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Philip AB, Brohan J, Goudra B. The Role of GABA Receptors in Anesthesia and Sedation: An Updated Review. CNS Drugs 2025; 39:39-54. [PMID: 39465449 PMCID: PMC11695389 DOI: 10.1007/s40263-024-01128-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/18/2024] [Indexed: 10/29/2024]
Abstract
GABA (γ-aminobutyric acid) receptors are constituents of many inhibitory synapses within the central nervous system. They are formed by 5 subunits out of 19 various subunits: α1-6, β1-3, γ1-3, δ, ε, θ, π, and ρ1-3. Two main subtypes of GABA receptors have been identified, namely GABAA and GABAB. The GABAA receptor (GABAAR) is formed by a variety of combinations of five subunits, although both α and β subunits must be included to produce a GABA-gated ion channel. Other subunits are γ, δ, ε, π, and ϴ. GABAAR has many isoforms, that dictate, among other properties, their differing affinities and conductance. Drugs acting on GABAAR form the cornerstone of anesthesia and sedation practice. Some such GABAAR agonists used in anesthesia practice are propofol, etomidate, methohexital, thiopental, isoflurane, sevoflurane, and desflurane. Ketamine, nitrous oxide, and xenon are not GABAR agonists and instead inhibit glutamate receptors-mainly NMDA receptors. Inspite of its many drawbacks such as pain in injection, quick and uncontrolled conversion from sedation to general anesthesia and dose-related cardiovascular depression, propofol remains the most popular GABAR agonist employed by anesthesia providers. In addition, being formulated in a lipid emulsion, contamination and bacterial growth is possible. Literature is rife with newer propofol formulations, aiming to address many of these drawbacks, and with some degree of success. A nonemulsion propofol formulation has been developed with cyclodextrins, which form inclusion complexes with drugs having lipophilic properties while maintaining aqueous solubility. Inhalational anesthetics are also GABA agonists. The binding sites are primarily located within α+/β- and β+/α- subunit interfaces, with residues in the α+/γ- interface. Isoflurane and sevoflurane might have slightly different binding sites providing unexpected degree of selectivity. Methoxyflurane has made a comeback in Europe for rapid provision of analgesia in the emergency departments. Penthrox (Galen, UK) is the special device designed for its administration. With better understanding of pharmacology of GABAAR agonists, newer sedative agents have been developed, which utilize "soft pharmacology," a term pertaining to agents that are rapidly metabolized into inactive metabolites after producing desired therapeutic effect(s). These newer "soft" GABAAR agonists have many properties of ideal sedative agents, as they can offer well-controlled, titratable activity and ultrashort action. Remimazolam, a modified midazolam and methoxycarbonyl-etomidate (MOC-etomidate), an ultrashort-acting etomidate analog are two such examples. Cyclopropyl methoxycarbonyl metomidate is another second-generation soft etomidate analog that has a greater potency and longer half-life than MOC-etomidate. Additionally, it might not cause adrenal axis suppression. Carboetomidate is another soft analog of etomidate with low affinity for 11β-hydroxylase and is, therefore, unlikely to have clinically significant adrenocortical suppressant effects. Alphaxalone, a GABAAR agonist, is recently formulated in combination with 7-sulfobutylether-β-cyclodextrin (SBECD), which has a low hypersensitivity profile.
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Affiliation(s)
| | | | - Basavana Goudra
- Department of Anesthesiology, Jefferson Surgical Center Endoscopy, Sidney Kimmel Medical College, Jefferson Health, 111 S 11th Street, #7132, Philadelphia, PA, 19107, USA.
