Pub Date : 2024-06-01DOI: 10.1097/ALN.0000000000004915
Simone C Jansen, Maarten van Lemmen, Erik Olofsen, Laurence Moss, Joseph V Pergolizzi, Thomas Miller, Robert D Colucci, Monique van Velzen, Philip Kremer, Albert Dahan, Rutger van der Schrier, Marieke Niesters
Background: The use of anesthetics may result in depression of the hypoxic ventilatory response. Since there are no receptor-specific antagonists for most anesthetics, there is the need for agnostic respiratory stimulants that increase respiratory drive irrespective of its cause. The authors tested whether ENA-001, an agnostic respiratory stimulant that blocks carotid body BK-channels, could restore the hypoxic ventilatory response during propofol infusion. They hypothesize that ENA-001 is able to fully restore the hypoxic ventilatory response.
Methods: In this randomized, double-blind crossover trial, 14 male and female healthy volunteers were randomized to receive placebo and low- and high-dose ENA-001 on three separate occasions. On each occasion, isohypercapnic hypoxic ventilatory responses were measured during a fixed sequence of placebo, followed by low- and high-dose propofol infusion. The authors conducted a population pharmacokinetic/pharmacodynamic analysis that included oxygen and carbon dioxide kinetics.
Results: Twelve subjects completed the three sessions; no serious adverse events occurred. The propofol concentrations were 0.6 and 2.0 µg/ml at low and high dose, respectively. The ENA-001 concentrations were 0.6 and 1.0 µg/ml at low and high dose, respectively. The propofol concentration that reduced the hypoxic ventilatory response by 50% was 1.47 ± 0.20 µg/ml. The steady state ENA-001 concentration to increase the depressed ventilatory response by 50% was 0.51 ± 0.04 µg/ml. A concentration of 1 µg/ml ENA-001 was required for full reversal of the propofol effect at the propofol concentration that reduced the hypoxic ventilatory response by 50%.
Conclusions: In this pilot study, the authors demonstrated that ENA-001 restored the hypoxic ventilatory response impaired by propofol. This finding is not only of clinical importance but also provides mechanistic insights into the peripheral stimulation of breathing with ENA-001 overcoming central depression by propofol.
{"title":"Reversal of Propofol-induced Depression of the Hypoxic Ventilatory Response by BK-channel Blocker ENA-001: A Randomized Controlled Trial.","authors":"Simone C Jansen, Maarten van Lemmen, Erik Olofsen, Laurence Moss, Joseph V Pergolizzi, Thomas Miller, Robert D Colucci, Monique van Velzen, Philip Kremer, Albert Dahan, Rutger van der Schrier, Marieke Niesters","doi":"10.1097/ALN.0000000000004915","DOIUrl":"10.1097/ALN.0000000000004915","url":null,"abstract":"<p><strong>Background: </strong>The use of anesthetics may result in depression of the hypoxic ventilatory response. Since there are no receptor-specific antagonists for most anesthetics, there is the need for agnostic respiratory stimulants that increase respiratory drive irrespective of its cause. The authors tested whether ENA-001, an agnostic respiratory stimulant that blocks carotid body BK-channels, could restore the hypoxic ventilatory response during propofol infusion. They hypothesize that ENA-001 is able to fully restore the hypoxic ventilatory response.</p><p><strong>Methods: </strong>In this randomized, double-blind crossover trial, 14 male and female healthy volunteers were randomized to receive placebo and low- and high-dose ENA-001 on three separate occasions. On each occasion, isohypercapnic hypoxic ventilatory responses were measured during a fixed sequence of placebo, followed by low- and high-dose propofol infusion. The authors conducted a population pharmacokinetic/pharmacodynamic analysis that included oxygen and carbon dioxide kinetics.</p><p><strong>Results: </strong>Twelve subjects completed the three sessions; no serious adverse events occurred. The propofol concentrations were 0.6 and 2.0 µg/ml at low and high dose, respectively. The ENA-001 concentrations were 0.6 and 1.0 µg/ml at low and high dose, respectively. The propofol concentration that reduced the hypoxic ventilatory response by 50% was 1.47 ± 0.20 µg/ml. The steady state ENA-001 concentration to increase the depressed ventilatory response by 50% was 0.51 ± 0.04 µg/ml. A concentration of 1 µg/ml ENA-001 was required for full reversal of the propofol effect at the propofol concentration that reduced the hypoxic ventilatory response by 50%.</p><p><strong>Conclusions: </strong>In this pilot study, the authors demonstrated that ENA-001 restored the hypoxic ventilatory response impaired by propofol. This finding is not only of clinical importance but also provides mechanistic insights into the peripheral stimulation of breathing with ENA-001 overcoming central depression by propofol.</p><p><strong>Editor’s perspective: </strong></p>","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":" ","pages":"1076-1087"},"PeriodicalIF":8.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11097949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139501897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01DOI: 10.1097/ALN.0000000000004984
