Karel Hejduk

Low-Dose or High-Dose Rocuronium Reversed with Neostigmine or Sugammadex for Cesarean Delivery Anesthesia: A Randomized Controlled Noninferiority Trial of Time to Tracheal Intubation and Extubation.

BACKGROUND:Rocuronium for cesarean delivery under general anesthesia is an alternative to succinylcholine for rapid-sequence induction of anesthesia because of the availability of sugammadex for reversal of neuromuscular blockade. However, there are no large well-controlled studies in women undergoing general anesthesia for cesarean delivery. The aim of this noninferiority trial was to determine whether rocuronium and sugammadex confer benefit in time to tracheal intubation (primary outcome) and other neuromuscular blockade outcomes compared with succinylcholine, rocuronium, and neostigmine in women undergoing general anesthesia for cesarean delivery. METHODS:We aimed to enroll all women undergoing general anesthesia for cesarean delivery in the 2 participating university hospitals (Brno, Olomouc, Czech Republic) in this single-blinded, randomized, controlled study. Women were randomly assigned to the ROC group (muscle relaxation induced with rocuronium 1 mg/kg and reversed with sugammadex 2–4 mg/kg) or the SUX group (succinylcholine 1 mg/kg for induction, rocuronium 0.3 mg/kg for maintenance, and neostigmine 0.03 mg/kg for reversal of the neuromuscular blockade). The interval from the end of propofol administration to tracheal intubation was the primary end point with a noninferiority margin of 20 seconds. We recorded intubating conditions (modified Viby-Mogensen score), neonatal outcome (Apgar score <7; umbilical artery pH), anesthesia complications, and subjective patient complaints 24 hours after surgery. RESULTS:We enrolled 240 parturients. The mean time to tracheal intubation was 2.9 seconds longer in the ROC group (95% confidence interval, −5.3 to 11.2 seconds), noninferior compared with the SUX group. Absence of laryngoscopy resistance was greater in the ROC than in the SUX groups (ROC, 87.5%; SUX, 74.2%; P = 0.019), but there were no differences in vocal cord position (P = 0.45) or intubation response (P = 0.31) between groups. No statistically significant differences in incidence of anesthesia complications or in neonatal outcome were found (10-minute Apgar score <7, P = 0.07; umbilical artery pH, P = 0.43). The incidence of postpartum myalgia was greater in the SUX group (ROC 0%; SUX 6.7%; P = 0.007). The incidence of subjective complaints was lower in the ROC group (ROC, 21.4%; SUX, 37.5%; P = 0.007). CONCLUSIONS:We conclude that rocuronium for rapid-sequence induction is noninferior for time to tracheal intubation and is accompanied by more frequent absence of laryngoscopy resistance and lower incidence of myalgia in comparison with succinylcholine for cesarean delivery under general anesthesia.

Rocuronium versus suxamethonium for rapid sequence induction of general anaesthesia for caesarean section: influence on neonatal outcomes

BACKGROUND In a previous study we compared rocuronium and suxamethonium for rapid-sequence induction of general anaesthesia for caesarean section and found no difference in maternal outcome. There was however, a significant difference in Apgar scores. As this was a secondary outcome, we extended the study to explore this finding on a larger sample. METHODS We included 488 parturients of whom 240 were women from the original study. Women were randomly assigned to receive either rocuronium 1mg/kg (ROC n=245) or suxamethonium 1mg/kg (SUX n=243) after propofol 2mg/kg. Anaesthesia was maintained with up to 50% nitrous oxide and up to one minimum alveolar concentration of sevoflurane until the umbilical cord was clamped. We compared neonatal outcome using Apgar scores and umbilical cord blood gases. RESULTS Data were analysed for 525 newborns (ROC n=263vs. SUX n=262). There was a statistically significant difference in the proportion of Apgar scores <7 at 1min (ROC 17.5% vs. SUX 10.3%, P=0.023) but no difference at 5min (ROC 8% vs. SUX 4.2%, P=0.1) or 10min (ROC 3.0% vs. SUX 1.9%, P=0.58). There was no difference between groups in other measured outcomes. CONCLUSION The use of rocuronium was associated with lower Apgar scores at 1min compared with suxamethonium. The clinical significance of this is unclear and warrants further investigation.