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Faine BA, Carroll E, Sharma A, Mohr N. Rapid Sequence Intubation, is it Time to Find an Alternative Induction Agent? A Narrative Review. J Pharm Pract 2024; 37:977-984. [PMID: 37594256 DOI: 10.1177/08971900231197501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/19/2023]
Abstract
Objective: To review the efficacy, safety, and place in therapy of fentanyl as an induction agent for rapid sequence intubation (RSI) in critically ill patients. Data Sources: A comprehensive search of PubMed, EMBASE, and clinical trial registries (1964-June 2021) was performed utilizing the keywords fentanyl, rapid sequence intubation, intubation, induction, anesthesia, hemodynamics, operating room (OR), and emergency. Study Selection and Data Extraction: Only primary literature evaluating fentanyl in combination with a sedative or as the sole induction agent was included in the final analysis. Primary literature included peer-reviewed publications and results posted on ClinicalTrials.gov actively recruiting participants. Data Synthesis: Fentanyl has been used for decades as an adjunct, and sole induction agent in the OR. Questions surrounding the use of fentanyl as a sole induction agent include optimal dosing and safety in critically ill patients as evaluation in non-OR settings remain limited. Relevance to Patient Care and Clinical Practice: Commonly used induction agents (eg, etomidate and ketamine) are associated with adverse events that may increase risk of morbidity and mortality. Fentanyl, a high-potency opioid could serve as an alternative induction agent for RSI due to its neutral hemodynamic response and fast onset of action. This paper compiles and describes existing data on the use of fentanyl as an induction agent for RSI. Conclusion: Fentanyl in combination with sedatives provides optimal intubating conditions with minimal impact on hemodynamic parameters. Future studies should focus on safety and impact of awareness during paralysis before fentanyl can be considered as a sole induction agent.
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Affiliation(s)
- Brett A Faine
- Department of Emergency Medicine and Pharmacy, University of Iowa, Iowa City, IA, USA
| | - Elisabeth Carroll
- Department of Pharmaceutical Care and Emergency Medicine, University of Iowa, Iowa City, IA, USA
| | - Archit Sharma
- Department of Anesthesia Critical Care, University of Iowa, Iowa City, IA, USA
| | - Nicholas Mohr
- Department of Emergency Medicine and Anesthesia Critical Care, University of Iowa, Iowa City, IA, USA
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Valk BI, Struys MMRF. Etomidate and its Analogs: A Review of Pharmacokinetics and Pharmacodynamics. Clin Pharmacokinet 2021; 60:1253-1269. [PMID: 34060021 PMCID: PMC8505283 DOI: 10.1007/s40262-021-01038-6] [Citation(s) in RCA: 69] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/11/2021] [Indexed: 01/09/2023]
Abstract
Etomidate is a hypnotic agent that is used for the induction of anesthesia. It produces its effect by acting as a positive allosteric modulator on the γ-aminobutyric acid type A receptor and thus enhancing the effect of the inhibitory neurotransmitter γ-aminobutyric acid. Etomidate stands out among other anesthetic agents by having a remarkably stable cardiorespiratory profile, producing no cardiovascular or respiratory depression. However, etomidate suppresses the adrenocortical axis by the inhibition of the enzyme 11β-hydroxylase. This makes the drug unsuitable for administration by a prolonged infusion. It also makes the drug unsuitable for administration to critically ill patients. Etomidate has relatively large volumes of distributions and is rapidly metabolized by hepatic esterases into an inactive carboxylic acid through hydrolyzation. Because of the decrease in popularity of etomidate, few modern extensive pharmacokinetic or pharmacodynamic studies exist. Over the last decade, several analogs of etomidate have been developed, with the aim of retaining its stable cardiorespiratory profile, whilst eliminating its suppressive effect on the adrenocortical axis. One of these molecules, ABP-700, was studied in extensive phase I clinical trials. These found that ABP-700 is characterized by small volumes of distribution and rapid clearance. ABP-700 is metabolized similarly to etomidate, by hydrolyzation into an inactive carboxylic acid. Furthermore, ABP-700 showed a rapid onset and offset of clinical effect. One side effect observed with both etomidate and ABP-700 is the occurrence of involuntary muscle movements. The origin of these movements is unclear and warrants further research.
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Affiliation(s)
- Beatrijs I Valk
- Department of Anesthesiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands
| | - Michel M R F Struys
- Department of Anesthesiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
- Department of Basic and Applied Medical Sciences, Ghent University, Ghent, Belgium.
