Methylprednisolone Does Not Enhance Paraoxonase 1 Activity During Cardiopulmonary Bypass Surgery-A Randomized, Controlled Clinical Trial.

OBJECTIVES: Cardiopulmonary bypass (CPB) is linked to systemic inflammatory responses and oxidative stress. Paraoxonase 1 (PON1) is an antioxidant enzyme with a cardioprotective role whose activity is decreased in systemic inflammation and in patients with acute myocardial and global ischemia. Glucocorticoids counteract the effect of oxidative stress by upregulating PON1 gene expression. The authors aimed to determine the effect of methylprednisolone on PON1 activity during cardiac surgery on CPB. DESIGN: Prospective, randomized, controlled clinical trial. SETTING: The University Medical Center Ljubljana, Slovenia. PARTICIPANTS: Forty adult patients who underwent complex cardiac surgery on CPB between February 2016 and December 2017 were randomized into methylprednisolone and control groups (n = 20 each). INTERVENTIONS: Patients in the methylprednisolone group received 1 g of methylprednisolone in the CPB priming solution, whereas patients in the control group were not given methylprednisolone during CPB. MEASUREMENTS AND MAIN RESULTS: The effect of methylprednisolone from the CPB priming solution was compared with standard care during CPB on PON1 activity until postoperative day 5. Correlations of PON1 activity with lipid status, mediators of inflammation, and hemodynamics were analyzed also. No significant differences were found between study groups for PON1 activity, high-density lipoprotein, and low-density lipoprotein in any of the measurement intervals (p > 0.016). The methylprednisolone group had significantly lower tumor necrosis factor alpha (p < 0.001) and interleukin-6 (p < 0.001), as well as C-reactive protein and procalcitonin (p < 0.016) after surgery. No significant difference was found between groups for hemodynamic parameters. A positive correlation existed between PON1 and lipid status, whereas a negative correlation was found between PON1 activity and tumor necrosis factor alpha, interleukin-6, and CPB duration. CONCLUSIONS: Methylprednisolone does not influence PON1 activity during cardiac surgery on CPB.

Erector spinae plane block versus intercostal nerve block for postoperative analgesia in lung cancer surgery.

BACKGROUND: A recent trend in postoperative analgesia for lung cancer surgery relies on regional nerve blocks with decreased opioid administration. Our study aims to critically assess the continuous ultrasound-guided erector spinae plane block (ESPB) at our institution and compare it to a standard regional anesthetic technique, the intercostal nerve block (ICNB). PATIENTS AND METHODS: A prospective randomized-control study was performed to compare outcomes of patients, scheduled for video-assisted thoracoscopic (VATS) lung cancer resection, allocated to the ESPB or ICNB group. Primary outcomes were total opioid consumption and subjective pain scores at rest and cough each hour in 48 h after surgery. The secondary outcome was respiratory muscle strength, measured by maximal inspiratory and expiratory pressures (MIP/MEP) after 24 h and 48 h. RESULTS: 60 patients met the inclusion criteria, half ESPB. Total opioid consumption in the first 48 h was 21. 64 ± 14.22 mg in the ESPB group and 38.34 ± 29.91 mg in the ICNB group (p = 0.035). The patients in the ESPB group had lower numerical rating scores at rest than in the ICNB group (1.19 ± 0.73 vs. 1.77 ± 1.01, p = 0.039). There were no significant differences in MIP/MEP decrease from baseline after 24 h (MIP p = 0.088, MEP p = 0.182) or 48 h (MIP p = 0.110, MEP p = 0.645), time to chest tube removal or hospital discharge between the two groups. CONCLUSIONS: In the first 48 h after surgery, patients with continuous ESPB required fewer opioids and reported less pain than patients with ICNB. There were no differences regarding respiratory muscle strength, postoperative complications, and time to hospital discharge. In addition, continuous ESPB demanded more surveillance than ICNB.

Endothelial Dysfunction in Patients Undergoing Cardiac Surgery: A Narrative Review and Clinical Implications.

