Local infiltration analgesia versus peripheral nerve block anaesthesia in total knee arthroplasty: a pharmaco-economic comparison

Background: A superior analgesic method in perioperative pain-management of patients receiving total knee arthroplasty is the subject of controversial debate. Although higher cost-efficiency is claimed for the local infiltration analgesia (LIA), there is a lack of data on its costs compared to peripheral nerve block anaesthesia (PNBA). The goal of this study was to investigate the differences in immediate perioperative costs between the LIA and PNBA in treatment of patients receiving total knee arthroplasty. Methods: The comparison was conducted based on a randomized controlled clinical trial examining 40 patients with elective, primary total knee arthroplasty (TKA, 20 patients with LIA and 20 patients with PNBA). The analysis included surgical case costs, anaesthesiological case costs, material, costs of postoperative opioid requirements and catheter review visits for patients receiving PNBA. Results: The overall mean costs for the LIA-group were 4328.72(sic) and 4368.12(sic) for the PNBA (p = 0.851). While there was no statistically significant difference in surgical case costs, the anaesthesiological costs were lower with the LIA procedure (1370.26(sic) vs. 1542.45(sic), p = 0.048). Material costs in the LIA group were 4.18(sic)/patient and 94.64(sic)/patient with the PNBA. Costs for postoperative opioid requirements showed no statistically significant difference between the two procedures. Conclusions: There is no relevant difference in immediate perioperative costs between LIA and PNBA. Shorter induction times lead to lower anaesthesiological case costs with the LIA. Overall economic aspects seem to play a less important role for determining an adequate procedure for perioperative pain management

Superior control of inflammatory pain by corticotropin-releasing factor receptor 1 via opioid peptides in distinct pain-relevant brain areas

Background: Under inflammatory conditions, the activation of corticotropin-releasing factor (CRF) receptor has been shown to inhibit pain through opioid peptide release from immune cells or neurons. CRF's effects on human and animal pain modulation depend, however, on the distribution of its receptor subtypes 1 and 2 (CRF-R1 and CRF-R2) along the neuraxis of pain transmission. The objective of this study is to investigate the respective role of each CRF receptor subtype on centrally administered CRF-induced antinociception during inflammatory pain. Methods: The present study investigated the role of intracerebroventricular (i.c.v.) CRF receptor agonists on nociception and the contribution of cerebral CRF-R1 and/or CRF-R2 subtypes in an animal model of Freund's complete adjuvant (FCA)-induced hind paw inflammation. Methods used included behavioral experiments, immunofluorescence confocal analysis, and reverse transcriptase-polymerase chain reaction. Results: Intracerebroventricular, but systemically inactive, doses of CRF elicited potent, dose-dependent antinociceptive effects in inflammatory pain which were significantly antagonized by i.c.v. CRF-R1-selective antagonist NBI 27914 (by approximately 60%) but less by CRF-R2-selective antagonist K41498 (by only 20%). In line with these findings, i.c.v. administration of CRF-R1 agonist stressin I produced superior control of inflammatory pain over CRF-R2 agonist urocortin-2. Intriguingly, i.c.v. opioid antagonist naloxone significantly reversed the CRF as well as CRF-R1 agonist-elicited pain inhibition. Consistent with existing evidence of high CRF concentrations in brain areas such as the thalamus, hypothalamus, locus coeruleus, and periaqueductal gray following its i.c.v. administration, double-immunofluorescence confocal microscopy demonstrated primarily CRF-R1-positive neurons that expressed opioid peptides in these pain-relevant brain areas. Finally, PCR analysis confirmed the predominant expression of the CRF-R1 over CRF-R2 in representative brain areas such as the hypothalamus. Conclusion: Taken together, these findings suggest that CRF-R1 in opioid-peptide-containing brain areas plays an important role in the modulation of inflammatory pain and may be a useful therapeutic target for inflammatory pain control

Identification of Mineralocorticoid Receptors, Aldosterone, and Its Processing Enzyme CYP11B2 on Parasympathetic and Sympathetic Neurons in Rat Intracardiac Ganglia

