Clinical chronobiology: a timely consideration in critical care medicine

A fundamental aspect of human physiology is its cyclical nature over a 24-h period, a feature conserved across most life on Earth. Organisms compartmentalise processes with respect to time in order to promote survival, in a manner that mirrors the rotation of the planet and accompanying diurnal cycles of light and darkness. The influence of circadian rhythms can no longer be overlooked in clinical settings; this review provides intensivists with an up-to-date understanding of the burgeoning field of chronobiology, and suggests ways to incorporate these concepts into daily practice to improve patient outcomes. We outline the function of molecular clocks in remote tissues, which adjust cellular and global physiological function according to the time of day, and the potential clinical advantages to keeping in time with them. We highlight the consequences of "chronopathology", when this harmony is lost, and the risk factors for this condition in critically ill patients. We introduce the concept of "chronofitness" as a new target in the treatment of critical illness: preserving the internal synchronisation of clocks in different tissues, as well as external synchronisation with the environment. We describe methods for monitoring circadian rhythms in a clinical setting, and how this technology may be used for identifying optimal time windows for interventions, or to alert the physician to a critical deterioration of circadian rhythmicity. We suggest a chronobiological approach to critical illness, involving multicomponent strategies to promote chronofitness (chronobundles), and further investment in the development of personalised, time-based treatment for critically ill patients

A Neurological Wake-Up Test in the Neurointensive Care Unit: Pros and Cons

Traumatic brain injury (TBI) induces a marked systemic biochemical stress response with the release of several stress-related hormones including cortisol and the catecholamines. A major aim of using continuous sedation in the neurointensive care unit (NIC) unit is to attenuate the TBI-induced stress response via reduction of the cerebral energy metabolic demands. In the era of modern multimodality monitoring and neuroimaging for patients with severe TBI, what is the role for neurological evaluation, a neurological wake-up test (NWT), of patients on continuous sedation and mechanical ventilation? In particular, does the information obtained by the NWT outweigh the risk of inducing a substantial stress response? The additional use of NWTs in NIC is controversial and is not mentioned in any recent TBI guidelines. Although daily interruption of continuous sedation is suggested for patients in general intensive care, reasons for not using the NWT in NIC may be a fear of an NWT-induced stress response and uncertainty to the additional value of NWTs in patients monitored with multimodality monitoring and frequent neuroradiological examinations. A recent survey showed that use of NWT varies markedly in Scandinavians’ NIC units where half of the evaluated centres never use the NWT, whereas others use the NWT up to six times daily. In a series of studies characterising the NWT-induced stress response, the NWT was found to induce a significant increase in ICP and CPP in severe TBI patients on controlled ventilation. Additionally, the NWT caused an increase in adrenocorticotrophic (ACTH) hormone, catecholamine and cortisol levels. In the absolute majority of patients, the ICP and CPP changes were modest and transient and the absolute increases in stress hormone levels were small. However, the stress response was marked in a small subset of patients. These studies suggest that the NWT is safe in the majority of patients but that the test should be individualised and avoided in patients reacting with markedly increased ICP and/or decreased CPP. Although important clinical information may be obtained from the NWT, future studies need to evaluate the risk-benefit ratio of the NWT in TBI management

Critical ischemia time in a model of spinal cord section. A study performed on dogs

Vascular changes after acute spinal cord trauma are important factors that predispose quadriplegia, in most cases irreversible. Repair of the spinal blood flow helps the spinal cord recovery. The average time to arrive and perform surgery is 3 h in most cases. It is important to determine the critical ischemia time in order to offer better functional prognosis. A spinal cord section and vascular clamping of the spinal anterior artery at C5–C6 model was used to determine critical ischemia time. The objective was to establish a critical ischemia time in a model of acute spinal cord section. Four groups of dogs were used, anterior approach and vascular clamp of spinal anterior artery with 1, 2, 3, and 4 h of ischemia and posterior hemisection of spinal cord at C5–C6 was performed. Clinical evaluation was made during 12 weeks and morphological evaluation at the end of this period. We obtained a maximal neurological coordination at 23 days average. Two cases showed sequels of right upper limb paresis at 1 and 3 ischemia hours. There was nerve conduction delay of 56% at 3 h of ischemia. Morphological examination showed 25% of damaged area. The VIII and IX Rexed’s laminae were the most affected. The critical ischemia time was 3 h. Dogs with 4 h did not exhibit any recovery