Since December 2019, SARS-CoV-2 virus has infected millions of people worldwide. In patients with COVID-19 pneumonia in need of oxygen therapy or mechanical ventilation, dexamethasone 6 mg per day is ...currently recommended. However, the dose of 6 mg of dexamethasone is currently being reappraised and may miss important therapeutic potential or may prevent potential deleterious effects of higher doses of corticosteroids.
REMED is a prospective, open-label, randomised controlled trial testing the superiority of dexamethasone 20 mg (dexamethasone 20 mg on days 1-5, followed by dexamethasone 10 mg on days 6-10) vs 6 mg administered once daily intravenously for 10 days in adult patients with moderate or severe ARDS due to confirmed COVID-19. Three hundred participants will be enrolled and followed up for 360 days after randomization. Patients will be randomised in a 1:1 ratio into one of the two treatment arms. The following stratification factors will be applied: age, Charlson Comorbidity Index, CRP levels and trial centre. The primary endpoint is the number of ventilator-free days (VFDs) at 28 days after randomisation. The secondary endpoints are mortality from any cause at 60 days after randomisation; dynamics of the inflammatory marker, change in WHO Clinical Progression Scale at day 14; and adverse events related to corticosteroids and independence at 90 days after randomisation assessed by the Barthel Index. The long-term outcomes of this study are to assess long-term consequences on mortality and quality of life at 180 and 360 days. The study will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic.
We aim to compare two different doses of dexamethasone in patients with moderate to severe ARDS undergoing mechanical ventilation regarding efficacy and safety.
EudraCT No. 2020-005887-70. ClinicalTrials.gov NCT04663555. Registered on December 11, 2020.
Abstract
Background
Providing palliative care at the end of life (EOL) in intensive care units (ICUs) seems to be modified during the COVID-19 pandemic with potential burden of moral distress to ...health care providers (HCPs). We seek to assess the practice of EOL care during the COVID-19 pandemic in ICUs in the Czech Republic focusing on the level of moral distress and its possible modifiable factors.
Methods
Between 16 June 2021 and 16 September 2021, a national, cross-sectional study in intensive care units (ICUs) in Czech Republic was performed. All physicians and nurses working in ICUs during the COVID-19 pandemic were included in the study. For questionnaire development ACADEMY and CHERRIES guide and checklist were used. A multivariate logistic regression model was used to analyse possible modifiable factors of moral distress.
Results
In total, 313 HCPs (14.5% out of all HCPs who opened the questionnaire) fully completed the survey. Results showed that 51.8% (
n
= 162) of respondents were exposed to moral distress during the COVID-19 pandemic. 63.1% (
n
= 113) of nurses and 71.6% of (
n
= 96) physicians had experience with the perception of inappropriate care. If inappropriate care was perceived, a higher chance for the occurrence of moral distress for HCPs (OR, 1.854; CI, 1.057–3.252;
p
= 0.0312) was found. When patients died with dignity, the chance for moral distress was lower (OR, 0.235; CI, 0.128–0.430;
p
< 0.001). The three most often reported differences in palliative care practice during pandemic were health system congestion, personnel factors, and characteristics of COVID-19 infection.
Conclusions
HCPs working at ICUs experienced significant moral distress during the COVID-19 pandemic in the Czech Republic. The major sources were perceiving inappropriate care and dying of patients without dignity. Improvement of the decision-making process and communication at the end of life could lead to a better ethical and safety climate.
Trial registration
:
NCT04910243
.
