Barna Babik

Elevated levels of inflammatory biomarkers in the cerebrospinal fluid after coronary artery bypass surgery are predictors of cognitive decline

Recovery from cardiac surgery is marred for many patients by the development of neurological, psychological or cognitive dysfunction. An uncontrolled inflammatory reaction, in response to surgical stress, may be responsible. To confirm this hypothesis, the present study evaluated changes in the levels of cytokines in cerebrospinal fluid after coronary artery bypass grafting. One week post-operatively, the concentration of the pro-inflammatory cytokine interleukin-6 markedly increased; 6 months after surgery, however, its level normalized with an increased concentration of the anti-inflammatory interleukin-4. This suggests that a regulated immune response may participate in developing adverse neurologic events and complications following cardiac interventions, and cytokines in the cerebrospinal fluid may serve as specific biomarkers and predictors of developing cognitive decline after coronary surgery.

Changes in respiratory mechanics during cardiac surgery

We investigated the role of cardiopulmonary bypass (CPB) in compromised lung function associated with cardiac surgery. Low-frequency respiratory impedance (Zrs) was measured in patients undergoing cardiac surgery with (n = 30; CPB group) or without (n = 29; off-pump coronary artery bypass [OPCAB] group) CPB. Another group of CPB patients received dopamine (DA) (n = 12; CPB-DA group). Extravascular lung water was determined in five CPB subjects. Zrs was measured before skin incision and after chest closure. Airway resistance and inertance and tissue damping and elastance were determined from Zrs data. Airway resistance increased in the CPB group (74.9% ± 20.8%;P < 0.05), whereas it did not change in the OPCAB group (11.8% ± 7.9%; not significant) and even decreased in the CPB-DA patients (−40.6% ± 9.2%;P < 0.05). Tissue damping increased in the CPB and OPCAB groups, whereas it remained constant in the CPB-DA patients. Significant increases in elastance were observed in all groups. There was no difference in extravascular lung water before and after CPB, suggesting that edema did not develop. These results indicate a significant and heterogeneous airway narrowing during CPB, which was counteracted by the administration of DA. The mild deterioration in tissue mechanics, reflecting partial closure of the airways, may be a consequence of the anesthesia itself.

Coronary artery bypass surgery provokes alzheimer's disease-like changes in the cerebrospinal fluid

Several biomarkers are used in confirming the diagnosis of cognitive disorders. This study evaluates whether the level of these markers after heart surgery correlates with the development of cognitive dysfunction, which is a frequent complication of cardiac interventions. Concentrations of amyloid-β peptide, tau, and S100β in the cerebro-spinal fluid were assessed, as well as cognitive functions were evaluated before and after coronary artery bypass grafting, utilizing immuno-assays and psychometric tests, respectively. A drastic rise in the level of S100β was observed one week after the surgery, a mark of a severe generalized cerebral injury. The level of amyloid-β peptide significantly decreased, whereas the concentration of tau markedly increased six months postoperatively. Gradual cognitive decline was also present. These findings clearly demonstrate post-surgical cognitive impairment associated with changes in biomarkers similar to that seen in Alzheimers disease, suggesting a unifying pathognomic factor between the two disorders. A holistic approach to coronary heart disease and Alzheimers type dementia is proposed.

Comparison of sedation and general anaesthesia for transcatheter aortic valve implantation on cerebral oxygen saturation and neurocognitive outcome

BACKGROUND Transcatheter aortic valve implantation (TAVI) is a treatment strategy for patients with severe aortic stenosis. Although general anaesthesia (TAVI-GA) and sedation (TAVI-S) have previously been described for TAVI, the difference in safety and efficacy of both methods has not been studied in a randomized trial. METHODS The INSERT trial was a single centre, controlled parallel-group trial with balanced randomization. Sixty-six patients (68-94 yr) with acquired aortic stenosis undergoing transfemoral CoreValve™ were assigned to TAVI-GA or TAVI-S. Comparable operative risk was determined from risk-scores (EUROscore, STS-Score). Monitoring and anaesthetic drugs were standardized. Near-Infrared-Spectroscopy was used to monitor cerebral-oxymetry blinded. Primary outcome was the perioperative cumulative cerebral desaturation. As secondary outcomes, changes in neurocognitive function and respiratory and haemodynamic adverse events were evaluated. RESULTS Of 66 included patients, 62 (TAVI-GA: n=31, TAVI-S: n=31) were finally analysed. Baseline characteristics were comparable. In 24 patients (39%) cerebral desaturation was observed. Cumulative cerebral desaturation was comparable (TAVI-GA:(median [IQR]) (0[0/1308] s%) vs. TAVI-S:(0[0/276] s%); P=0.505) between the groups. Neurocognitive function did not change within and between groups. Adverse events were more frequently observed in TAVI-S patients (P<0.001). Bradypnoea (n=16, 52%) and the need for airway manoeuvres (n=11, 36%) or bag-mask-ventilation (n=6, 19%) were the most common respiratory adverse events. CONCLUSIONS Cerebral desaturation occurred in both patient groups, but there was no significant difference between the two groups. Based on primary outcome, both methods were shown to be comparable. Neurocognitive outcome was similar. The higher incidence of adverse events in the sedation group suggests a potential advantage of general anaesthesia. CLINICAL TRIAL REGISTRATION NCT 01251328.