Cardiac surgery is one of the highest-risk procedures, usually involving cardiopulmonary bypass and commonly inducing endothelial injury that contributes to the development of perioperative and postoperative organ dysfunction. Substantial scientific efforts are being made to unravel the complex interaction of biomolecules involved in endothelial dysfunction to find new therapeutic targets and biomarkers and to develop therapeutic strategies to protect and restore the endothelium. This review highlights the current state-of-the-art knowledge on the structure and function of the endothelial glycocalyx and mechanisms of endothelial glycocalyx shedding in cardiac surgery. Particular emphasis is placed on potential strategies to protect and restore the endothelial glycocalyx in cardiac surgery. In addition, we have summarized and elaborated the latest evidence on conventional and potential biomarkers of endothelial dysfunction to provide a comprehensive synthesis of crucial mechanisms of endothelial dysfunction in patients undergoing cardiac surgery, and to highlight their clinical implications.

Comparison of Procedural Sedation With Propofol and Dexmedetomidine During Transcatheter Aortic Valve Replacement Using the Transfemoral Approach.

OBJECTIVES: Although procedural sedation is an established method of anesthesia for transcatheter aortic valve replacement (TAVR), reliable evidence to guide the choice of a suitable sedative agent remains scarce. Accordingly, this trial aimed to compare the effect of procedural sedation with dexmedetomidine versus propofol on postoperative neurocognitive and related clinical outcomes in patients undergoing TAVR. DESIGN: Prospective, randomized, double-blind clinical trial. SETTING: The study was conducted at the University Medical Centre Ljubljana, Slovenia. PARTICIPANTS: The study enrolled 78 patients who underwent TAVR under procedural sedation between January 2019 and June 2021. Seventy-one patients randomized into the propofol group (n = 34) and dexmedetomidine group (n = 37) were included in the final analysis. INTERVENTIONS: Patients in the propofol group received sedation with propofol (continuous intravenous infusion of 0.5-2.5 mg/kg/h), whereas patients in the dexmedetomidine group received sedation with dexmedetomidine (loading dose of 0.5 µg/kg over 10 minutes followed by continuous intravenous infusion of 0.2-1.0 µg/kg/h). MEASUREMENTS AND MAIN RESULTS: Minimental state examination (MMSE) was performed before and 48 hours after TAVR. There was no statistically significant difference in MMSE scores between groups before TAVR (p = 0.253), but the MMSE after the procedure revealed a significantly lower incidence of delayed neurocognitive recovery (p = 0.005) and thus better cognitive outcomes in the dexmedetomidine group (p = 0.022). CONCLUSIONS: Compared with propofol, procedural sedation with dexmedetomidine in TAVR was associated with a significantly lower incidence of delayed neurocognitive recovery.

PROCALCITONIN GUIDED ANTIBIOTIC STEWARDSHIP: A BALKAN EXPERT CONSENSUS STATEMENT.

Sepsis as a consequence of infection is a frequent cause of death among critically ill patients. The most common sites of infection are lover respiratory tract, abdominal, urinary tract and catheter-associated blood stream infections. Early empiric, broad-spectrum therapy in those with severe sepsis and/or shock with the aim of reducing mortality may lead to antibiotic overuse, resistance and increased costs. Among numerous serum biomarkers, procalcitonin (PCT) has proved to be one of the most reliable ones in the diagnosis of sepsis. An important means of limiting antibiotic resistance is the antibiotic stewardship program, especially in intensive care units with critically ill patients and prevalence of multiple drug-resistant pathogens. The PCT-guided antibiotic stewardship was first started in Western Europe and Asia-Pacific countries, as well as in the United States. Considering that this method has proven to be effective in reducing antibiotic consumption while improving clinical outcome, a group of experts from the Balkan region decided to make their own recommendations and PCT protocol. When creating this protocol for initiation and duration of antibiotic treatment, they especially reviewed the literature for lower respiratory tract infection and sepsis. In the protocol, they have included the severity of illness, clinical assessment, and PCT levels. Developing a consensus on the clinical algorithm by eminent experts/specialists in various fields of medicine should enable clinicians to use PCT for initiation of antibiotic therapy and monitoring PCT to stop antibiotics earlier. It is crucial that the PCT-guided algorithm becomes an integral part of institutional stewardship program.

PERIOPERATIVE PREPARATION OF CARDIAC PATIENTS IN REGIONAL ANESTHESIA.