Recent interest has focused on the mineralocorticoid receptor (MR) and its impact on the myocardium and the performance of the heart. However, there is a lack of evidence about MR expression and its endogenous ligand aldosterone synthesis with specific regard to the intrinsic cardiac nervous system. Therefore, we looked for evidence of MR and aldosterone in sympathetic and parasympathetic neurons of intracardiac ganglia. Tissue samples from rat heart atria were subjected to conventional reverse-transcriptase polymerase chain reaction (PCR), Western blot, and double immunofluorescence confocal analysis of MR, corticosterone-inactivating enzyme 11β-hydroxysteroid-dehydrogenase-2 (11β-HSD2), aldosterone, and its processing enzyme CYP11B2 together with the neuronal markers vesicular acetylcholine transporter (VAChT) and tyrosine hydroxylase (TH). Our results demonstrated MR, 11β-HSD2, and CYP11B2 specific mRNA and protein bands in rat heart atria. Double immunofluorescence labeling revealed coexpression of MR immunoreactivity with VAChT in large diameter parasympathetic principal neurons. In addition, MR immunoreactivity was identified in TH-immunoreactive small intensely fluorescent (SIF) cells and in nearby VAChT- and TH-immunoreactive nerve terminals. Interestingly, the aldosterone and its synthesizing enzyme CYP11B2 and 11β-HSD2 colocalized in MR– immunoreactive neurons of intracardiac ganglia. Overall, this study provides first evidence for the existence of not only local expression of MR, but also of 11β-HSD2 and aldosterone with its processing enzyme CYP11B2 in the neurons of the cardiac autonomic nervous system, suggesting a possible modulatory role of the mineralocorticoid system on the endogenous neuronal activity on heart performance

Functional and Anatomical Characterization of Corticotropin-Releasing Factor Receptor Subtypes of the Rat Spinal Cord Involved in Somatic Pain Relief

Corticotropin-releasing factor (CRF) orchestrates our body's response to stressful stimuli. Pain is often stressful and counterbalanced by activation of CRF receptors along the nociceptive pathway, although the involvement of the CRF receptor subtypes 1 and/or 2 (CRF-R1 and CRF-R2, respectively) in CRF-induced analgesia remains controversial. Thus, the aim of the present study was to examine CRF-R1 and CRF-R2 expression within the spinal cord of rats with Freund's complete adjuvant-induced unilateral inflammation of the hind paw using reverse transcriptase polymerase chain reaction, Western blot, radioligand binding, and immunofluorescence confocal analysis. Moreover, the antinociceptive effects of intrathecal (i.t.) CRF were measured by paw pressure algesiometer and their possible antagonism by selective antagonists for CRF-R1 and/or CRF-R2 as well as for opioid receptors. Our results demonstrated a preference for the expression of CRF-R2 over CRF-R1 mRNA, protein, binding sites and immunoreactivity in the dorsal horn of the rat spinal cord. Consistently, CRF as well as CRF-R2 agonists elicited potent dose-dependent antinociceptive effects which were antagonized by the i.t. CRF-R2 selective antagonist K41498, but not by the CRF-R1 selective antagonist NBI35965. In addition, i.t. applied opioid antagonist naloxone dose-dependently abolished the i.t. CRF- as well as CRF-R2 agonist-elicited inhibition of somatic pain. Importantly, double immunofluorescence confocal microscopy of the spinal dorsal horn showed CRF-R2 on enkephalin (ENK)-containing inhibitory interneurons in close opposition of incoming mu-opioid receptor-immunoreactive nociceptive neurons. CRF-R2 was, however, not seen on pre- or on postsynaptic sensory neurons of the spinal cord. Taken together, these findings suggest that i.t. CRF or CRF-R2 agonists inhibit somatic inflammatory pain predominantly through CRF-R2 receptors located on spinal enkephalinergic inhibitory interneurons which finally results in endogenous opioid-mediated pain inhibition

Orthostatic Resiliency During Successive Hypoxic, Hypoxic Orthostatic Challenge: Successful vs. Unsuccessful Cardiovascular and Oxygenation Strategies

