Morning or Afternoon Scheduling for Elective Coronary Artery Bypass Surgery: Influence of Longer Fasting Periods from Metabolic and Hemodynamic Perspectives.

BACKGROUND: Prolonged preoperative fasting may worsen postoperative outcomes. Cardiac surgery has higher perioperative risk, and longer fasting periods may be not well-tolerated. We analysed the postoperative metabolic and hemodynamic variables in patients undergoing elective coronary artery bypass grafting (CABG) according to their morning or afternoon schedule. METHODS: Single-centre retrospective study at University teaching hospital (1-year data collection from electronic medical records). Using a mixed-effects linear regression model adjusted for several covariates, we compared metabolic (lactatemia, pH, and base deficit [BD]) and haemodynamic values (patients on vasoactive support, and vasoactive inotropic score [VIS]) at 7 prespecified time-points (admission to intensive care, and 1st, 3rd, 6th, 12th, 18th, and 24th postoperative hours). RESULTS: 339 patients (n = 176 morning, n = 163 afternoon) were included. Arterial lactatemia and BD were similar (overall P = 0.11 and P = 0.84, respectively), while pH was significantly lower in the morning group (overall P < 0.05; mean difference -0.01). Postoperative urine output, fluid balance, mean arterial pressure, and central venous pressure were similar (P = 0.59, P = 0.96, P = 0.58 and P = 0.53, respectively). A subgroup analysis of patients with diabetes (n = 54 morning, n = 45 afternoon) confirmed the same findings. The VIS values and the proportion of patients on vasoactive support was higher in the morning cases at the 18th (P = 0.002 and p=0.04, respectively) and 24th postoperative hours (P = 0.003 and P = 0.04, respectively). Mean intensive care length of stay was 1.94 ± 1.36 days versus 2.48 ± 2.72 days for the afternoon and morning cases, respectively (P = 0.02). CONCLUSIONS: Patients undergoing elective CABG showed similar or better metabolic and hemodynamic profiles when scheduled for afternoon surgery.

Articulating Video Stylet Compared to Other Techniques for Endotracheal Intubation in Normal Airways: A Simulation Study in Consultants with No Prior Experience.

Simulation for airway management allows for acquaintance with new devices and techniques. Endotracheal intubation (ETI), most commonly performed with direct laryngoscopy (DL) or video laryngoscopy (VLS), can be achieved also with combined laryngo-bronchoscopy intubation (CLBI). Finally, an articulating video stylet (ProVu) has been recently introduced. A single-center observational cross-sectional study was performed in a normal simulated airway scenario comparing DL, VLS-Glidescope, VLS-McGrath, CLBI and ProVu regarding the success rate (SR) and corrected time-to-intubation (cTTI, which accounts for the SR). Up to three attempts/device were allowed (maximum of 60 s each). Forty-two consultants with no experience with ProVu participated (15 ± 9 years after training completion). The DL was significantly faster (cTTI) than all other devices (p = 0.033 vs. VLSs, and p < 0.001 for CLBI and Provu), no differences were seen between the two VLSs (p = 0.775), and the VLSs were faster than CLBI and ProVu. Provu had a faster cTTI than CLBI (p = 0.004). The DL and VLSs showed similar SRs, and all the laryngoscopes had a higher SR than CLBI and ProVu at the first attempt. However, by the third attempt, the SR was not different between the DL/VLSs and ProVu (p = 0.241/p = 0.616); ProVu was superior to CLBI (p = 0.038). In consultants with no prior experience, ProVu shows encouraging results compared to DL/VLSs under simulated normal airway circumstances and further studies are warranted.

Non-Invasive Monitoring during Caesarean Delivery: Prevalence of Hypotension and Impact on the Newborn.

