Reduced fixed dose tocilizumab 400 mg IV compared to weight-based dosing in critically ill patients with COVID-19: A before-after cohort study.

Background: Interleukin-6 inhibitors reduce mortality in severe COVID-19. British Columbia began using tocilizumab 8 mg/kg (maximum 800 mg) in January 2021 in critically ill patients with COVID-19, but due to drug shortages, decreased dosing to 400 mg IV fixed dose in April 2021. The aims of this study were twofold: to compare physiological responses and clinical outcomes of these two strategies, and examine the cost-effectiveness of treating all patients with 400 mg versus half the patients with 8 mg/kg and the other half without tocilizumab. Methods: This was a single-centre, before-after cohort study of critically ill COVID-19 patients treated with tocilizumab, and a control cohort treated with dexamethasone only. Physiological responses and clinical outcomes were compared between patients receiving both doses of tocilizumab and those receiving dexamethasone only. We built a decision tree model to examine cost-effectiveness. Findings: 152 patients were included; 40 received tocilizumab 8 mg/kg, 59 received 400 mg and 53 received dexamethasone only. Median CRP fell from 103 mg/L to 5.2 mg/L, 96 mg/L to 6.8 mg/L and from 81.3 mg/L to 48 mg/L in the 8 mg/kg, 400 mg tocilizumab, and dexamethasone only groups, respectively. 28-day mortality was 5% (n=2) vs 8% (n=5) vs 13% (n=7), with no significant difference in all pair-wise comparison. At an assumed willingness-to-pay threshold of $50,000 Canadian per life-year, utilizing 400 mg for all patients rather than 8 mg/kg for half the patients is cost-effective in 51.6% of 10,000 Monte Carlo simulations. Interpretation: Both doses of tocilizumab demonstrated comparable reduction of inflammation with similar 28-day mortality. Without consideration of equity, the net monetary benefits of providing 400 mg tocilizumab to all patients are comparable to 8 mg/kg to half the patients. In the context of ongoing drug shortages, fixed-dose 400 mg tocilizumab may be a practical, feasible and economical option. Funding: This work was supported by a gift donation from Hsu & Taylor Family to the VGH Foundation, and the Yale Bernard G. Forget Scholarship.

Dexmedetomidine Use in Intensive Care Unit Sedation and Postoperative Recovery in Elderly Patients Post-Cardiac Surgery (DIRECT).

OBJECTIVE: This study examined recovery, delirium, and neurocognitive outcome in elderly patients receiving dexmedetomidine or propofol sedation after undergoing cardiac surgery. DESIGN: Open-label randomized trial. SETTING: Single center. PARTICIPANTS: A total of 70 patients older than 75 years without English language limitations and Mini Mental State Examination scores >20. INTERVENTIONS: Patients received either propofol (group P) or dexmedetomidine (group D) postoperatively until normothermic and hemodynamically stable. MEASUREMENTS AND MAIN RESULTS: Quality of recovery (QoR) was measured by the QoR-40 questionnaire on postoperative day (POD) three. Secondary outcomes were incidence and duration of delirium, time to extubation, length of hospital stay, hospital mortality rate, postoperative quality of life (QoL; measured by SF-36 performed at baseline and six months postoperatively), and neurocognitive disorder (measured by Minnesota Cognitive Acuity Screen [MCAS] performed at baseline, POD5, and six months postoperatively). A total of sixty-seven patients completed the trial. There was no significant difference in QoR-40 scores (95% confidence interval [CI], -7.6081-to-10.9781; p = 1.000), incidence of delirium (group P, 42%; group D, 24%; p = 0.191), mean hospital stay (95% CI, -5.4838-to-1.5444; p = 0.297), mean time to extubation (95% CI, -19.2513-to-7.5561; p = 0.866), or mean duration of delirium (95% CI, -4.3065-to-1.067; p = 0.206) between groups. No patients died in the hospital. There were no significant differences in changes in SF-36 or MCAS scores over time between groups. There was a decline in MCAS score from preoperatively to POD5 in group P (95% CI, -8.95725-to- -2.61775; p = 0.0005), which was greater than that observed in group D. CONCLUSIONS: The authors' findings demonstrated that the use of dexmedetomidine compared with propofol in elderly patients undergoing cardiac surgery was unlikely to improve QoR/postoperative QoL. Although the study was underpowered to detect secondary outcomes, the results suggested no reductions in delirium, time to extubation, and hospital stay, but a potential decrease in delayed neurocognitive recovery.