Preliminary study regarding the predicted body weight-based dexamethasone therapy in patients with COVID-19 pneumonia

Abstract

Background The RECOVERY clinical trial reported that 6 mg of dexamethasone once daily for up to 10 days reduces the 28-day mortality in patients with coronavirus disease 2019 (COVID-19) receiving respiratory support. In our clinical setting, a fixed dose of dexamethasone has prompted the question of whether inflammatory modulation effects sufficiently reduce lung injury. Therefore, preliminary verification on the possibility of predicted body weight (PBW)-based dexamethasone therapy was conducted in patients with COVID-19 pneumonia. Methods This single-center retrospective study was conducted in a Japanese University Hospital to compare the treatment strategies/management in different periods. Consecutive patients (n = 90) with COVID-19 pneumonia requiring oxygen therapy and were treated with dexamethasone between June 2020 and May 2021 were analyzed. Initially, 60 patients administered a fixed dexamethasone dose of 6.6 mg/day were defined as the conventional group, and then, 30 patients were changed to PBW-based therapy. The 30-day discharged alive rate and duration of oxygen therapy were analyzed using the Kaplan–Meier method and compared using the log-rank test. The multivariable Cox regression was used to evaluate the effects of PBW-based dexamethasone therapy on high-flow nasal cannula (HFNC), noninvasive ventilation (NIV), or mechanical ventilation (MV). Results In the PBW-based group, 9, 13, and 8 patients were administered 6.6, 9.9, and 13.2 mg/day of dexamethasone, respectively. Additional respiratory support including HFNC, NIV, or MV was significantly less frequently used in the PBW-based group (P = 0.0046), with significantly greater cumulative incidence of being discharged alive and shorter oxygen demand within 30 days (92 vs. 89%, log-rank P = 0.0094, 90 vs. 92%, log-rank P = 0.0002, respectively). Patients treated with PBW-based therapy significantly decreased the use of additional respiratory support after adjusting for baseline imbalances (adjusted odds ratio, 0.224; 95% confidence interval, 0.062–0.813, P = 0.023). Infection occurred in 13 (21%) and 2 (7%) patients in the conventional and PBW-based groups, respectively (P = 0.082). Conclusions In patients with COVID-19 pneumonia requiring oxygen therapy, PBW-based dexamethasone therapy may potentially shorten the length of hospital stay and duration of oxygen therapy and risk of using HFNC, NPPV, or MV without increasing serious adverse events or 30-day mortality.

COVID-19 and Pulmonary Angiogenesis: The Possible Role of Hypoxia and Hyperinflammation in the Overexpression of Proteins Involved in Alveolar Vascular Dysfunction

“…The study found an association between patients who did not receive corticosteroids and the increased expression of IL-6. Studies have shown the benefits of corticosteroids, such as dexamethasone, in reducing mortality in COVID-19 patients and reducing biomarkers such as ICAM-1 and ANGPT-2 [ 61 , 62 , 63 , 64 ]. Our results suggest that corticosteroids may benefit not only in reducing inflammation but also in inhibiting endothelial dysfunction and angiogenesis.…”

Combination therapy with predicted body weight-based dexamethasone, remdesivir, and baricitinib in patients with COVID-19 pneumonia: A single-center retrospective cohort study during 5th wave in Japan

“…In this retrospective cohort study involving patients with COVID-19 pneumonia who needed oxygen therapy and were treated with dexamethasone, remdesivir, and baricitinib, the PBW-based dexamethasone was not significantly better than the fixed-dose of dexamethasone for additional respiratory support, length of hospital stay, or oxygen demand. In our previous study, wherein PBW-based dexamethasone therapy shortened the length of hospital stay and duration of oxygen therapy and decreased the risk of using additional respiratory support without increasing serious adverse events or 30-day mortality, we found that an increased dose of dexamethasone based on PBW could be effective for some patients with COVID-19 [ 12 ]. However, PBW-based dexamethasone therapy appears to have no discernible effect in the current study, which included the use of powerful drugs like remdesivir and baricitinib.…”

“…First, administering baricitinib at an adequate time, immediately before hypoxemia occurs, may suppress hyperimmune response due to COVID-19. Sufficient, but not excessive, dexamethasone dosing, such as PBW-based dose dexamethasone, may be beneficial for patients whose inflammation progresses to hypoxemia, allowing the host inflammation to be properly controlled and preventing progression to the next stage of severe respiratory failure [ 12 ]. Glucocorticoids are known to be beneficial in stopping the inflammatory storm resulting from excessive activation of the immune response to viral infection if used at an adequate time during the disease course [ 19 , 20 ].…”

“…The Pulmonary Department modified the therapeutic protocol, and the patients receiving a dose of 6.6 mg/day dexamethasone between June and August 2021 were considered the fixed-dose group. As in our previous study, the PBW-based dose group was divided into three subgroups based on height and sex to receive different dexamethasone doses as follows [ 12 ]: 1) 13.2 mg/day for men with height ≥ 170 cm (≥66 kg at PBW); 2) 9.9 mg/day for men with height < 170 cm (<66 kg at PBW) and for women with height ≥ 150 cm (≥43 kg at PBW); and 3) 6.6 mg/day for women with height < 150 cm (<43 kg at PBW). The protocol involved intravenous administration of dexamethasone once daily for up to 10 days or until hospital discharge for all the groups.…”

“…Our previous retrospective study revealed that predicted body weight (PBW)-based dexamethasone therapy without baricitinib compared with fixed-dose dexamethasone therapy at a dosage of 6.6 mg/day shortened the duration of hospital stay, oxygen therapy, and reduced the risk of using additional respiratory support, including high-flow nasal cannula (HFNC) therapy, noninvasive ventilation (NIV), or mechanical ventilation (MV), without increasing adverse events or 30-day mortality in patients with COVID-19 pneumonia who required oxygen therapy [ 12 ]. As proposed by the Acute Respiratory Distress Syndrome Network, PBW is often used to calculate tidal volume in MV; the PBW formula uses height and sex and reflects normal lung volume [ 13 , 14 ], that is, being overweight or underweight are not able to affect the calculation of PBW.…”