BACKGROUND: The aim of our study was to investigate the prevalence of perioperative hypotension after spinal anesthesia for cesarean section using non-invasive continuous hemodynamic monitoring and its correlation with neonatal well-being. METHODS: We included 145 patients. Spinal anesthesia was performed with a combination of hyperbaric bupivacaine 0.5% (according to a weight/height scheme) and fentanyl 20 µg. Hypotension was defined as a mean arterial pressure (MAP) < 65 mmHg or <60 mmHg. We also evaluated the impact of hypotension on neonatal well-being. RESULTS: Perioperative maternal hypotension occurred in 54.5% of cases considering a MAP < 65 mmHg and in 42.1% with the more conservative cut-off (<60 mmHg). Severe neonatal acidosis occurred in 1.4% of neonates, while an Apgar score ≥ 9 was observed in 95.9% at 1 min and 100% at 5 min. CONCLUSIONS: Continuous non-invasive hemodynamic monitoring allowed an early detection of maternal hypotension leading to a prompt treatment with satisfactory results considering neonatal well-being.

Anesthesia-induced Takotsubo cardiomyopathy in trigeminal neuralgia: illustrative case.

BACKGROUND: Takotsubo syndrome (TS) represents a form of nonischemic cardiomyopathy characterized by sudden and temporary weakening of the myocardium. Many data suggest a primary role for sympathetic overstimulation in its pathogenesis. Nevertheless, these correlates are less easily identified during anesthesia. OBSERVATIONS: A 50-year-old female patient with a 4-year history of drug-resistant left trigeminal neuralgia. She was scheduled for surgical microvascular decompression. In the operating room, after induction of general anesthesia and oral intubation, the electrocardiogram revealed a significant ST segment elevation along with a sudden decrease in systolic blood pressure and heart rate. Administration of atropine caused a conversion into ventricular tachycardia. The advanced cardiac life support protocols were applied with prompt defibrillation and rapid recovery at sinus rhythm. A transthoracic echocardiogram revealed apical akinesia with ballooning of the left ventricle with a reduction of systolic function. An emergency coronary arteriography was performed, showing normal epicardial coronary vessels. After 4 days, echocardiography revealed normalization of the left ventricular function with improvement of the ejection fraction. LESSONS: In patients affected by trigeminal neuralgia, chronic pain can lead to a state of adrenergic hyperactivation, which can promote TS during the induction of general anesthesia, probably through the trigeminocardiac reflex.

Propofol and α2-Agonists Attenuate Microglia Activation and Restore Mitochondrial Function in an In Vitro Model of Microglia Hypoxia/Reoxygenation.

Cerebrovascular ischemia is a common clinical disease encompassing a series of complex pathophysiological processes in which oxidative stress plays a major role. The present study aimed to evaluate the effects of Dexmedetomidine, Clonidine, and Propofol in a model of hypoxia/reoxygenation injury. Microglial cells were exposed to 1%hypoxia for 3 h and reoxygenated for 3 h, and oxidative stress was measured by ROS formation and the expression of inflammatory process genes. Mitochondrial dysfunction was assessed by membrane potential maintenance and the levels of various metabolites involved in energetic metabolism. The results showed that Propofol and α2-agonists attenuate the formation of ROS during hypoxia and after reoxygenation. Furthermore, the α2-agonists treatment restored membrane potential to values comparable to the normoxic control and were both more effective than Propofol. At the same time, Propofol, but not α2-agonists, reduces proliferation (Untreated Hypoxia = 1.16 ± 0.2, Untreated 3 h Reoxygenation = 1.28 ± 0.01 vs. Propofol hypoxia = 1.01 ± 0.01 vs. Propofol 3 h Reoxygenation = 1.12 ± 0.03) and microglial migration. Interestingly, all of the treatments reduced inflammatory gene and protein expressions and restored energy metabolism following hypoxia/reoxygenation (ATP content in hypoxia/reoxygenation 3 h: Untreated = 3.11 ± 0.8 vs. Propofol = 7.03 ± 0.4 vs. Dexmedetomidine = 5.44 ± 0.8 vs. Clonidine = 7.70 ± 0.1), showing that the drugs resulted in a different neuroprotective profile. In conclusion, our results may provide clinically relevant insights for neuroprotective strategies in intensive care units.