Crackle-sound recording to monitor airway closure and recruitment in ventilated pigs.

It was hypothesised that the recruitment of atelectatic lung areas is signified by changes in the airway and tissue mechanics, and by the appearance of crackle activity attributed to the sudden reopening of collapsed airways. The authors also assumed that the acoustic activity is an earlier indicator of lung recruitment than the change in the overall mechanical state of the lungs. Six thoracotomised and mechanically ventilated mini-pigs were studied. Low-frequency pulmonary impedance was measured at end-expiratory pauses at transpulmonary pressures of 4 and 1 hPa to estimate airway resistance (Raw) and the coefficient of lung tissue elastance (H), and tracheal sounds were recorded during subsequent slow inflations to 30 hPa, in the control state and following increasing doses of i.v. methacholine (Mch). Raw and H were higher at baseline and increased more in response to Mch at 1 hPa than at 4 hPa. The crackles detected during the subsequent inflations were concentrated around and associated with the development of the lower knee of the pressure–volume curve. The number of crackles increased faster following the Mch doses and reached statistical significance earlier than Raw and H. Crackle recording during mechanical ventilation can be employed as a simple method with which to monitor lung recruitment–derecruitment.

Role of Endogenous Histamine in Altered Lung Mechanics in Rabbits

Background Unlike the effects of exogenous histamine, those of endogenous histamine on the lung mechanics have not yet been characterized. The site of endogenous histamine liberation by mivacurium was determined, as were the effects of this histamine on the airway and parenchymal mechanics in control rabbits (group C) and rabbits pretreated with H1 and H2 receptor blockers (group AH). The effectiveness of the receptor blockade was ensured by challenges with exogenous histamine. Methods Pulmonary input impedance at low frequencies (ZL) was measured in anesthetized mechanically ventilated open-chest rabbits under control conditions and every minute after administration of an intravenous bolus of mivacurium (2 mg/kg) and exogenous histamine (10 &mgr;g/kg). Histamine levels were determined in serum samples taken from the carotid artery and jugular vein before and 1, 3, and 6 min after mivacurium injection. Parameters of airway resistance (Raw) and inertance and parenchymal damping (G) and elastance (H) were extracted from ZL spectra. Results Mivacurium induced significant increases in plasma histamine levels, with the venous concentrations being significantly higher than those in the artery. The mivacurium-induced increase in Raw (28.7 ± 2.3%; mean ± SD) in group C was significantly higher than that in group AH (6.6 ± 3.4%), whereas the responses in G were not inhibited significantly (23.9 ± 6.9%vs. 15.5 ± 3.0%). The significant increases in Raw (70.6 ± 12.6%) and G (21.0 ± 4.9%) after exogenous histamine administration were virtually completely abolished by antihistamine pretreatment (3.6 ± 3.7% and 0.3 ± 2.6%). Conclusions After mivacurium administration, endogenous histamine is liberated at least partly in the systemic circulation, and it induces primarily a heterogeneous airway constriction with minor changes in the parenchymal properties. This response was considerably reduced but not abolished by antihistamine pretreatment, a circumstance suggesting that mivacurium may liberate other constrictor mediators that might also contribute to the airway and parenchymal constriction.

Effects of respiratory mechanics on the capnogram phases: importance of dynamic compliance of the respiratory system.

IntroductionThe slope of phase III of the capnogram (SIII) relates to progressive emptying of the alveoli, a ventilation/perfusion mismatch, and ventilation inhomogeneity. SIII depends not only on the airway geometry, but also on the dynamic respiratory compliance (Crs); this latter effect has not been evaluated. Accordingly, we established the value of SIII for monitoring airway resistance during mechanical ventilation.MethodsSidestream capnography was performed during mechanical ventilation in patients undergoing elective cardiac surgery (n = 144). The airway resistance (Raw), total respiratory resistance and Crs displayed by the ventilator, the partial pressure of arterial oxygen (PaO2) and SIII were measured in time domain (ST-III) and in a smaller cohort (n = 68) by volumetry (SV-III) with and without normalization to the average CO2 phase III concentration. Measurements were performed at positive end-expiratory pressure (PEEP) levels of 3, 6 and 9 cmH2O in patients with healthy lungs (Group HL), and in patients with respiratory symptoms involving low (Group LC), medium (Group MC) or high Crs (Group HC).ResultsST-III and SV-III exhibited similar PEEP dependencies and distribution between the protocol groups formed on the basis of Crs. A wide interindividual scatter was observed in the overall Raw-ST-III relationship, which was primarily affected by Crs. Decreases in Raw with increasing PEEP were reflected in sharp falls in SIII in Group HC, and in moderate decreases in SIII in Group MC, whereas ST-III was insensitive to changes in airway caliber in Groups LC and HL.ConclusionsSIII assessed in the time domain and by volumetry provide meaningful information about alterations in airway caliber, but only within an individual patient. Although ST-III may be of value for bedside monitoring of the airway properties, its sensitivity depends on Crs. Thus, assessment of the capnogram shape should always be coupled with Crs when the airway resistance or oxygenation are evaluated.

