Improved survival in COVID-19 related sepsis and ARDS treated with a unique "triple therapy" including therapeutic plasma exchange: A single center retrospective analysis.

BACKGROUND: Throughout the COVID-19 pandemic, the mortality of critically ill patients remained high. Our group developed a treatment regimen targeting sepsis and ARDS which we labeled "triple therapy" consisting of (1) corticosteroids, (2) therapeutic plasma exchange (TPE), and (3) timely intubation with lung protective ventilation. Our propensity analysis assesses the impact of triple therapy on survival in COVID-19 patients with sepsis and ARDS. METHODS: Retrospective propensity analysis comparing triple therapy to no triple therapy in adult critically ill COVID-19 patients admitted to the Intensive Care Unit at Lexington Medical Center from 1 March 2020 through 31 October 2021. RESULTS: Eight hundred and fifty-one patients were admitted with COVID-19 and 53 clinical and laboratory variables were analyzed. Multivariable analysis revealed that triple therapy was associated with increased survival (OR: 1.91; P = .008). Two propensity score-adjusted models demonstrated an increased likelihood of survival in patients receiving triple therapy. Patients with thrombocytopenia were among those most likely to experience increased survival if they received early triple therapy. Decreased survival was observed with endotracheal intubation ≥7 days from hospital admission (P < .001) and there was a trend toward decreased survival if TPE was initiated ≥6 days from hospital admission (P = .091). CONCLUSION: Our analysis shows that early triple therapy, defined as high-dose methylprednisolone, TPE, and timely invasive mechanical ventilation within the first 96 hours of admission, may improve survival in critically ill septic patients with ARDS secondary to COVID-19 infection. Further studies are needed to define specific phenotypes and characteristics that will identify those patients most likely to benefit.

Early Versus Usual Palliative Care Consultation in the Intensive Care Unit.

OBJECTIVES: Palliative Medicine involvement in MICU patients have improved length of stay and mortality, but with varying effects on specific patient decision outcomes, such as, advance care planning. These studies have utilized Palliative Medicine later in the hospital or ICU course, with some evidence showing that earlier involvement resulted in better results. The purpose of this study was to evaluate the benefits of early (within 24 hours) palliative care consultation in medical ICU (MICU) patients to clinical and satisfaction outcomes. METHODS: An unblinded randomized study performed in the MICU in one academic hospital in the USA. Ninety-one adult patients admitted to MICU received a Palliative care medicine consultation within 24 hours as the intervention. MEASUREMENTS AND RESULTS: Ninety-one patients admitted to the MICU underwent randomization with 50 patients randomly assigned to receive Palliative Medicine consultation and 41 patients randomly assigned to receive standard-of-care based on predefined criteria. The median satisfaction score was 23 points higher for the patients in the intervention group (P < .001). The median length of MICU stay was 5 days shorter in the intervention group compared to the control group (95% CI; 1 day to 18 days, P = .018). Advance care planning was completed in the hospital for 34% of patients in the intervention arm and 12% of patients in the controls arm (absolute risk difference 22%, 95% CI 4% to 37%, P = .016). CONCLUSION: Early Palliative Medicine consultation within 24 hours of MICU admission showed significant benefits to patients by improving satisfaction and decreasing length of stay. This study provides evidence that Palliative Medicine involvement earlier in the course of severe disease is important. Further studies in other types of intensive care units (neurological and Cardiovascular) are necessary to determine their impact.

High-Frequency Oscillatory Ventilation for Refractory Hypoxemia in Severe COVID-19 Pneumonia: A Small Case Series.

BACKGROUND COVID-19 continues to place a tremendous burden on the healthcare system, with most deaths resulting from respiratory failure. Management strategies have varied, but the mortality rate for mechanically ventilated patients remains high. Conventional management with ARDSnet ventilation can improve outcomes but alternative and adjunct treatments continue to be explored. High-frequency oscillatory ventilation (HFOV), a modality now rarely used in adult critical care medicine, may offer an alternative treatment option by maximizing lung protection and limiting oxygen toxicity in critically ill patients failing conventional ventilator strategies. CASE REPORT We present 3 patients with severe acute respiratory distress syndrome (ARDS) and sepsis due to COVID-19 who all improved clinically after transitioning from conventional ventilation to HFOV. Two patients developed refractory hypoxemia with hemodynamic instability and multiple organ failure requiring vasopressor support and renal replacement therapy. After failing to improve with all available therapies, both patients stabilized and ultimately improved after being placed on HFOV. The third patient developed severe volutrauma/barotrauma despite extreme lung protection and ARDSnet ventilation. He showed improvement in oxygenation and signs of lung trauma slowly improved after initiating HFOV. All 3 patients were ultimately liberated from mechanical ventilation and discharged from the hospital to return to functional independence. CONCLUSIONS Our experience suggests that HFOV offers advantages in the management of certain critically ill patients with ARDS due to COVID-19 pneumonia and might be considered in cases refractory to standard management strategies.

Association between Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and Lung Cancer.

