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.

Intra-operative electroencephalogram frontal alpha-band spectral analysis and postoperative delirium in cardiac surgery: A prospective cohort study.

BACKGROUND: Postoperative delirium (POD) remains a frequent complication after cardiac surgery, with pre-operative cognitive status being one of the main predisposing factors. However, performing complete pre-operative neuropsychological testing is challenging. The magnitude of frontal electroencephalographic (EEG) α oscillations during general anaesthesia has been related to pre-operative cognition and could constitute a functional marker for brain vulnerability. OBJECTIVE: We hypothesised that features of intra-operative α-band activity could predict the occurrence of POD. DESIGN: Single-centre prospective observational study. SETTING: University hospital, from 15 May 2019 to 15 December 2021. PATIENTS: Adult patients undergoing elective cardiac surgery. MAIN OUTCOME MEASURES: Pre-operative cognitive status was assessed by neuropsychological tests and scored as a global z score. A 5-min EEG recording was obtained 30 min after induction of anaesthesia. Anaesthesia was maintained with sevoflurane. Power and peak frequency in the α-band were extracted from the frequency spectra. POD was assessed using the Confusion Assessment Method for Intensive Care Unit, the Confusion Assessment Method and a chart review. RESULTS: Sixty-five (29.5%) of 220 patients developed POD. Delirious patients were significantly older with median [IQR] ages of 74 [64 to 79] years vs. 67 [59 to 74] years; P  < 0.001) and had lower pre-operative cognitive z scores (-0.52 ±â€Š1.14 vs. 0.21 ±â€Š0.84; P  < 0.001). Mean α power (-14.03 ±â€Š4.61 dB vs. -11.59 ±â€Š3.37 dB; P  < 0.001) and maximum α power (-11.36 ±â€Š5.28 dB vs. -8.85 ±â€Š3.90 dB; P  < 0.001) were significantly lower in delirious patients. Intra-operative mean α power was significantly associated with the probability of developing POD (adjusted odds ratio, 0.88; 95% confidence interval (CI), 0.81 to 0.96; P  = 0.007), independently of age and only whenever cognitive status was not considered. CONCLUSION: A lower intra-operative frontal α-band power is associated with a higher incidence of POD after cardiac surgery. Intra-operative measures of α power could constitute a means of identifying patients at risk of this complication. TRIAL REGISTRATION: NCT03706989.

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.

Combined Use of Rotational Thromboelastometry (Rotem) and Platelet Impedance Aggregometry (Multiplate Analyzer) in Cyanotic and Acyanotic Infants and Children Undergoing Cardiac Surgery With Cardiopulmonary Bypass: Subgroup Analysis of a Randomized Clinical Trial.

OBJECTIVES: Few studies have investigated the Multiplate platelet function analyzer in pediatrics. The authors evaluated Multiplate combined with Rotem in terms of guiding platelet transfusion after pediatric cardiac surgery with cardiopulmonary bypass (CPB). The authors further compared coagulation parameters between cyanotic and acyanotic patients. DESIGN: Subgroup analysis of a randomized clinical trial. SETTING: Tertiary hospital. PARTICIPANTS: Patients weighing between seven and 15 kg. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Rotem and Multiplate tests were performed (1) after anesthesia induction, (2) upon CPB separation, and (3) upon intensive care unit arrival. Among a total of 59 subjects, 9 patients required platelet transfusion. In multivariate linear regression, analysis EXTEM maximum clot firmness upon CPB separation was associated with the volume of transfused platelets (regression coefficient = -0.348 [95% confidence interval -1.006 to -0.028]; p = 0.039). No such association was found for the Multiplate test. Acyanotic and cyanotic heart disease were present in 32 and 27 children, respectively. There were no significant differences between these two groups in terms of platelet count and function. Postoperative blood loss was significantly higher in the cyanotic group compared with the acyanotic arm (p = 0.015; difference [95% confidence interval -2.40 {-4.20 to -0.60}]). There were no differences between groups regarding transfusion of allogeneic blood products. CONCLUSIONS: This study showed that Rotem, but not Multiplate results, were associated with platelet transfusion in pediatric cardiac surgery with no intake of platelet inhibitors. The usefulness of combining these tests in platelet transfusion decision-making needs to be evaluated in larger populations.

An original backup technique to assess the correct positioning of right-sided double-lumen tubes without fiberoptic bronchoscopy: A pilot feasibility study.

