NOTACS — High-Flow Nasal Oxygen After Cardiac Surgery

1. Publication

• Title: High-Flow Nasal Oxygen Therapy After Cardiac Surgery: A Randomized Clinical Trial
• Acronym: NOTACS (Nasal High-Flow Oxygen Therapy After Cardiac Surgery)
• Year & Journal: JAMA Network Open, published April 8, 2026 (9(4):e265447)
• Citation: Litton E, Parke RL, McGuinness SP, et al; Nasal High-Flow Oxygen Therapy After Cardiac Surgery Investigators. High-Flow Nasal Oxygen Therapy After Cardiac Surgery: A Randomized Clinical Trial. JAMA Netw Open. 2026;9(4):e265447. doi:10.1001/jamanetworkopen.2026.5447

2. Context & Rationale

Background: Atelectasis occurs in up to 90% of patients after cardiac surgery and can progress to hypoxia, respiratory failure, and pneumonia; risk is amplified by smoking, COPD/asthma, and obesity. High-flow nasal oxygen therapy (HFNOT) delivers warm humidified oxygen with flow-dependent PEEP, reduces dead space, and improves secretion clearance. A prior pilot trial (Zochios et al., 2018) suggested routine postoperative HFNOT might reduce hospital stay and ICU readmission in high-risk groups, prompting this definitive effectiveness trial.

Research Question/Hypothesis: In patients at increased risk of pulmonary complications after nonemergent cardiac surgery, does prophylactic HFNOT (started at extubation) improve days alive and at home in the first 90 days without increased support (DAH90), compared with standard oxygen therapy (SOT)?

Why This Matters: HFNOT is widely used post-cardiac-surgery despite uncertain effectiveness and added equipment/cost; a definitive answer directly affects routine postoperative respiratory-support protocols at scale.

3. Design & Methods

• Study Type: Investigator-initiated, adaptive, international, multicenter, open-label, parallel-group RCT with blinded outcome assessment
• Setting & Centers: 17 cardiac surgery centers, UK/Australia/New Zealand; enrolled October 7, 2020 – June 19, 2024
• Population:
• Inclusion: Adults ≥18y undergoing elective/urgent cardiac surgery with cardiopulmonary bypass, with ≥1 risk factor: COPD, asthma, lower respiratory tract infection in last 4 weeks, BMI ≥35, or current/recent heavy smoking (>10 pack-years)
• Exclusions: Not further detailed beyond above eligibility framing
• Intervention: HFNOT started at 40% FiO2, flow 30→50 L/min over 5–10 min, for ≥16h post-extubation (escalated per protocol if SpO2 <93%)
• Comparator: SOT, 30–40% FiO2, flow 2–6 L/min via nasal prongs/non-rebreather (not humidified/heated), same escalation criteria
• Randomization: 1:1, stratified by center, permuted blocks of 4 or 6, concealed online allocation (Sealed Envelope)
• Blinding: Open-label for clinicians/patients; outcome adjudicators blinded
• Statistical Power & Follow-Up: Adaptive design; initial n=850 (pilot-based), sample-size re-estimated after 300 patients completed 90-day follow-up (independent statistician, blinded to treatment effect) → increased to 1280 for 90% power to detect a 2-day median DAH90 difference. Primary analysis: Mann-Whitney Wilcoxon test, ITT population. Follow-up to 90 days.

4. Key Results

1280 recruited (640/arm); 1224 (95.6%) had complete DAH90 data.

Adherence: Compliance with allocated treatment: 81.6% (HFNOT) vs 77.8% (SOT).

5. Internal Validity Assessment

• Randomization & Allocation: Concealed, center-stratified, permuted-block randomization via validated online tool — strong.
• Protocol Adherence & Separation: Good (81.6% vs 77.8% compliance); escalation protocol applied symmetrically in both arms.
• Blinding & Detection Bias: Open-label treatment delivery (inherent to comparing two oxygen-delivery devices), but outcome adjudicators were blinded, meaningfully reducing detection bias for the primary and secondary outcomes.
• Missing Data & Sensitivity Analyses: 95.6% primary-outcome completeness; per-protocol, time-on-treatment, and alternative primary-outcome-definition sensitivity analyses were all concordant with the null primary result.
• Overall Internal Validity Conclusion: High — large adequately-powered sample (adaptively re-estimated), blinded outcome assessment, high primary-outcome completeness, and consistent sensitivity analyses support a robust, high-confidence null result.

