Safe and long-lasting separation from invasive mechanical ventilation (MV) is a critical aspect of care provision in the intensive care unit (ICU), yet it remains a complex and heterogeneously applied process. Current weaning strategies often rely on fragmented assessments, personal judgment, and poorly integrated decision milestones that individually and collectively may contribute to delayed attempts, weaning and extubation failure. In this How I Do It article, we propose a comprehensive framework based on seven hallmarks, organized into three sequential and interrelated phases (3S framework): screening, separating, and securing. The screening phase includes sedation management, the facilitation phase (maintaining limb and respiratory muscles strength and functionality, as well as cardiac function) and the transition phase (which involves switching from controlled to partial support mode and the stepwise reduction of ventilatory support). The separating phase includes the assessment of readiness for spontaneous breathing trial (SBT), SBT conduct, and extubation risk assessment and decision-making. The securing phase focuses on post-extubation management and includes strategies to prevent respiratory failure. Rather than focusing on isolated physiological parameters or scores, this framework highlights the dynamic, staged, and integrative nature of the weaning process. By structuring current evidence around these hallmarks, we aim to provide both a patient-centered approach to ventilator liberation and a conceptual foundation for future research, protocol development, and clinical decision-making.

A 68-year-old man presented to our thoracic surgery department for evaluation of a left upper-lobe pulmonary nodule detected on chest CT scan. The oncologic history extended over 7 years. In December 2014, the patient was diagnosed with colorectal adenocarcinoma (ileocecal junction) by colonoscopy, and he underwent a laparoscopic right hemicolectomy and lymph node dissection. Postoperative pathological examination revealed a grade II-III adenocarcinoma of the ileocecal region (ulcerative type), infiltrating into the muscularis. Surgical margins were free of tumor. No metastasis was identified in the examined lymph nodes, including paracolic (19), paracolic (7), intermediate mesenteric (23), and central vascular (2) lymph nodes, corresponding to a pathologic stage of pT2N0M0. The patient recovered well and was placed on regular follow-up.

A 70-year-old man with transfusion-dependent myelodysplastic syndrome was treated with luspatercept. Nine months into treatment and 2 months after dose increase, he developed new hypoxemia with a room air resting oxygen saturation of 88%. He was admitted, requiring up to 90% Fio2 by high-flow nasal cannula to maintain saturations ≥ 92%. CT scan demonstrated stable mild probable usual interstitial pneumonia, without ground-glass, pulmonary embolism, or arteriovenous malformation. Agitated saline contrast-enhanced echocardiogram was late positive, consistent with intrapulmonary shunt. Macroaggregated albumin (MAA) shunt scintigraphy demonstrated a shunt of 7.5%. Extensive investigations ruled out congenital portosystemic shunt and hepatopulmonary syndrome. We diagnosed hypoxemia from intrapulmonary vascular dilatation (IPVD), with luspatercept as a possible cause. Oxygen requirements improved, and supplemental oxygen was discontinued by 7 weeks after cessation. Repeat MAA 10 weeks after cessation confirmed shunt resolution (3.6% shunt). This case of reversible IPVD attributable to luspatercept highlights important monitoring implications in treated patients.