Higher Cerebral Perfusion Pressure Research Articles

Influence of cerebrospinal fluid drainage in the first days after aneurysm rupture on the severity of early brain injury following aneurysmal subarachnoid hemorrhage

PurposeProgressive cerebral edema with refractory intracranial hypertension (ICP) requiring decompressive hemicraniectomy (DHC) is a severe manifestation of early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (aSAH). The purpose of the study was to investigate whether a more pronounced cerebrospinal fluid (CSF) drainage has an influence on cerebral perfusion pressure (CPP) and the extent of EBI after aSAH.MethodsPatients with aSAH and indication for ICP-monitoring admitted to our center between 2012 and 2020 were retrospectively included. EBI was categorized based on intracranial blood burden, persistent loss of consciousness, and SEBES (Subarachnoid Hemorrhage Early Brain Edema Score) score on the third day after ictus. The draining CSF and vital signs such as ICP and CPP were documented daily.Results90 out of 324 eligible aSAH patients (28%) were included. The mean age was 54.2 ± 11.9 years. DHC was performed in 24% (22/90) of patients. Mean CSF drainage within 72 h after ictus was 168.5 ± 78.5 ml. A higher CSF drainage within 72 h after ictus correlated with a less severe EBI and a less frequent need for DHC (r=-0.33, p = 0.001) and with a higher mean CPP on day 3 after ictus (r = 0.2351, p = 0.02).ConclusionA more pronounced CSF drainage in the first 3 days of aSAH was associated with higher CPP and a less severe course of EBI and required less frequently a DHC. These results support the hypothesis that an early and pronounced CSF drainage may facilitate blood clearance and positively influence the course of EBI.

Intracranial Pressure and Cerebral Hemodynamics in Infants Before and After Glenn Procedure.

This prospective cohort study aimed to investigate changes in intracranial pressure (ICP) and cerebral hemodynamics in infants with congenital heart disease undergoing the Glenn procedure, focusing on the relationship between superior vena cava pressure and estimated ICP. A single-center prospective cohort study. The study was conducted in a cardiac center over 4 years (2019-2022). Twenty-seven infants with congenital heart disease scheduled for the Glenn procedure were included in the study, and detailed patient demographics and primary diagnoses were recorded. Transcranial Doppler (TCD) ultrasound examinations were performed at three time points: baseline (preoperatively), postoperative while ventilated (within 24-48 hr), and at discharge. TCD parameters, blood pressure, and pulmonary artery pressure were measured. TCD parameters included systolic flow velocity, diastolic flow velocity (dFV), mean flow velocity (mFV), pulsatility index (PI), and resistance index. Estimated ICP and cerebral perfusion pressure (CPP) were calculated using established formulas. There was a significant postoperative increase in estimated ICP from 11 mm Hg (interquartile range [IQR], 10-16 mm Hg) to 15 mm Hg (IQR, 12-21 mm Hg) postoperatively (p = 0.002) with a trend toward higher CPP from 22 mm Hg (IQR, 14-30 mm Hg) to 28 mm Hg (IQR, 22-38 mm Hg) postoperatively (p = 0.1). TCD indices reflected alterations in cerebral hemodynamics, including decreased dFV and mFV and increased PI. Intracranial hemodynamics while on positive airway pressure and after extubation were similar. Glenn procedure substantially increases estimated ICP while showing a trend toward higher CPP. These findings underscore the intricate interaction between venous pressure and cerebral hemodynamics in infants undergoing the Glenn procedure. They also highlight the remarkable complexity of cerebrovascular autoregulation in maintaining stable brain perfusion under these circumstances.

Predictive value of intracranial pressure-related parameters and coagulation on the prognosis in patients with traumatic brain injury.

This study investigated the factors affecting the prognosis of patients with traumatic brain injury (TBI) and assessed the predictive value of intracranial pressure-related parameters and coagulation on prognosis. Seventy TBI patients admitted between January 2020 and January 2021 were catego-rized into good prognosis (n=42) and poor prognosis (n=28) groups according to the Glasgow Outcome Scale (GOS) score upon discharge. Factors affecting prognosis were analyzed, and differences in intracranial pressure and coagula-tion between the two groups were compared. The receiver operating charac-teristic curve (ROC) was used to calculate the predictive value of intracranial pressure-related parameters and coagulation function on prognosis. Within 24 h postoperatively, the good prognosis group had lower levels of intracra-nial pressure (ICP) and partial pressure of oxygen in brain tissue (PbtO2) and higher cerebral perfusion pressure (CPP) and cerebral hemodynamic param-eters than the poor prognosis group (p<0.05). The good prognosis group had significantly lower prothrombin time (PT), activated partial thromboplastin time (aPTT),and prothrombin time (TT) levels and higher platelets (PLT) and fibrinogen (Fib) levels than the poor prognosis group (p<0.05). Regression analysis revealed that CPP, systolic blood flow velocity (Vs), end-diastolic blood flow velocity (Vd), mean blood flow velocity (Vm), PLT, Fib were independent protective factors for the prognosis, and ICP, PbtO2, PT, APTT, and TT were risk factors for prognosis. The ROC revealed that ICP, CPP, PbtO2, Vs, Vd, Vm, APTT, PLT, Fib exhibited high diagnostic value for poor prognosis (AUC=0.732, 0.940, 0.796, 0.706, 0.914, 0.729, 0.876, 0.709, 0.866), with ICP showing the highest diagnostic sensitivity and Vd showing the highest diagnostic specificity. Intracranial pressure-related parameters and coagulation indicators are prog-nosis-related indexes in patients with TBI, and the prognosis and survival can be improved by controlling intracranial pressure and improving coagulation.

