Intraoperative Dexmedetomidine Use for Enhanced Recovery after Surgery (ERAS) in Cardiac Surgery-Single Center Retrospective Observational Cohort Study.

Background and Objectives: Dexmedetomidine, an alpha-2 agonist, is used as an adjunct to anesthesia in enhanced recovery after surgery (ERAS) programs. One of its advantages is the opioid-sparing effect which can facilitate early extubation and recovery. When the ERAS cardiac society was set in 2017, our facility was already using the ERAS program, in which the "fast-track Anesthesia" was facilitated by the intraoperative infusion of dexmedetomidine. Our objective is to share our experience and investigate the potential impact of intraoperative dexmedetomidine use as a part of the ERAS program on patient outcomes in elective cardiac surgery. Materials and Methods: An observational retrospective cohort study was conducted at a university hospital in Switzerland. The patients who underwent elective cardiac surgery with cardiopulmonary bypass between 1 June 2017 and 31 August 2018 were included in this analysis (n = 327). Regardless of the surgery type, all the patients received a standardized fast-track anesthesia protocol inclusive of dexmedetomidine infusion, reduced opioid dose, and parasternal nerve block. The primary outcome was the postoperative time when the criteria for extubation were met. Three groups were identified: group 0-(extubated in the operating room), group < 6 (extubated in less than 6 h), and group > 6 (extubated in >6 h). The secondary outcomes were adverse events, length of stay in ICU and in hospital, and total hospitalization costs. Results: Dexmedetomidine was well-tolerated, with no significant adverse events reported. Early extubation was performed in 187 patients (57%). Group 3 had a significantly longer length of stay in the ICU (median: 70 h vs. 25 h) and in hospital (17 vs. 12 days), and consequently higher total hospitalization costs (CHF 62,551 vs. 38,433) compared to the net data from the other two groups (p < 0.0001). Conclusions: Our findings suggest that dexmedetomidine can be safely used as part of the opioid-sparing anesthesia protocol in patients undergoing elective cardiac surgery with cardiopulmonary bypass with the potential to facilitate early extubation, shorter ICU and hospital stays, and reduced hospitalization costs.

Blood biomarkers in early bacterial infection and sepsis diagnostics in feverish young children.

BACKGROUND AND OBJECTIVES: While most feverish children have self-limiting diseases, 5-10% develop a serious and potentially life-threatening bacterial infection (BI). Due to potential risk, prompt recognition of BI and sepsis in the pediatric emergency department (PED) remains a clinical priority. The aim of the study was to evaluate the role of certain cytokines and chemokines separately and in combination with routine blood tests in early BI and sepsis diagnostics at PED. MATERIALS AND METHODS: We prospectively studied children younger than 5 presenting to the PED with fever lasting for under 12 hours with high risk for serious illness. Clinical data, routine blood analysis, and inflammatory cytokine and chemokine panels were evaluated for their diagnostic abilities. Two separate analyses were carried out on the patients' data: one contrasting BI and viral infection (VI) groups, the other comparing septic and non-septic patients. RESULTS: The sample comprised 70 patients (40% with BI). IL-2 was found to be the most specific biomarker to identify BI with specificity of 100%. The best discriminative ability was demonstrated by combining IL-2, IL-6, CRP, WBC, and neutrophil count: AUC 0.942 (95% Cl 0.859-0.984). IL-10 exhibited a greater AUC (0.837. 95% CI: 0.730-0.915 p<0.05) than CRP (0.807. 95% CI: 0.695-0.895 p<0.05) when predicting sepsis and showed high specificity (98%) and moderate sensitivity (75%). CONCLUSIONS: IL-6 and IL-2 could increase the diagnostic ability of routine blood tests for predicting BI, as IL-10 raises specificity for recognizing sepsis in the early hours of disease onset.

GYY4137 and Sodium Hydrogen Sulfide Relaxations Are Inhibited by L-Cysteine and KV7 Channel Blockers in Rat Small Mesenteric Arteries.

