Adjunct low-dose ketamine infusion vs standard of care in mechanically ventilated critically ill patients at a Tertiary Saudi Hospital (ATTAINMENT Trial): study protocol for a randomized, prospective, pilot, feasibility trial

Abstract

Background: A noticeable interest in ketamine infusion for sedation management has developed among critical care physicians for critically ill patients. The 2018 Pain, Agitation/sedation, Delirium, Immobility, and Sleep disruption guideline suggested low-dose ketamine infusion as an adjunct to opioid therapy to reduce opioid requirements in post-surgical patients in the intensive care unit (ICU). This was, however, rated as conditional due to the very low quality of evidence. Ketamine has favorable characteristics, making it an especially viable alternative for patients with respiratory and hemodynamic instability. The Analgo-sedative adjuncT keTAmine Infusion iN Mechanically vENTilated ICU patients (ATTAINMENT) trial aims to assess the effect and safety of adjunct low-dose continuous infusion of ketamine as an analgo-sedative compared to standard of care in critically ill patients on mechanical ventilation (MV) for ≥ 24 h.Methods/design: This trial is a prospective, randomized, active controlled, open-label, pilot, feasibility study of adult ICU patients (> 14 years old) on MV. The study will take place in the adult ICUs in the King Faisal Specialist Hospital and Research Center (KFSH&RC), Riyadh, Saudi Arabia, and will enroll 80 patients. Patients will be randomized postintubation into two groups: the intervention group will receive an adjunct low-dose continuous infusion of ketamine plus standard of care. Ketamine will be administered over a period of 48 h at a fixed infusion rate of 2 μg/ kg/min (0.12 mg/kg/h) in the first 24 h followed by 1 μg/kg/min (0.06 mg/kg/h) in the second 24 h. The control group will receive standard of care in the ICU (propofol and/or fentanyl and/or midazolam) according to the KFSH&RC sedation and analgesia protocol as clinically appropriate. The primary outcome is MV duration until ICU discharge, death, extubation, or 28 days post-randomization, whichever comes first.

Adjunctive ketamine for sedation in critically ill mechanically ventilated patients: an active-controlled, pilot, feasibility clinical trial

“…This was an investigator-initiated, pilot, single-center, parallel-group, open-label RCT (Registered with ClinicalTrials.gov: NCT04075006, current controlled trials: ISRCTN14730035, and Saudi Food and Drug Authority 19063002). The study was approved by King Faisal Specialist Hospital and Research Center (KFSH&RC) Institutional Review Board (IRB) (Riyadh, SA, IRB# 2191187) and full study protocol was published previously [ 23 ]. The trial was conducted according to CONSORT guidelines for pilot and feasibility trials and reported according to pilot study checklist [ 24 ].…”

“…Successful recruitment was defined as > 3 patients enrolled per month. Protocol adherence was defined as > 75% of protocolized intervention and assessment of protocol deviation and violation [ 23 ]. We conducted educational sessions for clinicians, nurses, and hospital pharmacies to facilitate implementation of protocol.…”

Adjunctive Ketamine for Sedation in Critically Ill Mechanically Ventilated Patients: An Active-Controlled, Pilot, Feasibility Clinical Trial

“…The ATTAINMENT trial was registered with ClinicalTrials.gov: NCT04075006, current controlled trials: ISRCTN14730035, and Saudi Food and Drug Authority: SCTR #19063002. The full study protocol has been published previously [13] . The study was conducted according to the Consolidated Standards of Reporting Trials (CONSORT) guidelines.…”

“…Data were stored online in REDCap web application and data quality assessments were executed routinely to ensure completion and accuracy. Details about the variables extracted from the electronic medical record were reported previously [13] .…”

“…We used random source data verification to monitor data integrity and ensure data fidelity. An independent Research Advisory Council at our institution served as a Data Safety Monitoring Committee (DSMC) and reviewed all adverse events (including all deaths) [13] .…”