Effects of Remimazolam on Breathing Patterns, Respiratory Drive, and Inspiratory Effort in Mechanically Ventilated Patients
Sedatives and analgesics are usually given for analgesic, anxiolytic, or sedating purposes for patients with critical illness, while they inevitably inhibit respiratory and circulatory function. Sometimes, patients receive deep sedation to induce hypoventilation or suppress spontaneous respiratory effort. The sedation level in clinical practice is usually assessed with subjective sedation scoring systems, such as the Richmond Agitation Sedation Scale (RASS). However, studies have found that sedation depth based on RASS is not a reliable marker of respiratory drive during critical illness. In recent years, researchers have proposed to monitor the effects of sedatives and analgesics on respiratory indicators and to implement lung-protective sedation, such as airway occlusion pressure (P0.1), airway occlusion pressure (Pocc). However, different pharmacological characteristics, different depths of sedation, and different sedation regimens among different sedatives and analgesics make a great difference in their effects on respiration. Remimazolam is a new benzodiazepine sedative developed by adding a methyl propionate side chain to the structure of midazolam. As an organic weak base, remimazolam forms a salt with benzenesulfonic acid, which enhances its solubility and stability. The sedative effect of remimazolam primarily occurs through binding to γ-aminobutyric acid type A (GABAA) receptors, opening chloride channels, promoting chloride ion influx, hyperpolarizing neuronal membranes, and thereby suppressing neuronal excitability. The drug acts rapidly, achieving maximum sedation within three minutes after administration. Research on adverse effects of remimazolam remains limited, particularly regarding its impact on respiratory function. Therefore, this study aims to investigate the effects of remimazolam on breathing patterns, respiratory drive, and inspiratory effort in mechanically ventilated patients.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Ikke anvendelig
Kontakter og lokationer
Studiesteder
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Beijing, Kina
- Beijing Tiantan Hospital
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion criteria:
- Patients admitted to the ICU after surgery under general anesthesia;
- Patients with an artificial airway and receiving assisted ventilation in pressure support mode;
- Patients expected to achieve a sedation depth corresponding to a Richmond Agitation and Sedation Scale (RASS) score of -2 to +1;
Exclusion Criteria:
- Patients with brainstem tumors or neuromuscular disorders;
- Patients unable to undergo RASS assessment due to various reasons, such as history of psychiatric disorders (schizophrenia, mania, delirium, cognitive impairment), status epilepticus, or coma;
- Patients with known or suspected allergy or contraindication to any component of the study drug or opioids;
- Severe hepatic dysfunction (Child-Pugh class C);
- Chronic kidney disease (estimated glomerular filtration rate < 60 ml/min/1.73 m²);
- Mean arterial pressure (MAP) < 65 mmHg, or requiring norepinephrine infusion > 0.5 μg/kg/min to maintain MAP ≥ 65 mmHg;
- Age <18 years old;
- Pregnant or breastfeeding women;
- Body mass index (BMI) <18 kg/m² or >30 kg/m²
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: Remimazolam
The investigators conducted a single-arm, prospective physiological trial to assess the respiratory effects of remimazolam. The study enrolled 20 patients receiving invasive mechanical ventilation. Remimazolam was initiated at 0.15 mg/kg/h and increased it by 0.025 mg/kg/h every 30 minutes, up to a maximum of 0.3 mg/kg/h. The primary outcomes were changes in breathing pattern (respiratory rate (RR), tidal volume (VT), and minute ventilation (Vmin)), respiratory drive (airway occlusion pressure (P0.1)), and inspiratory effort (pressure muscle index (PMI) and airway occlusion pressure (ΔPocc)) after 0.15 mg/kg/h infusion of remimazolam. |