Use of nafamostat mesilate for anticoagulation during extracorporeal membrane oxygenation: A systematic review.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) represents an advanced option for supporting refractory respiratory and/or cardiac failure. Systemic anticoagulation with unfractionated heparin (UFH) is routinely used. However, patients with bleeding risk and/or heparin-related side effects may necessitate alternative strategies: among these, nafamostat mesilate (NM) has been reported. METHODS: We conducted a systematic literature search (PubMed and EMBASE, updated 12/08/2021), including all studies reporting NM anticoagulation for ECMO. We focused on reasons for starting NM, its dose and the anticoagulation monitoring approach, the incidence of bleeding/thrombosis complications, the NM-related side effects, ECMO weaning, and mortality. RESULTS: The search revealed 11 relevant findings, all with retrospective design. Of these, three large studies reported a control group receiving UFH, the other were case series (n = 3) or case reports (n = 5). The main reason reported for NM use was an ongoing or high risk of bleeding. The NM dose varied largely as did the anticoagulation monitoring approach. The average NM dose ranged from 0.46 to 0.67 mg/kg/h, but two groups of authors reported larger doses when monitoring anticoagulation with ACT. Conflicting findings were found on bleeding and thrombosis. The only NM-related side effect was hyperkalemia (n = 2 studies) with an incidence of 15%-18% in patients anticoagulated with NM. Weaning and survival varied across studies. CONCLUSION: Anticoagulation with NM in ECMO has not been prospectively studied. While several centers have experience with this approach in high-risk patients, prospective studies are warranted to establish the optimal space of this approach in ECMO.

Proactive Management of Intraoperative Hypotension Reduces Biomarkers of Organ Injury and Oxidative Stress during Elective Non-Cardiac Surgery: A Pilot Randomized Controlled Trial.

BACKGROUND: Intraoperative hypotension is associated with increased postoperative morbidity and mortality. METHODS: We randomly assigned patients undergoing major general surgery to early warning system (EWS) and hemodynamic algorithm (intervention group, n = 20) or standard care (n = 20). The primary outcome was the difference in hypotension (defined as mean arterial pressure < 65 mmHg) and as secondary outcome surrogate markers of organ injury and oxidative stress. RESULTS: The median number of hypotensive episodes was lower in the intervention group (-5.0 (95% CI: -9.0, -0.5); p < 0.001), with lower time spent in hypotension (-12.8 min (95% CI: -38.0, -2.3 min); p = 0.048), correspondent to -4.8% of total surgery time (95% CI: -12.7, 0.01%; p = 0.048).The median time-weighted average of hypotension was 0.12 mmHg (0.35) in the intervention group and 0.37 mmHg (1.11) in the control group, with a median difference of -0.25 mmHg (95% CI: -0.85, -0.01; p = 0.025). Neutrophil Gelatinase-Associated Lipocalin (NGAL) correlated with time-weighted average of hypotension (R = 0.32; p = 0.038) and S100B with number of hypotensive episodes, absolute time of hypotension, relative time of hypotension and time-weighted average of hypotension (p < 0.001 for all). The intervention group showed lower Neuronal Specific Enolase (NSE) and higher reduced glutathione when compared to the control group. CONCLUSIONS: The use of an EWS coupled with a hemodynamic algorithm resulted in reduced intraoperative hypotension, reduced NSE and oxidative stress.

Tracheal intubation while wearing personal protective equipment in simulation studies: a systematic review and meta-analysis with trial-sequential analysis.

