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Cerebral Blood Flow Deviations in Critically Ill Patients: Potential Insult Contributing to Ischemic and Hyperemic Injury.

ABSTRACT: Background: Ischemic and hyperemic injury have emerged as biologic mechanisms that contribute to cognitive impairment in critically ill patients. Spontaneous deviations in cerebral blood flow (CBF) beyond ischemic and hyperemic thresholds may represent an insult that contributes to this brain injury, especially if they accumulate over time and coincide with impaired autoregulation. Methods: We used transcranial Doppler to measure the proportion of time that CBF velocity (CBFv) deviated beyond previously reported ischemic and hyperemic thresholds in a cohort of critically ill patients with respiratory failure and/or shock within 48 h of ICU admission. We also assessed whether these CBFv deviations were more common during periods of impaired dynamic autoregulation, and whether they are explained by concurrent variations in mean arterial pressure (MAP) and end-tidal PCO₂ (PetCO₂). Results: We enrolled 12 consecutive patients (three females) who were monitored for a mean duration of 462.6 ± 39.8 min. Across patients, CBFv deviated by more than 20-30% from its baseline for 17-24% of the analysis time. These CBFv deviations occurred equally during periods of preserved and impaired autoregulation, while concurrent variations in MAP and PetCO₂ explained only 13-21% of these CBFv deviations. Conclusion: CBFv deviations beyond ischemic and hyperemic thresholds are common in critically ill patients with respiratory failure or shock. These deviations occur irrespective of the state of dynamic autoregulation and are not explained by changes in MAP and CO₂. Future studies should explore mechanisms responsible for these CBFv deviations and establish whether their cumulative burden predicts poor neurocognitive outcomes.

SUBMITTER: Slessarev M

PROVIDER: S-EPMC7854569 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Cerebral Blood Flow Deviations in Critically Ill Patients: Potential Insult Contributing to Ischemic and Hyperemic Injury.

Slessarev Marat M Mahmoud Ossama O McIntyre Christopher W CW Ellis Christopher G CG

Frontiers in medicine 20210120

<b>Background:</b> Ischemic and hyperemic injury have emerged as biologic mechanisms that contribute to cognitive impairment in critically ill patients. Spontaneous deviations in cerebral blood flow (CBF) beyond ischemic and hyperemic thresholds may represent an insult that contributes to this brain injury, especially if they accumulate over time and coincide with impaired autoregulation. <b>Methods:</b> We used transcranial Doppler to measure the proportion of time that CBF velocity (CBFv) devi ...[more]

PMID: 33553208

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Project description:ObjectiveThe objective of this study was to characterize the population pharmacokinetics of fentanyl and identify factors that contribute to exposure variability in critically ill pediatric patients.MethodsWe conducted a single-center, retrospective cohort study using electronic record data and remnant blood samples in the setting of a mixed medical/surgical intensive care unit (ICU) at a quaternary children's hospital. Children with a predicted ICU length of stay of at least 3 days and presence of an indwelling central venous or arterial line were included. Serum fentanyl measurements were performed for 278 unique remnant samples from 66 patients. Both one- and two-compartment models were evaluated to describe fentanyl disposition. Covariates were introduced into the model in a forward/backward, stepwise approach and included age, sex, race, weight, cytochrome P450 (CYP) 3A5 genotype, and the presence of CYP3A4 or CYP3A5 inducers or inhibitors. Simulations were performed using the successful model to depict the influence of inducers on fentanyl concentrations.ResultsA two-compartment base model best described the data. There was good agreement between observed and predicted concentrations in the final model. The typical fentanyl clearance for 70 kg (reference weight) and 20.1 kg (median weight) patients were 34.6 and 13.6 L/h, respectively. The magnitude of the unexplained random inter-individual variability was high for both clearance (60.7%) and apparent volume of the central compartment (V1) (107.2%). Coadministration of the known CYP3A4/5 inducers fosphenytoin and/or phenobarbital was associated with significantly increased fentanyl clearance. Simulations demonstrate that the effect of inducer administration was most pronounced following discontinuation of a fentanyl infusion.ConclusionsIn this study we show the feasibility and utility of using electronic record data and remnant blood samples to successfully construct population pharmacokinetic models for a heterogeneous cohort of critically ill children. A clinically relevant effect of concomitant CYP3A4/5 inducers was identified. Scaling this population pharmacokinetic approach is necessary to craft precision approaches to fentanyl administration for critically ill children.

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Project description:Cerebral oximetry by near-infrared spectroscopy is used frequently in critically ill children but guidelines on its use for decision making in the PICU are lacking. We investigated cerebral near-infrared spectroscopy oximetry in its ability to predict severe acute kidney injury after pediatric cardiac surgery and assessed its additional predictive value to routinely collected data.DesignProspective observational study. The cerebral oximeter was blinded to clinicians.SettingTwelve-bed tertiary PICU, University Hospitals Leuven, Belgium, between October 2012 and November 2015.PatientsCritically ill children with congenital heart disease, younger than 12 years old, were monitored with cerebral near-infrared spectroscopy oximetry from PICU admission until they were successfully weaned off mechanical ventilation.InterventionsNone.Measurements and main resultsThe primary outcome was prediction of severe acute kidney injury 6 hours before its occurrence during the first week of intensive care. Near-infrared spectroscopy-derived predictors and routinely collected clinical data were compared and combined to assess added predictive value. Of the 156 children included in the analysis, 55 (35%) developed severe acute kidney injury. The most discriminant near-infrared spectroscopy-derived predictor was near-infrared spectroscopy variability (area under the receiver operating characteristic curve, 0.68; 95% CI, 0.67-0.68), but was outperformed by a clinical model including baseline serum creatinine, cyanotic cardiopathy pre-surgery, blood pressure, and heart frequency (area under the receiver operating characteristic curve, 0.75; 95% CI, 0.75-0.75; p < 0.001). Combining clinical and near-infrared spectroscopy information improved model performance (area under the receiver operating characteristic curve, 0.79; 95% CI, 0.79-0.80; p < 0.001).ConclusionsAfter pediatric cardiac surgery, near-infrared spectroscopy variability combined with clinical information improved discrimination for acute kidney injury. Future studies are required to identify whether supplementary, timely clinical interventions at the bedside, based on near-infrared spectroscopy variability analysis, could improve outcome.

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Cerebral Blood Flow Deviations in Critically Ill Patients: Potential Insult Contributing to Ischemic and Hyperemic Injury.

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Cerebral Blood Flow Deviations in Critically Ill Patients: Potential Insult Contributing to Ischemic and Hyperemic Injury.

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