Case study observational research: inflammatory cytokines in the bronchial epithelial lining fluid of COVID-19 patients with acute hypoxemic respiratory failure.

BACKGROUND: In this study, the concentrations of inflammatory cytokines were measured in the bronchial epithelial lining fluid (ELF) and plasma in patients with acute hypoxemic respiratory failure (AHRF) secondary to severe coronavirus disease 2019 (COVID-19). METHODS: We comprehensively analyzed the concentrations of 25 cytokines in the ELF and plasma of 27 COVID-19 AHRF patients. ELF was collected using the bronchial microsampling method through an endotracheal tube just after patients were intubated for mechanical ventilation. RESULTS: Compared with those in healthy volunteers, the concentrations of interleukin (IL)-6 (median 27.6 pmol/L), IL-8 (1045.1 pmol/L), IL-17A (0.8 pmol/L), IL-25 (1.5 pmol/L), and IL-31 (42.3 pmol/L) were significantly greater in the ELF of COVID-19 patients than in that of volunteers. The concentrations of MCP-1 and MIP-1ß were significantly greater in the plasma of COVID-19 patients than in that of volunteers. The ELF/plasma ratio of IL-8 was the highest among the 25 cytokines, with a median of 737, and the ELF/plasma ratio of IL-6 (median: 218), IL-1ß (202), IL-31 (169), MCP-1 (81), MIP-1ß (55), and TNF-α (47) were lower. CONCLUSIONS: The ELF concentrations of IL-6, IL-8, IL-17A, IL-25, and IL-31 were significantly increased in COVID-19 patients. Although high levels of MIP-1 and MIP-1ß were also detected in the blood samples collected simultaneously with the ELF samples, the results indicated that lung inflammation was highly compartmentalized. Our study demonstrated that a comprehensive analysis of cytokines in the ELF is a feasible approach for understanding lung inflammation and systemic interactions in patients with severe pneumonia.

The frequency of postoperative BNP measurement and intervention threshold of BNP concentration in pediatric cardiac intensive care unit: a prospective multicenter observational study.

PURPOSE: The purpose of this study is to investigate the current status of postoperative BNP measurement in the pediatric cardiac intensive care unit (PCICU). METHODS: This was a prospective multicenter observational study. Children under 15 years old who underwent pediatric cardiac surgery were included. Postoperatively, all BNP measurement was collected in PCICU. We checked whether each BNP measurement was used for the decision-making of intervention or not. We divided the BNP measurements into 4 groups: group A 0-299 pg/ml (reference), group B 300-999 pg/ml, group C 1000-1999 pg/ml, group D ≧ 2000 pg/ml. We performed logistic regression analysis to compare the intervention ratio between group A and B, C, D. We also did multiple comparison analyses to compare the intervention ratio in each group. RESULTS: Thirty-nine (15.8%) measurements were used as a criterion to intervene in all BNP measurements. There was no protocol for the measurement of BNP in all institutions. The number of BNP measurements in each group is as follows: group A 113 (45.9%), group B 81 (32.9%), group C 45 (18.3%), group D 7 (2.8%). The intervention ratio in each group was 6.2% (group A), 8.6% (group B), 44.4% (group C), and 71.4% (group D). The intervention ratio of group C and D were significantly higher than group A: (Odds ratio (95%CI): 12.1(4.8-33.9), p < 0.0001, 25.2(5.2-146.2), p < 0.0001). The result of multiple comparisons is similar to logistic regression analysis. CONCLUSION: High BNP concentration, especially more than 1000 pg/ml, was more often intervened upon compared to that of less than 1000 pg/ml.

[Risk Factors for the Postsurgical Hoarseness Contribution of the Intubation Device].

