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Ginsenosides have antioxidant and anti-inflammatory features. This study aimed to evaluate the biologic effects of ginsenoside Rb2 pretreatment on ventilator-induced lung injury (VILI) in rats. Rats were divided into four groups with 12 rats per group: control; low tidal volume (TV), TV of 6 mL/kg, VILI, TV of 20 mL/kg, positive end-expiratory pressure of 5 cm H2O, and respiratory rate of 60 breaths per minute for 3 h at an inspiratory oxygen fraction of 0.21; and ginsenosides, treated the same as the VILI group but with 20 mg/kg intraperitoneal ginsenoside pretreatment. Morphology was observed with a microscope to confirm the VILI model. Wet-to-dry weight ratios, protein concentrations, and pro-inflammatory cytokines in the bronchoalveolar lavage fluid were measured. RNA sequencing of the lung tissues was conducted to analyze gene expression. High TV histologically induced VILI with alveolar edema and infiltration of inflammatory cells. Ginsenosides pretreatment significantly reduced the histologic lung injury score compared to the VILI group. Wet-to-dry weight ratios, malondialdehyde, and TNF-α in bronchoalveolar lavage fluid were significantly higher in the VILI group and ginsenoside pretreatment mitigated these effects. In the immunohistochemistry assay, ginsenoside pretreatment attenuated the TNF-α upregulation induced by VILI. We identified 823 genes differentially presented in the VILI group compared to the control group. Of the 823 genes, only 13 genes (Arrdc2, Cygb, Exnef, Lcn2, Mroh7, Nsf, Rexo2, Srp9, Tead3, Ephb6, Mvd, Sytl4, and Ube2l6) recovered to control levels in the ginsenoside group. Ginsenosides inhibited the inflammatory and oxidative stress response in VILI. Further studies are required on the 13 genes, including LCN2.

Dynamic change of heart rate in the acute phase and clinical outcomes after intracerebral hemorrhage (ICH) remains unknown. We aimed to investigate the associations of heart rate trajectories and variability with functional outcome and mortality in patients with acute ICH. This prospective study was conducted among 332 patients with acute ICH. Latent mixture modeling was used to identify heart rate trajectories during the first 72 h of hospitalization after ICH onset. Mean and coefficient of variation of heart rate measurements were calculated. The study outcomes included unfavorable functional outcome, ordinal shift of modified Rankin Scale score, and all-cause mortality. We identified 3 distinct heart rate trajectory patterns (persistent-high, moderate-stable, and low-stable). During 3-month follow-up, 103 (31.0%) patients had unfavorable functional outcome and 46 (13.9%) patients died. In multivariable-adjusted model, compared with patients in low-stable trajectory, patients in persistent-high trajectory had the highest odds of poor functional outcome (odds ratio 15.06, 95% CI 3.67–61.78). Higher mean and coefficient of variation of heart rate were also associated with increased risk of unfavorable functional outcome (P trend < 0.05), and the corresponding odds ratios (95% CI) comparing two extreme tertiles were 4.69 (2.04–10.75) and 2.43 (1.09–5.39), respectively. Likewise, similar prognostic effects of heart rate dynamic changes on high modified Rankin Scale score and all-cause mortality were observed. Persistently high heart rate and higher variability in the acute phase were associated with increased risk of unfavorable functional outcome in patients with acute ICH.

Transpulmonary pressure is an essential physiologic concept as it reflects the true pressure across the alveoli, and is a more precise marker for lung stress. To calculate transpulmonary pressure, one needs an estimate of both alveolar pressure and pleural pressure. Airway pressure during conditions of no flow is the most widely accepted surrogate for alveolar pressure, while esophageal pressure remains the most widely measured surrogate marker for pleural pressure. This review will cover important concepts and clinical applications for esophageal manometry, with a particular focus on how to use the information from esophageal manometry to adjust or titrate ventilator support. The most widely used method for measuring esophageal pressure uses an esophageal balloon catheter, although these measurements can be affected by the volume of air in the balloon. Therefore, when using balloon catheters, it is important to calibrate the balloon to ensure the most appropriate volume of air, and we discuss several methods which have been proposed for balloon calibration. In addition, esophageal balloon catheters only estimate the pleural pressure over a certain area within the thoracic cavity, which has resulted in a debate regarding how to interpret these measurements. We discuss both direct and elastance-based methods to estimate transpulmonary pressure, and how they may be applied for clinical practice. Finally, we discuss a number of applications for esophageal manometry and review many of the clinical studies published to date which have used esophageal pressure. These include the use of esophageal pressure to assess lung and chest wall compliance individually which can provide individualized information for patients with acute respiratory failure in terms of setting PEEP, or limiting inspiratory pressure. In addition, esophageal pressure has been used to estimate effort of breathing which has application for ventilator weaning, detection of upper airway obstruction after extubation, and detection of patient and mechanical ventilator asynchrony.