Donors of H2S may be beneficial in treating cardiovascular diseases where the plasma levels of H2S are decreased. Therefore, we investigated the mechanisms involved in relaxation of small arteries induced by GYY4137 [(4-methoxyphenyl)-morpholin-4-yl-sulfanylidene-sulfido-λ5-phosphane;morpholin-4-ium], which is considered a slow-releasing H2S donor. Sulfides were measured by use of 5,5'-dithiobis-(2-nitro benzoic acid), and small rat mesenteric arteries with internal diameters of 200-250 µm were mounted in microvascular myographs for isometric tension recordings. GYY4137 produced similar low levels of sulfides in the absence and the presence of arteries. In U46619-contracted small mesenteric arteries, GYY4137 (10-6-10-3 M) induced concentration-dependent relaxations, while a synthetic, sulfur-free, GYY4137 did not change the vascular tone. L-cysteine (10-6-10-3 M) induced only small relaxations reaching 24 ± 6% at 10-3 M. Premixing L-cysteine (10-3 M) with Na2S and GYY4137 decreased Na2S relaxation and abolished GYY4137 relaxation, an effect prevented by an nitric oxide (NO) synthase inhibitor, L-NAME (Nω-nitro-L-arginine methyl ester). In arteries without endothelium or in the presence of L-NAME, relaxation curves for GYY4137 were rightward shifted. High extracellular K+ concentrations decreased Na2S and abolished GYY4137 relaxation suggesting potassium channel-independent mechanisms are also involved Na2S relaxation while potassium channel activation is pivotal for GYY4137 relaxation in small arteries. Blockers of large-conductance calcium-activated (BKCa) and voltage-gated type 7 (KV7) potassium channels also inhibited GYY4137 relaxations. The present findings suggest that L-cysteine by reaction with Na2S and GYY4137 and formation of sulfides, inhibits relaxations by these compounds. The low rate of release of H2S species from GYY4137 is reflected by the different sensitivity of these relaxations towards high K+ concentration and potassium channel blockers compared with Na2S. The perspective is that the rate of release of sulfides plays an important for the effects of H2S salt vs. donors in small arteries, and hence for a beneficial effect of GYY4137 for treatment of cardiovascular disease.

Low-Frequency (20 kHz) Ultrasonic Modulation of Drug Action.

We tested the effect of low-frequency ultrasound (LUS, 20 kHz, 4 W/cm2) on the function of rat mesentery and human pulmonary arteries with wire myography. The vessels were induced to contract with either noradrenaline or physiologic saline solution (PSS) with a high potassium concentration (KPSS) and then incubated with capsaicin (2.1 × 10-7 M, TRPV1 [transient receptor potential vanilloid 1] activator), dopamine (1 × 10-4 M, dopamine and α2-receptor activator), or fenoldopam (dopamineA1 receptor agonist, 1 × 10-4 M) with and without glibenclamide (1 µM, KATP [adenosine triphosphate {sensitive potassium channel (ATP)}-sensitive potassium channel] inhibitor and α2-receptor modulator), and insonated. Vessels were incubated in Ca2+-free PSS and induced to contract with added extracellular Ca2+ and noradrenaline. Pulmonary arteries were induced to contract with KPSS and dopamine. Then the vessels were insonated. LUS inhibited the influx of external Ca2+, inhibited the dopamine-induced vasoconstriction in the KPSS (glibenclamide reversible), reduced the capsaicin-induced vasorelaxation, increased the gentamicin-induced vasorelaxation and increased the dopamine-induced contraction in the KPSS in human pulmonary arteries.

A case report and literature review: previously excluded tuberculosis masked by amiodarone induced lung injury.