Diagnosing COPD: advances in training and practice – a systematic review

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung syndrome, caused by long-term inhalation of noxious gases and particles, which leads to gradual airflow limitation. All health care professionals who care for COPD patients should have full access to high-quality spirometry testing, as postbronchodilator spirometry constitutes the principal method of COPD diagnosis. One out of four smokers 45 years or older presenting respiratory symptoms in primary care, have non-fully reversible airflow limitation compatible with COPD and are mostly without a known diagnosis. Approximately 50.0%–98.3% of patients are undiagnosed worldwide. The majority of undiagnosed COPD patients are isolated at home, are in nursing or senior-assisted living facilities, or are present in oncology and cardiology clinics as patients with lung cancers and coronary artery disease. At this time, the prevalence and mortality of COPD subjects is increasing, rapidly among women who are more susceptible to risk factors. Since effective management strategies are currently available for all phenotypes of COPD, correctly performed and well-interpreted postbronchodilator spirometry is still an essential component of all approaches used. Simple educational training can substantially improve physicians’ knowledge relating to COPD diagnosis. Similarly, a physician inhaler education program can improve attitudes toward inhaler teaching and facilitate its implementation in routine clinical practices. Spirometry combined with inhaled technique education improves the ability of predominantly nonrespiratory physicians to correctly diagnose COPD, to adequately assess its severity, and to increase the percentage of correct COPD treatment used in a real-life setting.

Czech multicenter research database of severe COPD

Purpose Chronic obstructive pulmonary disease (COPD) has been recognized as a heterogeneous, multiple organ system-affecting disorder. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) places emphasis on symptom and exacerbation management. The aim of this study is examine the course of COPD and its impact on morbidity and all-cause mortality of patients, with respect to individual phenotypes and GOLD categories. This study will also evaluate COPD real-life patient care in the Czech Republic. Patients and methods The Czech Multicentre Research Database of COPD is projected to last for 5 years, with the aim of enrolling 1,000 patients. This is a multicenter, observational, and prospective study of patients with severe COPD (post-bronchodilator forced expiratory volume in 1 second ≤60%). Every consecutive patient, who fulfils the inclusion criteria, is asked to participate in the study. Patient recruitment is done on the basis of signed informed consent. The study was approved by the Multicentre Ethical Committee in Brno, Czech Republic. Results The objective of this paper was to outline the methodology of this study. Conclusion The establishment of the database is a useful step in improving care for COPD subjects. Additionally, it will serve as a source of data elucidating the natural course of COPD, comorbidities, and overall impact on the patients. Moreover, it will provide information on the diverse course of the COPD syndrome in the Czech Republic.

Thyroid transcription factor 1 expression is associated with outcome of patients with non-squamous non-small cell lung cancer treated with pemetrexed-based chemotherapy

Pemetrexed is an antifolate cytostatic agent targeting several folate-dependent enzymatic pathways, widely used in the treatment of locally advanced or metastatic stage non-small cell lung cancer. Aside from the non-squamous histology, there is still no available molecular biomarker predicting treatment efficacy of pemetrexed-based chemotherapy. The aim of our retrospective study was to evaluate the association of thyroid transcription factor 1 expression with outcome of a large cohort of patients with non-squamous non-small cell lung cancer treated with pemetrexed. We retrospectively analysed clinical data of 463 patients with advanced-stage non-small cell lung cancer (IIIB or IV) treated with pemetrexed-based chemotherapy. Thyroid transcription factor 1 expression was assessed using indirect immunohistochemical detection in formalin-fixed paraffin-embedded tumour tissue at the time of diagnosis. Thyroid transcription factor 1 expression was detected in the tumour tissue from 76.0% of patients, and tumours from 24.0% of patients were thyroid transcription factor 1 negative. The median progression-free survival and overall survival for patients with thyroid transcription factor 1 positive tumours were 4.8 and 11.8 months compared to 2.8 and 8.3 months for those with thyroid transcription factor 1 negative tumours (p = 0.001 and p < 0.001). The multivariable Cox proportional hazards model revealed that thyroid transcription factor 1 expression was significantly associated with progression-free survival (hazard ratio = 1.57, p < 0.001) and also with overall survival (hazard ratio = 1.73, p < 0.001). In conclusion, the results of the conducted retrospective study suggest that the thyroid transcription factor 1 expression was independently associated with progression-free survival and overall survival in patients with advanced-stage non-squamous non-small cell lung cancer treated with pemetrexed-based chemotherapy.

