Serum Neurofilament Light and Postoperative Delirium in Cardiac Surgery: A Preplanned Secondary Analysis of a Prospective Observational Study.

BACKGROUND: Impaired cognition is a major predisposing factor for postoperative delirium, but it is not systematically assessed. Anesthesia and surgery may cause postoperative delirium by affecting brain integrity. Neurofilament light in serum reflects axonal injury. Studies evaluating the perioperative course of neurofilament light in cardiac surgery have shown conflicting results. The authors hypothesized that postoperative serum neurofilament light values would be higher in delirious patients, and that baseline concentrations would be correlated with patients' cognitive status and would identify patients at risk of postoperative delirium. METHODS: This preplanned secondary analysis included 220 patients undergoing elective cardiac surgery with cardiopulmonary bypass. A preoperative cognitive z score was calculated after a neuropsychological evaluation. Quantification of serum neurofilament light was performed by the Simoa (Quanterix, USA) technique before anesthesia, 2 h after surgery, on postoperative days 1, 2, and 5. Postoperative delirium was assessed using the Confusion Assessment Method for Intensive Care Unit, the Confusion Assessment Method, and a chart review. RESULTS: A total of 65 of 220 (29.5%) patients developed postoperative delirium. Delirious patients were older (median [25th percentile, 75th percentile], 74 [64, 79] vs. 67 [59, 74] yr; P < 0.001) and had lower cognitive z scores (-0.52 ± 1.14 vs. 0.21 ± 0.84; P < 0.001). Postoperative neurofilament light concentrations increased in all patients up to day 5, but did not predict delirium when preoperative concentrations were considered. Baseline neurofilament light values were significantly higher in patients who experienced delirium. They were influenced by age, cognitive z score, renal function, and history of diabetes mellitus. Baselines values were significantly correlated with cognitive z scores (r, 0.49; P < 0.001) and were independently associated with delirium whenever the patient's cognitive status was not considered (hazard ratio, 3.34 [95% CI, 1.07 to 10.4]). CONCLUSIONS: Cardiac surgery is associated with axonal injury, because neurofilament light concentrations increased postoperatively in all patients. However, only baseline neurofilament light values predicted postoperative delirium. Baseline concentrations were correlated with poorer cognitive scores, and they independently predicted postoperative delirium whenever patient's cognitive status was undetermined.

Propofol plus low-dose dexmedetomidine infusion and postoperative delirium in older patients undergoing cardiac surgery.

BACKGROUND: Postoperative delirium (POD) is a frequent complication in older patients. Dexmedetomidine might be effective in decreasing the incidence of POD. We hypothesised that adding low-dose rate dexmedetomidine infusion to a propofol sedation regimen would have fewer side-effects and would counteract the possible delirium producing properties of propofol, resulting in a lower risk of POD than propofol with placebo. METHODS: In this double-blind placebo-controlled trial, patients ≥60 yr old undergoing on-pump cardiac surgery were randomised 1:1 to the following postoperative sedative regimens: a propofol infusion and dexmedetomidine (0.4 µg kg-1 h-1) or a propofol infusion and saline 0.9% (placebo group). The study drug was started at chest closure and continued for 10 h. The primary endpoint was in-hospital POD, assessed using the Confusion Assessment Method and chart review method. RESULTS: POD over the course of hospital stay occurred in 31/177 (18%) and 33/172 (19%) patients in the dexmedetomidine and placebo arm, respectively (P=0.687; odds ratio=0.89; 95% confidence interval, 0.52-1.54). The incidence of POD in the intensive care alone, or on the ward alone, was also not significantly different between the groups. Subjects in the dexmedetomidine group spent less median time in a delirious state (P=0.026). Median administered postoperative norepinephrine was significantly higher in the dexmedetomidine group (P<0.001). One patient in the dexmedetomidine group and 10 patients in the placebo group died in the hospital. CONCLUSIONS: Adding low-dose rate dexmedetomidine to a sedative regimen based on propofol did not result in a different risk of in-hospital delirium in older patients undergoing cardiac surgery. With a suggestion of both harm and benefit in secondary outcomes, supplementing postoperative propofol with dexmedetomidine cannot be recommended based on this study. CLINICAL TRIAL REGISTRATION: NCT03388541.

Hemodilution and anemia in patients with cardiac disease: what is the safe limit?

PURPOSE OF THE REVIEW: Anemia is associated with increased perioperative morbidity and mortality, especially in patients with cardiovascular disease. Although blood transfusions are commonly used in these patients, there is little evidence that such an approach improved patients' clinical outcome. RECENT FINDINGS: From an experimental point of view, tolerance to acute anemia is significantly reduced in animals with externally applied coronary artery stenosis. In rats subjected to transient coronary occlusion, however, moderate isovolemic hemodilution attenuated myocardial damage and improved survival. Tolerance to severe anemia could also be improved by hyperoxic ventilation and maintenance of adequate coronary perfusion pressure. From the clinical perspective, tolerance to anemia in patients with cardiovascular disease closely depends on myocardial oxygen demand, in particular on the level of heart rate. A reduction in heart rate as observed in anesthetized patients undergoing moderate hemodilution may confer some cardioprotection. SUMMARY: The absolute lowest threshold for anemia in patients with cardiac disease cannot be established. Further studies are needed to develop evidence-based transfusion guidelines for these patients. Rather than primarily focusing on transfusion, physicians should first administer therapies that have been shown to improve outcome. In the setting of coronary artery disease, control of heart rate appears of paramount importance.