Preoperative cardiovascular management is an essential component of overall perioperative cardiovascular care. It involves preoperative detection and management of cardiovascular disease and prediction of both short-term and long-term cardiovascular risk. It affects anesthetic perioperative management and surgical decision making. This requires individualized management. Careful preoperative preparation at least a week before surgery, rational decisions regarding necessary tests and examinations, good cooperation with the cardiologist and surgeon and careful planning of early postoperative treatment are key for better outcome after surgery and reduction of postoperative complications.

Relationship Between Quality of Life Indicators and Cardiac Status Indicators in Chemotherapy Patients.

AIM: With the aim of improving personalized treatment of patients on chemotherapy, the objective of the study was to assess the degree of association between selected Quality of life (QoL) indicators and both clinical and imaging cardiac status indicators when detecting deterioration in QoL of these patients. METHODS: In a cohort clinical study in Hamburg, from August 2017 through October 2020, 59 cancer patients, aged 18-80 years, were evaluated before chemotherapy, and at several follow-ups, using EQ-5D and SF-36 QoL questionnaires, fast strain-encoded (fast-SENC) cardiac magnetic resonance (CMR), conventional CMR, and echocardiography, and further received a clinical and biomarker examination. Data was analyzed using survival analyses. A decline of more than 5% in each observed QoL metric value was defined as the observed event. Patient were separated into groups according to the presentation of cardiotoxicity as per its clinical definition, the establishment of the indication for cardioprotective therapy initiation, and by a worsening in the value of each observed imaging metric by more than 5% in the previous follow-up compared to the corresponding pre-chemotherapy baseline value. RESULTS: Among clinical cardiac status indicators, the indication for cardioprotective therapy showed statistically good association with QoL scores (EQ-5D p=0.028; SF-36 physical component p=0.016; SF-36 mental component p=0.012). In terms of imaging metrics, the MyoHealth segmental myocardial strain score was the only one demonstrating consistently good QoL score association (EQ-5D p=0.005; SF-36 physical component p=0.056; SF-36 mental component p=0.002). CONCLUSIONS: Established fast-SENC CMR scores are capable of highlighting patients with reduced QoL, who require more frequent/optimal management.

Cardiac Melanoma Metastasis with ERBB2 Gene Amplification: A Potential for Future Targeted Therapy.

Cardiac tumors are rare, and their treatment differs interindividually regarding the histopathological proprieties and the stage of disease. Authors present a case of symptomatic cardiac melanoma metastasis that expressed an ERBB2 (HER2) gene amplification in a course of the disease that has not yet been reported. The frail patient with a history of pulmonary and renal carcinoma, was admitted to the hospital due to a symptomatic left atrial tumor mass. The patient underwent a tumor-resecting cardiac surgery. At first mistaken for myxoma on echocardiography, the histopathological examination of the tumor revealed a melanoma of acral or mucosal origin. The melanoma metastasis was negative for common genetic mutations in BRAF, NRAS or KIT genes, and for the presence of NTRK genes fusions, but carried ERBB2 (HER2) gene amplification. The absence of standard gene mutations rendered it unresponsive to treatment with BRAF and MEK inhibitors. This molecular finding is rare in melanomas and represented a therapeutic target for off-label systemic treatment with drugs, primarily aimed at ERBB2 positive breast, gastric, and gastroesophageal junction cancers. A rare finding like this justifies molecular genetic analysis of unusual tumor specimen and guarantees optimal treatment for uncommon types of cardiac metastatic tumors.

Cerebral microemboli in mini-sternotomy compared to mini- thoracotomy for aortic valve replacement: a cross sectional cohort study.