Association of the postoperative white blood cells (WBC) count in peripheral blood after radical surgical treatment of left upper lobe non-small cell lung cancer (NSCLC) with overall survival - single center results

INTRODUCTION The individual patient prognosis after radical surgery for Non-small cell lung cancer (NSCLC) of left upper lobe remains still unclear. The purpose of this study is to evaluate the predictive value of elevated white blood cell count in peripheral blood as early indicator of postoperative NSCLC prognosis. METHODS A retrospective statistical analysis was performed studying patients subject to radical treatment of left upper lobe NSCLC in period of five years with subsequent one to three-year monitoring of morbidity and mortality of the patient population. The statistical ROC (Receiver Operating Characteristic) analysis of the WBC count in peripheral blood third day after the operation was used to evaluate the relationship with overall survival, with respect to patients surviving for at least 24 months. RESULTS Based on the results of the ROC analysis with a total area under the curve (AUC) of 0.67, it is possible to confirm that the WBC count established third day after the operation allows us to classify patients into groups according to the 24-month overall survival. CONCLUSION Our findings confirm the potential of using WBC count to improve current protocols to establish postoperative prognosis for NSCLC of the upper left lobe (Tab. 2, Fig. 1, Ref. 11).

Respiratory parameters predict poor outcome in COPD patients, category GOLD 2017 B

Background Respiratory parameters are important predictors of prognosis in the COPD population. Global Initiative for Obstructive Lung Disease (GOLD) 2017 Update resulted in a vertical shift of patients across COPD categories, with category B being the most populous and clinically heterogeneous. The aim of our study was to investigate whether respiratory parameters might be associated with increased all-cause mortality within GOLD category B patients. Methods The data were extracted from the Czech Multicentre Research Database, a prospective, noninterventional multicenter study of COPD patients. Kaplan–Meier survival analyses were performed at different levels of respiratory parameters (partial pressure of oxygen in arterial blood [PaO2], partial pressure of arterial carbon dioxide [PaCO2] and greatest decrease of basal peripheral capillary oxygen saturation during 6-minute walking test [6-MWT]). Univariate analyses using the Cox proportional hazard model and multivariate analyses were used to identify risk factors for mortality in hypoxemic and hypercapnic individuals with COPD. Results All-cause mortality in the cohort at 3 years of prospective follow-up reached 18.4%. Chronic hypoxemia (PaO2 <7.3 kPa), hypercapnia (PaCO2 >7.0 kPa) and oxygen desaturation during the 6-MWT were predictors of long-term mortality in COPD patients with forced expiratory volume in 1 second ≤60% for the overall cohort and for GOLD B category patients. Univariate analyses confirmed the association among decreased oxemia (<7.3 kPa), increased capnemia (>7.0 kPa), oxygen desaturation during 6-MWT and mortality in the studied groups of COPD subjects. Multivariate analysis identified PaO2 <7.3 kPa as a strong independent risk factor for mortality. Conclusion Survival analyses showed significantly increased all-cause mortality in hypoxemic and hypercapnic GOLD B subjects. More important, PaO2 <7.3 kPa was the strongest risk factor, especially in category B patients. In contrast, the majority of the tested respiratory parameters did not show a difference in mortality in the GOLD category D cohort.