The Effect of Recruitment Maneuvers on Cerebrovascular Dynamics and Right Ventricular Function in Patients with Acute Brain Injury: A Single-Center Prospective Study.

Optimization of ventilatory settings is challenging for patients in the neurointensive care unit, requiring a balance between precise gas exchange control, lung protection, and managing hemodynamic effects of positive pressure ventilation. Although recruitment maneuvers (RMs) may enhance oxygenation, they could also exert profound undesirable systemic impacts. The single-center, prospective study investigated the effects of RMs (up-titration of positive end-expiratory pressure) on multimodal neuromonitoring in patients with acute brain injury. Our primary focus was on intracranial pressure and secondarily on cerebral perfusion pressure (CPP) and other neurological parameters: cerebral autoregulation [pressure reactivity index (PRx)] and regional cerebral oxygenation (rSO2). We also assessed blood pressure and right ventricular (RV) function evaluated using tricuspid annular plane systolic excursion. Results are expressed as the difference (Δ) from baseline values obtained after completing the RMs. Thirty-two patients were enrolled in the study. RMs resulted in increased intracranial pressure (Δ = 4.8mm Hg) and reduced CPP (ΔCPP = -12.8mm Hg) and mean arterial pressure (difference in mean arterial pressure = -5.2mm Hg) (all p < 0.001). Cerebral autoregulation worsened (ΔPRx = 0.31 a.u.; p < 0.001). Despite higher systemic oxygenation (difference in partial pressure of O2 = 4mm Hg; p = 0.001) and unchanged carbon dioxide levels, rSO2 marginally decreased (ΔrSO2 = -0.5%; p = 0.031), with a significant drop in arterial content and increase in the venous content. RV systolic function decreased (difference in tricuspid annular plane systolic excursion = -0.1cm; p < 0.001) with a tendency toward increased RV basal diameter (p = 0.06). Grouping patients according to ΔCPP or ΔPRx revealed that those with poorer tolerance to RMs had higher CPP (p = 0.040) and a larger RV basal diameter (p = 0.034) at baseline. In patients with acute brain injury, RMs appear to have adverse effects on cerebral hemodynamics. These findings might be partially explained by RM's impact on RV function. Further advanced echocardiography monitoring is required to prove this hypothesis.

Autoregulatory Cerebral Perfusion Pressure Insults in Traumatic Brain Injury and Aneurysmal Subarachnoid Hemorrhage: The Role of Insult Intensity and Duration on Clinical Outcome.

This single-center, retrospective study investigated the outcome effect of the combined intensity and duration of differences between actual cerebral perfusion pressure (CPP) and optimal cerebral perfusion pressure (CPPopt), and also for absolute CPP, in patients with traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (aSAH). A total of 378 TBI and 432 aSAH patients treated in a neurointensive care unit between 2008 and 2018 with at least 24 hours of CPPopt data during the first 10 days following injury, and with 6-month (TBI) or 12-month (aSAH) extended Glasgow Outcome Scale (GOS-E) scores, were included in the study. ∆CPPopt-insults (∆CPPopt=actual CPP-CPPopt) and CPP-insults were visualized as 2-dimensional plots to highlight the combined effect of insult intensity (mmHg) and duration (min) on patient outcome. In TBI patients, a zone of ∆CPPopt ± 10mmHg was associated with more favorable outcome, with transitions towards unfavorable outcome above and below this zone. CPP in the range of 60 to 80mmHg was associated with higher GOS-E, whereas CPP outside this range was associated with lower GOS-E. In aSAH patients, there was no clear transition from higher to lower GOS-E for ∆CPPopt-insults; however, there was a transition from favorable to unfavorable outcome when CPP was <80mmHg. TBI patients with CPP close to CPPopt exhibited better clinical outcomes, and absolute CPP within the 60 to 80mmHg range was also associated with favorable outcome. In aSAH patients, there was no clear transition for ∆CPPopt-insults in relation to outcome, whereas generally high absolute CPP values were associated overall with favorable recovery.

Lung Injury Risk in Traumatic Brain Injury Managed With Optimal Cerebral Perfusion Pressure Guided-Therapy.