BACKGROUND: Recently adopted mini-thoracotomy approach for surgical aortic valve replacement has shown benefits such as reduced pain and shorter recovery, compared to more conventional mini-sternotomy access. However, whether limited exposure of the heart and ascending aorta resulting from an incision in the second intercostal space may lead to increased intraoperative cerebral embolization and more prominent postoperative neurologic decline, remains inconclusive. The aim of our study was to assess potential neurological complications after two different minimal invasive surgical techniques for aortic valve replacement by measuring cerebral microembolic signal during surgery and by follow-up cognitive evaluation. METHODS: Trans-cranial Doppler was used for microembolic signal detection during aortic valve replacement performed via mini-sternotomy and mini-thoracotomy. Patients were evaluated using Addenbrooke's Cognitive Examination Revised Test before and 30 days after surgical procedure. RESULTS: A total of 60 patients were recruited in the study. In 52 patients, transcranial Doppler was feasible. Of those, 25 underwent mini-sternotomy and 27 had mini-thoracotomy. There were no differences between groups with respect to sex, NYHA class distribution, Euroscore II or aortic valve area. Patients in mini-sternotomy group were younger (60.8 ± 14.4 vs.72 ± 5.84, p = 0.003), heavier (85.2 ± 12.4 vs.72.5 ± 12.9, p = 0.002) and had higher body surface area (1.98 ± 0.167 vs. 1.83 ± 0.178, p = 0.006). Surgery duration was longer in mini-sternotomy group compared to mini-thoracotomy (158 ± 24 vs. 134 ± 30 min, p < 0.001, respectively). There were no differences between groups in microembolic load, length of ICU or total hospital stay. Total microembolic signals count was correlated with cardiopulmonary bypass duration (5.64, 95%CI 0.677-10.60, p = 0.027). Addenbrooke's Cognitive Examination Revised Test score decreased equivalently in both groups (p = 0.630) (MS: 85.2 ± 9.6 vs. 82.9 ± 11.4, p = 0.012; MT: 85.2 ± 9.6 vs. 81.3 ± 8.8, p = 0.001). CONCLUSION: There is no difference in microembolic load between the groups. Total intraoperative microembolic signals count was associated with cardiopulmonary bypass duration. Age, but not micorembolic signals load, was associated with postoperative neurologic decline. TRIAL REGISTRY NUMBER: clinicaltrials.gov , NCT02697786 14.

Effectiveness of wound infusion of 0.2% ropivacaine by patient control analgesia pump after minithoracotomy aortic valve replacement: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Local anesthetic wound infusion has become an invaluable technique in multimodal analgesia. The effectiveness of wound infusion of 0.2% ropivacaine delivered by patient controlled analgesia (PCA) pump has not been evaluated in minimally invasive cardiac surgery. We tested the hypothesis that 0.2% ropivacaine wound infusion by PCA pump reduces the cumulative dose of opioid needed in the first 48 h after minithoracothomy aortic valve replacement (AVR). METHODS: In this prospective, randomized, double-blind, placebo-controlled study, 70 adult patients (31 female and 39 male) were analyzed. Patients were randomized to receive 0.2% ropivacaine or 0.9% saline wound infusion by PCA pump for 48 h postoperatively. PCA pump was programmed at 5 ml h- 1 continuously and 5 ml of bolus with 60 min lockout. Pain levels were assessed and recorded hourly by Numeric Rating Scale (NRS). If NRS score was higher than three the patient was administered 3 mg of opioid piritramide repeated and titrated as needed until pain relief was achieved. The primary outcome was the cumulative dose of the opioid piritramide in the first 48 h after surgery. Secondary outcomes were frequency of NRS scores higher than three, patient's satisfaction with pain relief, hospital length of stay, side effects related to the local anesthetic and complications related to the wound catheter. RESULTS: The cumulative dose of the opioid piritramide in the first 48 h after minithoracotomy AVR was significantly lower (p < 0.001) in the ropivacaine (R) group median 3 mg (IQR 6 mg) vs. 9 mg (IQR 9 mg). The number of episodes of pain where NRS score was greater than three median 2 (IQR 2), vs 3 (IQR 3), (p = 0.002) in the first 48 h after surgery were significantly lower in the ropivacaine group, compared to control. Patient satisfaction with pain relief in our study was high. There were no wound infections and no side-effects from the local anesthetic. CONCLUSIONS: Wound infusion of local anesthetic by PCA pump significantly reduced opioid dose needed and improves pain control postoperatively. We have also shown that it is a feasible method of analgesia and it should be considered in the multimodal pain control strategy following minimally invasive cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT03079830 , date of registration: March 15, 2017. Retrospecitvely registered.

Extracorporeal Hemadsorption versus Glucocorticoids during Cardiopulmonary Bypass: A Prospective, Randomized, Controlled Trial.