Thomas K Henthorn
{"title":"Reversal for Respiratory Depression: Let's Take a Breath!","authors":"Thomas K Henthorn","doi":"10.1097/ALN.0000000000004984","DOIUrl":"10.1097/ALN.0000000000004984","url":null,"abstract":"","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":"140 6","pages":"1059-1061"},"PeriodicalIF":9.1,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01DOI: 10.1097/ALN.0000000000004928
{"title":"Evaluation of Malignant Hyperthermia Features in Patients with Pathogenic or Likely Pathogenic RYR1 Variants Disclosed through a Population Genomic Screening Program: Erratum.","authors":"","doi":"10.1097/ALN.0000000000004928","DOIUrl":"10.1097/ALN.0000000000004928","url":null,"abstract":"","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":" ","pages":"1057"},"PeriodicalIF":8.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139904800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01DOI: 10.1097/ALN.0000000000004913
Katherine T Forkin, Nicole R Guinn, Matthew A Warner, Anil K Panigrahi
{"title":"Addressing Patient Concerns with Blood Transfusion from Donors Vaccinated Against COVID-19: A Clinician Primer.","authors":"Katherine T Forkin, Nicole R Guinn, Matthew A Warner, Anil K Panigrahi","doi":"10.1097/ALN.0000000000004913","DOIUrl":"10.1097/ALN.0000000000004913","url":null,"abstract":"","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":" ","pages":"1020-1025"},"PeriodicalIF":8.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140058499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01DOI: 10.1097/ALN.0000000000004944
Victor M Neira, Ahmed AlFaraj, Luke Wiseman, Rince John, Pantelis Andreou, Alejandro Cohen
{"title":"Stability of Epinephrine, Norepinephrine, and Phenylephrine for Intravenous Infusions Stored in Three Commercial Plastic Syringe Brands.","authors":"Victor M Neira, Ahmed AlFaraj, Luke Wiseman, Rince John, Pantelis Andreou, Alejandro Cohen","doi":"10.1097/ALN.0000000000004944","DOIUrl":"10.1097/ALN.0000000000004944","url":null,"abstract":"","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":" ","pages":"1047-1049"},"PeriodicalIF":8.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140058501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01DOI: 10.1097/ALN.0000000000004907
Amber K Brooks
{"title":"Unmasking the Pain: Preserving Humanity in Medicine.","authors":"Amber K Brooks","doi":"10.1097/ALN.0000000000004907","DOIUrl":"10.1097/ALN.0000000000004907","url":null,"abstract":"","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":" ","pages":"1045-1046"},"PeriodicalIF":8.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140058502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Identifying the state-related "neural correlates of consciousness" for anesthetics-induced unconsciousness is challenging. Spatiotemporal complexity is a promising tool for investigating consciousness. The authors hypothesized that spatiotemporal complexity may serve as a state-related but not drug-related electroencephalography (EEG) indicator during an unconscious state induced by different anesthetic drugs (e.g., propofol and esketamine).
Methods: The authors recorded EEG from patients with unconsciousness induced by propofol (n = 10) and esketamine (n = 10). Both conventional microstate parameters and microstate complexity were analyzed. Spatiotemporal complexity was constructed by microstate sequences and complexity measures. Two different EEG microstate complexities were proposed to quantify the randomness (type I) and complexity (type II) of the EEG microstate series during the time course of the general anesthesia.
Results: The coverage and occurrence of microstate E (prefrontal pattern) and the duration of microstate B (right frontal pattern) could distinguish the states of preinduction wakefulness, unconsciousness, and recovery under both anesthetics. Type I EEG microstate complexity based on mean information gain significantly increased from awake to unconsciousness state (propofol: from mean ± SD, 1.562 ± 0.059 to 1.672 ± 0.023, P < 0.001; esketamine: 1.599 ± 0.051 to 1.687 ± 0.013, P < 0.001), and significantly decreased from unconsciousness to recovery state (propofol: 1.672 ± 0.023 to 1.537 ± 0.058, P < 0.001; esketamine: 1.687 ± 0.013 to 1.608 ± 0.028, P < 0.001) under both anesthetics. In contrast, type II EEG microstate fluctuation complexity significantly decreased in the unconscious state under both drugs (propofol: from 2.291 ± 0.771 to 0.782 ± 0.163, P < 0.001; esketamine: from 1.645 ± 0.417 to 0.647 ± 0.252, P < 0.001), and then increased in the recovery state (propofol: 0.782 ± 0.163 to 2.446 ± 0.723, P < 0.001; esketamine: 0.647 ± 0.252 to 1.459 ± 0.264, P < 0.001).