BACKGROUND: Tracheal intubation in patients with coronavirus disease-19 is a high-risk procedure that should be performed with personal protective equipment (PPE). The influence of PPE on operator's performance during tracheal intubation remains unclear. METHODS: We conducted a systematic review and meta-analysis of simulation studies to evaluate the influence of wearing PPE as compared to standard uniform regarding time-to-intubation (TTI) and success rate. Subgroup analyses were conducted according to device used and operator's experience. RESULTS: The TTI was prolonged when wearing PPE (eight studies): Standard Mean Difference (SMD) -0.54, 95% Confidence Interval [-0.75, -0.34], p <  0.0001. Subgroup analyses according to device used showed similar findings (direct laryngoscopy, SMD -0.63 [-0.88, -0.38], p < 0.0001; videolaryngoscopy, SMD -0.39 [-0.75, -0.02], p =  0.04). Considering the operator's experience, non-anesthesiologists had prolonged TTI (SMD -0.75 [-0.98, -0.52], p < 0.0001) while the analysis on anesthesiologists did not show significant differences (SMD -0.25 [-0.51, 0.01], p = 0.06). The success rate of tracheal intubation was not influenced by PPE: Risk Ratio (RR) 1.02 [1.00, 1.04]; p = 0.12). Subgroup analyses according to device demonstrated similar results (direct laryngoscopy, RR 1.03 [0.99, 1.07], p = 0.15, videolaryngoscopy, RR 1.01 [0.98, 1.04], p =  0.52). Wearing PPE had a trend towards negative influence on success rate in non-anesthesiologists (RR 1.05 [1.00, 1.10], p = 0.05), but not in anesthesiologists (RR 1.00 [0.98, 1.03], p = 0.84). Trial-sequential analyses for TTI and success rate indicated robustness of both results. CONCLUSIONS: Under simulated conditions, wearing PPE delays the TTI as compared to dressing standard uniform, with no influence on the success rate. However, certainty of evidence is very low. Performing tracheal intubation with direct laryngoscopy seems influenced to a greater extent as compared to videolaryngoscopy. Similarly, wearing PPE affects more the non-anesthesiologists subgroup as compared to anesthesiologists.

Neurocognitive Performance Improvement after Obstructive Sleep Apnea Treatment: State of the Art.

BACKGROUND: Obstructive Sleep Apnea (OSA) syndrome is a respiratory sleep disorder characterized by partial or complete episodes of upper airway collapse with reduction or complete cessation of airflow. Although the connection remains debated, several mechanisms such as intermittent hypoxemia, sleep deprivation, hypercapnia disruption of the hypothalamic-pituitary-adrenal axis have been associated with poor neurocognitive performance. Different treatments have been proposed to treat OSAS patients as continuous positive airway pressure (CPAP), mandibular advancement devices (MAD), surgery; however, the effect on neurocognitive functions is still debated. This article presents the effect of OSAS treatments on neurocognitive performance by reviewing the literature. METHODS: We performed a comprehensive review of the English language over the past 20 years using the following keywords: neurocognitive performance and sleep apnea, neurocognitive improvement and CPAP, OSAS, and cognitive dysfunction. We included in the analysis papers that correlated OSA treatment with neurocognitive performance improvement. All validated tests used to measure different neurocognitive performance improvements were considered. RESULTS: Seventy papers reported neurocognitive Performance improvement in OSA patients after CPAP therapy. Eighty percent of studies found improved executive functions such as verbal fluency or working memory, with partial neural recovery at long-term follow-up. One article compared the effect of MAD, CPAP treatment on cognitive disorders, reporting better improvement of CPAP and MAD than placebo in cognitive function. CONCLUSIONS: CPAP treatment seems to improve cognitive defects associated with OSA. Limited studies have evaluated the effects of the other therapies on cognitive function.

Intraoperative protective ventilation in patients undergoing major neurosurgical interventions: a randomized clinical trial.