OBJECTIVES: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are the most commonly prescribed antihypertensives, with prior studies identifying a possible association between long-term use and increased rates of lung cancer. This study evaluated this potential association in a large population using propensity matching. METHODS: This was a population-based cohort study in a large healthcare system in three regions of the United States. Pairwise propensity score matching was performed using demographics and comorbidities. All of the adult patients in the healthcare system from January 1, 2000 to April 30, 2018 with at least 1 year of follow-up were included. RESULTS: In total, 3,253,811 patients with a median age of 59 (range 18-103) years were included. The ACEI group had a higher freedom from lung cancer versus controls at 15 years (98.47%, 95% confidence interval [CI] 98.41-98.54) versus 98.26%, (95% CI 98.20-98.33), whereas ARBs had similar rates versus controls at all time points. For patients diagnosed as having lung cancer, median all-cause survival was significantly higher in the ACEI (34.7 months, 95% CI 32.8-36.6) and ARB (30.9 months, 95% CI 28.1-33.8) groups than the control group (20.6 months, 95% CI 20.1-21.1). CONCLUSIONS: This study showed lower rates of lung cancer with ACEI use and no difference in risk with ARBs. In addition, use of these medications was found to be associated with increased survival in those diagnosed as having lung cancer. This study supports the continued use of these medications without concern for increasing the risk of lung cancer.

Transbronchial Forceps Biopsy in the Intensive Care Unit: A Systematic Review and Meta-analysis.

BACKGROUND: A transbronchial forceps lung biopsy performed in mechanically ventilated patients with respiratory failure of unknown etiology has significant uncertainty of diagnostic yield and safety along with sparse literature. This study investigated the complication rate of transbronchial biopsies in mechanically ventilated patients in the intensive care unit and its ability to obtain a diagnosis and change current therapy. METHODS: PubMed, Ovid MEDLINE, and Ovid Cochrane Central Register of Controlled Trials databases were systematically searched for all publications of transbronchial lung biopsies in mechanically ventilated patients. We pooled the results of individual studies using random-effects meta-analysis models to achieve the summary proportions. RESULTS: Of the identified 9 observational studies with a total of 232 patients undergoing a transbronchial biopsy, complications occurred in 67 patients [25.2%; 95% confidence interval (CI), 11.5%-42.0%; I2=70.0%]. Pneumothorax occurred in 24 patients (9.5%; 95% CI, 4.5%-16.2%; I2=15.9%) and bleeding in 18 patients (8.9%; 95% CI, 4.1%-15.3%; I2=0%). A diagnosis was given in 146 patients (62.9%; 95% CI, 56.0%-69.1%; I2=74.6%), with 103 of 210 patients (49.0%; 95% CI, 44.6%-55.1%; I2=74.9%) having a change in treatment. CONCLUSION: The results of this meta-analysis suggest that a transbronchial forceps biopsy when performed in mechanically ventilated patients with respiratory failure of unclear etiology had a moderate complication rate. These biopsies resulted in varied diagnoses with a high rate of management change. Randomized controlled trials are necessary to identify the ideal patients to perform a transbronchial forceps biopsy on in the intensive care unit.

Social comparison impacts stimulus evaluation in a competitive social learning task.

When we perform an action, the outcome that follows it can change the value we place on that behaviour, making it more or less likely to be repeated in the future. However, the values that we learn are not objective: we interpret the outcomes that we receive for ourselves relative to those that share our environment, i.e. we engage in social comparison. The temporal dynamics of physiological responses to stimulus valuation in social learning tasks are poorly understood, particularly in human participants. Therefore, we recorded stimulus-locked event-related potentials with 64-channel EEG to examine stimulus valuation, following the design of a study previously used in macaques. Pairs of participants performed a social learning task in which they received outcomes sequentially for a presented stimulus (partner first) by pressing a button in response to a cue. There were two conditions: one in which stimulus values varied for the participant but output a constant rate of reward for the partner (self-variable blocks), and another condition in which this payout was reversed (other-variable blocks). We then measured participants' self-reported competitiveness. Approximately 200 ms post-stimulus, an ERP related to stimulus evaluation and attentional processing appeared to encode own stimulus value in self-variable blocks. In other-variable blocks the same pattern of activity was reversed, even though the value of the stimulus for the participant did not depend on the stimulus presented. Outcome-locked analyses further showed that attention dedicated to the partner's outcome was greater in more competitive participants. We conclude that subjective stimulus value can be reflected in early stimulus-locked ERP responses and that competitive participants may be more invested in their own performance relative to the other player, hence their increased interest in the outcome of their partner.

The feedback-related negativity indexes prediction error in active but not observational learning.

Reinforcement learning (RL) theory states that learning is driven by prediction errors (PEs)-the discrepancy between the predicted and actual outcome of an action. When participants learn from their own actions, PEs correlate with the feedback-related negativity (FRN), but it is not clear if the FRN reflects a PE in observational learning. We use a model-based regression analysis of single-trial event-related potentials to determine if the FRN in observational learning is PE driven. Twenty participants (16 female) learned the stimulus-outcome contingencies for a probabilistic three-armed bandit task. They played in pairs, with the acting and observing player switching every one to three trials. An RL-learning algorithm was fit to participants' choices in the task to extract individual PE estimates for every trial of the experiment. In the acting condition, model-estimated PEs covaried positively with neural signal at electrode FCz, 200-350 ms after outcome presentation, which is a typical time frame for the FRN. There was no PE effect in the observation condition in the same time frame. From 300 ms the outcome correlated negatively with the frontal P300 component at FCz and parietal P300 at Pz. At Pz the effect was greater in the acting than the observing condition. The frontal and parietal P300 components have been linked to attentional reorienting and stimulus value updating, respectively. These findings indicate that observed outcomes undergo processing that is distinguishable from directly experienced outcomes in the time windows of the FRN and P3b but that attention dedicated to the two outcomes types is comparable.