Acute effects of esketamine on hypoxic ventilatory response, haemodynamics, and brain function in healthy volunteers.
Simone C Jansen, Monique van Velzen, Elise Sarton, Albert Dahan, Marieke Niesters, Rutger van der Schrier
British Journal of Anaesthesia February 1, 2025 DOI: 10.1016/j.bja.2024.08.040 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Open-label study Peer reviewed |
|---|---|
| Sample size | 18 |
| Population | Healthy subjects |
| Intervention | Esketamine |
| Dose | 1.0 mg kg-1 |
| Duration | 3-hour escalating i.v. infusion |
| Topics | Esketamine Ketamine |
| Keywords | Haemodynamics Hypoxic ventilatory response Anesthesia Respiratory medicine Drug safety Cardiovascular effects Clinical research |
| Citations | 11 |
| Key points | Esketamine up to 1 mg per kg does not affect the ventilatory response to hypoxia but increases blood pressure, heart rate, anxiety, and alertness. |
Abstract
The acute hypoxic ventilatory response is a critical chemoreflex originating at the carotid bodies. This study investigates the impact of low-dose i.v. esketamine on the ventilatory response to 20 min of isocapnic hypoxia to test the hypothesis that esketamine does not affect hypoxic ventilation. In this open-label study, 18 healthy subjects received a 3-h escalating i.v. infusion of esketamine, totalling 1.0 mg kg-1. Before the esketamine infusion (control condition) and during the last 30 min of infusion, the ventilatory response to 20 min of isocapnic hypoxia (oxygen saturation ∼80%) was measured. We assessed the increase in ventilation from baseline to its peak during the first 5 min of isocapnic hypoxia (hypoxic ventilatory response) and the increase in ventilation from baseline to 20 min of isocapnic hypoxia (sustained hypoxia). Haemodynamics and acute brain function were also measured. Independent of hypoxia, a small excitatory effect of ketamine on isocapnic ventilation was observed: the mean increase in ventilation (95% confidence interval) was 3.1 (2.4-3.7) L min-1 (P<0.0001). Esketamine had no effect on the isocapnic ventilatory response to acute and sustained hypoxia but increased MAP (+10 mm Hg) and heart rate (+10 beats min-1), similarly during normoxia and hypoxia. Esketamine increased anxiety and alertness and affected external perception. I.V. esketamine up to 1 mg kg-1 does not affect the ventilatory response to hypoxia, but affects haemodynamics and acute brain function. Increases in anxiety and alertness could be a cause of the sustained ventilatory response to hypoxia during esketamine infusion. The trial was registered at the ISRCTN registry on June 27, 2023 under identifier ISRCTN 42617929 (https://www.isrctn.com/ISRCTN42617929).
Comparable studies
Other non-randomized and open-label trials on esketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression Adults (≥ 18 years) with treatment-resistant depression | 2020 | Phase 3, open-label, multicenter, long-term study | n = 802 |
| Long-Term Safety and Maintenance of Response With Esketamine Nasal Spray in Participants With Treatment-Resistant Depression: Interim Results of the SUSTAIN-3 Study Adults with treatment-resistant depression | 2023 | Open-label, long-term extension study | n = 1,148 |
| Safety and efficacy with esketamine in treatment-resistant depression: long-term extension study. Adults with treatment-resistant depression who participated in ≥1 of 6 phase 3 parent... | 2025 | Open-label, single-arm long-term extension study | n = 1,148 |
| Efficacy and Safety of Intranasal Esketamine in Patients With Treatment-Resistant Depression and Comorbid Chronic Post-traumatic Stress Disorder: Open-Label Single-Arm Pilot Study Patients with treatment-resistant major depressive disorder and comorbid post-traumatic... | 2022 | Open-label, single-arm, retrospective pilot study | n = 11 |
| Managing Esketamine Treatment Frequency Toward Successful Outcomes: Analysis of Phase 3 Data Patients with treatment-resistant depression | 2020 | Post-hoc analysis of an open-label, long-term study | n = 778 |
Citations in the library
Cited by 4
- Esketamine for postoperative sleep disturbance: clinical evidence, mechanisms, and future directions. Frontiers in Psychiatry 2025
- Esketamine versus fentanyl as adjuncts to hepatic hilar nerve block for ambulatory percutaneous liver tumor ablation focusing on respiratory safety: protocol for a randomized controlled trial Frontiers in Pharmacology September 17, 2025
- Esketamine Preserves Network Connectivity and Promotes Recovery in Consciousness Disorders. CNS Neuroscience & Therapeutics May 1, 2026
- Effects of sub-anesthetic doses of esketamine on immune function and postoperative negative emotions in acoustic neuroma patients: a randomized clinical trial. Annals of medicine July 3, 2026