BACKGROUND: Post-operative pulmonary complications (PPC) can develop in up to 13% of patients undergoing neurosurgical procedures and may adversely affect clinical outcome. The use of intraoperative lung protective ventilation (LPV) strategies, usually including the use of a low Vt, low PEEP and low plateau pressure, seem to reduce the risk of PPC and are strongly recommended in almost all surgical procedures. Nonetheless, feasibility of LPV strategies in neurosurgical patients are still debated because the use of low Vt during LPV might result in hypercapnia with detrimental effects on cerebrovascular physiology. Aim of our study was to determine whether LPV strategies would be feasible compared with a control group in adult patients undergoing cranial or spinal surgery. METHODS: This single-centre, pilot randomized clinical trial was conducted at the University Hospital "Maggiore della Carità" (Novara, Italy). Adult patients undergoing major cerebral or spinal neurosurgical interventions with risk index for pulmonary post-operative complications > 2 and not expected to need post-operative intensive care unit (ICU) admission were considered eligible. Patients were randomly assigned to either LPV (Vt = 6 ml/kg of ideal body weight (IBW), respiratory rate initially set at 16 breaths/min, PEEP at 5 cmH2O and application of a recruitment manoeuvre (RM) immediately after intubation and at every disconnection from the ventilator) or control treatment (Vt = 10 ml/kg of IBW, respiratory rate initially set at 6-8 breaths/min, no PEEP and no RM). Primary outcomes of the study were intraoperative adverse events, the level of cerebral tension at dura opening and the intraoperative control of PaCO2. Secondary outcomes were the rate of pulmonary and extrapulmonary complications, the number of unplanned ICU admissions, ICU and hospital lengths of stay and mortality. RESULTS: A total of 60 patients, 30 for each group, were randomized. During brain surgery, the number of episodes of intraoperative hypercapnia and grade of cerebral tension were similar between patients randomized to receive control or LPV strategies. No difference in the rate of intraoperative adverse events was found between groups. The rate of postoperative pulmonary and extrapulmonary complications and major clinical outcomes were similar between groups. CONCLUSIONS: LPV strategies in patients undergoing major neurosurgical intervention are feasible. Larger clinical trials are needed to assess their role in postoperative clinical outcome improvements. TRIAL REGISTRATION: registered on the Australian New Zealand Clinical Trial Registry ( www.anzctr.org.au ), registration number ACTRN12615000707561.

The Therapeutic Potential of Carnosine/Anserine Supplementation against Cognitive Decline: A Systematic Review with Meta-Analysis.

Carnosine is a natural occurring endogenous dipeptide that was proposed as an anti-aging agent more than 20 years ago. Carnosine can be found at low millimolar concentrations at brain level and different preclinical studies have demonstrated its antioxidant, anti-inflammatory, and anti-aggregation activity with neuroprotective effects in animal models of Alzheimer's disease (AD). A selective deficit of carnosine has also been linked to cognitive decline in AD. Different clinical studies have been conducted to evaluate the impact of carnosine supplementation against cognitive decline in elderly and AD subjects. We conducted a systematic review with meta-analysis, in accordance with the PRISMA guidelines coupled to the PICOS approach, to investigate the therapeutic potential of carnosine against cognitive decline and depressive symptoms in elderly subjects. We found five studies matching the selection criteria. Carnosine/anserine was administered for 12 weeks at a dose of 1 g/day and improved global cognitive function, whereas no effects were detected on depressive symptoms. These data suggest a preliminary evidence of clinical efficacy of carnosine against cognitive decline both in elderly subjects and mild cognitive impairment (MCI) patients, although larger and long-term clinical studies are needed in MCI patients (with or without depression) to confirm the therapeutic potential of carnosine.

Association of Systemic Sclerosis and Periodontitis with Vitamin D Levels.

The aim of the present study was to analyze the association among systemic sclerosis (SSc), periodontitis (PT); we also evaluated the impact of PT and SSc on vitamin D levels. Moreover, we tested the association with potential confounders. A total of 38 patients with SSc, 40 subjects with PT, 41 subjects with both PT and SSc, and 41 healthy controls were included in the study. The median vitamin D levels in PT subject were 19.1 (17.6-26.8) ng/mL, while SSc + PT group had vitamin d levels of 15.9 (14.7-16.9) ng/mL, significantly lower with respect to SSc patients (21.1 (15.4-22.9) ng/mL) and to healthy subjects (30.5 (28.8-32.3) ng/mL) (p < 0.001). In all subjects, vitamin D was negatively associated with c-reactive protein (CRP) (p < 0.001) and with probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and plaque score (PI) (p < 0.001 for all parameters) and positively related to the number of teeth (p < 0.001). Moreover, univariate regression analysis demonstrated an association among high low-density lipoproteins (LDL) cholesterol (p = 0.021), CRP (p = 0.014), and PT (p < 0.001) and reduced levels of vitamin D. The multivariate regression analysis showed that PT (p = 0.011) and CRP (p = 0.031) were both predictors of vitamin D levels. Subjects with PT and SSc plus PT had significant lower vitamin D values with respect to SSc and to healthy subjects. In addition, PT seems negatively associated with levels of vitamin D in all analyzed patients.