Although factor Xa inhibitors have become a popular choice for chronic oral anticoagulation, effective drug reversal remains difficult due to a lack of specific antidote. Currently, 4-factor prothrombin complex concentrate (4F-PCC) is considered the treatment of choice for factor Xa inhibitor-related major bleeding. However, safety of 4F-PCC and its risk of thrombosis when used for this off-label purpose remain unclear. The purpose of this retrospective study is to determine the rate of thromboembolism when 4F-PCC is used for the emergent reversal of factor Xa inhibitors. We conducted a single-center retrospective review of medical records between 2013 and 2017. Patients were included if they received 4F-PCC to reverse rivaroxaban, apixaban, or edoxaban for emergent invasive procedures or during episodes of major bleeding defined as bleeding with hemodynamic instability, fall in hemoglobin of 2 g/dL, or bleeding requiring blood transfusion. Thrombotic events including myocardial infarction, pulmonary embolism, deep vein thrombosis, cerebral vascular accident, and arterial thrombosis of the limb or mesentery were recorded if they occurred within 14 days of 4F-PCC administration. Data was analyzed using point and interval estimation to approximate the rate and confidence interval of thromboembolic events. Forty-three patients were identified in our review. Doses of 4F-PCC were determined by the treating physician and mainly ranged from 25 to 50 IU/kg. Twenty-two patients (51.2%) received both sequential compression devices (SCDs) and subcutaneous heparin for DVT prophylaxis. Twenty-one patients (48.8%) were placed on SCDs only. Three patients received concomitant FFP. Thrombotic events within 14 days of 4F-PCC administration occurred in 1 out of 43 patients (2.1%, 95% CI [0.1–12.3]). This thrombotic event was an upper extremity DVT which occurred 1 day after the patient received 1325 IU (25 IU/kg) of 4F-PCC to reverse rivaroxaban for traumatic intracranial hemorrhage. The patient was taken for emergent decompressive craniotomy after rivaroxaban reversal. In patients who did not undergo surgery or who underwent minor invasive procedures, no thrombotic events were noted. Based on our preliminary data, the thromboembolic rate of 4F-PCC when given at a dose of 25–50 IU/kg to emergently reverse rivaroxaban and apixaban appears acceptable. Since many patients who require 4F-PCC to emergently reverse factor Xa inhibitors will be at high risk of developing thrombotic events, practitioners should be highly vigilant of these complications. Large, multicenter prospective trials are needed to further determine this risk.

To demonstrate feasibility of a music medicine intervention trial in pediatric intensive care and to obtain information on sedation and analgesia dose variation to plan a larger trial. Pilot randomized controlled trial (RCT) was conducted at the Stollery Children’s Hospital general and cardiac intensive care units (PICU/PCICU). The study included children 1 month to 16 years of age on mechanical ventilation and receiving sedation drugs. Patients were randomized in a 1:1:1 ratio to music, noise cancellation or control. The music group received classical music for 30 min three times/day using headphones. The noise cancellation group received the same intervention but with no music. The control group received usual care. A total of 60 patients were included. Average enrollment rate was 4.8 patients/month, with a consent rate of 69%. Protocol adherence was achieved with patients receiving > 80% of the interventions. Overall mean (SD) daily Sedation Intensity Score was 52.4 (30.3) with a mean (SD) sedation frequency of 9.75 (7.21) PRN doses per day. There was a small but statistically significant decrease in heart rate at the beginning of the music intervention. There were no study related adverse events. Eighty-eight percent of the parents thought the headphones were comfortable; 73% described their child more settled during the intervention. This pilot RCT has demonstrated the feasibility of a music medicine intervention in critically ill children. The study has also provided the necessary information to plan a larger trial.

Sepsis-associated encephalopathy (SAE) is related to increased short-term mortality in patients with sepsis. We aim to establish a user-friendly nomogram for individual prediction of 30-day risk of mortality in patients with SAE. Data were retrospectively retrieved from the Medical Information Mart for Intensive Care (MIMIC III) open source clinical database. SAE was defined by Glasgow Coma Score (GCS) < 15 or delirium at the presence of sepsis. Prediction model with a nomogram was constructed in the training set by logistic regression analysis and then undergone internal validation and sensitivity analysis. SAE accounted for about 50% in patients with sepsis and was independently associated with the 30-day mortality of sepsis. Variables eligible for the nomogram included patient’s age and clinical parameters on the first day of ICU admission including the GCS score, lactate, bilirubin, red blood cell distribution width (RDW), mean value of respiratory rate and temperature, and the use of vasopressor. Compared with Sequential Organ Failure Assessment (SOFA) and Logistic Organ Dysfunction System (LODS), the nomogram exhibited better discrimination with an area under the receiver operating characteristic curve (AUROC) of 0.763 (95%CI 0.736–0.791, p < 0.001) and 0.753 (95%CI 0.713–0.794, p < 0.001) in the training and validation sets, respectively. The calibration plot revealed an adequate fit of the nomogram for predicting the risk of 30-day mortality in both sets. Regarding to clinical usefulness, the DCA of the nomogram exhibited greater net benefit than SOFA and LODS in both of the training and validation sets. Besides, the nomogram exhibited acceptable discrimination, calibration, and clinical usefulness in sensitivity analysis. SAE is related to increased 30-day mortality of patients with sepsis. The nomogram presents excellent performance in predicting 30-day risk of mortality in SAE patients, which can be used to evaluate the prognosis of patients with SAE and may be more beneficial once specific treatments towards SAE are developed.