Graphical abstract
Abstract Background The aim of this study was to compare the estimated glomerular filtration rate (eGFR) from serum creatinine (eGFRcrea) and cystatin C (eGFRcys) in patients with elevated serum ...trough levels of gentamicin before the next planned dose during treatment in the intensive care unit (ICU). Methods This was a retrospective observational study. Patients who stayed in an ICU, received a once-daily dose of gentamicin, and who had results from all serum gentamicin trough levels, eGFRcrea and eGFRcys analyses were included in the study. Overdosed patients were defined as those with serum gentamicin trough levels above 1 mg/L before the next dose. Gentamicin was measured by a particle-enhanced turbidimetric immunoassay (PETIA). Creatinine and cystatin C were measured by standardized methods. Results The median age (range) was lower in all patients with gentamicin concentration measurements than in overdosed patients (67 19–96 vs. 75 48–99 years, respectively; p < 0.0001). The median interquartile range (IQR) of the eGFRcrea was higher than that of the eGFRcys in overdosed patients (60 44–79 mL/min/1.73 m 2 vs. 41 29–58 mL/min/1.73 m 2 , respectively; p < 0.0001). The median IQR of the eGFRcrea was higher than that of the eGFRcys in controls (87 78–98 mL/min/1.73 m 2 vs. 66 54–93 mL/min/1.73 m 2 , respectively; p < 0.0001). Conclusions Overdosed patients had both a lower eGFRcrea and eGFRcys than controls. Elderly patients are the most commonly overdosed patients. We recommend measuring cystatin C and calculating the eGFRcys and combined equation (eGFRcrea + cys) in ICU patients over 65 years of age, which would enable improved gentamicin dosage adjustments.
Superior laryngeal (SL) neuralgia is paroxysmal pain above the thyrohyoid membrane. We present a case of SL neuralgia that was resistant to conservative treatment and eventually required surgical ...intervention. The patient was a 39-year-old woman with a 5-year history of debilitating pain above the thyroid cartilage. After having undergone different imaging scans with negative results, she tried various treatments (e.g., antibiotics, analgesics, stellate ganglion block, radiofrequency SL neurotomy, and stereotactic radiosurgery), all of which were ineffective. Finally, she underwent bilateral surgical SL neurotomy. Postoperatively, she immediately noticed a significant alleviation of her pain. Her postoperative course was completely uneventful, as she experienced no dysphagia or dysphonia, even transiently. One month later, she no longer required regular painkillers, and at 14 months, she remained essentially pain-free. While medical management remains the treatment of choice for SL neuralgia, we recommend that refractory cases be treated initially with a neural block with local anesthesia. Patients who do not respond are candidates for surgery. We consider selective peripheral SL neurotomy to be safe and effective when performed by experienced hands. We also discuss the difficulties of managing SL neuralgia.
Pancreatic cancer (PDAC) has a poor prognosis despite surgical removal and adjuvant therapy. Additionally, the effects of postoperative analgesia with morphine and piritramide on survival among PDAC ...patients are unknown, as are their interactions with opioid/cannabinoid receptor gene expressions in PDAC tissue. Cancer-specific survival data for 71 PDAC patients who underwent radical surgery followed by postoperative analgesia with morphine (n = 48) or piritramide (n = 23) were therefore analyzed in conjunction with opioid/cannabinoid receptor gene expressions in the patients’ tumors. Receptor gene expressions were determined using the quantitative real-time polymerase chain reaction. Patients receiving morphine had significantly longer cancer-specific survival (CSS) than those receiving piritramide postoperative analgesia (median 22.4 vs. 15 months; p = 0.038). This finding was supported by multivariate modelling (p < 0.001). The morphine and piritramide groups had similar morphine equipotent doses, receptor expression, and baseline characteristics. The opioid/cannabinoid receptor gene expression was analyzed in a group of 130 pancreatic cancer patients. Of the studied receptors, high cannabinoid receptor 2 (CB2) and opioid growth factor receptor (OGFR) gene expressions have a positive influence on the length of overall survival (OS; p = 0.029, resp. p = 0.01). Conversely, high delta opioid receptor gene expression shortened OS (p = 0.043). Multivariate modelling indicated that high CB2 and OGFR expression improved OS (HR = 0.538, p = 0.011, resp. HR = 0.435, p = 0.001), while high OPRD receptor expression shortened OS (HR = 2.264, p = 0.002). Morphine analgesia, CB2, and OGFR cancer tissue gene expression thus improved CSS resp. OS after radical PDAC surgery, whereas delta opioid receptor expression shortened OS.