Extracorporeal hemadsorption may reduce inflammatory reaction in cardiopulmonary bypass (CPB) surgery. Glucocorticoids have been used during open-heart surgery for alleviation of systemic inflammation after CPB. We compared intraoperative hemadsorption and methylprednisolone, with usual care, during complex cardiac surgery on CPB, for inflammatory responses, hemodynamics, and perioperative course. Seventy-six patients with prolonged CPB were recruited and randomized, with 60 included in final analysis. Allocation was into three groups: Methylprednisolone (n = 20), Cytosorb (n = 20), and Control group (usual care, n = 20). Proinflammatory (TNF-α, IL-1ß, IL-6, and IL-8) and anti-inflammatory (IL-10) cytokines which complement C5a, CD64, and CD163 expression by immune cells were analyzed within the first five postoperative days, in addition to hemodynamic and clinical outcome parameters. Methylprednisolone group, compared to Cytosorb and Control had significantly lower levels of TNF-α (until the end of surgery, p < 0.001), IL-6 (until 48 h after surgery, p < 0.001), and IL-8 (until 24 h after surgery, p < 0.016). CD64 expression on monocytes was the highest in the Cytosorb group and lasted until the 5th postoperative day (p < 0.016). IL-10 concentration (until the end of surgery) and CD163 expression on monocytes (until 48 h after surgery) were the highest in the Methylprednisolone group (p < 0.016, for all measurements between three groups). No differences between groups in the cardiac index or clinical outcome parameters were found. Methylprednisolone more effectively ameliorates inflammatory responses after CPB surgery compared to hemadsorption and usual care. Hemadsorption compared with usual care causes higher prolonged expression of CD64 on monocytes but short lasting expression of CD163 on granulocytes. Hemadsorption with CytoSorb® was safe and well tolerated. This trial is registered with clinicaltrials.gov (NCT02666703).

Dopamine Autoxidation Is Controlled by Acidic pH.

We studied the reaction mechanism of dopamine autoxidation using quantum chemical methods. Unlike other biogenic amines important in the central nervous system, dopamine and noradrenaline are capable of undergoing a non-enzymatic autoxidative reaction giving rise to a superoxide anion that further decomposes to reactive oxygen species. The reaction in question, which takes place in an aqueous solution, is as such not limited to the mitochondrial membrane where scavenging enzymes such as catalase and superoxide dismutase are located. With the experimental rate constant of 0.147 s-1, the dopamine autoxidation reaction is comparably as fast as the monoamine oxidase B catalyzed dopamine decomposition with a rate constant of 1 s-1. By using quantum chemical calculations, we demonstrated that the rate-limiting step is the formation of a hydroxide ion from a water molecule, which attacks the amino group that enters intramolecular Michael addition, giving rise to a pharmacologically inert aminochrome. We have shown that for dopamine stability on a time scale of days, it is essential that the pH value of the synaptic vesicle interior is acidic. The pathophysiologic correlates of the results are discussed in the context of Parkinson's disease as well as the pathology caused by long-term amphetamine and cocaine administration.

The Role of Levosimendan in Patients with Decreased Left Ventricular Function Undergoing Cardiac Surgery.

The postoperative low cardiac output is one of the most important complications following cardiac surgery and is associated with increased morbidity and mortality. The condition requires inotropic support to achieve adequate hemodynamic status and tissue perfusion. While catecholamines are utilised as a standard therapy in cardiac surgery, their use is limited due to increased oxygen consumption. Levosimendan is calcium sensitising inodilatator expressing positive inotropic effect by binding with cardiac troponin C without increasing oxygen demand. Furthermore, the drug opens potassium ATP (KATP) channels in cardiac mitochondria and in the vascular muscle cells, showing cardioprotective and vasodilator properties, respectively. In the past decade, levosimendan demonstrated promising results in treating patients with reduced left ventricular function when administered in peri- or post- operative settings. In addition, pre-operative use of levosimendan in patients with severely reduced left ventricular ejection fraction may reduce the requirements for postoperative inotropic support, mechanical support, duration of intensive care unit stay as well as hospital stay and a decrease in post-operative mortality. However, larger studies are needed to clarify clinical advantages of levosimendan versus conventional inotropes.

Dexamethasone does not diminish sugammadex reversal of neuromuscular block - clinical study in surgical patients undergoing general anesthesia.

