversible, with restoration as early as one month after OHT and this remaind six month after heart transplantation.

Introduction: The primary goals of cardiopulmonary resuscitation (CPR) are to generate adequate myocardial blood flow to enable restoration of mechanical function and adequate brain blood flow to minimize ischemic injury. While the correlation between myocardial blood flow and coronary perfusion pressure during CPR is well established, the correlation between cerebral blood flow and cerebral perfusion pressure is less clear. Common carotid artery (CCA) blood flow is an accessible metric of brain blood flow during CPR in large animal studies. Here, we evaluate the relationships between CCA and several pressure values during CPR. Methods: Analysis was performed on 28 swine. Animals were instrumented to monitor arterial blood pressure (ABP), central venous blood pressure (CVP), intracranial pressure (ICP) and common carotid artery flow. Cerebral perfusion pressure (CePP) was calculated as mean arterial pressure (MAP) minus ICP. Following baseline measurements, ventricular fibrillation cardiac arrest was initiated and CPR started after 8 minutes. Pressure waveforms from the first 8 minutes of CPR (prior to epinephrine administration) were separated into 5 second segments used to calculate all parameters ( A ). Datapoints from the same individual were averaged together and relationships between variables were evaluated using ordinary least-squares regression. Models were compared using R 2 and Root Mean Squared Error (RMSE). Results: Figure panel A illustrates pressures and flow during the chest compression cycle. Regression between ABP value at the systolic peak and % baseline CCA flow ( B ) was weakest (R 2 = 0.31, p=0.003, RMSE=7.1%). Regression between MAP and % baseline CCA flow ( C ) resulted in a moderate positive relationship (R 2 = 0.46, p&lt;0.001, RMSE = 6.2%), while regression between CePP and % baseline CCA flow ( D ) was slightly weaker (R 2 = 0.34, p=0.001, RMSE = 6.9%). Conclusion: While all three parameters showed positive, significant relationships with percent prearrest CCA flow, they may not be adequately reliable surrogates for achieving specific brain blood flow goals during CPR. While all three parameters showed positive, significant relationships with percent prearrest CCA flow, they may not be adequately reliable surrogates for achieving specific brain blood flow goals during CPR. These results emphasize the importance of developing new techniques to quantitatively monitor brain blood flow during physiology-guided CPR.

Background: Head Up Position (HUP) Cardiopulmonary Resuscitation (CPR) and Resuscitation Balloon Occlusion of the Aorta (REBOA) are emerging interventions for non-traumatic cardiac arrest. HUP-CPR includes automated head and thorax elevation, active compression decompression CPR, and an impedance threshold device. Pilot animal studies have shown a possible hemodynamic synergy with HUP-CPR +REBOA . Hypothesis: HUP-CPR+REBOA will result in superior hemodynamics compared to Conventional (C) CPR+REBOA in the supine flat position, in a porcine model of prolonged cardiac arrest. Methods: Farm pigs (n=10) were sedated, intubated, and anesthetized. Femoral central venous, arterial, and intracranial access was obtained and pressures were measured throughout the study. End tidal CO2 andcerebral oximetry were also monitored. Ventricular Fibrillation was induced and left untreated for 10 minutes and animals were randomized to either HUP-CPR+REBOA or C-CPR+REBOA. After 18 minutes of CPR, the REBOA was inflated in the Zone 1 region in both groups. After 26 minutes, epinephrine and amiodarone were given and defibrillation performed a minute later. An unpaired t-test was used for comparison between HUP-CPR and C-CPR groups. A paired t-test was used for comparison within groups, before and after REBOA. Results: Hemodynamics are presented for each group in Table 1. Before REBOA inflation at 18 minutes, nearly all measurements were significantly higher in the HUP-CPR group than the C-CPR group. After REBOA inflation after 23 minutes of CPR, all hemodynamics were again significantly higher with HUP-CPR+REBOA versus C-CPR+REBOA. Mean arterial pressure (MAP) (mmHg, 42.6 ± 7 vs 51.6 ± 5, p &lt; 0.01) and cerebralperfusion pressure (CerPP) (mmHg, 33.5 ± 9 vs 42.2 ± 7, p&lt;0.01) were significantly higher after REBOA inflation within the HUP-CPR group (Figures 1,2). No significant changes were noted in the C-CPR groupbefore versus after REBOA inflation. Conclusions: In this ongoing study, HUP-CPR resulted in superior hemodynamics versus C-CPR beforeREBOA inflation. After 18 minutes of CPR, MAP and CerPP were significantly higher after REBOA inflation in the HUP-CPR group. By contrast, no significant hemodynamic changes were observed in the C-CPR group after REBOA inflation. Further study is needed regarding the optimal timing of REBOA treatment to maximize hemodynamics during HUP-CPR. Overall, the HUP-CPR +REBOA combination is promising and should beconsidered for clinical study.

