Statistical analysis plan for the replacing protein via enteral nutrition in a stepwise approach in critically ill patients (REPLENISH) randomized clinical trial.

BACKGROUND: The optimal amount and timing of protein intake in critically ill patients are unknown. REPLENISH (Replacing Protein via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients) trial evaluates whether supplemental enteral protein added to standard enteral nutrition to achieve a high amount of enteral protein given from ICU day five until ICU discharge or ICU day 90 as compared to no supplemental enteral protein to achieve a moderate amount of enteral protein would reduce all-cause 90-day mortality in adult critically ill mechanically ventilated patients. METHODS: In this multicenter randomized trial, critically ill patients will be randomized to receive supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition to achieve a high amount of enteral protein (range of 2-2.4 g/kg/day) or no supplemental enteral protein to achieve a moderate amount of enteral protein (0.8-1.2 g/kg/day). The primary outcome is 90-day all-cause mortality; other outcomes include functional and health-related quality-of-life assessments at 90 days. The study sample size of 2502 patients will have 80% power to detect a 5% absolute risk reduction in 90-day mortality from 30 to 25%. Consistent with international guidelines, this statistical analysis plan specifies the methods for evaluating primary and secondary outcomes and subgroups. Applying this statistical analysis plan to the REPLENISH trial will facilitate unbiased analyses of clinical data. CONCLUSION: Ethics approval was obtained from the institutional review board, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia (RC19/414/R). Approvals were also obtained from the institutional review boards of each participating institution. Our findings will be disseminated in an international peer-reviewed journal and presented at relevant conferences and meetings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04475666 . Registered on July 17, 2020.

Replacing protein via enteral nutrition in a stepwise approach in critically ill patients: the REPLENISH randomized clinical trial protocol.

BACKGROUND: Protein intake is recommended in critically ill patients to mitigate the negative effects of critical illness-induced catabolism and muscle wasting. However, the optimal dose of enteral protein remains unknown. We hypothesize that supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition formula to achieve high amount of enteral protein (range 2-2.4 g/kg/day) given from ICU day 5 until ICU discharge or ICU day 90 as compared to no supplemental enteral protein to achieve moderate amount enteral protein (0.8-1.2 g/kg/day) would reduce all-cause 90-day mortality in adult critically ill mechanically ventilated patients. METHODS: The REPLENISH (Replacing Protein Via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients) trial is an open-label, multicenter randomized clinical trial. Patients will be randomized to the supplemental protein group or the control group. Patients in both groups will receive the primary enteral formula as per the treating team, which includes a maximum protein 1.2 g/kg/day. The supplemental protein group will receive, in addition, supplemental protein at 1.2 g/kg/day starting the fifth ICU day. The control group will receive the primary formula without supplemental protein. The primary outcome is 90-day all-cause mortality. Other outcomes include functional and quality of life assessments at 90 days. The trial will enroll 2502 patients. DISCUSSION: The study has been initiated in September 2021. Interim analysis is planned at one third and two thirds of the target sample size. The study is expected to be completed by the end of 2025. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04475666 . Registered on July 17, 2020.

Managing critical care during COVID-19 pandemic: The experience of an ICU of a tertiary care hospital.

BACKGROUND: The COVID-19 pandemic has strained ICUs worldwide. To learn from our experience, we described the critical care response to the outbreak. METHODS: This is a case study of the response of the Intensive Care Department (75-bed capacity) at a tertiary-care hospital to COVID-19 pandemic, which resulted in a high number of critically ill patients. RESULTS: Between March 1 and July 31, 2020, 822 patients were admitted to the adult non-cardiac ICUs with suspected (72%)/confirmed (38%) COVID-19. At the peak of the surge, 125 critically ill patients with COVID-19 were managed on single day. To accommodate these numbers, the bed capacity of 4 ICUs was increased internally from 58 to 71 beds (+40%) by cohorting 2 patients/room in selected rooms; forty additional ICUs beds were created in 2 general wards; one cardiac ICU was converted to managed non-COVID-19 general ICU patients and one ward was used as a stepdown for COVID-19 patients. To manage respiratory failure, 53 new ICU ventilators, 90 helmets for non-invasive ventilation and 47 high-flow nasal cannula machines were added to the existing capacity. Dedicated medical teams cared for the COVID-19 patients to prevent cross-contamination. The nurse-to-patient and RT-to-patient ratio remained mostly 1:1 and 1:6, respectively. One-hundred-ten ward nurses were up-skilled to care for COVID-19 and other ICU patients using tiered staffing model. Daily executive rounds were conducted to identify patients for transfer and at least 10 beds were made available for new COVID-19 admissions/day. The consumption of PPE increased multiple fold compared with the period preceding the pandemic. Regular family visits were not allowed and families were updated daily by videoconferencing and phone calls. CONCLUSIONS: Our ICU response to the COVID-19 pandemic required almost doubling ICU bed capacity and changing multiple aspects of ICU workflow to be able to care for high numbers of affected patients.