Development and clinical evaluation of a contextually adapted respiratory critical care nurse specialist protocol (RESPIRE study): A sequential multimethod, single-center study

Purpose: To systematically develop and evaluate a contextually-adapted Respiratory Critical Care Nurse Specialist (RCCNS) protocol in healthcare settings structurally lacking Registered Respiratory Therapists (RTs). Methods: A prospective, single-center, sequential multimethod design (scoping review, qualitative analysis, Delphi consensus) formalized the RCCNS protocol. This randomized, open-label, blinded-endpoint trial allocated critically ill patients in a 1:1 ratio to two parallel arms (n = 50 each) receiving either continuous RCCNS intervention or standard care. Inverse probability of treatment weighting (IPTW) equilibrated baseline covariates (age, prognostic scores, comorbidities). Endpoints included alive ICU discharge, 28-day post-hospital mortality, length of stay (LOS), and Ventilator-Associated Pneumonia (VAP), adjudicated primarily by Ventilator-Associated Condition (VAC) criteria maximizing objectivity. Firth’s penalized Cox models, progressive sensitivity analyses, and causal mediation analysis evaluated intervention robustness and mechanisms. Results: The protocol-driven intervention correlated with reduced early mechanical ventilation (80.0% vs. 96.0%, P = 0.014), median ICU LOS (12.0 vs. 29.0 days, P < 0.001), and objectively-adjudicated VAP (10.0% vs. 28.0%, P = 0.022). IPTW-adjusted Cox models yielded adjusted hazard ratios (aHR) of 1.45 (95%CI: 1.10–1.95) for alive ICU discharge and 0.62 (95%CI: 0.31–1.22) for 28-day mortality. Sensitivity models incorporating clinical trajectory proxies and terminal events yielded stable estimates, indicating mortality shifts lacked premature discharge biases. Causal mediation confirmed effects operated primarily via direct mechanisms (NDE OR 0.144, 95%CI: 0.052–0.430) independent of early VAP. Conclusion: The intervention did not significantly reduce 28-day mortality (primary outcome) versus standard care. However, exploratory secondary outcome analyses demonstrated significant ICU LOS and mechanical ventilation duration reductions. These findings do not support routine implementation for survival benefits but warrant adequately-powered multicenter trials. Implication for clinical practice: In infrastructures lacking RTs, delegating advanced respiratory care requires systematic standardization. This study indicates that implementing a formally derived, protocol-driven Respiratory Critical Care Nurse Specialist intervention is associated with reduced intensive care LOS, decreased early mechanical ventilation, and lower VAP incidence, offering an evidence-based framework to optimize resource utilization. These exploratory causal findings merely generate hypotheses, requiring confirmation via adequately powered multicenter trials.