Meningitis is a serious concern after traumatic brain injury (TBI) or neurosurgery. This study tested the level of reactive oxygen species (ROS) in cerebrospinal fluid (CSF) to diagnose meningitis in ...febrile patients several days after trauma or surgery.
Febrile patients (temperature > 38°C) after TBI or neurosurgery were included prospectively. ROS were measured in CSF within 4 hours after sampling using luminescence in the basal state and after cell stimulation with phorbol 12-myristate 13-acetate (PMA). The study was conducted in a single-center cohort 1 (n = 54, training cohort) and then in a multicenter cohort 2 (n = 136, testing cohort) in the Intensive Care and Neurosurgery departments of two teaching hospitals. The performance of the ROS test was compared with classical CSF criteria, and a diagnostic decision for meningitis was made by two blinded experts.
The production of ROS was higher in the CSF of meningitis patients than in non-infected CSF, both in the basal state and after PMA stimulation. In cohort 1, ROS production was associated with a diagnosis of meningitis with an AUC of 0.814 (95% confidence interval (CI) 0.684-0.820) for steady-state and 0.818 (95% CI 0.655-0.821) for PMA-activated conditions. The best threshold value obtained in cohort 1 was tested in cohort 2 and showed high negative predictive values and low negative likelihood ratios of 0.94 and 0.36 in the basal state, respectively, and 0.96 and 0.24 after PMA stimulation, respectively.
The ROS test in CSF appeared suitable for eliminating a diagnosis of bacterial meningitis.
Background
Somatosensory (SSEP) and brainstem auditory (BAEP) evoked potentials are neurophysiological tools which, respectively, explore the intracranial conduction time (ICCT) and the intrapontine ...conduction time (IPCT). The prognostic values of prolonged cerebral conduction times in deeply sedated patients have never been assessed. Sedated patients are at risk of developing new neurological complications, undetected. In this prospective observational bi-center pilot study, we investigated whether early impairment of SSEP’s ICCT and/or BAEP’s IPCT could predict in-ICU mortality or altered mental status (AMS), in deeply sedated critically ill patients.
Methods
SSEP by stimulation of the median nerve and BAEP were assessed in critically ill patients receiving deep sedation on day 3 following ICU admission. Deep sedation was defined by a Richmond Assessment sedation Scale (RASS) <−3. Mean left- and right-side ICCT and IPCT were measured for each patient. Primary and secondary outcomes were, respectively, in-ICU mortality and AMS defined as the occurrence of delirium and/or delayed awakening after discontinuation of sedation.
Results
Eighty-six patients were studied of which 49 (57%) were non-brain-injured and 37 (43%) were brain-injured. Impaired ICCT was a predictor of in-ICU mortality after adjustment on the global Sequential Organ Failure Assessment score (SOFA) OR (95% CI) = 2.69 (1.05–6.85);
p
= 0.039 and on the non-neurological SOFA components 2.67 (1.05–6.81);
p
= 0.040. IPCT was more frequently delayed in the subgroup of patients who developed post-sedation AMS (24%) compared those without AMS (0%). However, this difference did not reach statistical significance (
p
= 0.053). Impairment rates of ICCT and IPCT were not found to be significantly different between non-brain- and brain-injured subgroups of patients.
Conclusion
In critically ill patients receiving deep sedation, early ICCT impairment was associated with mortality. Somatosensory and brainstem auditory evoked potentials may be useful early warning indicators of brain dysfunction as well as prognostic markers in deeply sedated critically ill patients.
Abstract Purpose We searched for factors independently associated with the prescription of multimodal (balanced) analgesia in mechanically ventilated critically ill patients. Methods In this post hoc ...analysis of a cohort study, 172 patients who received a combination of 1 opioid with nonopioids, that is, paracetamol and/or nefopam, (multimodal analgesia), were compared with 302 patients who received opioid only on day 2 of their stay in the intensive care unit. Results Patients given multimodal analgesia were more likely to have fewer organ failures and received fewer hypnotics compared with patients who received opioid only. They self-reported more frequently their pain level. There were no differences in the daily dose of opioids between the 2 groups. A low illness severity score, no more than 1 organ failure on day 2, the ability to self-rate pain, and a moderate-to-severe pain rated on day 2 were factors independently associated with the prescription of multimodal analgesia on day 2 (all P < .01). Conclusions In mechanically ventilated patients, the addition of nonopioids to opioids is mostly prescribed for patients with lower illness severity scores and who are able to self-rate their pain intensity. These findings suggest that the concept of multimodal analgesia must be promoted in the intensive care unit.
The neuroprotective efficacy of anesthetics observed in experimental models remains unproven in the clinical setting. The nonreceptor tyrosine kinase focal adhesion kinase (FAK) has been suggested to ...be involved in the neuroprotective effect of anesthetics observed experimentally. In the present work, we investigated whether FAK and the duration of ischemia play a role in the preconditioning effect of sevoflurane on brain tissue.
Rat acute hippocampal slices were subjected to oxygen and glucose deprivation (OGD) challenge during increasing periods of time (10, 20, 30, 45, 50, and 60 min) followed by 1 h reperfusion. A preconditioning sevoflurane concentration (10(-4) M, 1 h) was applied 3 h before initiation of OGD. Protein expression of FAK and cleaved caspase 3 (a marker of activation of the apoptotic cascade) was measured by immunoblotting. Cell death was assessed by propidium iodide (PI) fluorescence.
Both PI fluorescence and expression of cleaved caspase 3 significantly increased with duration of ischemia until reaching a ceiling effect for durations of ischemia longer than 30 min. Sevoflurane (10(-4) M) increased FAK expression and markedly reduced the increase in PI fluorescence and cleaved caspase 3 expression for periods of ischemia of 10, 20, and 30 min. In contrast, the protective effect was no longer observed for periods of ischemia longer than 30 min. 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo3,4-d pyrimidine (PP2, 10(-5) M, an inhibitor of src tyrosine kinases) application 60 min before and throughout that of sevoflurane significantly reduced the neuroprotective effect of sevoflurane on both caspase 3 expression and PI fluorescence.
In the OGD rat acute hippocampal slice, the preconditioning effect of a clinically relevant concentration of sevoflurane was very likely to involve FAK and was observed only for periods of ischemia <or=30 min.
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