Remimazolam will be infused at 0.15，0.175，0.20，0.225，0.25，0.275, 0.3 mg/kg/h in sequence for 30 minutes at each dose. |
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Tidal volume
Tidsramme: At baseline (before sedation with remimazolam) and 0.15 mg/kg/h remimazolam continuous infusion for 30 minutes
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The change in tidal volume 30 minutes after remimazolam was infused at a rate of 0.15mg/kg/h compared to the baseline level without the use of sedative drugs. |
At baseline (before sedation with remimazolam) and 0.15 mg/kg/h remimazolam continuous infusion for 30 minutes
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Respiratory rate
Tidsramme: At baseline (before sedation with remimazolam) and 0.15 mg/kg/h remimazolam continuous infusion for 30 minutes
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The change in respiratory rate 30 minutes after remimazolam was infused at a rate of 0.15mg/kg/h compared to the baseline level without the use of sedative drugs. |
At baseline (before sedation with remimazolam) and 0.15 mg/kg/h remimazolam continuous infusion for 30 minutes
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Minute ventilation
Tidsramme: At baseline (before sedation with remimazolam) and 0.15 mg/kg/h remimazolam continuous infusion for 30 minutes
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The change in minute ventilation 30 minutes after remimazolam was infused at a rate of 0.15mg/kg/h compared to the baseline level without the use of sedative drugs. |
At baseline (before sedation with remimazolam) and 0.15 mg/kg/h remimazolam continuous infusion for 30 minutes
|
|
Airway occlusion pressure (P0.1)
Tidsramme: At baseline (before sedation with remimazolam) and 0.15 mg/kg/h remimazolam continuous infusion for 30 minutes
|
The change in P0.1 30 minutes after remimazolam was infused at a rate of 0.15mg/kg/h compared to the baseline level without the use of sedative drugs. |
At baseline (before sedation with remimazolam) and 0.15 mg/kg/h remimazolam continuous infusion for 30 minutes
|
|
Pressure muscle index (PMI)
Tidsramme: At baseline (before sedation with remimazolam) and 0.15 mg/kg/h remimazolam continuous infusion for 30 minutes
|
The change in PMI 30 minutes after remimazolam was infused at a rate of 0.15mg/kg/h compared to the baseline level without the use of sedative drugs. |
At baseline (before sedation with remimazolam) and 0.15 mg/kg/h remimazolam continuous infusion for 30 minutes
|
|
Airway occlusion pressure (Pocc)
Tidsramme: At baseline (before sedation with remimazolam) and 0.15 mg/kg/h remimazolam continuous infusion for 30 minutes
|
The change in Pocc 30 minutes after remimazolam was infused at a rate of 0.15mg/kg/h compared to the baseline level without the use of sedative drugs. |
At baseline (before sedation with remimazolam) and 0.15 mg/kg/h remimazolam continuous infusion for 30 minutes
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Respiratory rate
Tidsramme: Remimazolam was initiated at 0.15 mg/kg/h and increased it by 0.025 mg/kg/h every 30 minutes, up to a maximum of 0.3 mg/kg/h, respiratory rate was measured after each infusion rate adjustment (0.15，0.175，0.20，0.225，0.25, 0.275, 0.3mg/kg/h)
|
Changing trends in respiratory rate during remimazolam infusion from 0.15 mg/kg/h to 0.3 mg/kg/h |
Remimazolam was initiated at 0.15 mg/kg/h and increased it by 0.025 mg/kg/h every 30 minutes, up to a maximum of 0.3 mg/kg/h, respiratory rate was measured after each infusion rate adjustment (0.15，0.175，0.20，0.225，0.25, 0.275, 0.3mg/kg/h)
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Tidal volume
Tidsramme: Remimazolam was initiated at 0.15 mg/kg/h and increased it by 0.025 mg/kg/h every 30 minutes, up to a maximum of 0.3 mg/kg/h, tidal volume was measured after each infusion rate adjustment (0.15，0.175，0.20，0.225，0.25, 0.275, 0.3mg/kg/h)