Different Inflammatory Biomarker Patterns in the Cerebro-Spinal Fluid Following Heart Surgery and Major Non-Cardiac Operations

Cognitive decline occurs frequently after cardiac surgery and it may lead to patient morbidity. The purpose of this study is to focus on the static incidence of neuro-psychiatric impairment associated with altered inflammatory biomarkers in the cerebro-spinal fluid (CSF) that may provide an insight into the mechanisms of acute peri-operative cognitive disturbances related to heart surgery. Immuno-assays were used to evaluate concentrations of several cytokines in CSF of patients undergoing either off-pump coronary artery bypass grafting (OP-CABG) or major non-cardiac surgeries. Inter-group analysis showed no differences in baseline cytokine abundance. Levels of IL-8 have markedly increased both after OP-CABG and major non-cardiac surgeries (34.59+/-7.15 vs. 99.45+/-6.35, and 27.44+/-7.17 vs. 66.63+/-15.18). Rantes showed significantly greater quantity in CSF of the non-cardiac group after surgery (8.71+/-3.37 vs. 114.56+/-65.42), whereas it became somewhat less abundant in the post-operative period but statistically unchanged in the OP-CABG cohort (19.87+/-15.71 vs. 9.37+/-3.65). IP-10 and MCP-1 did not show significant changes in their concentrations in either patient population (OP-CABG: 254.41+/-160.01 vs. 224.55+/-214.39, and 140.37+/-40.98 vs. 147.16+/-37.98; non-cardiac: 274.99+/-219.44 vs. 395.09+/-468.30, and 126.56+/-31.24 vs. 124.41+/-49.89, respectively). These findings suggest that cardiac surgery provokes alterations in the levels of various cytokines in the CSF, and the OP-CABG induced changes in biomarker profile differs from that seen after major non-cardiac surgeries. This, along with other biomarkers, may offer an explanation for relationships between the pronounced incidence of cognitive impairment after heart operations.

Changes in Airway and Respiratory Tissue Mechanics After Cardiac Surgery

BACKGROUND Because of the critical importance of the first postoperative week in the development of respiratory complications after cardiac surgery, the mechanical properties of the respiratory system in this period were followed up systematically. METHODS The input impedance of the respiratory system (Zrs) was measured during spontaneous breathing in patients (n=35) undergoing cardiac surgery on the day before surgery to establish the baseline, and for six days thereafter. The airway resistance was inferred from the average of the resistive component of Zrs, while the changes in respiratory elastance were assessed from the imaginary part of Zrs by model fitting. An assessment was made of the impact on the postoperative changes of factors characteristic of the patients (gender, age, smoking, and obesity) or the surgery duration and the need or not for a cardiopulmonary bypass. RESULTS Airway resistance increased immediately after extubation (peak rise on day 1, evening: 48+/-10%) and subsequently gradually decreased to the initial level, the recovery proving prolonged in obese patients. Postoperative elevation in elastance peaked later (day 2, evening: 83+/-14%), lasted longer, and was affected by both cardiopulmonary bypass (p<0.05) and obesity (p<0.005). CONCLUSIONS These findings demonstrate the need for particular attention in the postoperative management of patients after cardiac surgery in order to reduce the immediate airway symptoms, and to take steps to maintain the lungs open during the critical postoperative days 2 and 3, especially in obese patients and (or) if the surgery involves the use of cardiopulmonary bypass.

Components of respiratory resistance monitored in mechanically ventilated patients

The interrupter technique is commonly adopted to monitor respiratory resistance (Rrs,int) during mechanical ventilation; however, Rrs,int is often interpreted as an index of airway resistance (Raw). This study compared the values of Rrs,int provided by a Siemens 940 Lung Mechanics Monitor with total respiratory impedance (Zrs) parameters in 39 patients with normal spirometric parameters, who were undergoing elective coronary bypass surgery. Zrs was determined at the airway opening with pseudorandom oscillations of 0.2–6 Hz at end inspiration. Raw and tissue resistance (Rti) were derived from the Zrs data by model fitting; Rti and total resistance (Rrs,osc=Raw+Rti) were calculated at the actual respirator frequencies. Lower airway resistance (Rawl) was estimated by measuring tracheal pressure. Although good agreement was obtained between Rrs,osc and Rrs,int, with a ratio of 1.07±0.19 (mean±sd), they correlated poorly (r2=0.36). Rti and the equipment component of Raw accounted for most of Rrs,osc (39.8±11.9 and 43.0±6.9%, respectively), whereas only a small portion belonged to Rawl (17.2±6.3%). It is concluded that respiratory resistance may become very insensitive to changes in lower airway resistance and therefore, inappropriate for following alterations in airway tone during mechanical ventilation, especially in patients with relatively normal respiratory mechanics, where the tissue and equipment resistances represent the vast majority of the total resistance.