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Mohr NM, Pape SG, Runde D, Kaji AH, Walls RM, Brown CA. Etomidate Use Is Associated With Less Hypotension Than Ketamine for Emergency Department Sepsis Intubations: A NEAR Cohort Study. Acad Emerg Med 2020; 27:1140-1149. [PMID: 32602974 DOI: 10.1111/acem.14070] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 06/23/2020] [Accepted: 06/24/2020] [Indexed: 12/20/2022]
Abstract
OBJECTIVE The objectives of this study were 1) to describe the current use of etomidate and other induction agents in patients with sepsis and 2) to compare adverse events between etomidate and ketamine in sepsis. METHODS This was an observational cohort study of the prospective National Emergency Airway Registry (NEAR) data set. Descriptive statistics were used to report the distribution of induction agents used in patients with sepsis. Adverse events were compared using bivariate analysis, and a sensitivity analysis was conducted using a propensity score-adjusted analysis of etomidate versus ketamine. RESULTS A total of 531 patients were intubated for sepsis, and the majority (71%) were intubated with etomidate as the initial induction agent. Etomidate was less frequently used in sepsis patients than nonsepsis patients (71% vs. 85%, odds ratio [OR] = 0.4, 95% confidence interval [CI] = 0.4 to 0.5). Sepsis patients had a greater risk of adverse events, and vasopressor therapy was required for 25% of patients after intubation. Postprocedure hypotension was higher between those intubated for sepsis with ketamine versus etomidate (74% vs. 50%, OR = 2.9, 95% CI = 1.9 to 4.5). After confounding by indication in the propensity score-adjusted analysis was accounted for, ketamine was associated with more postprocedure hypotension (OR = 2.7, 95% CI = 1.1 to 6.7). No difference in emergency department deaths was observed. CONCLUSIONS Etomidate is used less frequently in sepsis patients than nonsepsis patients, with ketamine being the most frequently used alternative. Ketamine was associated with more postprocedural hypotension than etomidate. Future clinical trials are needed to determine the optimal induction agent in patients with sepsis.
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Affiliation(s)
- Nicholas M. Mohr
- From the Department of Emergency Medicine University of Iowa Carver College of Medicine Iowa City IA USA
- the Division of Critical Care Department of Anesthesia University of Iowa Carver College of Medicine Iowa City IA USA
- the Department of Epidemiology University of Iowa College of Public Health Iowa City IA USA
| | - Stephen G. Pape
- From the Department of Emergency Medicine University of Iowa Carver College of Medicine Iowa City IA USA
| | - Dan Runde
- From the Department of Emergency Medicine University of Iowa Carver College of Medicine Iowa City IA USA
| | - Amy H. Kaji
- the Department of Emergency Medicine University of California–Los Angeles Los Angeles CA USA
| | - Ron M. Walls
- and the Department of Emergency Medicine Brigham and Women's Hospital Boston MA USA
| | - Calvin A. Brown
- and the Department of Emergency Medicine Brigham and Women's Hospital Boston MA USA
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Abstract
GABA (γ-aminobutyric acid) receptors, of which there are two types, are involved in inhibitory synapses within the central nervous system. The GABAA receptor (GABAAR) has a central role in modern anesthesia and sedation practice, which is evident from the high proportion of agents that target the GABAAR. Many GABAAR agonists are used in anesthesia practice and sedation, including propofol, etomidate, methohexital, thiopental, isoflurane, sevoflurane, and desflurane. There are advantages and disadvantages to each GABAAR agonist currently in clinical use. With increasing knowledge regarding the pharmacology of GABAAR agonists, however, newer sedative agents have been developed which employ 'soft pharmacology', a term used to describe the pharmacology of agents whereby their chemical configuration allows rapid metabolism into inactive metabolites after the desired therapeutic effect(s) has occurred. These newer 'soft' GABAAR agonists may well approach ideal sedative agents, as they can offer well-controlled, titratable activity and ultrashort action. This review provides an overview of the role that GABAAR agonists currently play in sedation and anesthesia, in addition to discussing the future role of novel GABAAR agonists in anesthesia and sedation.