Introduction: Rapid environmental changes, such as successive hypoxic-hypoxic orthostatic challenges (SHHOC) occur in the aerospace environment, and the ability to remain orthostatically resilient (OR) relies upon orchestration of physiological counter-responses. Counter-responses adjusting for hypoxia may conflict with orthostatic responses, and a misorchestration can lead to orthostatic intolerance (OI). The goal of this study was to pinpoint specific cardiovascular and oxygenation factors associated with OR during a simulated SHHOC. Methods: Thirty one men underwent a simulated SHHOC consisting of baseline (P0), normobaric hypoxia (Fi02 = 12%, P1), and max 60 s of hypoxic lower body negative pressure (LBNP, P2). Alongside anthropometric variables, non-invasive cardiovascular, central and peripheral tissue oxygenation parameters, were recorded. OI was defined as hemodynamic collapse during SHHOC. Comparison of anthropometric, cardiovascular, and oxygenation parameters between OR and OI was performed via Student's t-test. Within groups, a repeated measures ANOVA test with Holm-Sidak post hoc test was performed. Performance diagnostics were performed to assess factors associated with OR/OI (sensitivity, specificity, positive predictive value PPV, and odd's ratio OR). Results: Only 9/31 were OR, and 22/31 were OI. OR had significantly greater body mass index (BMI), weight, peripheral Sp02, longer R-R Interval (RRI) and lower heart rate (HR) at P0. During P1 OR exhibited significantly higher cardiac index (CI), stroke volume index (SVI), and lower systemic vascular resistance index (SVRI) than OI. Both groups exhibited a significant decrease in cerebral oxygenation (TOIc) with an increase in cerebral deoxygenated hemoglobin (dHbc), while the OI group showed a significant decrease in cerebral oxygenated hemoglobin (02Hbc) and peripheral oxygenation (TOIp) with an increase in peripheral deoxygenated hemoglobin (dHbp). During P2, OR maintained significantly greater CI, systolic, mean, and diastolic pressure (SAP, MAP, DAP), with a shortened RRI compared to the OI group, while central and peripheral oxygenation were not different. Body weight and BMI both showed high sensitivity (0.95), low specificity (0.33), a PPV of 0.78, with an OR of 0.92, and 0.61. P0 RRI showed a sensitivity of 0.95, specificity of 0.22, PPV 0.75, and OR of 0.99. Delta SVI had the highest performance diagnostics during P1 (sensitivity 0.91, specificity 0.44, PPV 0.79, and OR 0.8). Delta SAP had the highest overall performance diagnostics for P2 (sensitivity 0.95, specificity 0.67, PPV 0.87, and OR 0.9). Discussion: Maintaining OR during SHHOC is reliant upon greater BMI, body weight, longer RRI, and lower HR at baseline, while increasing CI and SVI, minimizing peripheral 02 utilization and decreasing SVRI during hypoxia. During hypoxic LBNP, the ability to remain OR is dependent upon maintaining SAP, via CI increases rather than SVRI. Cerebral oxygenation parameters, beyond 02Hbc during P1 did not differ between groups, suggesting that the during acute hypoxia, an increase in cerebral 02 consumption, coupled with increased peripheral 02 utilization does seem to play a role in OI risk during SHHOC. However, cardiovascular factors such as SVI are of more value in assessing OR/OI risk. The results can be used to implement effective aerospace crew physiological monitoring strategies

Comparison of the non-invasive Nexfin® monitor with conventional methods for the measurement of arterial blood pressure in moderate risk orthopaedic surgery patients

Objective Continuous invasive arterial blood pressure (IBP) monitoring remains the gold standard for BP measurement, but traditional oscillometric non- invasive intermittent pressure (NIBP) measurement is used in most low-to- moderate risk procedures. This study compared non-invasive continuous arterial BP measurement using a Nexfin® monitor with NIBP and IBP monitors. Methods This was a single-centre, prospective, pilot study in patients scheduled for elective orthopaedic surgery. Systolic BP, diastolic BP and mean arterial blood pressure (MAP) were measured by Nexfin®, IBP and NIBP at five intraoperative time-points. Pearson correlation coefficients, Bland–Altman plots and trending ability of Nexfin® measurements were used as criteria for success in the investigation of measurement reliability. Results A total of 20 patients were enrolled in the study. For MAP, there was a sufficient correlation between IBP/Nexfin® (Pearson = 0.75), which was better than the correlation between IBP/NIBP (Pearson = 0.70). Bland–Altman analysis of the data showed that compared with IBP, there was a higher percentage error for MAPNIBP (30%) compared with MAPNexfin® (27%). Nexfin® and NIBP underestimated systolic BP; NIBP also underestimated diastolic BP and MAP. Trending ability for MAPNexfin® and MAPNIBP were comparable to IBP. Conclusion Non-invasive BP measurement with Nexfin® was comparable with IBP and tended to be more precise than NIBP