Management of traumatic brain injury (TBI) has to counterbalance prevention of secondary brain injury without systemic complications, namely lung injury. The potential risk of developing acute respiratory distress syndrome (ARDS) leads to therapeutic decisions such as fluid balance restriction, high PEEP and other lung protective measures, that may conflict with neurologic outcome. In fact, low cerebral perfusion pressure (CPP) may induce secondary ischemic injury and mortality, but disproportionate high CPP may also increase morbidity and worse lung compliance and hypoxia with the risk of developing ARDS and fatal outcome. The evaluation of cerebral autoregulation at bedside and individualized (optimal CPP) CPPopt-guided therapy, may not only be a relevant measure to protect the brain, but also a safe measure to avoid systemic complications. We aimed to study the safety of CPPopt-guided-therapy and the risk of secondary lung injury association with bad outcome. Single-center retrospective analysis of 92 severe TBI patients admitted to the Neurocritical Care Unit managed with CPPopt-guided-therapy by PRx (pressure reactivity index). During the first 10 days, we collected data from blood gas, ventilation and brain variables. Evolution along time was analyzed using linear mixed-effects regression models. 86% were male with mean age 53±21 years. 49% presented multiple trauma and 21% thoracic trauma. At hospital admission, median GCS was 7 and after 3-months GOS was 3. Monitoring data was CPP 86±7mmHg, CPP-CPPopt -2.8±10.2mmHg and PRx 0.03±0.19. The average PFratio (PaO2/FiO2) was 305±88 and driving pressure 15.9±3.5cmH2O. PFratio exhibited a significant quadratic dependence across time and PRx and driving pressure presented significant negative association with PFRatio. CPP and CPPopt did not present significant effect on PFratio (p=0.533; p=0.556). A significant positive association between outcome and the difference CPP-CPPopt was found. Management of TBI using CPPopt-guided-therapy was associated with better outcome and seems to be safe regarding the development of secondary lung injury.

Accuracy of Manual Intracranial Pressure Recording Compared to a Computerized High-Resolution System: A CENTER-TBI Analysis

BackgroundMonitoring intracranial pressure (ICP) and cerebral perfusion pressure (CPP) is crucial in the management of the patient with severe traumatic brain injury (TBI). In several institutions ICP and CPP are summarized hourly and entered manually on bedside charts; these data have been used in large observational and interventional trials. However, ICP and CPP may change rapidly and frequently, so data recorded in medical charts might underestimate actual ICP and CPP shifts. The aim of this study was to evaluate the accuracy of manual data annotation for proper capturing of ICP and CPP. For this aim, we (1) compared end-hour ICP and CPP values manually recorded (MR) with values recorded continuously by computerized high-resolution (HR) systems and (2) analyzed whether MR ICP and MR CPP are reliable indicators of the burden of intracranial hypertension and low CPP.MethodsOne hundred patients were included. First, we compared the MR data with the values stored in the computerized system during the first 7 days after admission. For this point-to-point analysis, we calculated the difference between end-hour MR and HR ICP and CPP. Then we analyzed the burden of high ICP (> 20 mm Hg) and low CPP (< 60 mm Hg) measured by the computerized system, in which continuous data were stored, compared with the pressure–time dose based on end-hour measurements.ResultsThe mean difference between MR and HR end-hour values was 0.02 mm Hg for ICP (SD 3.86 mm Hg) and 1.54 mm Hg for CPP (SD 8.81 mm Hg). ICP > 20 mm Hg and CPP < 60 mm Hg were not detected by MR in 1.6% and 5.8% of synchronized measurements, respectively. Analysis of the pathological ICP and CPP throughout the recording, however, indicated that calculations based on manual recording seriously underestimated the ICP and CPP burden (in 42% and 28% of patients, respectively).ConclusionsManual entries fairly represent end-hour HR ICP and CPP. However, compared with a computerized system, they may prove inadequate, with a serious risk of underestimation of the ICP and CPP burden.

Tantangan dalam Menjaga Cerebral Perfusion Pressure (CPP) yang Aman pada Cedera Otak Traumatik

Cerebral perfusion pressure (CPP) is the net pressure gradient that drives oxygen delivery to cerebral tissue. It is the difference between the mean arterial pressure (MAP) and the intracranial pressure (ICP), CPP = MAP-CVP or CPP =MAP – ICP if ICP&gt;CVP. Cerebral perfusion pressure must be maintained within narrow limits because too litle pressure could cause brain tissue become ischemic, and too much could raise intracranial pressure. The normal range lies between 60 and 80 mmHg, but these values can shift to the left or right depending on individual patient physiology. As CPP is a calculated measure, MAP and ICP must be measured simultaneously, most commonly by invasive means. When brain injury occurs, cerebral capillaries can become “leaky” or more permeable to water. In addition, cerebral blood vessels may dilate in respons to brain tissue injury, hypoxemia, hypercarbia, acidosis, or hypotension. If blood pressure becomes elevated, the increased CPP can lead to increased cerebral blood flow. The recommended goal of CPP per the Brain Trauma Foundation (BTF) guideline is 50-70 mmHg. Targeting high CPP &gt;70 mmHg has not been shown to be beneficial in patient with traumatic brain injury and is associated with an increased risk of acute respiratory distress syndrome (ARDS).