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Upadhye S, Cyganik O. Is Single-Dose Etomidate Induction Safe in Emergency Intubation of Critically Ill Patients? Ann Emerg Med 2016; 67:399-400. [DOI: 10.1016/j.annemergmed.2015.10.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2015] [Indexed: 11/26/2022]
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Qin B, Hu H, Cao B, Zhu Z. Effects of continuous infusion of etomidate at various dose rates on adrenal function in dogs. BMC Anesthesiol 2016; 16:2. [PMID: 26743223 PMCID: PMC4705599 DOI: 10.1186/s12871-015-0171-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2015] [Accepted: 12/30/2015] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Etomidate is a commonly used sedative in intravenous anesthesia. The aim of this study was to compare the effects of various etomidate doses administered by continuous infusion on adrenal function in dogs under general anesthesia. METHODS Thirty-six healthy adult male dogs were randomly divided into six groups. Sodium pentobarbital alone was administered to the control group (group C); five experimental groups (E1, E2, E3, E4, and E5) were also given etomidate at doses of 10, 15, 20, 25, and 30 μg · kg(-1) · min(-1), respectively, to maintain anesthesia. Heart rate (HR), mean arterial pressure (MAP), and bispectral index (BIS) were monitored. Serum cortisol, aldosterone, adrenaline, and noradrenaline levels were measured, and HR, MAP, and BIS values recorded, before intubation (T0), and at 1 h, 2 h, and 3 h after intubation (T1-3). RESULTS Cortisol and aldosterone levels in groups E1-5 decreased as the doses and times of continuous infusion of etomidate increased. The cortisol level was significantly decreased compared with baseline at T3 in group E1 and at T1-3 in groups E2-5 (P < 0.05). Compared with the corresponding levels in group C, cortisol levels were significantly lower than T0 values at T3 in group E1 and at T1-3 in groups E2-5 (P < 0.05). The aldosterone level was significantly lower at T3 in group E2 and at T1-3 in groups E3-5 (P < 0.05). Significant reductions in cortisol levels at T2-3 in group E2 and at T1-3 in groups E3-5 compared with group C were also observed (P < 0.05). The plasma adrenaline and noradrenaline levels, HR, MAP, and BIS in groups E1-5 were within the normal range at the different times and with the different doses (P > 0.05). CONCLUSIONS Cortisol and aldosterone levels decreased with time and continuous infusion of etomidate; there were no significant changes in adrenaline and noradrenaline levels, HR, MAP, and BIS in any group.
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Affiliation(s)
- Bangyong Qin
- Department of Anesthesiology, Affliated Hospital of Zunyi Medical College, No. 149 Dalian Road, Zunyi, Guizhou Province, 563003, China.
| | - Hongzhuan Hu
- Department of Anesthesiology, Affliated Hospital of Zunyi Medical College, No. 149 Dalian Road, Zunyi, Guizhou Province, 563003, China
| | - Baofeng Cao
- Department of Anesthesiology, Affliated Hospital of Zunyi Medical College, No. 149 Dalian Road, Zunyi, Guizhou Province, 563003, China
| | - Zhaoqiong Zhu
- Department of Anesthesiology, Affliated Hospital of Zunyi Medical College, No. 149 Dalian Road, Zunyi, Guizhou Province, 563003, China
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Abstract
BACKGROUND Although a single dose of etomidate can cause relative adrenal insufficiency, the impact of etomidate exposure on postoperative outcomes is unknown. The objective of this study was to examine the association between a single induction dose of etomidate and clinically important postoperative outcomes after cardiac surgery. METHODS The authors retrospectively examined the association between etomidate exposure during induction of anesthesia and postoperative outcomes in patients undergoing cardiac surgery from January 2007 to December 2009 by using multivariate logistic regression analyses and Cox proportional hazards regression analyses. Postoperative outcomes of interest were severe hypotension, mechanical ventilation hours, hospital length of stay, and in-hospital mortality. RESULTS Sixty-two percent of 3,127 patients received etomidate. Etomidate recipients had a higher incidence of preoperative congestive heart failure (23.0 vs. 18.3%; P = 0.002) and a lower incidence of preoperative cardiogenic shock (1.3 vs. 4.0%; P < 0.001). The adjusted odds ratio for severe hypotension and in-hospital mortality associated with receiving etomidate was 0.80 (95% CI, 0.58-1.09) and 0.75 (95% CI, 0.45-1.24), respectively, and the adjusted hazard ratio for time to mechanical ventilation removal and time to hospital discharge was 1.10 (95% CI, 1.00-1.21) and 1.07 (95% CI, 0.97-1.18), respectively. Propensity score analysis did not change the association between etomidate use and postoperative outcomes. CONCLUSIONS In this study, there was no evidence to suggest that etomidate exposure was associated with severe hypotension, longer mechanical ventilation hours, longer length of hospital stay, or in-hospital mortality. Etomidate should remain an option for induction of anesthesia in cardiac surgery patients.