The aim of the study was to compare the validity of bronchial secretion sampling and bronchoscopy-assisted protected specimen brushing (PSB) in patients with hospital-acquired pneumonia (HAP).
In ...patients with HAP, bronchial secretion samples (aspiration of lower airway secretions from an orotracheal tube with a suctioning catheter) and PSB (bronchoscopy-assisted sampling from the most affected area of the lung, verified by CT scan) were taken at the same time. Both samples were processed by semiquantitative routine microbiological techniques. Identification of microorganisms was performed by standard microbiological techniques using the MALDI-TOF automated system. For similarity or identity determination of bacterial isolates from bronchial secretion sampling and PSB, pulsed-field gel electrophoresis was used.
Thirty patients were enrolled into the study. Thirty pairs of bronchial secretion samples and PSB samples were obtained and processed. The samples were positive in 23 patients (77 %) and 15 patients (50 %), respectively. In 15 cases, the same pathogen was determined in both samples, and in all those cases, the isolates were genetically identical.
The results of the study show that bronchial secretion samples analysis enabled identification of all pathogens that were identified by PSB. Given the high sensitivity of the bronchial secretion aspiration technique and genetic identity of isolates in both samples, bronchial secretion sampling may be recommended for determining HAP etiological agents as the samples are much easier to obtain from patients.
Hospital-acquired pneumonia (HAP) is associated with high mortality. In Central Europe, there is a dearth of information on the prevalence and treatment of HAP. This project was aimed at collecting ...multicenter epidemiological data on patients with HAP in the Czech Republic and comparing them with supraregional data.
This prospective, multicenter, observational study processed data from a database supported by a Czech Ministry of Health grant project. Included were all consecutive patients aged 18 and over who were admitted to participating intensive care units (ICUs) between 1 May 2013 and 31 December 2014 and met the inclusion criterion of having HAP. The primary endpoint was to analyze the relationships between 30-day mortality (during the stay in or after discharge from ICUs) and the microbiological etiological agent and adequacy of initial empirical antibiotic therapy in HAP patients.
The group dataset contained data on 330 enrolled patients. The final validated dataset involved 214 patients, 168 males (78.5%) and 46 females (21.5%), from whom 278 valid lower airway samples were obtained. The mean patient age was 59.9 years. The mean APACHE II score at admission was 21. Community-acquired pneumonia was identified in 13 patients and HAP in 201 patients, of whom 26 (12.1%) had early-onset and 175 (81.8%) had late-onset HAP. Twenty-two bacterial species were identified as etiologic agents but only six of them exceeded a frequency of detection of 5% (Klebsiella pneumoniae 20.4%, Pseudomonas aeruginosa 20.0%, Escherichia coli 10.8%, Enterobacter spp. 8.1%, Staphylococcus aureus 6.2% and Burkholderia cepacia complex 5.8%). Patients infected with Staphylococcus aureus had significantly higher rates of early-onset HAP than those with other etiologic agents. The overall 30-day mortality rate for HAP was 29.9%, with 19.2% mortality for early-onset HAP and 31.4% mortality for late-onset HAP. Patients with late-onset HAP receiving adequate initial empirical antibiotic therapy had statistically significantly lower 30-day mortality than those receiving inadequate initial antibiotic therapy (23.8% vs 42.9%). Patients with ventilator-associated pneumonia (VAP) had significantly higher mortality than those who developed HAP with no association with mechanical ventilation (34.6% vs 12.7%). Patients having VAP treated with adequate initial antibiotic therapy had lower 30-day mortality than those receiving inadequate therapy (27.2% vs 44.8%).