BACKGROUND: Sugammadex reverses neuromuscular block (NMB) through binding aminosteroid neuromuscular blocking agents. Although sugammadex appears to be highly selective, it can interact with other drugs, like corticosteroids. A prospective single-blinded randomized clinical trial was designed to explore the significance of interactions between dexamethasone and sugammadex. METHODS: Sixty-five patients who were anesthetized for elective abdominal or urological surgery were included. NMB was assessed using train-of-four stimulation (TOF), with rocuronium used to maintain the desired NMB depth. NMB reversal at the end of anaesthesia was achieved using sugammadex. According to their received antiemetics, the patients were randomized to either the granisetron or dexamethasone group. Blood samples were taken before and after NMB reversal, for plasma dexamethasone and rocuronium determination. Primary endpoint was time from sugammadex administration to NMB reversal. Secondary endpoints included the ratios of the dexamethasone and rocuronium concentrations after NMB reversal versus before sugammadex administration. RESULTS: There were no differences for time to NMB reversal between the control (mean 121 ± 61 s) and the dexamethasone group (mean 125 ± 57 s; P = 0.760). Time to NMB reversal to a TOF ratio ≥0.9 was significantly longer in patients with lower TOF prior to sugammadex administration (Beta = -0.268; P = 0.038). The ratio between the rocuronium concentrations after NMB reversal versus before sugammadex administration was significantly affected by sugammadex dose (Beta = -0.375; P = 0.004), as was rocuronium dose per hour of operation (Beta = -0.366; p = 0.007), while it was not affected by NMB depth before administration of sugammadex (Beta = -0.089; p = 0.483) and dexamethasone (Beta = -0.186; p = 0.131). There was significant drop in plasma dexamethasone after sugammadex administration and NMB reversal (p < 0.001). CONCLUSIONS: Administration of dexamethasone to anesthetized patients did not delay NMB reversal by sugammadex. TRIAL REGISTRATION: The trial was retrospectively registered with The Australian New Zealand Clinical Trials Registry (ANZCTR) on February 28th 2012 (enrollment of the first patient on February 2nd 2012) and was given a trial ID number ACTRN12612000245897 and universal trial number U1111-1128-5104.

The response of aminopeptidases of Phaseolus vulgaris to drought depends on the developmental stage of the leaves.

Aminopeptidases, together with other proteases, execute and regulate the total and specifically limited protein breakdown involved in plant physiology, raising the possibility of their involvement in response to drought. We have identified, in leaves of Phaseolus vulgaris L., five aminopeptidases (E.C.3.4.11) whose levels of activity changed when three week old plants were subjected to drought. First, second and third trifoliate leaves were investigated separately. The aminopeptidases were first identified then isolated using ion exchange chromatography of leaf extracts. Three, named PvAP1, PvAP2 and PvAP4, are metallo aminopeptidases with broad substrate specificity, active against substrates conjugated to alanine and lysine. Two others, PvAP3 and PvAP5, are apparently serine aminopeptidases, the former active against substrates conjugated to phenylalanine and leucine, and the latter characterised by narrow specificity against substrates conjugated to phenylalanine. Their apparent molecular weights range from ∼37 kDa to ∼80 kDa. Levels of activity of individual aminopeptidases in both watered and drought stressed plants are shown to depend on the age of leaves. In watered plants they were generally highest in young, and very low in older, trifoliate leaves, the latter with the exception of PvAP5. Drought initiated an almost general increase of their activities, although to different extents, with the exception of PvAP4 and PvAP5 in young trifoliate leaves. Thus, in such studies it is necessary to investigate the effects of drought separately in leaves of different ages in order to elucidate the different complex and probably specific roles of aminopeptidases in the response of common bean to drought.

USE OF RECOMBINANT ACTIVATED FACTOR VIIa IN A-SIX-MONTH-OLD CHILD DUE TO MASSIVE HEMORRHAGE DURING ELECTIVE SURGERY FOR CHOROID PLEXUS CARCINOMA: CASE REPORT.

We present the use of recombinant activated factor VIIa (rFVIIa) in a 6-month-old infant that suffered massive bleeding and subsequent coagulation disturbances during elective surgery for choroid plexus carcinoma in the lateral ventricle. The administration of rFVIIa resulted in good hemostasis. No intra- or postoperative thromboembolic complications were observed.

Dexamethasone produces dose-dependent inhibition of sugammadex reversal in in vitro innervated primary human muscle cells.