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Ye YA, Machuzak MS, Doyle DJ. Endoscopic removal of a self-expanding metallic airway stent: A case report. World J Anesthesiol 2014; 3:129-133. [DOI: 10.5313/wja.v3.i1.129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2013] [Revised: 08/19/2013] [Accepted: 08/29/2013] [Indexed: 02/06/2023] Open
Abstract
Self-expanding metallic stents are sometimes placed for the management of obstructing airway lesions or conditions such as airway wall malacia or tracheal stenosis. However, endoscopic removal of these devices from the airway can pose extreme challenges for both clinical airway management as well as for the administration of general anesthesia. We report on a 61-year-old man with a complex cardiac history presenting for endoscopic stent removal necessitated by the formation of extensive granulation tissue. Comorbidities included a history of myocardial infarction, an ischemic cardiomyopathy with severe left heart failure (ejection fraction of 25%), mild right heart failure, 2+ tricuspid regurgitation status post tricuspid valve repair, and atrial fibrillation. An automatic external (wearable) cardiac defibrillator (Zoll Life Vest) was also in place. Induction of anesthesia was carried out using etomidate, with maintenance of anesthesia carried out with a propofol infusion (total intravenous anesthesia). Rocuronium was used for neuromuscular blockade. A size 4 iGel supraglottic airway and, later, rigid bronchoscopy formed the basis for airway management. Stable conditions were met through the 2-h procedure, and the patient recovered uneventfully. Our successful experience in this case leads us to propose further use of a supraglottic airway in conjunction with total intravenous anesthesia for these procedures.
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Thompson Bastin ML, Baker SN, Weant KA. Effects of etomidate on adrenal suppression: a review of intubated septic patients. Hosp Pharm 2014; 49:177-83. [PMID: 24623871 DOI: 10.1310/hpj4902-177] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND Etomidate is a commonly used sedative during rapid sequence intubation (RSI). Septic patients are at an increased risk of independently developing adrenal suppression, which has been associated with increased mortality in some studies. Since etomidate affects cortisol production, its use in septic patients is controversial. However, data are still lacking to prove that etomidate should be avoided in this patient population. OBJECTIVES The objective was to review patients diagnosed with sepsis who received etomidate during RSI. Our hypothesis is that patients who receive etomidate will experience clinically significant hypotension within the first 24 hours of intubation. METHODS A retrospective cohort study was conducted on patients intubated in the emergency department (ED) and medical/surgical floors at our institution from 2004 to 2010. Once patients with a diagnosis of sepsis were identified, it was determined whether the patients received etomidate or a different sedative during intubation. The primary endpoint was clinically significant hypotension: systolic blood pressure <90 mm Hg or mean arterial pressure <60 mm Hg. RESULTS One hundred fifty-seven patients, 110 etomidate and 47 non-etomidate, were included in the final analysis. Hypotension was seen in 79 (71.8%) patients who received etomidate and in 14 (29.8%) patients who received another sedative (P ≤ .001). There were no statistically significant differences in secondary objectives. CONCLUSION Etomidate use for induction of anesthesia during RSI was associated with clinically significant hypotension when compared to other sedatives. The hypotension was transient and did not translate into statistically significant differences in the secondary clinical endpoints.
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Affiliation(s)
| | - Stephanie N Baker
- Department of Pharmacy, University of Kentucky HealthCare , Lexington, Kentucky . ; Department of Emergency Services, University of Kentucky HealthCare , Lexington, Kentucky
| | - Kyle A Weant
- Department of Pharmacy, University of Kentucky HealthCare , Lexington, Kentucky . ; Department of Emergency Services, University of Kentucky HealthCare , Lexington, Kentucky
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Price B, Arthur AO, Brunko M, Frantz P, Dickson JO, Judge T, Thomas SH. Hemodynamic consequences of ketamine vs etomidate for endotracheal intubation in the air medical setting. Am J Emerg Med 2013; 31:1124-32. [PMID: 23702065 DOI: 10.1016/j.ajem.2013.03.041] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2013] [Revised: 03/22/2013] [Accepted: 03/23/2013] [Indexed: 10/26/2022] Open
Abstract
OBJECTIVE Recent drug shortages have required the occasional replacement of etomidate for endotracheal intubation (ETI) by helicopter emergency medical services (HEMS), with ketamine. The purpose of this study was to assess whether there was an association between ketamine vs etomidate use as the main ETI drug, with hemodynamic or clinical (airway) end points. METHODS This retrospective study used data entered into medical records at the time of HEMS transport. Subjects, 50 ketamine and 50 etomidate, were accrued from 3 US HEMS programs. The study period was from August 2011 through May 2012. Data collection included demographics, diagnostic category, ETI drugs use, ETI success, and complications. Hemodynamic parameters were assessed for up to 2 sets of vital signs before airway management and up to 5 sets of post-ETI vital signs. Significance was defined at the P < .05 level. RESULTS Patients on ketamine and etomidate were similar (P > .05) with respect to age, sex, scene/interfacility mission type, trauma vs nontrauma, neuromuscular blocking agent use, and rates of coadministration of fentanyl or midazolam. All patients had successful airway placement. Peri-ETI hypoxemia was seen in 10% of etomidate and 16% of ketamine cases (P = .55). The pre-ETI and post-ETI were similar between the ketamine and etomidate groups with respect to systolic blood pressure and heart rate at every vital signs assessment after ETI. CONCLUSION Initial assessment of ETI success and complication rates, as well as peri-ETI hemodynamic changes, suggests no concerning complications associated with large-scale replacement of etomidate with ketamine as the major airway management drug for HEMS.