BACKGROUND: Postsurgical hoarseness is one of the major postoperative complications. METHODS: Risk factors associated with the postsur- gical hoarseness were investigated from medical records of 579 adult patients undergoing general anes- thesia with tracheal intubation. Postsurgical hoarseness was judged if a patient developed hoarseness at PODO or PODI by postanesthesia round. Multivariate logistic regression was performed to identify the parameters associated with postsurgical hoarseness. RESULTS: Postsurgical hoarseness developed in 16.1% of patients. None of the patients suffered hoarseness continuing more than 4 days. Multivariate logistic regression revealed increased BMI (odds ratio (OR) 1.06 [95% confidence interval (CI):1.00-1.131], depth of tracheal tube (OR 0.71 [95% CI : 0.57-0.86]), intu- bation performed by doctors in training (OR 4.07 [95% CI : 2.42-7.10]) and intubation with Airway Scope® (OR 2.03 [95% CI : 1.10-3.66]). CONCLUSIONS: Increased BMI, depth of tracheal tube, intubation performed by doctors in training and intu- bation with Airway Scope® are risk factors of postsur- gical hoarseness.

Addition of cilostazol to aspirin therapy for secondary prevention of cardiovascular and cerebrovascular disease in patients undergoing percutaneous coronary intervention: A randomized, open-label trial.

BACKGROUND: Patients with established coronary artery disease are at increased risk for future ischemic events and require secondary prevention for systemic vascular disease. We performed a randomized clinical trial to evaluate the impact of cilostazol on cardiovascular and cerebrovascular disease in patients undergoing percutaneous coronary intervention. METHODS: A total of 514 patients who had undergone coronary stent implantation >6 months previously and were thought to no longer need dual antiplatelet therapy with aspirin and a thienopyridine were randomly assigned to receive aspirin plus cilostazol therapy or aspirin therapy alone after discontinuation of thienopyridine therapy. The primary efficacy end point was a composite of all-cause death, myocardial infarction, stroke, or cardiovascular or cerebrovascular revascularization at 2 years after randomization. The main safety end point was major or minor bleeding, according to the Thrombolysis in Myocardial Infarction bleeding definition. RESULTS: At 2 years, follow-up clinical data were available for 98.1% of patients. The primary efficacy end point occurred in 13.9% of the aspirin plus cilostazol group versus 22.1% of the aspirin-only group (hazard ratio 0.61, 95% CI 0.40-0.93, P = .021). The rate of major or minor bleeding was not significantly different between the aspirin plus cilostazol and aspirin-only groups (1.6% and 4.0%, respectively, hazard ratio 0.40, 95% CI 0.13-1.28, P = .12). CONCLUSIONS: In patients who underwent coronary stent implantation, the addition of cilostazol to aspirin therapy was associated with lower rates of cardiovascular and cerebrovascular events at 2 years compared with aspirin monotherapy.

NURSE-LED proactive rounding and automatic early-warning score systems to prevent resuscitation incidences among Adults in ward-based Hospitalised patients.

Objectives: In this study, we investigated the impact of critical care outreach implemented to overcome the problem of rapid response system (RRS) activation. The aim was to evaluate the impact of nurse-led proactive rounding on the rate of adverse events in a hospital setting using an automatic early-warning score system, without a call-activated team. Methods: This observational study was conducted at a university hospital in Japan. Beginning in September 2019, critical care outreach via nurse-led proactive rounding of the general ward was conducted, using an automatic early-warning score system. We retrospectively assessed the computerised records of all inpatient days (N = 497,284) of adult inpatients admitted to the hospital from September 2017 to 2020. We compared the adverse event occurrences before and after implementation of the critical care outreach program. The main outcome measures were: unexpected death in the general ward, code blue (an in-hospital resuscitation request code directed towards all staff via broadcast) for non-intensive care unit inpatients and unexpected intensive care unit admissions from the general ward. The secondary outcome was the proportion of patients who received respiratory rate measurement. Results: The incidence rate ratios of the occurrence of unexpected deaths (0.19, 95% confidence interval: 0.04-0.57) and code blue in the general ward (0.15, 95% confidence interval: 0.025-0.50) decreased. There was no change in unexpected intensive care unit admissions from the general ward (1.25, confidence interval: 0.84-1.82). The proportion of patients who received respiratory rate measurement increased (10.2% vs 16.2%). Conclusion: Our results suggest that in RRSs, drastic control of the failure of the mechanism to activate a response team may produce positive outcomes. Proactive rounding that bypasses the mechanism to activate a response team component of RRSs may relieve ward nurses of activation failure responsibility and help them overcome the hierarchical hospital structure.