Background: Accurate positioning of a right-sided double-lumen tube is essential but challenging due to the location and the potential obstruction of the right upper lobe bronchus. Fiberoptic bronchoscopy is, therefore, necessary but requires a specific training period for the anesthesiologist and might not always be available. Objective: We describe an original backup technique to assess the correct placement of these tubes in cases a fiberopetic bronchoscopy is lacking. Design: Prospective pilot feasibility study with 10 adult patients scheduled for a left thoracic surgery. Setting: Operating theater in a universitary hospital. Materials and Methods: The new technique uses a fluoroscopy and an adult central venous catheter wire. The time needed to perform the new technique, its success rate and its efficacy in properly exclude the left lung were evaluated. Any oxygen desaturation episode (SpO2 <90%) was considered. The technique was performed by two anesthesiologists with different experience in thoracic anesthesia. Results: The success rate of our technique was 90%, which did not depend on the anesthesiologist's experience. The range of time to successfully place the tube in the dorsal decubitus position and subsequently in the right lateral decubitus position was respectively 1 min-6 min and 1 min-15 min. None of the patients presented any desaturation episodes. Conclusions: We describe an original, safe, and acceptable backup technique to properly insert right-sided double-lumen endobronchial tubes, whenever a fiberoptic bronchoscopy is not available. Moreover, this technique is easy enough to be performed by anesthesiologists with limited experience in thoracic anesthesia.

Fresh Frozen Plasma versus Crystalloid Priming of Cardiopulmonary Bypass Circuit in Pediatric Surgery: A Randomized Clinical Trial.

BACKGROUND: In congenital cardiac surgery, priming cardiopulmonary bypass (CPB) with fresh frozen plasma (FFP) is performed to prevent coagulation abnormalities. The hypothesis was that CPB priming with crystalloids would be different compared with FFP in terms of bleeding and/or need for blood product transfusion. METHODS: In this parallel-arm double-blinded study, patients weighing between 7 and 15 kg were randomly assigned to a CPB priming with 15 ml · kg PlasmaLyte or 15 ml · kg FFP in addition to a predefined amount of packed red blood cells used in all patients. The decision to transfuse was clinical and guided by point-of-care tests. The primary endpoints included postoperative bleeding tracked by chest tubes, number of patients transfused with any additional blood products, and the total number of additional blood products administered intra- and postoperatively. The postoperative period included the first 6 h after intensive care unit arrival. RESULTS: Respectively, 30 and 29 patients in the FFP and in the crystalloid group were analyzed in an intention-to-treat basis. Median postoperative blood loss was 7.1 ml · kg (5.1, 9.4) in the FFP group and 5.7 ml · kg (3.8, 8.5) in the crystalloid group (P = 0.219); difference (95% CI): 1.2 (-0.7 to 3.2). The proportion of patients additionally transfused was 26.7% (8 of 30) and 37.9% (11 of 29) in the FFP and the crystalloid groups, respectively (P = 0.355; odds ratio [95% CI], 1.7 [0.6 to 5.1]). The median number of any blood products transfused in addition to priming was 0 (0, 1) and 0 (0, 2) in the FFP and crystalloid groups, respectively (P = 0.254; difference [95% CI], 0 [0 to 0]). There were no study-related adverse events. CONCLUSIONS: The results demonstrate that in infants and children, priming CPB with crystalloids does not result in a different risk of postoperative bleeding and need for transfusion of allogeneic blood products.

Predicting postoperative delirium and postoperative cognitive decline with combined intraoperative electroencephalogram monitoring and cerebral near-infrared spectroscopy in patients undergoing cardiac interventions.

Studies have associated electroencephalogram (EEG) suppression with postoperative delirium (POD) and postoperative cognitive decline (POCD). Otherwise, improving cerebral tissue oxygen saturation (rScO2) seems beneficial. No study has evaluated the impact of EEG suppression and decreased rScO2 on the incidence of POD and POCD when the intraoperative management of patients is performed with a depth-of-anesthesia (DOA) monitor and a cerebral oximetry. In this prospective study patients undergoing cardiac interventions were monitored with the NeuroSENSE® DOA monitor and bilateral cerebral oximetry. An algorithm was used to optimize cerebral oxygenation. EEG suppression was presented as total area under the curve (AUC) of suppression ratio (SR) > 0 s (AUCEEGSR>0s). Cerebral desaturation was defined as AUC of 25% drop of oximetry values as compared to baseline. POD was evaluated by the chart review method. POCD was defined as a Z-score ≤ 2 based on Mini Mental State Examination at baseline and day 5 or if the patient reported any cognitive decline at 3 and at 6 months postoperatively. Among the 1616 patients, 1513 underwent normothermic surgery and were further analyzed. POD and POCD were respectively evaluated in 1504 and 1350 patients of whom 303 (20%) and 270 (20%) were respectively diagnosed positive. Having experienced high magnitudes of EEG suppression (fourth quartile of AUCEEGSR>0s) was significantly associated with POD (OR = 2.247; 95% CI = 1.414-3.571; P = 0.001). Low rScO2 at the end of surgery was statistically associated with POCD (OR = 0.981; 95% CI = 0.965-0.997; P = 0.018). The results of our study show that the degree of intraoperative EEG suppression on one hand, and low rScO2 at the end of procedure on the other hand, are associated with respectively POD and POCD in patients undergoing cardiac interventions.

Anesthetic Care of 2 Siblings With Neonatal Ichthyosis and Sclerosing Cholangitis Syndrome: Case Reports.