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Affiliation(s)
- Brian Price
- University Medical Center Brackenridge, Austin, TX 78701, USA
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Elliot M, Brown G, Kuo IF. Does etomidate increase vasopressor requirements in patients needing mechanical ventilation? Can J Hosp Pharm 2012; 65:272-6. [PMID: 22919104 DOI: 10.4212/cjhp.v65i4.1157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
BACKGROUND Single-dose etomidate is used as an induction agent for rapid-sequence intubation and is associated with transient adrenal insufficiency. There is ongoing debate as to the clinical consequences of this transient adrenal insufficiency for critically ill patients. OBJECTIVE To determine if the use of etomidate is associated with higher requirements for a vasopressor, relative to other induction agents, at a single time point (24 h after administration of the induction agent) in patients needing mechanical ventilation. METHODS In this retrospective observational study utilizing electronic health records, a convenience sample of 50 patients who had undergone intubation in the emergency department with etomidate were matched (1:1) with patients who had received other induction agents. Matching was based on primary admitting diagnosis relating to the cause of shock, APACHE II (Acute Physiology and Chronic Health Evaluation II) score, age, and sex. All patients were subsequently admitted to critical care areas for management. As a surrogate marker of hemodynamic instability, the vasopressor dose was recorded 24 h after intubation. Vasopressor doses were converted to norepinephrine equivalents for comparison. RESULTS The mean dose of vasopressors, in norepinephrine equivalents, was 4 μg/min(-1) for patients receiving etomidate and 3 μg/min(-1) for the control group (mean difference 0.7 μg min(-1), 95% confidence interval [CI] -1.9 to 3.2 μg min(-1), p = 0.61). Twelve of the patients in the etomidate group and 16 of those in the control group required the use of vasopressors at 24 h following intubation (odds ratio 2.3, 95% CI 0.53 to 13.99, p = 0.34). CONCLUSIONS Single-dose etomidate does not adversely affect hemodynamic stability, as measured by the dose of vasopressors required at 24 h after administration.
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Affiliation(s)
- Mary Elliot
- , BScPharm, ACPR, is a Clinical Pharmacist with Vancouver General Hospital, Vancouver, British Columbia
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Banh KV, James S, Hendey GW, Snowden B, Kaups K. Single-dose etomidate for intubation in the trauma patient. J Emerg Med 2012; 43:e277-82. [PMID: 22560133 DOI: 10.1016/j.jemermed.2012.02.027] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2011] [Revised: 11/02/2011] [Accepted: 02/26/2012] [Indexed: 11/16/2022]
Abstract
BACKGROUND Concerns over adrenal suppression caused by a single dose of etomidate for intubation led to limiting its use in trauma patients in 2006. OBJECTIVE The purpose of this study was to compare mortality, hypotension, and intensive care unit (ICU) and hospital length of stay (LOS) for trauma patients requiring intubation during periods of liberal vs. limited etomidate use. METHODS A retrospective review of trauma patients requiring emergent intubation who presented between August 2004 and December 2008, before and after we decided to limit the use of etomidate. Data were collected on patient demographics, induction agents used, episodes of hypotension in the first 24h, ICU and total hospital LOS, and survival. RESULTS Of 1325 trauma patients intubated in the Emergency Department during the study period, 443 occurred during the 23 months before July 2006 (liberal etomidate use) and 882 in the 30 months after July 2006 (limited etomidate use). During the liberal use period, 258/443 (58%) were intubated using etomidate, compared to 205/882 (23%, p<0.0001) during the period of limited use. We found no significant differences in mortality (30% vs. 29%, p=0.70), mean ICU days (8.2 vs. 8.8, p=0.356), or mean hospital LOS (13.8 vs. 14.4 days, p=0.55). Episodes of hypotension were more common in the limited etomidate use group (45% vs. 33%, p<0.0001). CONCLUSIONS A significant reduction in the use of etomidate in trauma patients was not associated with differences in mortality, ICU days, or hospital LOS, but was associated with an increase in episodes of hypotension within 24h of presentation.
