Comparative Effects of Respiratory Stimulants in Mechanically Ventilated Patients: A Network Meta-Analysis of Randomized Controlled Trials Publisher Pubmed



Sahebnasagh A ; Hoseini SM ; Mojtahedzadeh M ; Jelodar MG ; Hoseinzadeh F ; Salehiabargouei A ; Saghafi F
Source: Scientific Reports Published:2025

Abstract

Mechanical ventilation (MV) is a cornerstone of supportive care in intensive care units (ICUs), but prolonged ventilation is associated with adverse outcomes. Several pharmacologic agents with respiratory stimulants have been investigated to facilitate weaning and improve clinical outcomes; yet no comprehensive comparison across available agents exists. This network meta-analysis (NMA) aimed to compare and rank available interventions in adult patients receiving MV. A systematic search of PubMed, Web of Science, and Scopus (up to November 10, 2023) identified 15 randomized controlled trials (1,528 participants) evaluating ten respiratory stimulants in mechanically ventilated critically ill adults: Almitrine Bismesylate (AB), Doxofylline (DX), Progesterone (PRG), Acetazolamide (ACZT), Growth Hormone (GH), Oxandrolone (OXA), Nandrolone (NA), Caffeine (CAF), Donepezil (DPZ), and a multi-agent adjuvant therapeutic (AT) regimen containing anisodamine. Data were analyzed using a frequentist network meta-analysis with treatment rankings based on SUCRA values. Risk of bias was assessed using the modified Cochrane RoB 2 tool. No pharmacologic intervention significantly reduced hospital or ICU mortality, duration of mechanical ventilation, or time to successful weaning compared with placebo. According to SUCRA rankings, NA, OXA, and PRG had the highest probabilities of reducing hospital mortality, with NA also associated with shorter ICU and hospital stays. DPZ and PRG significantly shortened weaning duration, while GH showed the greatest reduction in mechanical ventilation duration. GH, PRG, and DPZ had the highest likelihood of successful weaning. Heterogeneity and inconsistency were generally low, except for the duration of mechanical ventilation (I² = 86.2%, p < 0.001). No pharmacologic intervention significantly reduced hospital mortality. However, agents such as NA, GH, and DPZ may help shorten ICU stay, reduce duration of mechanical ventilation, or improve weaning efficiency. These findings underscore the potential value of multi-agent adjuvant approaches and highlight the need for larger, high-quality trials to confirm their clinical benefits. Trial registration: CRD42023454122 (18/10/2023). © The Author(s) 2025.