The present study was the first to collect multicenter data on the epidemiology of HAP in the Central European Region, with respect to the incidence of etiologic agents causing HAP. It was concerned with relationships between 30-day patient mortality and the type of HAP, etiologic agent and adequacy of initial empirical antibiotic therapy.
Opioids and epidural analgesia are a mainstay of perioperative analgesia but their influence on cancer recurrence remains unclear. Based on retrospective data, we found that cancer recurrence ...following colorectal cancer surgery correlates with the number of circulating tumor cells (CTCs) in the early postoperative period. Also, morphine- but not piritramide-based postoperative analgesia increases the presence of CTCs and shortens cancer-specific survival. The influence of epidural analgesia on CTCs has not been studied yet.
We intend to enroll 120 patients in four centers in this prospective randomized controlled trial. The study protocol has been approved by Ethics Committees in all participating centers. Patients undergoing radical open colorectal cancer surgery are randomized into epidural, morphine, and piritramide groups for perioperative analgesia. The primary outcome is the difference in the number of CTCs in the peripheral blood before surgery, on the second postoperative day, and 2-4 weeks after surgery. The number of CTCs is measured using molecular biology methods. Perioperative care is standardized, and relevant data is recorded. A secondary outcome, if feasible, would be the expression and activity of various receptor subtypes in cancer tissue. We intend to perform a 5-year follow-up with regard to metastasis development.
The mode of perioperative analgesia favorably affecting cancer recurrence would decrease morbidity/mortality. To identify such techniques, trials with long-term follow-up periods seem suboptimal. Given complex oncological therapeutic strategies, such trials likely disable the separation of perioperative analgesia effects from other factors. We believe that early postoperative CTCs presence/dynamics may serve as a sensitive marker of various perioperative interventions´ influences on cancer recurrence. Importantly, it is unbiased to the influence of long-term factors and minimally invasive. Analysis of opioid/cannabinoid receptor subtypes in cancer tissue would improve understanding of underlying mechanisms and promote personalization of treatment. We are not aware of any similar ongoing studies.
NCT03700411, registration date: October 3, 2018.
recruiting.
Purpose
Extreme lateral interbody fusion (XLIF) is a method for stabilization of the lumbar spine. Intraoperatively, the surgeon identifies the lumbar nerve roots with a stimulator to prevent their ...injury. The objective of this study was to determine the extent to which shallow rocuronium-induced neuromuscular block must be intraoperatively reversed for reliable identification of nerve roots.
Methods
General anesthesia (midazolam–propofol–sufentanil–oxygen/air/sevoflurane–rocuronium) was administered to all patients. Train-of-four (TOF) stimulation of the ulnar nerve at 15-s intervals and electromyographic response of the adductor pollicis muscle were used. During operation, the surgeon stimulated the lumbar nerve roots (5–10 mA) to identify their course. At the appearance of two twitches to the TOF stimuli, sugammadex (2 mg/kg) or neostigmine (0.04 mg/kg) was administered. When the response to nerve root stimulation appeared, the TOF ratio was recorded.
Results
When the response to nerve root stimulation with 10 mA became detectable, the median (range) TOF ratios were 0.67 (0.50–0.81) and 0.65 (0.42–0.71) after sugammadex and neostigmine, respectively. Similarly, TOF ratios at the first detectable response to stimulation with 5 mA were 0.88 (0.67–0.93) and 0.83 (0.61–0.93). After sugammadex and neostigmine, the respective intervals until TOF ratio ≥0.90 were 2.0 (0.8–3.3) and 15.9 (7.3–28.8) min.
Conclusion
Intraoperative reversal of shallow rocuronium-induced block with either sugammadex or neostigmine is an efficient method. For reliable detection of lumbar nerve roots with a stimulating current of 10 mA, the block should be reversed to a TOF ratio of at least 0.70. For a current intensity of 5 mA, the TOF ratio should reach 0.90.
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