Low Morbidity and Mortality in Children with Severe Traumatic Brain Injury Treated According to the Lund Concept: A Population-Based Study.

Previous reports of mortality and morbidity in pediatric severe traumatic brain injury (TBI) vary considerably, with few population-based studies. Mortality rates from 3-33 % and varying morbidity have been reported, most commonly using the Extended Glasgow Outcome Scale (eGOS). The Lund concept is a treatment algorithm for severe TBI aiming at controlling intracranial pressure (ICP) by reducing cerebral perfusion pressure (CPP). The aim of the present study was to retrospectively assess mortality and morbidity in a population of pediatric TBI treated according to the Lund concept. All cases of severe pediatric TBI (age <18 years) in the southern region of Sweden during 19 years were identified. Patients were treated according to the Lund concept. Mortality, eGOS, ICP, CPP, time in the neurosurgical intensive care unit (NICU), drugs delivered and surgical procedures were recorded. Data were analyzed both by dichotomized outcomes and by ordinal statistics. A total of 135 cases of severe TBI <18 years of age were recorded (incidence 2.0/100000) and 86 patients were admitted to the tertiary NICU. Mortality including all cases was 43% (mortality rate 0.7/100,000) and in NICU 10%. Outcome was good in 60%, moderate in 25%, unfavorable in 15%, with none in a vegetative status. In both dichotomized and ordinal analyses, CPP <40 mm Hg and ICP >15 were associated with poor outcome, supporting current guidelines. However, high CPP also was associated with increased mortality and morbidity, supporting that elevated CPP might increase cerebral edema. In this study, the Lund concept resulted in low mortality and a favorable outcome in a majority of severe pediatric TBI patients; however, randomized controlled trials are warranted to verify this.

Cerebral Blood Flow and Oxygen Delivery in Aneurysmal Subarachnoid Hemorrhage: Relation to Neurointensive Care Targets

BackgroundThe primary aim was to determine to what extent continuously monitored neurointensive care unit (neuro-ICU) targets predict cerebral blood flow (CBF) and delivery of oxygen (CDO2) after aneurysmal subarachnoid hemorrhage. The secondary aim was to determine whether CBF and CDO2 were associated with clinical outcome.MethodsIn this observational study, patients with aneurysmal subarachnoid hemorrhage treated at the neuro-ICU in Uppsala, Sweden, from 2012 to 2020 with at least one xenon-enhanced computed tomography (Xe-CT) obtained within the first 14 days post ictus were included. CBF was measured with the Xe-CT and CDO2 was calculated based on CBF and arterial oxygen content. Regional cerebral hypoperfusion was defined as CBF < 20 mL/100 g/min, and poor CDO2 was defined as CDO2 < 3.8 mL O2/100 g/min. Neuro-ICU variables including intracranial pressure (ICP), pressure reactivity index, cerebral perfusion pressure (CPP), optimal CPP, and body temperature were assessed in association with the Xe-CT. The acute phase was divided into early phase (day 1–3) and vasospasm phase (day 4–14).ResultsOf 148 patients, 27 had underwent a Xe-CT only in the early phase, 74 only in the vasospasm phase, and 47 patients in both phases. The patients exhibited cerebral hypoperfusion and poor CDO2 for medians of 15% and 30%, respectively, of the cortical brain areas in each patient. In multiple regressions, higher body temperature was associated with higher CBF and CDO2 in the early phase. In a similar regression for the vasospasm phase, younger age and longer pulse transit time (lower peripheral resistance) correlated with higher CBF and CDO2, whereas lower hematocrit only correlated with higher CBF but not with CDO2. ICP, CPP, and pressure reactivity index exhibited no independent association with CBF and CDO2. R2 of these regressions were below 0.3. Lower CBF and CDO2 in the early phase correlated with poor outcome, but this only held true for CDO2 in multiple regressions.ConclusionsSystemic and cerebral physiological variables exhibited a modest association with CBF and CDO2. Still, cerebral hypoperfusion and low CDO2 were common and low CDO2 was associated with poor outcome. Xe-CT imaging could be useful to help detect secondary brain injury not evident by high ICP and low CPP.

Differential Hemodynamic Response of Pial Arterioles Contributes to a Quadriphasic Cerebral Autoregulation Physiology.

