Marc Giménez-Milà, PL Gambús
During the last decade research published about perioperative neurocognitive disorders (PNCD) after surgery has been trying to elucidate the cause for this condition. Some of these projects focused on anaesthetic aspects such as possible long-term duration of anaesthetic drug effects, altered physiology of the brain due to anaesthesia and/or surgery, hypotension or other hemodynamic changes, and, more recently, altered inflammatory response to surgical aggression. Basic science data in animals and humans has shown a link between upregulation of inflammatory response and changes in the central nervous system1,2 that mimic postoperative cognitive dysfunction. Although much progress has been made on identification of cellular and humoral mediators, efforts of modulation of this inflammatory response with the objective of decreasing the incidence of PNCD has provided controversial results. For instance, administration of dexamethasone in a randomized controlled trial in cardiac surgery did not reduce incidence of delirium6 but decreased respiratory complications and length of stay in hospital in another study.4
Evered et al.5 propose a new view analysing the time course of two potential biomarkers (neurofilament light and tau) as a surrogate of neurologic injury after surgery. Their findings seem to contradict the common belief that anaesthesia for surgery is a fully reversible phenomenon based on the known mechanism of action of anaesthetic drugs. In a clinical practice setting this lack of complete reversibility of anaesthetics is seen in a significant number of patients, 25% in the first week and 10% after 3 months6 will develop postoperative cognitive dysfunction.
The results reported by Evered et al. were based on analysis of blood samples obtained from 30 patients older than 60 years enrolled in two different studies (CAPACITY and ARCADIAN); 23 of them underwent lower limb surgery, six cardiac surgery, and 1 oesophagectomy. There was heterogeneity on anaesthetic regime in both studies, as either a volatile agent or intravenous anaesthesia was used and some of the patients also received loco-regional anaesthesia – spinal, femoral block, and/or sciatic. Samples were obtained preoperatively and at 30 min and 6, 24, and 48 hours after the surgical procedure, measuring plasmatic concentrations of Tau and light neurofilament. In both studies there was a follow-up test at 18 months, but this data is not available as analysis has not yet been performed.
Neurofilament light and Tau both increase after the procedure in all types of surgeries and anaesthesia. While the first one peaked at 6 hours, the concentration of the second continued to increase after 48 hours. Neurofilament light is a component of the axonal skeleton; increase in its plasmatic concentration correlates with neurologic injury in different conditions, such as multiple sclerosis and traumatic brain injury. Tau protein intervenes in integrity of axons and dysfunctional Tau is responsible for so-called Tauopathies that include Alzheimer’s disease.
The detected increase in both markers does not provide, yet suggests, a possible mechanism of action of the neuronal injury or even a correlation with clinical syndromes such as delirium or postoperative cognitive dysfunction. If that would be the case, it would be interesting to know whether they are surrogates of transient cognitive dysfunction or rather a more permanent one. Further studies will be needed to study biomarkers in specific high-risk populations such as patients with dementia, paediatrics, and patients undergoing cardiopulmonary by-pass. Above all, however, focus should be on development of interventions that enable anaesthesiologists to provide an effective modulation of this perioperative neuronal injury.
Biomarkers will be key for a future personalized anaesthesia allowing anaesthesiologists to give individualized care based on surgical procedure and risk of developing PCND. This study undoubtedly represents a significant step forward in the understanding of the physiopathology of PCND, but how it integrates to previous hypotheses such as neuroimmune mechanism or other described risk factors, still needs to be elucidated to provide the clinician with effective prophylactic and therapeutic measures against postoperative cognitive dysfunction.
Some of these interesting findings will be presented in Copenhagen at the next Euroanaesthesia Congress.
- Buvanendran A, Kroin JS, Berger RA, et al. Anesthesiology 2006;104(3):403-10.
- Cibelli M, Fidalgo AR, Terrando N, et al. Ann Neurol 2010;68(3):360-8.
- Sauër AM, Slooter AJ, Veldhuijzen DS, et al. Anesth Analg 2014;119(5):1046-52.
- Dieleman JM, Nierich AP, Rosseel PM, et al. JAMA 2012;308:1761.
- Evered L, Silbert B, Scott DA, et al. JAMA Neurol 2018. doi: 10.1001/jamaneurol.2017.4913
- Moller JT, Cluitmans P, Rasmussen LS, et al. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. Lancet. 1998 21;351(9106):857-61.