a retrospective analysis

Background Several animal studies suggest beneficial effects on kidney function upon administration of levosimendan. As recent data from clinical studies are heterogeneous, we sought to investigate whether levosimendan is associated with improved postoperative kidney function in cardiac surgery patients with respect to timing of its administration. Methods Retrospective, single centre, observational analysis at a university hospital in Berlin, Germany. All adult patients without preoperative renal dysfunction that underwent coronary artery bypass grafting and/or valve reconstruction/replacement between 01/01/2007 and 31/12/2011 were considered for analyses. Results Out of 1.095 included patients, 46 patients were treated with levosimendan due to a severely reduced left ventricular systolic function preoperatively (LVEF < 35%) and/or clinical signs of a low cardiac output syndrome. Sixty-one percent received the drug whilst in the OR, 39% after postoperative intensive care unit admission. When levosimendan was given immediately after anaesthesia induction, creatinine plasma levels (p = 0.009 for nonparametric analysis of longitudinal data in a two-factorial design) and incidence of postoperative renal dysfunction (67.9% vs. 94.4%; p = 0.033) were significantly reduced in contrast to a later start of treatment. In addition, duration of renal replacement therapy was significantly shorter (79 [35;332] vs. 272 [132;703] minutes; p = 0.046) in that group. Conclusions Postoperative kidney dysfunction is a common condition in patients under going cardiac surgery. Patients with severely reduced left ventricular function and/or clinical signs of a low cardiac output syndrome who preoperatively presented with a normal kidney function may benefit from an early start of levosimendan administration, i.e. immediately after anaesthesia

Intraoperative Beat-to-Beat Pulse Transit Time (PTT) Monitoring via Non-Invasive Piezoelectric/Piezocapacitive Peripheral Sensors Can Predict Changes in Invasively Acquired Blood Pressure in High-Risk Surgical Patients

Background: Non-invasive tracking of beat-to-beat pulse transit time (PTT) via piezoelectric/piezocapacitive sensors (PES/PCS) may expand perioperative hemodynamic monitoring. This study evaluated the ability for PTT via PES/PCS to correlate with systolic, diastolic, and mean invasive blood pressure (SBPIBP, DBPIBP, and MAPIBP, respectively) and to detect SBPIBP fluctuations. Methods: PES/PCS and IBP measurements were performed in 20 patients undergoing abdominal, urological, and cardiac surgery. A Pearson’s correlation analysis (r) between 1/PTT and IBP was performed. The predictive ability of 1/PTT with changes in SBPIBP was determined by area under the curve (reported as AUC, sensitivity, specificity). Results: Significant correlations between 1/PTT and SBPIBP were found for PES (r = 0.64) and PCS (r = 0.55) (p < 0.01), as well as MAPIBP/DBPIBP for PES (r = 0.6/0.55) and PCS (r = 0.5/0.45) (p < 0.05). A 7% decrease in 1/PTTPES predicted a 30% SBPIBP decrease (0.82, 0.76, 0.76), while a 5.6% increase predicted a 30% SBPIBP increase (0.75, 0.7, 0.68). A 6.6% decrease in 1/PTTPCS detected a 30% SBPIBP decrease (0.81, 0.72, 0.8), while a 4.8% 1/PTTPCS increase detected a 30% SBPIBP increase (0.73, 0.64, 0.68). Conclusions: Non-invasive beat-to-beat PTT via PES/PCS demonstrated significant correlations with IBP and detected significant changes in SBPIBP. Thus, PES/PCS as a novel sensor technology may augment intraoperative hemodynamic monitoring during major surgery.German Government sponsored ZIM (Zentrales Innovationsprogramm Mittelstand) programPeer Reviewe

Pleural effusions are associated with adverse outcomes after cardiac surgery: a propensity-matched analysis