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Affiliation(s)
- Kenny V Banh
- Department of Emergency Medicine, University of California San Francisco-Fresno, Fresno, California 93701-2302, USA
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Wang HE, Balasubramani GK, Cook LJ, Yealy DM, Lave JR. Medical conditions associated with out-of-hospital endotracheal intubation. PREHOSP EMERG CARE 2011; 15:338-46. [PMID: 21612386 PMCID: PMC3103090 DOI: 10.3109/10903127.2011.569850] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND While prior studies describe the clinical presentation of patients requiring paramedic out-of-hospital endotracheal intubation (ETI), limited data characterize the underlying medical conditions or comorbidities. OBJECTIVE To characterize the medical conditions and comorbidities of patients receiving successful paramedic out-of-hospital ETI. METHODS We used Pennsylvania statewide emergency medical services (EMS) clinical data, including all successful ETIs performed during 2003-2005. Using multiple imputation triple-match algorithms, we probabilistically linked EMS ETI to statewide death and hospital admission data. Each hospitalization record contained one primary and up to eight secondary diagnoses, classified according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). We determined the proportion of patients in each major ICD-9-CM diagnostic group and subgroup. We calculated the Charlson Comorbidity Index score for each patient. Using binomial proportions with confidence intervals (CIs), we analyzed the data and combined imputed results using Rubin's method. RESULTS Across the imputed sets, we linked 25,733 (77.7% linkage) successful ETIs to death or hospital records; 56.3% patients died before and 43.7% survived to hospital admission. Of the 14,478 patients who died before hospital admission, most (92.7%; 95% CI: 92.5-93.3%) had presented to EMS in cardiac arrest. Of the 11,255 hospitalized patents, the leading primary diagnoses were circulatory diseases (32.0%; 95% CI: 30.2-33.7%), respiratory diseases (22.8%; 95% CI: 21.9-23.7%), and injury or poisoning (25.2%; 95% CI: 22.7-27.8%). Prominent primary diagnosis subgroups included asphyxia and respiratory failure (15.2%), traumatic brain injury and skull fractures (11.3%), acute myocardial infarction and ischemic heart disease (10.9%), poisonings and drug and alcohol disorders (6.7%), dysrhythmias (6.7%), hemorrhagic and nonhemorrhagic stroke (5.9%), acute heart failure and cardiomyopathies (5.6%), pneumonia and aspiration (4.9%), and sepsis, septicemia, and septic shock (3.2%). Most of the admitted ETI patients had a secondary circulatory (70.8%), respiratory (61.4%), or endocrine, nutritional, or metabolic (51.4%) secondary diagnosis. The mean Charlson Index score was 1.6 (95% CI: 1.5-1.7). CONCLUSIONS The majority of successful paramedic ETIs occur on patients with cardiac arrest and circulatory and respiratory conditions. Injuries, poisonings, and other conditions compromise smaller but important portions of the paramedic ETI pool. Patients undergoing ETI have multiple comorbidities. These findings may guide the systemic planning of paramedic airway management care and education.