BACKGROUND: Corticosteroids are frequently used during anesthesia to provide substitution therapy in patients with adrenal insufficiency, as a first-line treatment of several life-threatening conditions, to prevent postoperative nausea and vomiting, and as a component of multimodal analgesia. For these last 2 indications, dexamethasone is most frequently used. Due to the structural resemblance between aminosteroid muscle relaxants and dexamethasone, concerns have been raised about possible corticosteroid inhibition in the reversal of neuromuscular block by sugammadex. We thus investigated the influence of dexamethasone on sugammadex reversal of rocuronium-induced neuromuscular block, which could be relevant in certain clinical situations. METHODS: The unique co-culture model of human muscle cells innervated in vitro with rat embryonic spinal cord explants to form functional neuromuscular junctions was first used to explore the effects of 4 and 10 µM rocuronium on muscle contractions, as quantitatively evaluated by counting contraction units in contraction-positive explant co-cultures. Next, equimolar and 3-fold equimolar sugammadex was used to investigate the recovery of contractions from 4 and 10 µM rocuronium block. Finally, 1, 100, and 10 µM dexamethasone (normal, elevated, and high clinical levels) were used to evaluate any effects on the reversal of rocuronium-induced neuromuscular block by sugammadex. RESULTS: Seventy-eight explant co-cultures from 3 time-independent experiments were included, where the number of contractions increased to 10 days of co-culturing. Rocuronium showed a time-dependent effect on depth of neuromuscular block (4 µM rocuronium: baseline, 10, 20 minutes administration; P < 0.0001), while the dose-dependent effect was close to nominal statistical significance (4, 10 µM; P = 0.080). This was reversed by equimolar concentrations of sugammadex, with further and virtually complete recovery of contractions with 3-fold equimolar sugammadex (P < 0.0001). Dexamethasone diminished 10 µM sugammadex-induced recovery of contractions from rocuronium-induced neuromuscular block in a dose-dependent manner (P = 0.026) with a higher sugammadex concentration (30 µM) being close to statistically significantly improving recovery (P = 0.065). The highest concentration of dexamethasone decreased the recovery of contractions by equimolar sugammadex by 26%; this effect was more pronounced when 3-fold equimolar (30 µM) sugammadex was used for reversal (48%). CONCLUSIONS: This is the first report in which the effects of rocuronium and sugammadex interactions with dexamethasone have been studied in a highly accessible in vitro experimental model of functionally innervated human muscle cells. Sugammadex reverses rocuronium-induced neuromuscular block; however, concomitant addition of high dexamethasone concentrations diminishes the efficiency of sugammadex. Further studies are required to determine the clinical relevance of these interactions.

Antiinflammatory effect of sevoflurane in open lung surgery with one-lung ventilation.

AIM: To prospectively assess the antiinflammatory effect of volatile anesthetic sevoflurane in patients undergoing open lung surgery with one lung ventilation (OLV). METHODS: This prospective, randomized study included 40 patients undergoing thoracic surgery with OLV (NCT02188407). The patients were randomly allocated into two equal groups that received either propofol or sevoflurane. Four patients were excluded from the study because after surgery they received blood transfusion or non-steroid antiinflammatory drugs. Inflammatory mediators (interleukins 6, 8, and 10, C-reactive protein [CRP], and procalcitonin) were measured perioperatively. The infiltration of the nonoperated lung was assessed on chest x-rays and the oxygenation index was calculated. The major postoperative complications were counted. RESULTS: Interleukin 6 levels were significantly higher in propofol than in sevoflurane group (P=0.014). Preoperative CRP levels did not differ between the groups (P=0.351) and in all patients they were lower than 20 mg/L, but postoperative CRP was significantly higher in propofol group (31±6 vs 15±7 ng/L; P=0.035); Pre- and postoperative procalcitonin was within the reference range (<0.04 µg/L) in both groups. The oxygenation index was significantly lower in propofol group (339±139 vs 465±140; P=0.021). There was no significant difference between the groups in lung infiltrates (P=0.5849). The number of postoperative adverse events was higher in propofol group, but the difference was not-significant (5 vs 1; P=0.115). CONCLUSION: The study suggests an antiinflammatory effect of sevoflurane in patients undergoing thoracotomy with OLV.