Choice of respiratory therapy for COVID-19 patients with acute hypoxemic respiratory failure: a retrospective case series study.

Background: In the treatment of acute hypoxemic respiratory failure (AHRF) due to coronavirus 2019 (COVID-19), physicians choose respiratory management ranging from low-flow oxygen therapy to more invasive methods, depending on the severity of the patient's symptoms. Recently, the ratio of oxygen saturation (ROX) index has been proposed as a clinical indicator to support the decision for either high-flow nasal cannulation (HFNC) or mechanical ventilation (MV). However, the reported cut-off value of the ROX index ranges widely from 2.7 to 5.9. The objective of this study was to identify indices to achieve empirical physician decisions for MV initiation, providing insights to shorten the delay from HFNC to MV. We retrospectively analyzed the ROX index 6 hours after initiating HFNC and lung infiltration volume (LIV) calculated from chest computed tomography (CT) images in COVID-19 patients with AHRF. Methods: We retrospectively analyzed the data for 59 COVID-19 patients with AHRF in our facility to determine the cut-off value of the ROX index for respiratory therapeutic decisions and the significance of radiological evaluation of pneumonia severity. The physicians chose either HFNC or MV, and the outcomes were retrospectively analyzed using the ROX index for initiating HFNC. LIV was calculated using chest CT images at admission. Results: Among the 59 patients who required high-flow oxygen therapy with HFNC at admission, 24 were later transitioned to MV; the remaining 35 patients recovered. Four of the 24 patients in the MV group died, and the ROX index values of these patients were 9.8, 7.3, 5.4, and 3.0, respectively. These index values indicated that the ROX index of half of the patients who died was higher than the reported cut-off values of the ROX index, which range from 2.7-5.99. The cut-off value of the ROX index 6 hours after the start of HFNC, which was used to classify the management of HFNC or MV as a physician's clinical decision, was approximately 6.1. The LIV cut-off value on chest CT between HFNC and MV was 35.5%. Using both the ROX index and LIV, the cut-off classifying HFNC or MV was obtained using the equation, LIV = 4.26 × (ROX index) + 7.89. The area under the receiver operating characteristic curve, as an evaluation metric of the classification, improved to 0.94 with a sensitivity of 0.79 and specificity of 0.91 using both the ROX index and LIV. Conclusion: Physicians' empirical decisions associated with the choice of respiratory therapy for HFNC oxygen therapy or MV can be supported by the combination of the ROX index and the LIV index calculated from chest CT images.

Reduction of the rocuronium-induced withdrawal reflex by MR13A10A, a generic rocuronium with a novel solution: A randomized, controlled study.

BACKGROUND: Rocuronium induces venous pain and the withdrawal reflex during injection. MR13A10A, generic rocuronium with a novel solution, reduced the injection-induced withdrawal reflex in rodents. We hypothesized that MR13A10A would reduce the frequency and severity of injection-induced withdrawal reflexes compared with original rocuronium during clinical anesthesia induction. METHODS: This prospective, open (but assessor-blinded), randomized, controlled study was conducted at a single academic hospital. The assessor was blinded to the study condition in order to minimize observer bias. Participants were allocated to either MR13A10A or traditional formula groups by a blocked stratified randomization method. Participants in the MR13A10A group received MR13A10A, whereas the original rocuronium group received the same amount of original rocuronium. The primary outcome was presence of the withdrawal reflex after rocuronium injection. Severity of the withdrawal reflex, changes in blood pressure and heart rate, and the train of four (TOF) ratio were measured as secondary outcomes. The withdrawal reflex was assessed using a video recording in a blinded manner. RESULTS: Of the 149 participants, 76 were allocated to the MR13A10A group and 73 to the original rocuronium group. The frequency of the withdrawal reflex was significantly lower with MR13A10A compared with original rocuronium (19.7% and 54.8% for MR13A10A and original rocuronium groups, respectively, p<0.001). The odds ratio adjusted for cannulation site, cannula size, induction agent and age was 6.27 (95% CI, 2.87, 13.73 p<0.001). Original rocuronium was an independent factor related to a higher post-treatment heart rate. The proportions of TOF ratios = 0 were similar between the two groups. CONCLUSION: The frequency and severity of the withdrawal reflex after injection were significantly reduced by using MR13A10A. MR13A10A might contribute to safe and less invasive anesthesia management.