BackgroundCerebrovascular autoregulation (CA) regulates cerebral vascular tone to maintain near‐constant cerebral blood flow during fluctuations in cerebral perfusion pressure (CPP). Preclinical and clinical research has challenged the classic triphasic pressure‐flow relationship, leaving the normal pressure‐flow relationship unclear.Methods and ResultsWe used in vivo imaging of the hemodynamic response in pial arterioles to study CA in a porcine closed cranial window model during nonpharmacological blood pressure manipulation. Red blood cell flux was determined in 52 pial arterioles during 10 hypotension and 10 hypertension experiments to describe the pressure‐flow relationship. We found a quadriphasic pressure‐flow relationship with 4 distinct physiological phases. Smaller arterioles demonstrated greater vasodilation during low CPP when compared with large arterioles (P<0.01), whereas vasoconstrictive capacity during high CPP was not significantly different between arterioles (P>0.9). The upper limit of CA was defined by 2 breakpoints. Increases in CPP lead to a point of maximal vasoconstriction of the smallest pial arterioles (upper limit of autoregulation [ULA] 1). Beyond ULA1, only larger arterioles maintain a limited additional vasoconstrictive capacity, extending the buffer for high CPP. Beyond ULA2, vasoconstrictive capacity is exhausted, and all pial arterioles passively dilate. There was substantial intersubject variability, with ranges of 29.2, 47.3, and 50.9 mm Hg for the lower limit, ULA1, and ULA2, respectively.ConclusionsWe provide new insights into the quadriphasic physiology of CA, differentiating between truly active CA and an extended capacity to buffer increased CPP with progressive failure of CA. In this experimental model, the limits of CA widely varied between subjects.

Intracranial Pressure and Cerebral Perfusion Pressure in Large Spontaneous Intracranial Hemorrhage and Impact of Minimally Invasive Surgery

Introduction: We investigated the effect of hematoma volume reduction with minimally invasive surgery (MIS) on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in patients with large spontaneous intracerebral hemorrhage (ICH).Methods:Post-hoc analysis of the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation (MISTIE III) study, a clinical trial with blinded outcome assessments. The primary outcome was the proportion of ICP readings ≥20 and 30 mmHg, and CPP readings <70 and 60 mm Hg. Secondary outcomes included major disability (modified Rankin scale >3) and mortality at 30 and 365 days. We assessed the relationship between proportion of high ICP and low CPP events and MIS using binomial generalized linear models, and outcomes using multiple logistic regression.Results: Of 499 patients enrolled in MISTIE III, 72 patients had guideline based ICP monitors placed, 34 in the MIS group and 38 in control (no surgery) group. Threshold ICP and CPP events ≥20/ <70 mmHg occurred in 31 (43.1%) and 52 (72.2%) patients respectively. On adjusted analyses, proportion of ICP readings ≥20 and 30 mmHg were significantly lower in the MIS group vs. control group [Odds Ratio (OR) 0.27, 95% Confidence Interval [CI] 0.11–0.63 (p = 0.002); OR = 0.18, 0.04–0.75, p = 0.02], respectively. Proportion of CPP readings <70 and 60 mm Hg were also significantly lower in MIS patients [OR 0.31, 95% CI 0.15–0.63 (p = 0.001); OR 0.30, 95% CI 0.11–0.83 (p = 0.02)], respectively. Higher proportions of CPP readings <70 and 60 mm were significantly associated with short term mortality (p = 0.04), and (p = 0.006), respectively. Long term mortality was significantly associated with higher proportion of time with ICP ≥ 20 (p = 0.04), ICP ≥ 30 (p = 0.04), and CPP <70 mmHg (p = 0.01).Conclusion: Our results are consistent with the hypothesis that surgical reduction of ICH volume decreases proportion of high ICP and low CPP events and that these variables are associated with short- and long-term mortality.

The neuroprotective effects of AMN082 on neuronal apoptosis in rats after traumatic brain injury

BackgroundThe aim of this study was to investigate whether AMN082 exerts its neuroprotective effect by attenuating glutamate receptor-associated neuronal apoptosis and improving functional outcomes after traumatic brain injury (TBI).MethodsAnesthetized male Sprague–Dawley rats were divided into the sham-operated, TBI + vehicle, and TBI + AMN082 groups. AMN082 (10 mg/kg) was intraperitoneally injected 0, 24, or 48 h after TBI. In the 120 min after TBI, heart rate, mean arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were continuously measured. Motor function, the infarct volume, neuronal nitrosative stress-associated apoptosis, and N-methyl-d-aspartate receptor 2A (NR2A) and NR2B expression in the pericontusional cortex were measured on the 3rd day after TBI.ResultsThe results showed that the AMN082-treated group had a lower ICP and higher CPP after TBI. TBI-induced motor deficits, the increase in infarct volume, neuronal apoptosis, and 3-nitrotyrosine and inducible nitric oxide synthase expression in the pericontusional cortex were significantly improved by AMN082 therapy. Simultaneously, AMN082 increased NR2A and NR2B expression in neuronal cells.ConclusionsWe concluded that intraperitoneal injection of AMN082 for 3 days may ameliorate TBI by attenuating glutamate receptor-associated nitrosative stress and neuronal apoptosis in the pericontusional cortex. We suggest that AMN082 administration in the acute stage may be a promising strategy for TBI.

