Key result
Closed-loop IV esmolol achieves ~52% systolic BP time-in-range in preclinical testing.
Why the study?
Manual drug titration for acute hypertension is prone to operator delays, dose imprecision, and haemodynamic overshoot, while short-term beat-to-beat blood pressure variability contributes to haemodynamic stress. Autonomous closed-loop control may simultaneously achieve precise target attainment and variability minimisation, but preclinical validation with integrated safety supervision was lacking.
Does an autonomous closed-loop intravenous esmolol infusion system with safety supervision improve systolic blood pressure time-in-range and reduce beat-to-beat blood pressure variability compared to the untreated phase in a Yorkshire swine model?
Does an autonomous closed-loop intravenous esmolol infusion system with safety supervision improve systolic blood pressure time-in-range and reduce beat-to-beat blood pressure variability compared to the untreated phase in a Yorkshire swine model?
This large-animal preclinical study provides proof-of-concept that an autonomous closed-loop intravenous esmolol system can simultaneously regulate systolic blood pressure within a target band and reduce beat-to-beat blood pressure variability while maintaining automated safety supervision.
Animal validation supports closed-loop esmolol feasibility; hypothesis-generating and leaves open human translation.
Background/Introduction Acute hypertension management in high-acuity settings - including hypertensive emergencies and perioperative care - relies on manual drug titration, which is subject to operator delays, dose imprecision, and haemodynamic overshoot.1 Beyond threshold attainment, blood pressure variability (BPV) is increasingly recognised as an independent cardiovascular risk factor, with the contribution of short-term beat-to-beat fluctuations to haemodynamic stress in the acute setting requiring further exploration.2,3,4 Autonomous closed-loop control offers the potential to achieve both precise target attainment and BPV minimisation simultaneously, but preclinical validation with integrated safety supervision is lacking. Purpose To develop and validate a closed-loop intravenous esmolol infusion system for automated systolic blood pressure (SBP) regulation and BPV reduction in a large-animal model, incorporating real-time safety supervision and pharmacological rescue. Methods Following institutional ethical approval, five female Yorkshire swine underwent intravenous esmolol infusion across five experimental days. Open-loop dose-response characterisation (n=1) informed controller design. Closed-loop control employed a multi-layer feedback architecture with adaptive modulation to accommodate evolving haemodynamic conditions and variability dynamics. An independent supervisory safety layer provided autonomous override and pharmacological counter-regulation in the event of excessive blood pressure reduction. A predefined SBP reduction band was specified. Performance metrics included time-in-range (TIR) and average real variability (ARV). Results In closed-loop validation experiments, representative performance demonstrated TIR of 51.7% versus 0% during the untreated phase. During steady-state regulation, ARV was reduced by 31% (0.91 vs 1.32 mmHg), confirming simultaneous target attainment and beat-to-beat variability suppression. Diastolic blood pressure and heart rate decreased by 6.0% and 9.1% respectively, remaining within safe limits. In dedicated safety stress-testing, four autonomous SBP threshold violations triggered immediate pump suspension and drug rescue with successful controller re-engagement, without operator input. Conclusions A closed-loop intravenous esmolol system achieved autonomous SBP regulation within a predefined target band while simultaneously reducing beat-to-beat BPV, with preserved secondary haemodynamic stability and reliable automated safety responses in a large-animal model. These findings provide proof-of-concept for device-based autonomous hypertension and BPV control warranting translation to human studies.
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Curneen et al. (2026) studied Acute systolic blood pressure regulation and beat-to-beat blood pressure variability (n=5). Autonomous closed-loop intravenous esmolol infusion system with safety supervision vs. Untreated phase was evaluated on Systolic blood pressure time-in-range (TIR) and average real variability (ARV). Closed-loop IV esmolol achieved 51.7% systolic BP time-in-range vs 0% untreated and reduced beat-to-beat variability by 31% (0.91 vs 1.32 mmHg) in swine.
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