Influence of Habitual Dairy Food Intake on LDL Cholesterol in a Population-Based Cohort.

BACKGROUND: Cholesterol has a pivotal role in human physiology, exerting both structural and functional activity. However, higher blood cholesterol levels, especially low-density lipoprotein cholesterol (LDL-C), are a major cardiovascular risk factor. Therefore, special attention has been given to the effect of dietary factors in influencing LDL-C blood levels. In particular, much research has focused on dairy products, since they are a main component of different dietary patterns worldwide. A large body of evidence did not support the hypothesis that dairy products significantly increase circulating LDL-C, but no definitive data are available. Hence, we aimed to assess the relationships among LDL-C, habitual dairy food intake and anthropometric variables in a cohort representative of the general population in a Mediterranean area. METHODS: We evaluated 802 healthy adults included in the ABCD_2 (Alimentazione, Benessere Cardiovascolare e Diabete) study (ISRCTN15840340), a longitudinal observational single-center study of a cohort representative of the general population of Palermo, Sicily. The habitual intake of dairy products was assessed with a validated food frequency questionnaire, and LDL-C serum levels and several anthropometric parameters were measured. RESULTS: The group with high LDL-C serum concentrations (≥130 vs. <130 mg/dL) exhibited higher age, body mass index (BMI), waist-to-hip ratio (WHR), body fat percentage, systolic and diastolic blood pressure, carotid intima-media thickness and glycated hemoglobin. The habitual diet was not different between the groups in terms of macronutrient, cholesterol, egg and dairy food intake, with the exception of the weekly number of portions of milk (higher in the low LDL-C group vs. the high LDL-C group) and ricotta cheese (higher in the high LDL-C group vs. the LDL-C group). No significant correlation was found between LDL-C blood levels and the habitual intake of dairy products or the dietary intake of cholesterol and fats. The multivariate regression analyses (R2 = 0.94) showed that LDL-C blood levels were significantly associated with the habitual intake of milk (p < 0.005) and ricotta cheese (p < 0.001) and with BMI (p < 0.001). CONCLUSION: Our study reported that total dairy food consumption was not correlated with LDL-C blood levels. However, multivariate analyses showed an inverse association between serum LDL-C and milk intake as well as a positive association between ricotta cheese intake and LDL-C concentrations. More studies are needed to better characterize the relationship between dairy products and circulating LDL-C.

Self-citation policies and journal self-citation rate among Critical Care Medicine journals.

BACKGROUND: Inappropriate authors' self-citation (A-SC) is a growing mal-practice possibly boosted by the raising importance given to author's metrics. Similarly, also excessive journals' self-citation (J-SC) practice may factitiously influence journal's metrics (impact factor, IF). Evaluating the appropriateness of each self-citation remains challenging. MAIN BODY: We evaluated the presence of policies discouraging A-SC in Critical Care Medicine (CCM) journals with IF. We also calculated the J-SC rate of these journals. In order to evaluate if J-SC rates are influenced by the focus of interest of CCM journals, we separated them in three sub-categories ("multidisciplinary", "broad" or "topic-specific" CCM journals). We analyzed 35 CCM journals and only 5 (14.3%) discouraged excessive and inappropriate A-SC. The median IF was higher in CCM journals with A-SC policies [4.1 (3-12)] as compared to those without [2.5 (2-3.5); p = 0.02]. The J-SC rate was highly variable (0-35.4%), and not influenced by the presence of A-SC policies (p = 0.32). However, J-SC rate was different according to the focus of interest (p = 0.01): in particular, it was higher in "topic-specific" CCM journals [15.3 (8.8-23.3%)], followed by "broad" CCM [11.8 (4.8-17.9%)] and "multidisciplinary" journals [6.1 (3.6-9.1%)]. CONCLUSIONS: A limited number of CCM journals have policies for limiting A-SC, and these have higher IF. The J-SC rate among CCM journals is highly variable and higher in "topic-specific" interest CCM journals. Excluding self-referencing practice from scientific metrics calculation could be valuable to tackle this scientific malpractice.