Cerebral perfusion and metabolism with mean arterial pressure 90 vs. 60 mmHg in a porcine post cardiac arrest model with and without targeted temperature management

AimTo determine whether targeting a mean arterial pressure of 90 mmHg (MAP90) would yield improved cerebral blood flow and less ischaemia compared to MAP 60 mmHg (MAP60) with and without targeted temperature management at 33 °C (TTM33) in a porcine post-cardiac arrest model. MethodsAfter 10 min of cardiac arrest, 41 swine of either sex were resuscitated until return of spontaneous circulation (ROSC). They were randomised to TTM33 or no-TTM, and MAP60 or MAP90; yielding four groups. Temperatures were managed with intravasal cooling and blood pressure targets with noradrenaline, vasopressin and nitroprusside, as appropriate. After 30 min of stabilisation, animals were observed for two hours. Cerebral perfusion pressure (CPP), cerebral blood flow (CBF), pressure reactivity index (PRx), brain tissue pCO2 (PbtCO2) and tissue intermediary metabolites were measured continuously and compared using mixed models. ResultsAnimals randomised to MAP90 had higher CPP (p < 0.001 for both no-TTM and TTM33) and CBF (no-TTM, p < 0.03; TH, p < 0.001) compared to MAP60 during the 150 min observational period post-ROSC. We also observed higher lactate and pyruvate in MAP60 irrespective of temperature, but no significant differences in PbtCO2 and lactate/pyruvate-ratio. We found lower PRx (indicating more intact autoregulation) in MAP90 vs. MAP60 (no-TTM, p = 0.04; TTM33, p = 0.03). ConclusionIn this porcine cardiac arrest model, targeting MAP90 led to better cerebral perfusion and more intact autoregulation, but without clear differences in ischaemic markers, compared to MAP60. Institutional protocol numberFOTS, id 8442.

Temporal Dynamics of ICP, CPP, PRx, and CPPopt in High-Grade Aneurysmal Subarachnoid Hemorrhage and the Relation to Clinical Outcome

BackgroundHigh intracranial pressure (ICP) and low cerebral perfusion pressure (CPP) may induce secondary brain injury following aneurysmal subarachnoid hemorrhage (aSAH). In the current study, we aimed to determine the temporal incidence of insults above/below certain ICP/CPP thresholds, the role of pressure autoregulation in CPP management (PRx and CPPopt), and the relation to clinical outcome.MethodsIn this retrospective study, 242 patients were included with aSAH, who were treated in the neurointensive care unit, Uppsala University Hospital, Sweden, 2008–2018, with ICP monitoring the first 10 days post-ictus. Data from ICP, pressure autoregulation (PRx), CPP, and CPPopt (the CPP with the lowest/optimal PRx) were analyzed the first 10 days. The percentage of good monitoring time (GMT) above/below various ICP and CPP thresholds was calculated, e.g., ICP > 20 mm Hg (%), CPP < 60 mm Hg (%), and ∆CPPopt (CPP–CPPopt) < − 10 mm Hg (%).ResultsOf the 242 patients, 63 (26%) had favorable (GOS-E 5–8) and 179 (74%) had unfavorable (GOS-E 1–4) outcome at 12 months. Higher proportion (GMT) of ICP insults above 20 mm Hg was most common the first 3 days post-ictus and was then independently associated with unfavorable outcome. CPP gradually increased throughout the 10 days post-ictus, and higher proportion of GMT with CPP < 90 mm Hg was independently associated with unfavorable outcome in the late vasospasm phase (days 6.5–10). PRx was above 0 throughout the 10 days and deteriorated in the late vasospasm phase. Higher values were then independently associated with unfavorable outcome. There was no difference in GMT of CPP deviations from CPPopt between the outcome groups.ConclusionsAvoiding intracranial hypertension early and maintaining a high CPP in the vasospasm phase when the pressure autoregulation is most disturbed may improve clinical outcome after aSAH.

Improving post-cardiac arrest cerebral perfusion pressure by elevating the head and thorax

AimThe optimal head and thorax position after return of spontaneous circulation (ROSC) following cardiac arrest (CA) is unknown. This study examined whether head and thorax elevation post-ROSC is beneficial, in a porcine model. MethodsProtocol A: 40 kg anesthetized pigs were positioned flat, after 7.75 min of untreated CA the heart and head were elevated 8 and 12 cm, respectively, above the horizontal plane, automated active compression decompression (ACD) plus impedance threshold device (ITD) CPR was started, and 2 min later the heart and head were elevated 10 and 22 cm, respectively, over 2 min to the highest head up position (HUP). After 30 min of CPR pigs were defibrillated and randomized 10 min later to four 5-min epochs of HUP or flat position. Multiple physiological parameters were measured. In Protocol B, after 6 min of untreated VF, pigs received 6 min of conventional CPR flat, and after ROSC were randomized HUP versus Flat as in Protocol A. The primary endpoint was cerebral perfusion pressure (CerPP). Multivariate analysis-of-variance (MANOVA) for repeated measures was used. Data were reported as mean ± SD. ResultsIn Protocol A, intracranial pressure (ICP) (mmHg) was significantly lower post-ROSC with HUP (9.1 ± 5.5) versus Flat (18.5 ± 5.1) (p < 0.001). Conversely, CerPP was higher with HUP (62.5 ± 19.9) versus Flat (53.2 ± 19.1) (p = 0.004), respectively. Protocol A and B results comparing HUP versus Flat were similar. ConclusionPost-ROSC head and thorax elevation in a porcine model of cardiac arrest resulted in higher CerPP and lower ICP values, regardless of VF duration or CPR method. IACUC Protocol Number19-09.