A pilot data analysis of a metabolomic HPLC-MS/MS study of patients with COPD

BACKGROUND Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition with multiple clinical faces. Metabolomic profiling studies small molecules present in biological samples by combined use of chromatography with mass spectrometry. OBJECTIVES The goal of our work was to perform a high performance liquid chromatography combined with tandem mass spectrometry (HPLC-MS/MS) metabolomic study to compare the concentrations of metabolites in COPD patients and in controls. MATERIAL AND METHODS Participants were recruited at the University Hospital, Hradec Králové, Czech Republic, with the approval of the ethics committee. The analysis of blood samples was performed at Health Sciences Center (HSC) in Kuwait. The blood samples were analyzed for concentrations of acylcarnitines and amino acids by high performance liquid chromatography (Waters 2690 HPLC; Waters, Milford, USA) and a triple-quadruple tandem mass spectrometer (Quattro LC, Micromass, Manchester, United Kingdom). RESULTS Groups of 10 subjects with COPD and 10 healthy controls were analyzed. Carnitine analysis showed that the free carnitine to acylcarnitine ratio (C0/AC ratio) was significantly lower in COPD (0.58 μM/L) compared to the controls (0.73 μM/L; p = 0.002). The mean C8/C2 ratio in the COPD group was significantly higher (0.03 μM/L) - in the control group it was 0 μM/L (p = 0.03). Amino acid analysis showed lower levels of phenylalanine in the COPD group (22.05 μM/L) compared to the controls (30.05 μM/L; p = 0.008). The alanine concentrations were significantly lower in the COPD group (173 μM/L) than in the control group (253 μM/L; p = 0.001). The pyroglutamate levels were higher in COPD (1.58 μM/L) than in the controls (1 μM/L; p = 0.040). CONCLUSIONS The carnitine and acylcarnitine levels in COPD subjects in this study possibly indicate a predisposition to atherosclerosis as a result of inadequate β-oxidation of fatty acids and show the presence of oxidative stress. Furthermore, the high sensitivity to changes in circulating amino acid levels may allow us to detect subclinical malnutrition and take early preventative interventions such as nutritional supplementation and patient education.

Prognostic role of serum C-reactive protein in patients with advanced-stage NSCLC treated with pemetrexed

Pemetrexed is an intravenously administered antifolate cytostatic agent targeting several folate-dependent enzymatic pathways, widely used in the treatment of patients with advanced non-small cell lung cancer (NSCLC). It has been previously demonstrated that the superiority of pemetrexed is limited to patients with non-squamous histology. Aside from the non-squamous histology, there is still no available molecular biomarker predicting treatment efficacy of pemetrexed-based chemotherapy. The aim of our retrospective study was to evaluate the association of baseline serum levels of C-reactive protein (CRP) with outcomes in a large cohort of patients with non-squamous NSCLC treated with pemetrexed. Clinical data of 325 patients were analysed. Serum samples were collected within one week before the initiation of treatment. The median progression-free (PFS) and overall survival (OS) for patients with high CRP was 2.1 and 9.5 compared to 4.2 and 20.5 months for those with normal CRP (p=0.002 and p<0.001, respectively). The multivariable Cox proportional hazards model revealed that serum CRP (HR=1.46, p=0.002) was significantly associated with PFS and also with OS (HR=1.95, p<0.001). In conclusion, the study results suggest that pretreatment serum CRP is associated with poor outcome of non-squamous NSCLC patients treated with pemetrexed.

SAT0366 Effect of First-Line Anti-TNF Therapy on Fatigue in Patients with Ankylosing Spondylitis – Results from the Czech BIOLOGICS Registry Attra

Objectives The aim of this study was to describe the influence of anti-TNF therapy on the fatigue in patients with ankylosing spondylitis (AS) and compare the results with the influence of the therapy on the disease activity Methods We used Vitality score (subscale from SF-36) for the assessment of fatigue and BASDAI for the evaluation of the disease activity. Values of Vitality score, BASDAI and their improvements were described using median and interquartile range (IQR). Statistical significance of differences between 3-month visit and treatment initiation and between one-year visit and 3-month visit were assessed using Wilcoxon Signed Ranks Test. Kruskal-Wallis H test was used to assess differences between gender and age categories (while level of significance α =0.05). Results 588 AS patients [mean age of 37,6 years (standard deviation 10,5) and mean disease duration of 8 years (standard deviation 7,4) at the start of anti-TNF treatment]were included in the analyses. Men assessed Vitality at the start of treatment better than women (p=0.003), but there was no difference in improvement in Vitality after therapy between the sexes. Compare to patients aged >50 years, there was more improvement in BASDAI assessment in patients aged <30 years (p=0.002) and also in group aged 30-39 (p=0.020) after 3 months of therapy, but there were no statistical differences between various age groups in the improvement of Vitality score after 3 and 12 months of therapy. Conclusions Based on subanalysis of age groups there were significant improvements in fatigue and disease activity after 3 months and also significant improvement in disease activity between 12 and 3 months within all age groups, but interestingly there was no significant improvement in fatigue between 12 and 3 months within all age groups besides group of patients aged 30-39 years. Acknowledgements Supported by project 00023728 from Ministry of Health in the Czech Republic. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3184