6. External Validity Assessment

• Population Representativeness: International (3-country), 17-center trial in patients specifically at elevated risk of pulmonary complications (COPD, asthma, obesity, recent LRTI, heavy smoking) — directly targets the population for whom HFNOT is most commonly considered.
• Practice Context: Reflects real-world post-cardiac-surgery ICU/ward care in high-income health systems (UK, Australia, New Zealand).
• Overall External Validity Conclusion: High — largest combined sample of any HFNOT-after-cardiac-surgery trial, purpose-built to test the exact clinical question (and exact at-risk population) for which HFNOT is used in practice.

7. Strengths & Limitations

Strengths:

• Larger sample than all previous HFNOT-after-cardiac-surgery RCTs combined
• International multicenter design with blinded outcome assessment
• Adaptive sample-size re-estimation preserved power without using treatment-effect data
• Comprehensive post-discharge, patient-centered outcome measurement (DAH90, EQ-5D-5L, Barthel index) plus health-economic analysis

Limitations:

• Open-label treatment delivery (unavoidable given device comparison)
• Primary outcome definition was refined mid-trial (addition of the "increased support" component), introducing data-collection complexity and some approximation-bias risk via patient-reported diaries
• Findings apply specifically to nonemergent cardiac surgery; generalizability to other postoperative or emergency populations uncertain

8. Interpretation & Practice Impact

• Clinical Implications: Does not support routine implementation of prophylactic HFNOT after cardiac surgery in patients at elevated pulmonary-complication risk — HFNOT and standard oxygen produce equivalent patient-centered outcomes.
• Mechanistic Coherence: Consistent with a recent systematic review/meta-analysis of 9 smaller, mostly single-center trials showing HFNOT increases oxygenation as intended but without consistent clinical benefit; NOTACS additionally found no reduction in treatment escalation, which that prior meta-analysis had suggested.
• Systems-Level Takeaway: Given equivalent outcomes and HFNOT's added equipment/cost, standard oxygen therapy is a reasonable default for postoperative cardiac surgery respiratory support, reserving HFNOT for specific clinical indications rather than routine prophylaxis.

9. Controversies & Subsequent Evidence

• Editorial Commentary/Debates: A cardiac surgeon commentator (Verma, via TCTMD) suggested the more relevant open question may not be whether prophylactic (blanket) HFNOT works, but whether a "response-guided" window exists for selectively applying HFNOT — NOTACS tested blanket 16-hour prophylactic therapy, not a response-adaptive strategy.
• Guideline Integration: Results are consistent with (and now the largest, most definitive contributor to) existing equipoise in postoperative cardiac surgery respiratory-support guidance; do not support a guideline shift toward routine HFNOT.

10. Summary & Executive Takeaway

Summary: NOTACS randomized 1280 patients at elevated pulmonary-complication risk after nonemergent cardiac surgery to prophylactic HFNOT or standard oxygen for ≥16h post-extubation. The primary outcome (DAH90 without increased support) was identical between groups (median 0 both arms; P=0.75), with concordant null secondary outcomes and sensitivity analyses.

Overall Takeaway: The largest HFNOT-after-cardiac-surgery trial to date provides high-quality evidence that routine prophylactic HFNOT does not improve patient-centered recovery outcomes compared with standard oxygen — arguing against blanket prophylactic use, though a response-guided (rather than blanket) application strategy remains an open question for future trials.

11. Bibliography

• Zochios V, Collier T, Blaudszun G, et al. The effect of high-flow nasal oxygen on hospital length of stay in cardiac surgical patients at high risk for respiratory complications. Anaesthesia. 2018;73(12):1478-1488.
• Liu C, Lin Q, Li D. High-flow nasal cannula therapy versus conventional oxygen therapy for adult patients after cardiac surgery: systematic review and meta-analysis. Heart Lung. 2024;66:47-55.
• Earwaker M, Villar S, Fox-Rushby J, et al. NOTACS study protocol. Trials. 2022;23(1):232.