We report for the first time the anesthetic management of 2 sisters suffering from neonatal ichthyosis and sclerosing cholangitis syndrome. They both presented with neonatal cholestatic jaundice and ichthyosis. The first was admitted for orthotopic liver transplantation at the age of 1 year, and the second patient underwent open pyeloplasty for a pyeloureteric junction syndrome at the age of 4 years. These 2 case reports highlight that, except for the potential difficulties with securing the catheters, dressings and endotracheal tube to the skin, the anesthetic implications of neonatal ichthyosis and sclerosing cholangitis syndrome are mainly related to the liver disease: cirrhosis and portal hypertension.

What is the normal value of the neutrophil-to-lymphocyte ratio?

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has proven its prognostic value in cardiovascular diseases, infections, inflammatory diseases and in several types of cancers. However, no cut-off has been proposed on the basis of reference values coming from healthy population. METHODS: Routine blood samples were obtained (n = 413) from workers (age: median 38, range: 21-66 years) involved in a health care prevention program, to determine means, standard deviations (SDs), 95% confidence intervals (95% CI), percentiles P2.5 and P97.5. A second independent sample of healthy volunteers is compared (n = 29). RESULTS: The mean NLR is 1.65 [±1.96 SD: 0.78-3.53] (95% CI [0.75-0.81] and [3.40-3.66]). In the second cohort (healthy control), the NLR values are in the same range, whichever the used analyzer. No NLR assessed in the validation series is out of the proposed limits. CONCLUSIONS: We have identified that the normal NLR values in an adult, non-geriatric, population in good health are between 0.78 and 3.53. These data will help to define the normal values of the NLR.

A coherent organization of differentiation proteins is required to maintain an appropriate thyroid function in the Pendred thyroid.

CONTEXT: Pendred syndrome is caused by mutations in the gene coding for pendrin, an apical Cl-/I- exchanger. OBJECTIVE: To analyze intrathyroidal compensatory mechanisms when pendrin is lacking, we investigated the thyroid of a patient with Pendred syndrome. The expression of proteins involved in thyroid hormone synthesis, markers of oxidative stress (OS), cell proliferation, apoptosis, and antioxidant enzymes were analyzed. RESULTS: Three morphological zones were identified: nearly normal follicles with iodine-rich thyroglobulin in the colloid (zone 1.a), small follicles without iodine-rich thyroglobulin in lumina (zone 1.b), and destroyed follicles (zone 2). In zones 1.a, dual oxidase (Duox) and thyroid peroxidase (TPO) were localized at the apical pole, OS and cell apoptosis were absent, but ClC-5 expression was strongly increased. In zones 1.b, Duox and TPO were aberrantly present and increased in the cytosol and associated with high OS, apoptosis, cell proliferation, and increased expression of peroxiredoxin-5, catalase, and dehalogenase-1 but moderate ClC-5 expression. CONCLUSION: In conclusion, the absence of pendrin is accompanied by increased ClC-5 expression that may transiently compensate for apical iodide efflux. In more affected follicles, Duox and TPO are relocated in the cytosol, leading to abnormal intracellular thyroid hormone synthesis, which results in cell destruction presumably because intracellular OS cannot be buffered by antioxidant defenses.

Role of caveolin-1 in thyroid phenotype, cell homeostasis, and hormone synthesis: in vivo study of caveolin-1 knockout mice.

In human thyroid, caveolin-1 is localized at the apex of thyrocytes, but its role there remains unknown. Using immunohistochemistry, (127)I imaging, transmission electron microscopy, immunogold electron microscopy, and quantification of H(2)O(2), we found that in caveolin-1 knockout mice thyroid cell homeostasis was disrupted, with evidence of oxidative stress, cell damage, and apoptosis. An even more striking phenotype was the absence of thyroglobulin and iodine in one-half of the follicular lumina and their presence in the cytosol, suggesting that the iodide organification and binding to thyroglobulin were intracellular rather than at the apical membrane/extracellular colloid interface. The latter abnormality may be secondary to the observed mislocalization of the thyroid hormone synthesis machinery (dual oxidases, thyroperoxidase) in the cytosol. Nevertheless, the overall uptake of radioiodide, its organification, and secretion as thyroid hormones were comparable to those of wild-type mice, suggesting adequate compensation by the normal TSH retrocontrol. Accordingly, the levels of free thyroxine and TSH were normal. Only the levels of free triiodothyronine showed a slight decrease in caveolin-1 knockout mice. However, when TSH levels were increased through low-iodine chow and sodium perchlorate, the induced goiter was more prominent in caveolin-1 knockout mice. We conclude that caveolin-1 plays a role in proper thyroid hormone synthesis as well as in cell number homeostasis. Our study demonstrates for the first time a physiological function of caveolin-1 in the thyroid gland. Because the expression and subcellular localization of caveolin-1 were similar between normal human and murine thyroids, our findings in caveolin-1 knockout mice may have direct relevance to the human counterpart.