Background: The efficacy of different conventional ventilation during automated head-up (AHUP) CPR using active decompression and impedance threshold device with head and torso elevation is unknown. We sought to determine the central and peripheral hemodynamics while using the 10:1 versus the 30:2 positive pressure ventilation (PPV). Research Question: Does the PPV delivery method affect the hemodynamics during AHUP-CPR? Methods: Ventricular fibrillation was induced in anesthetized pigs (n=5), followed by AHUP-CPR initiation with positive pressure ventilations applied using an automated bag compressor to deliver 10ml/kg of tidal volume over 1 sec at a rate of 10 breaths/min. After 15 minutes of CPR using a 10:1 ratio, ventilation was changed to a 30:2 ratio for 2 minutes with 2 PPV delivered consecutively. Thereafter 10:1 ratio was resumed followed by another 2-minute round of 30:2 PPV mode. Intraventricular pressures and volumes using conductance catheters placed in the right ventricle (RV), along with other hemodynamic parameters were recorded continuously, during the 2-minute intervals between PPV delivery. A mixed-effects model was used to evaluate the effects of PPV mode on pressure-volume (PV) loop parameters while using a Spearman correlation to explore the relationship between PV loop indices. Results: There was no statistically significant difference between RV stroke volume (SV) with 10:1 versus 30:2 PPV mode (Table 1). Throughout 2 minutes, 30:2 ventilation mode resulted in a significantly higher end-tidal CO2 (ETCO2), and higher pressures with a higher pulmonary elastance (Ea) imposed on RV (p&lt;0.05). Higher Ea was strongly correlated with lower SV and ETCO2 (Spearman's rho correlation confidence of -0.97 and -0.83, respectively). No significant differences were observed between the two ventilation modes in any other hemodynamic parameters, including intrathoracic, aortic and right atrial pressures, as well as coronary and cerebral perfusion pressures. Conclusion: No significant difference was found for right ventricular stroke volume when comparing one breath after 10 chest compressions to two breaths after 30 compressions during automated head-up CPR. Delivering two consecutive breaths after 30 continuous compressions led to an overall higher ETCO2, but it also imposed greater ventricular pressure and afterload, which were significantly correlated with reduced SV and ETCO2.

Introduction: Current pediatric cardiopulmonary resuscitation (CPR) guidelines recommend that a rescuer performs manual ventilation at a rate of 20-30 breaths per minute (bpm) with an avoidance of excessive ventilation during CPR. Despite these recommendations, excessive ventilation is common during CPR, and performing manual ventilation can be difficult in settings with limited personnel. Using mechanical ventilation during CPR can provide relatively constant minute ventilation and offloads a rescuer to perform other tasks. Research Question: Does mechanical ventilation produce similar gas exchange and intra-arrest hemodynamics compared to manual ventilation during CPR? Aims: To compare gas exchange and intra-arrest hemodynamics when using manual ventilation versus three mechanical ventilation strategies: sustained inflation (SI), pressure-controlled mechanical ventilation (PCV), and volume-controlled mechanical ventilation (VCV). Methods: This was a randomized, crossover study design. Twenty 4-5 kg swine were anesthetized and underwent up to 4 episodes of 1 minute of ventricular fibrillation-induced (VF) cardiac arrest and resuscitation. Each swine was assigned 4 different intra-arrest ventilatory strategies in random order including: 1) manual ventilation at a rate of 25 bpm, 2) SI at 15 cm H 2 O, 3) PCV using pre-arrest peak inspiratory pressures, and 4) VCV using a pre-arrest tidal volume. Swine were resuscitated with chest compressions at 120 compressions per minute, epinephrine administration every 4 minutes, and defibrillation as clinically indicated starting 8 minutes into resuscitation. Arterial blood gases were obtained at baseline and at 4 and 8 min of resuscitation. Arterial diastolic blood pressure (DBP), myocardial perfusion pressure (MPP), and cerebral perfusion pressure (CPP) were measured at baseline and continuously during resuscitation. Results: The twenty swine underwent a total of 32 VF cardiac arrests and resuscitation. At 4 and 8 minutes of CPR, SI, PCV, and VCV produced PaCO 2 and PaO 2 levels similar to that of manual ventilation ( Figure 1 ). DBP, MPP, and CPP levels were also similar among the 4 groups at 4 and 8 minutes of resuscitation ( Figure 2 ). Conclusion: In this swine model of short VF pediatric cardiac arrest, sustained inflation, pressure-controlled and volume-controlled mechanical ventilation are feasible and provide adequate gas exchange and similar hemodynamics compared to manual ventilation.

Background: Ventriculo-arterial (VA) coupling characterizes the interaction between the cardiac function and the arterial circulation afterload and reflects cardiovascular performance. We found, for the first time, that there is a significant VA decoupling with conventional CPR, which was ameliorated by automated head-up (AHUP)-CPR using active compression-decompression (ACD), impedance threshold device (ITD) as well as head and thorax elevation. Research Questions: How does the degree of active decompression (AD) influence VA coupling and its association with hemodynamic and perfusion outcomes during AHUP-CPR? Methods: Farm pigs (~40 kg) were intubated, ventilated, and monitored for hemodynamics, including end-tidal CO2 (ETCO2), and pressure-volume loops in right (RV | n=10) and left (LV | n =4) ventricles. After 10 minutes of untreated ventricular fibrillation, CPR started with 2 minutes each of C-CPR, ACD+ITD, and AHUP-CPR at 3 cm elevation. At minute 15, AD was paused, then resumed incrementally up to 4 cm. Statistical analysis was performed using a mixed-effects model to evaluate the effects of incremental AD on VA coupling, and a Spearman correlation to explore the relationship between VA coupling and hemodynamics. Results: Full AD (3cm or more) resulted in significantly enhanced VA coupling compared to no AD (p&lt;0.05 in both ventricles) or minimal AD (1cm | p&lt;0.05 RV and p=0.24 LV). Improved RV and LV VA coupling with full AD was associated with higher SV in both ventricles, as well as higher aortic pressures, and coronary and cerebral perfusions (table 1 and figure 1). Optimized VA coupling was also correlated with enhanced compression efficiency, which led to end compression volumes as a result of more efficient cardiac output. Conclusion: Full AD (3cm or more) when used with ITD during AHUP-CPR leads to optimal VA circulation. Optimized VA coupling in both ventricles resulted in enhanced cardiac filling and output, and subsequently, increased systemic, coronary and cerebral perfusion pressures. RV showed a different pattern to LV, likely due to its different load and contractile efficiency.