Significance of circadian rhythms in severely brain-injured patients: A clue to consciousness?
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ABSTRACT: Objective
To investigate the relationship between the presence of a circadian body temperature rhythm and behaviorally assessed consciousness levels in patients with disorders of consciousness (DOC; i.e., vegetative state/unresponsive wakefulness syndrome or minimally conscious state).Methods
In a cross-sectional study, we investigated the presence of circadian temperature rhythms across 6 to 7 days using external skin temperature sensors in 18 patients with DOC. Beyond this, we examined the relationship between behaviorally assessed consciousness levels and circadian rhythmicity.Results
Analyses with Lomb-Scargle periodograms revealed significant circadian rhythmicity in all patients (range 23.5-26.3 hours). We found that especially scores on the arousal subscale of the Coma Recovery Scale-Revised were closely linked to the integrity of circadian variations in body temperature. Finally, we piloted whether bright light stimulation could boost circadian rhythmicity and found positive evidence in 2 out of 8 patients.Conclusion
The study provides evidence for an association between circadian body temperature rhythms and arousal as a necessary precondition for consciousness. Our findings also make a case for circadian rhythms as a target for treatment as well as the application of diagnostic and therapeutic means at times when cognitive performance is expected to peak.
SUBMITTER: Blume C
PROVIDER: S-EPMC5444311 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Healthy circadian rhythmicity has been suggested to relate to a better state of brain-injured patients and to support the emergence of consciousness in patient groups characterized by a relative instability thereof such as patients with disorders of consciousness (DOC). METHODS:Going beyond earlier studies, a systems-level perspective was adopted and, using multilevel modelling, the joint predictive value of three indices of circadian rhythm integrity derived from skin temperature variations, melatoninsulfate secretion, and physical activity (wrist actigraphy) patterns was evaluated for the behaviourally assessed state [Coma Recovery Scale - Revised (CRS-R) score] of DOC patients [13 unresponsive wakefulness syndrome; seven minimally conscious (exit) state]. Additionally, it was assessed in a subset of 16 patients whether patients' behavioural repertoire (CRS-R score) varied (i) with time of day or (ii) offset from the body temperature maximum (BTmax ), i.e. when cognitive performance is expected to peak. RESULTS:The results reveal that better integrity of circadian melatoninsulfate and temperature rhythms relate to a richer behavioural repertoire. Moreover, higher CRS-R scores are, by trend, related to assessments taking place at a later daytime or deviating less from the pre-specified time of occurrence of BTmax . CONCLUSIONS:In conclusion, the results suggest that therapeutic approaches aimed at improving circadian rhythms in brain-injured patients are promising and should be implemented in hospitals or nursing homes. Beyond this, it might be helpful to schedule diagnostic procedures and therapies around the (pre-assessed) BTmax (≈4 pm in healthy individuals) as this is when patients should be most responsive.
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Project description:IntroductionCrises like the COVID-19 pandemic create blood product shortages. Patients requiring transfusions are placed at risk and institutions may need to judiciously administer blood during massive blood transfusions protocols (MTP). The purpose of this study is to provide data-driven guidance for the modification of MTP when the blood supply is severely limited.MethodsThis is a retrospective cohort study of 47 Level I and II trauma centers (TC) within a single healthcare system whose patients received MTP from 2017 to 2019. All TC used a unifying MTP protocol for balanced blood product transfusions. The primary outcome was mortality as a function of volume of blood transfused and age. Hemoglobin thresholds and measures of futility were also estimated. Risk-adjusted analyses were performed using multivariable and hierarchical regression to account for confounders and hospital variation.ResultsProposed MTP maximum volume thresholds for three age groupings are as follows: 60 units for ages 16-30 y, 48 units for ages 31-55 y, and 24 units for >55 y. The range of mortality under the transfusion threshold was 30%-36% but doubled to 67-77% when the threshold was exceeded. Hemoglobin concentration differences relative to survival were clinically nonsignificant. Prehospital measures of futility were prehospital cardiac arrest and nonreactive pupils. In hospital risk factors of futility were mid-line shift on brain CT and cardiopulmonary arrest.ConclusionsEstablishing MTP threshold practices under blood shortage conditions, such as the COVID pandemic, could sustain blood availability by following relative thresholds for MTP use according to age groups and key risk factors.
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