Abstract 121: A Pre-Clinical Randomized Blinded Trial of Inhaled Nitric Oxide During Pediatric Cardiopulmonary Resuscitation

Introduction: Inhaled nitric oxide (iNO) may result in higher systemic BP during CPR and may have a neuroprotective role post-arrest, but its effects on cerebral perfusion pressure (CePP), cerebral blood flow (CBF), and mitochondrial function when administered during CPR are unknown. Hypotheses: We hypothesized that administration of iNO during CPR would lead to higher CePP, higher CBF, and less brain injury as measured by cerebral mitochondrial function, neuronal apoptosis, and microglial activation. Methods: In 1-month-old swine (n=20), lipopolysaccharide was intravenously infused to induce a shock state, followed by induction of VF and treatment with hemodynamic-directed CPR (HD-CPR). Animals were randomized to blinded treatment with either: 1) HD-CPR with iNO (beginning 1 minute into CPR), or 2) HD-CPR without iNO. Defibrillation attempts began at 10 minutes with a maximum CPR duration of 20 minutes. Among animals surviving 1-hour post-arrest, cerebral tissue underwent high-resolution respirometry to evaluate the mitochondrial electron transport system and quantification of neuronal apoptosis and microglial activation. Chi-square test, Fisher’s exact test, Student’s t-test, Wilcoxon rank-sum test, and a generalized estimating equation regression model compared the two groups. Results: During CPR, the iNO group had higher mean aortic pressure (41.6±2.0 vs. 36.0±1.4 mmHg; p=0.005); diastolic BP (32.4±2.4 vs. 27.1±1.7 mmHg; p=0.03); CePP (25.0±2.6 vs. 19.1±1.8 mmHg; p=0.02); and CBF relative to pre-CPR baseline (243.2±54.1 vs. 115.5±37.2%; p=0.02). Among the 8/10 survivors in each group, the iNO group had higher mitochondrial Complex I oxidative phosphorylation in the cerebral cortex (3.60 [3.56, 3.99] vs. 3.23 [2.44, 3.46] pmol O 2 /s*mg; p=0.01) and hippocampus (4.79 [4.35, 5.18] vs. 3.17 [2.75, 4.58] pmol O 2 /s*mg; p=0.02). There were no other differences in mitochondrial respiration or brain injury between groups. Conclusions: Blinded treatment with iNO during CPR in a model of pediatric shock-associated cardiac arrest resulted in superior CePP, CBF, and cerebral mitochondrial Complex I respiration. These data suggest that iNO treatment during CPR may lead to improved neurologic outcomes from pediatric cardiac arrest.

The neuroprotective effect of quetiapine in critically ill traumatic brain injury patients.

Quetiapine is an atypical antipsychotic commonly used in critical care. Cellular and animal models demonstrated its novel anti-inflammatory properties in traumatic brain injury (TBI). Our study aimed to assess the effect of quetiapine on outcomes in critically ill TBI patients. We hypothesize that quetiapine improves neurological outcomes. The Multiparameter Intelligent Monitoring in Intensive Care database was queried, and all adult (age, ≥18 years) isolated TBI patients (extracranial Abbreviated Injury Scale, < 2) admitted to the intensive care unit for a period of >48 hours. Patients were stratified into quetiapine (+) and no-quetiapine (-) groups. Propensity score matching was performed (1:2 ratio). Outcome measures were intensive care unit length of stay, discharge Glasgow Coma Scale (GCS), and mortality. A subanalysis was performed for patients who underwent intracranial pressure (ICP) monitoring to ascertain the effect of quetiapine dose on ICP, and cerebral perfusion pressure (CPP). Survival curves and regression analyses were performed. A matched cohort of (quetiapine, 116 vs. no-quetiapine, 232) patients was obtained. Mean ± SD age was 65 ± 21 years, median head Abbreviated Injury Scale was 3 (3-4), and median GCS was 10 (9-16). The median quetiapine dose given was 50 (25-125) mg. Patients who received quetiapine had lower mortality (17.2% vs. 27.6%; p = 0.03) and a higher median GCS at discharge (12 [11-14] vs. 11 [10-13]; p < 0.04) but no difference in intensive care unit length of stay (4.1 days vs. 4.7 days; p = 0.75) or discharge to skilled nursing facility (34.5% vs. 31.9%; p = 0.63). On subanalysis of patients who received quetiapine, 40% had ICP monitoring. Higher doses of quetiapine were independently associated with progressively lower ICP (β = -0.022 mm Hg/mg of quetiapine; p = 0.01) and higher CPP (β = 0.031 mm Hg/mg quetiapine; p = 0.01). Quetiapine may decrease mortality and improve neurological outcomes in critically ill TBI patients. It has a dose-dependent effect to decrease ICP and increase CPP. Quetiapine may be a potential therapeutic modality in critically ill TBI patients, but further studies are required to explore these mechanisms. Systematic Review, level III.