Background: Pleural effusions commonly occur in patients recovering from cardiac surgery; however, the impact on outcomes is not well characterized. The purpose of this study is to characterize the clinical outcomes of cardiac surgery patients with pleural effusion. Methods: All patients undergoing cardiac surgery between 2006 and 2019 at a tertiary care university hospital were included in this observational, cross-sectional analysis using propensity matching. Results: Of 11,037 patients that underwent cardiac surgery during the study period, 6461 (58.5%) had no pleural effusion (Group 0), 3322 (30.1%) had pleural effusion only (Group 1), and 1254 (11.4%) required at least one secondary drainage procedure after the index operation (Group 2). After propensity matching, the mortality of patients who underwent secondary drainage procedures was 6.1% higher than in Group 1 (p < 0.001). Intensive care unit (ICU) stay was longer for those with pleural effusions (18 [IQR 9-32] days in Group 2, 10 [IQR 6-17] days for Group 1, and 7 [IQR 4-11] days for Group 0, p < 0.001). Patients with pleural effusions had a higher incidence of hemodialysis (246 [20.0%] in Group 2, 137 [11.1%] in Group 1, 98 [7.98%] in Group 0), and a longer ventilation time in the ICU (57 [IQR 21.0-224.0] hours in Group 2, 25.0 [IQR 14.0-58.0] hours in Group 1, 16.0 [IQR 10.0-29.0] hours in Group 0). Conclusion: Pleural effusions, especially those that require a secondary drainage procedure during recovery, are associated with significantly worse outcomes including increased mortality, longer length of stay, and higher complication rates. These insights may be of great interest to scientists, clinicians, and industry leaders alike to foster research into innovative methods for preventing and treating pleural effusions with the aim of improving outcomes for patients recovering from cardiac surgery

Routine frailty assessment predicts postoperative complications in elderly patients across surgical disciplines – a retrospective observational study

BACKGROUND: Frailty is a frequent and underdiagnosed functional syndrome involving reduced physiological reserves and an increased vulnerability against stressors, with severe individual and socioeconomic consequences. A routine frailty assessment was implemented at our preoperative anaesthesia clinic to identify patients at risk. OBJECTIVE: This study examines the relationship between frailty status and the incidence of in-hospital postoperative complications in elderly surgical patients across several surgical disciplines. DESIGN: Retrospective observational analysis. SETTING: Single center, major tertiary care university hospital. Data collection took place between June 2016 and March 2017. PATIENTS: Patients 65 years old or older were evaluated for frailty using Fried's 5-point frailty assessment prior to elective non-cardiac surgery. Patients were classified into non-frail (0 criteria, reference group), pre-frail (1-2 positive criteria) and frail (3-5 positive criteria) groups. MAIN OUTCOME MEASURES: The incidence of postoperative complications was assessed until discharge from the hospital, using the roster from the National VA Surgical Quality Improvement Program. Propensity score matching and logistic regression analysis were performed. RESULTS: From 1186 elderly patients, 46.9% were classified as pre-frail (n = 556), and 11.4% as frail (n = 135). The rate of complications were significantly higher in the pre-frail (34.7%) and frail groups (47.4%), as compared to the non-frail group (27.5%). Similarly, length of stay (non-frail: 5.0 [3.0;7.0], pre-frail: 7.0 [3.0;9.0], frail 8.0 [4.5;12.0]; p < 0.001) and discharges to care facilities (non-frail:1.6%, pre-frail: 7.4%, frail: 17.8%); p < 0.001) were significantly associated with frailty status. After propensity score matching and logistic regression analysis, the risk for developing postoperative complications was approximately two-fold for pre-frail (OR 1.78; 95% CI 1.04-3.05) and frail (OR 2.08; 95% CI 1.21-3.60) patients. CONCLUSIONS: The preoperative frailty assessment of elderly patients identified pre-frail and frail subgroups to have the highest rate of postoperative complications, regardless of age, surgical discipline, and surgical risk. Significantly increased length of hospitalisation and discharges to care facilities were also observed. Implementation of routine frailty assessments appear to be an effective tool in identifying patients with increased risk. Now future studies are needed to investigate whether patients benefit from optimization of patient counselling, process planning, and risk reduction protocols based on the application of risk stratification