Conclusions: Both type I and type II EEG microstate complexities are drug independent. Thus, the EEG microstate complexity measures that the authors proposed are promising tools for building state-related neural correlates of consciousness to quantify anesthetic-induced unconsciousness.
{"title":"State-related Electroencephalography Microstate Complexity during Propofol- and Esketamine-induced Unconsciousness.","authors":"Zhenhu Liang, Bo Tang, Yu Chang, Jing Wang, Duan Li, Xiaoli Li, Changwei Wei","doi":"10.1097/ALN.0000000000004896","DOIUrl":"10.1097/ALN.0000000000004896","url":null,"abstract":"<p><strong>Background: </strong>Identifying the state-related \"neural correlates of consciousness\" for anesthetics-induced unconsciousness is challenging. Spatiotemporal complexity is a promising tool for investigating consciousness. The authors hypothesized that spatiotemporal complexity may serve as a state-related but not drug-related electroencephalography (EEG) indicator during an unconscious state induced by different anesthetic drugs (e.g., propofol and esketamine).</p><p><strong>Methods: </strong>The authors recorded EEG from patients with unconsciousness induced by propofol (n = 10) and esketamine (n = 10). Both conventional microstate parameters and microstate complexity were analyzed. Spatiotemporal complexity was constructed by microstate sequences and complexity measures. Two different EEG microstate complexities were proposed to quantify the randomness (type I) and complexity (type II) of the EEG microstate series during the time course of the general anesthesia.</p><p><strong>Results: </strong>The coverage and occurrence of microstate E (prefrontal pattern) and the duration of microstate B (right frontal pattern) could distinguish the states of preinduction wakefulness, unconsciousness, and recovery under both anesthetics. Type I EEG microstate complexity based on mean information gain significantly increased from awake to unconsciousness state (propofol: from mean ± SD, 1.562 ± 0.059 to 1.672 ± 0.023, P < 0.001; esketamine: 1.599 ± 0.051 to 1.687 ± 0.013, P < 0.001), and significantly decreased from unconsciousness to recovery state (propofol: 1.672 ± 0.023 to 1.537 ± 0.058, P < 0.001; esketamine: 1.687 ± 0.013 to 1.608 ± 0.028, P < 0.001) under both anesthetics. In contrast, type II EEG microstate fluctuation complexity significantly decreased in the unconscious state under both drugs (propofol: from 2.291 ± 0.771 to 0.782 ± 0.163, P < 0.001; esketamine: from 1.645 ± 0.417 to 0.647 ± 0.252, P < 0.001), and then increased in the recovery state (propofol: 0.782 ± 0.163 to 2.446 ± 0.723, P < 0.001; esketamine: 0.647 ± 0.252 to 1.459 ± 0.264, P < 0.001).</p><p><strong>Conclusions: </strong>Both type I and type II EEG microstate complexities are drug independent. Thus, the EEG microstate complexity measures that the authors proposed are promising tools for building state-related neural correlates of consciousness to quantify anesthetic-induced unconsciousness.</p><p><strong>Editor’s perspective: </strong></p>","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":" ","pages":"935-949"},"PeriodicalIF":8.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139073166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01DOI: 10.1097/ALN.0000000000004916
Kunal Panda, Laurent G Glance, Michael Mazzeffi, Yang Gu, Katherine L Wood, Vivek K Moitra, Isaac Y Wu
{"title":"Perioperative Extracorporeal Cardiopulmonary Resuscitation in Adult Patients: A Review for the Perioperative Physician.","authors":"Kunal Panda, Laurent G Glance, Michael Mazzeffi, Yang Gu, Katherine L Wood, Vivek K Moitra, Isaac Y Wu","doi":"10.1097/ALN.0000000000004916","DOIUrl":"10.1097/ALN.0000000000004916","url":null,"abstract":"","PeriodicalId":7970,"journal":{"name":"Anesthesiology","volume":" ","pages":"1026-1042"},"PeriodicalIF":8.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140093302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}