Abstract 274: Identifying the Optimal Cerebral Perfusion Pressure Following Hypoxic-Ischemic Brain Injury

Introduction: The optimal cerebral perfusion pressure (CPP) following hypoxic-ischemic brain injury (HIBI) is currently unknown. We retrospectively analyzed intracranial monitoring data from a cohort of patients with HIBI to identify a threshold level for CPP that optimizes cerebrovascular pressure reactivity (a surrogate for CA) while limiting the risk of intracranial hypertension and brain tissue hypoxia. Hypothesis: We hypothesized that higher CPP values would be associated with improved cerebrovascular pressure reactivity. Methods: ICP, brain tissue oxygen (P bt O 2 ), MAP, and CPP (defined as MAP - ICP) were recorded continuously and time synchronized for all patients using a bedside monitor (CNS Monitor, Moberg Research). Pressure Reactivity Index (PRx) was calculated as the time varying correlation between MAP and ICP over 5 min intervals updated every minute. The degree of CA impairment (defined as % time PRx &gt; 0.2) was plotted against MAP and CPP, respectively. The relationships between ICP and P bt O 2 versus CPP, as well as ICP and P bt O 2 versus % time PRx &gt; 0.2, were similarly calculated. Results: We analyzed 37 patients (33 cardiac arrest, 4 prolonged hypoxia) with HIBI who underwent intracranial neuromonitoring over a 3 year period. Lower CPP values were associated with higher degrees of CA impairment. The cumulative burden of elevated PRx was significantly lower for CPP values above a cutoff of 85 mmHg compared to lower CPP values (p &lt; 0.001, Wilcoxon rank sum test). A similar cutoff for MAP could not be identified, although lower MAP values were also associated with greater CA impairment. Intracranial hypertension (ICP &gt; 20 mmHg) and brain hypoxia (P bt O2 &lt; 20 mmHg) were both associated with CA impairment (p &lt; 0.001 and p &lt; 0.001, respectively, Wilcoxon rank sum test). Conclusions: Higher CPP and MAP values appear to be associated with improved CA after HIBI. Given that CA impairment is associated with both intracranial hypertension and brain hypoxia, our work reaffirms the notion that higher blood pressure targets may improve outcome after HIBI. The identification of a distinct CPP cutoff for CA optimization suggests that targeting CPP instead of MAP may be advantageous, although further work is required to clarify this issue.

Abstract 17: Controlled Progressive Elevation Maximizes Cerebral Perfusion Pressure During Head up CPR in a Swine Model of Cardiac Arrest

Background: Elevation of the head and thorax (HUP) during cardiopulmonary resuscitation (CPR) has been shown to result in a doubling of brain blood flow with higher Cerebral Perfusion Pressures (CerPP) after prolonged active compression-decompression (ACD) CPR with an impedance threshold device (ITD). However, the optimal angle and speed of elevation are unknown. Methods: In study A, in an anesthetized female 40 kg pig model of untreated ventricular fibrillation for 8 min, different HUP angles were assessed (20°, 30°, 40°) in a randomized manner each over a 5-minute periods of ACD+ITD CPR. Based upon study A results, study B was performed, wherein animals were randomized to the two following sequences: 20°, 30°, 40° or 40°, 30°, 20° using the same protocol. The primary endpoint was mean ± SD CerPP (mmHg) for both studies. Results: In study A, 18 pigs were studied. Overall, there was no optimal HUP angle: CerPP was 36 ± 19 for 20°, 42 ± 21 for 30°, and 44 ± 27 for 40° (p = 0.57). However, CerPPs were higher if 40 o HUP was performed during the last 5 minutes of the resuscitation (77 ± 17), versus 20 o HUP and 30 o HUP (44± 18, p = 0.003), suggestive of a sequence effect. To test this hypothesis, study B then enrolled additional animals to compare two elevation sequences 20°, 30°, 40° (n = 6) or 40°, 30°, 20° (n = 5). At 15 min of CPR, the CerPP for 20°, 30°, 40° group was 60 ± 17 and for 40°, 30°, 20° the CerPP was 23 ± 19 (p = 0.01). CerPPs were higher for the 20°, 30°, 40° group throughout the resuscitation (Figure 1). Coronary perfusion pressure was also significantly higher in the 20°, 30°, 40° group (50 ± 17 mmHg versus 22 ± 16 mmHg, p = 0.036) Conclusions: There did not appear to be an optimal HUP angle during ACD+ITD CPR. By contrast, there was an optimal HUP sequence (20,30,40) that resulted in significantly higher CerPP, suggesting controlled progressive elevation is important when performing HUP CPR as compared to an absolute immediate elevation of the head and thorax.