Classification of acute pain trajectory after breast cancer surgery identifies patients at risk for persistent pain: a prospective observational study.

PURPOSE: Predictive value and accuracy of the acute pain trajectory were compared with those of pain intensity at 1 day after the surgery for pain prevalence at 6 months after the surgery. MATERIALS AND METHODS: Female patients scheduled for breast cancer surgery were eligible for this study. Patients were questioned about pain intensity daily during the 7 days after surgery. Presence of pain, its location, and intensity as well as the Japanese version of the quality of the recovery-40 (QOR-40) were determined in an interview prior to and at 6 months after the surgery. Acute pain trajectory was determined by a group-based trajectory modeling analysis that was based on the pain intensity at 1-7 days after surgery. Predictive value of the acute pain trajectory for the presence of pain at 6 months after the surgery was assessed by a logistic regression model. The predictive value was compared with pain intensity at 1 day after the surgery. RESULTS: A total of 123 participants completed the 6-month follow-up. The three-cluster model (mild, moderate, and severe pain) was considered to be the most statistically appropriate model for the acute pain trajectory. After 6 months, 51.2% and 8.9% of participants reported pain and severe pain, respectively. Presence of pain at 6 months after the surgery was associated with poor recovery. The severe pain cluster was significantly associated with the presence of pain at 6 months after the surgery (adjusted odds ratio, 9.40; P<0.001 vs mild pain cluster). CONCLUSION: Classification of patients according to the acute pain trajectory, when compared with the classification according to pain intensity at 1 day after the surgery, made it possible to predict with better precision those patients who will develop persistent postsurgical pain.

Risk factors and prognosis of pain events during mechanical ventilation: a retrospective study.

BACKGROUND: Pain assessment is highly recommended in patients receiving mechanical ventilation. However, pain intensity and its impact on outcomes in these patients remain obscure. We collected the results of routine pain assessments, utilizing the behavioral pain scale (BPS), from 151 patients receiving mechanical ventilation. Risk factors associated with a pain event, defined as BPS of >5, and its impact on patient outcomes were investigated. METHODS: A total of 151 consecutive adult patients receiving mechanical ventilation for more than 24 h in a single 10-bed ICU were enrolled in this study. The highest BPS within 48 h after the initiation of mechanical ventilation was collected, as well as information about the patients' characteristics and medication received. We also recorded patient outcomes, including time to successful weaning from mechanical ventilation, time to successful ICU discharge, and 30-day in-hospital mortality. Multivariate logistic regression analysis was used to determine factors independently associated with patients with a BPS of >5. Clinical outcomes were also assessed using multivariate logistic regression analysis, correcting for risk factors. RESULTS: We analyzed 151 patients. The median highest BPS was 4. The percentage of patients who recorded a BPS of >5 was 19.9% (n = 30). Multivariate logistic regression analysis revealed that the disuse of fentanyl and inotropic support was an independent predictor of pain event. Multivariable Cox regression analysis suggested that the development of a BPS of >5 was associated with increased mortality and a not statistically significant trend towards prolonged mechanical ventilation. CONCLUSIONS: A significant proportion of ventilated patients experienced a BPS of >5 soon after the initiation of mechanical ventilation. Disuse of fentanyl and use of inotropic agents increased the risk of developing a BPS of >5 during mechanical ventilation. An association between adequate analgesia and improved patient outcomes provides a rationale for the assessment of pain during mechanical ventilation, with subsequent intervention if necessary. Pain events were common among ventilated patients. In critical care settings, appropriate and adequate pain management is warranted, given the association with improved patient outcomes.