BACKGROUND: Amiodarone is an antiarrhythmic drug which is used to treat and prevent several dysrhythmias. This includes ventricular tachycardia and fibrillation, wide complex tachycardia, as well as atrial fibrillation (AF) and paroxysmal supraventricular tachycardia. Amiodarone may prove to be the agent of choice where the patient is hemodynamically unstable and unsuitable for direct current (DC) cardioversion. Although, it is not recommended for long-term use. The physician might encounter issues when differentiating amiodarone-induced lung toxicity with suspicion of interstitial lung disease, cancer or vasculitis. Adverse drug reactions are difficult to confirm and it leads to serious problems of pharmacotherapy. CASE PRESENTATION: A 78-year-old Caucasian male pensioner complaining of fever, dyspnea, malaise, non-productive cough, fatigue, weight loss, diagnosed with acute respiratory failure with a 16-year long history of amiodarone use and histologically confirmed temporal arteritis with long-term glucocorticosteroid (GCC) therapy. Patient was treated for temporal arteritis with GCC for ~ 1 year, then fever and dyspnea occurred, and the patient was hospitalized for treatment of bilateral pneumonia. Chest X-ray and chest high resolution computed tomography (HRCT) indicated several possible diagnoses: drug-induced interstitial lung disease, autoimmune interstitial lung disease, previously excluded pulmonary TB. Amiodarone was discontinued. Antibiotic therapy for bilateral pneumonia was started. Fiberoptic bronchoscopy with bronchial washings and brushings was performed. Acid fast bacilli (AFB) were found on Ziehl-Nielsen microscopy and tuberculosis (TB) was confirmed (later confirmed to be Mycobacterium tuberculosis in culture), initial treatment for TB was started. After a few months of treating for TB, patient was diagnosed with pneumonia and sepsis, empiric antibiotic therapy was prescribed. After reevaluation and M. Tuberculosis identification, the patient was referred to the Tuberculosis hospital for further treatment. After 6 months of TB treatment, pneumonia occurred which was complicated by sepsis. Despite the treatment, multiple organ dysfunction syndrome evolved and patient died. Probable cause of death: pneumonia and sepsis. CONCLUSIONS: The current clinical case emphasizes issues that a physician may encounter in the differential diagnostics of amiodarone-induced lung toxicity with other lung diseases.

Experimental investigation of the determination for the safe operating regime of ultrasound tube-shaped waveguide wire for internal blood vessel debulking.

BACKGROUND: Majority of limb amputations are caused by circulatory disturbances such as vascular occlusions and strictures. Discovery of modern and more advanced ultrasonic interventional vascular debulking methodology would likely save limbs of CVD patients and their lives in an economical way. However, there is a lack of researches regarding the ultrasound's effect on physiological functions of human blood cells. The tube-shaped ultrasound waveguide wire with orifices at its operational end was offered as the alternative to some currently patented interventional thrombosis treatment solutions. OBJECTIVE: To establish the safe operating regime of the proposed device. METHODS: The temperature rise induced by the cavitation process and friction between the waveguide and surrounding fluids was measured and microscopic pictures of human blood were made. RESULTS: Blood insonation lasting 15 seconds, leads to blood clot formation. If insonation continues for 30 seconds some cells are totally destroyed. In addition, the safe operating regime was established. To avoid heating of the environment to the temperature harmful for the medium (blood) and surrounding tissues, is achieved when the system should be on for 40%, and of for 60% of the period of 1 second. CONCLUSIONS: The safe operating regime of the proposed device was established.

Cisplatin-induced sudden cardiac death with hemodynamic collapse: a severe adverse drug reaction: Case report.

RATIONALE: Cisplatin is responsible for a significant percentage of adverse drug reactions (ADRs) in oncology setting. A great proportion of cisplatin-induced severe adverse events are difficult to foresee, and giving premedication does not always prevent the occurrence of such events. PATIENT CONCERNS: A 53-year-old woman with progressive T4 N0 M0 stage IV pleural mesothelioma experienced cardiac arrest with hemodynamic collapse after cisplatin and pemetrexed chemotherapy administration. DIAGNOSES: Progressive pleural T4 N0 M0 stage IV mesothelioma of the right lung, primary arterial hypertension, and cardiac arrest with hemodynamic collapse. INTERVENTIONS: The cisplatin and pemetrexed chemotherapy was administered intravenously for progressive pleural T4 N0 M0 stage IV mesothelioma of the right lung. During infusion of cisplatin the patient developed cardiac arrest, and cardiopulmonary resuscitation was initiated. OUTCOMES: The patient was treated in intensive care unit and recovered successfully. Further chemotherapy with cisplatin and pemetrexed was withheld due to this severe adverse reaction to cisplatin. LESSONS: Cisplatin therapy should be thoroughly monitored including electrolyte, especially magnesium levels. Absence of previous ADRs to cisplatin and premedication should not give false sense of security.