|
Changing trends in tidal volume during remimazolam infusion from 0.15 mg/kg/h to 0.3 mg/kg/h |
Remimazolam was initiated at 0.15 mg/kg/h and increased it by 0.025 mg/kg/h every 30 minutes, up to a maximum of 0.3 mg/kg/h, tidal volume was measured after each infusion rate adjustment (0.15，0.175，0.20，0.225，0.25, 0.275, 0.3mg/kg/h)
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Minute ventilation
Tidsramme: Remimazolam was initiated at 0.15 mg/kg/h and increased it by 0.025 mg/kg/h every 30 minutes, up to a maximum of 0.3 mg/kg/h, minute ventilation was measured after each infusion rate adjustment (0.15，0.175，0.20，0.225，0.25, 0.275, 0.3mg/kg/h)
|
Changing trends in minute ventilation during remimazolam infusion from 0.15 mg/kg/h to 0.3 mg/kg/h |
Remimazolam was initiated at 0.15 mg/kg/h and increased it by 0.025 mg/kg/h every 30 minutes, up to a maximum of 0.3 mg/kg/h, minute ventilation was measured after each infusion rate adjustment (0.15，0.175，0.20，0.225，0.25, 0.275, 0.3mg/kg/h)
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P0.1
Tidsramme: Remimazolam was initiated at 0.15 mg/kg/h and increased it by 0.025 mg/kg/h every 30 minutes, up to a maximum of 0.3 mg/kg/h, P0.1 was measured after each infusion rate adjustment (0.15，0.175，0.20，0.225，0.25, 0.275, 0.3mg/kg/h)
|
Changing trends in P0.1 during remimazolam infusion from 0.15 mg/kg/h to 0.3 mg/kg/h |
Remimazolam was initiated at 0.15 mg/kg/h and increased it by 0.025 mg/kg/h every 30 minutes, up to a maximum of 0.3 mg/kg/h, P0.1 was measured after each infusion rate adjustment (0.15，0.175，0.20，0.225，0.25, 0.275, 0.3mg/kg/h)
|
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PMI
Tidsramme: Remimazolam was initiated at 0.15 mg/kg/h and increased it by 0.025 mg/kg/h every 30 minutes, up to a maximum of 0.3 mg/kg/h, PMI was measured after each infusion rate adjustment (0.15，0.175，0.20，0.225，0.25, 0.275, 0.3mg/kg/h)
|
Changing trends in PMI during remimazolam infusion from 0.15 mg/kg/h to 0.3 mg/kg/h |
Remimazolam was initiated at 0.15 mg/kg/h and increased it by 0.025 mg/kg/h every 30 minutes, up to a maximum of 0.3 mg/kg/h, PMI was measured after each infusion rate adjustment (0.15，0.175，0.20，0.225，0.25, 0.275, 0.3mg/kg/h)
|
|
Pocc
Tidsramme: Remimazolam was initiated at 0.15 mg/kg/h and increased it by 0.025 mg/kg/h every 30 minutes, up to a maximum of 0.3 mg/kg/h, Pocc was measured after each infusion rate adjustment (0.15，0.175，0.20，0.225，0.25, 0.275, 0.3mg/kg/h)
|
Changing trends in Pocc during remimazolam infusion from 0.15 mg/kg/h to 0.3 mg/kg/h |
Remimazolam was initiated at 0.15 mg/kg/h and increased it by 0.025 mg/kg/h every 30 minutes, up to a maximum of 0.3 mg/kg/h, Pocc was measured after each infusion rate adjustment (0.15，0.175，0.20，0.225，0.25, 0.275, 0.3mg/kg/h)
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Richmond Agitation and Sedation Scale (RASS) score
Tidsramme: Remimazolam was initiated at 0.15 mg/kg/h and increased it by 0.025 mg/kg/h every 30 minutes, up to a maximum of 0.3 mg/kg/h, RASS score was measured after each infusion rate adjustment (0.15，0.175，0.20，0.225，0.25, 0.275, 0.3mg/kg/h).
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Changing trends in RASS score during remimazolam infusion from 0.15 mg/kg/h to 0.3 mg/kg/h. The RASS scale ranges from -5 to +4. The lower the score, the deeper the level of sedation. |
Remimazolam was initiated at 0.15 mg/kg/h and increased it by 0.025 mg/kg/h every 30 minutes, up to a maximum of 0.3 mg/kg/h, RASS score was measured after each infusion rate adjustment (0.15，0.175，0.20，0.225，0.25, 0.275, 0.3mg/kg/h).
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Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Ledende efterforsker: Jian-Xin Zhou, Capital Medical University
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- KY2023-182-04
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