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Affiliation(s)
- Henry E. Wang
- Department of Emergency Medicine, University of Alabama at Birmingham, Birmingham, Alabama
| | - G. K. Balasubramani
- Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Lawrence J. Cook
- Intermountain Injury Control and Research Center, Department of Pediatrics, University of Utah, Salt Lake City, Utah
| | - Donald M. Yealy
- Department of Emergency Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Judith R. Lave
- Department of Health Policy and Management, University of Pittsburgh, Pittsburgh, Pennsylvania
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Abstract
This review focuses on the unique clinical and molecular pharmacologic features of etomidate. Among general anesthesia induction drugs, etomidate is the only imidazole, and it has the most favorable therapeutic index for single-bolus administration. It also produces a unique toxicity among anesthetic drugs: inhibition of adrenal steroid synthesis that far outlasts its hypnotic action and that may reduce survival of critically ill patients. The major molecular targets mediating anesthetic effects of etomidate in the central nervous system are specific γ-aminobutyric acid type A receptor subtypes. Amino acids forming etomidate binding sites have been identified in transmembrane domains of these proteins. Etomidate binding site structure models for the main enzyme mediating etomidate adrenotoxicity have also been developed. Based on this deepening understanding of molecular targets and actions, new etomidate derivatives are being investigated as potentially improved sedative-hypnotics or for use as highly selective inhibitors of adrenal steroid synthesis.
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Jones AE. The etomidate debate. Ann Emerg Med 2010; 56:490-1. [PMID: 21036291 DOI: 10.1016/j.annemergmed.2010.07.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2010] [Revised: 07/06/2010] [Accepted: 07/07/2010] [Indexed: 01/01/2023]
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The Effect of a Bolus Dose of Etomidate on Cortisol Levels, Mortality, and Health Services Utilization: A Systematic Review. Ann Emerg Med 2010; 56:105-13.e5. [DOI: 10.1016/j.annemergmed.2010.01.030] [Citation(s) in RCA: 55] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2009] [Revised: 01/21/2010] [Accepted: 01/29/2010] [Indexed: 11/23/2022]
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Dmello D, Taylor S, O'Brien J, Matuschak GM. Outcomes of etomidate in severe sepsis and septic shock. Chest 2010; 138:1327-32. [PMID: 20651024 DOI: 10.1378/chest.10-0790] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Abstract
BACKGROUND The use of single-dose etomidate to facilitate intubation in critically ill patients has recently been debated given its suppression of steroidogenesis with possible resultant adverse outcomes. Our objective was to assess the effects of single-dose etomidate used during rapid-sequence intubation (RSI) on various measures of outcome, such as mortality, vasopressor use, corticosteroid use, ICU length of stay (ICU-LOS), and number of ventilator days. METHODS A retrospective 18-month cohort study was performed in a multidisciplinary ICU of an academic tertiary care institution. Consecutive patients with severe sepsis or septic shock who were intubated and mechanically ventilated were identified and grouped as having received single-dose etomidate during intubation or not. Hospital mortality, ICU length of stay, number of ventilator days, corticosteroid use, vasopressor use, and demographic and clinical variables were recorded. RESULTS Two hundred twenty-four patients were identified; 113 had received etomidate. The mean Acute Physiology and Chronic Health Evaluation II scores in the etomidate and nonetomidate groups were 21.3 ± 8.1 and 21.9 ± 8.3, respectively (P = .62). The relative risks for mortality and vasopressor use were 0.92 (CI, 0.74-1.14; P = 0.51) and 1.16 (CI, 0.9-1.51; P = .31), respectively, in the etomidate group. There were no significant differences in ICU-LOS (mean, 14 vs 12 days; P = .31) or number of ventilator days (mean, 11 vs 8 days; P = .13) between the etomidate and nonetomidate groups, respectively. The relative risk for corticosteroid use in the etomidate group was 1.34 (CI, 1.11-1.61; P = .003). Multivariate analysis using logistic regression demonstrated no significant association of etomidate with mortality (OR, 0.9; CI, 0.45-1.83; P = .78). CONCLUSION Single-dose etomidate used during RSI in critically ill patients with severe sepsis and septic shock was not associated with increased mortality, vasopressor use, ICU-LOS, or number of ventilator days. Patients intubated with etomidate had an increased incidence of subsequent corticosteroid use, with no difference in outcomes.
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Affiliation(s)
- Dayton Dmello
- Division of Pulmonary, Critical Care, and Sleep Medicine, Saint Louis University Hospital, Louis, MO 63104, USA.
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Andrade FM. Is etomidate really that bad in septic patients? Intensive Care Med 2010; 36:1266-7; author reply 1269-70. [DOI: 10.1007/s00134-010-1878-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/29/2009] [Indexed: 10/19/2022]
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Andrade FM. Postintubation hypotension: the "etomidate paradox". THE JOURNAL OF TRAUMA 2009; 67:417. [PMID: 19667906 DOI: 10.1097/ta.0b013e3181a56ead] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/28/2023]
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Mittal MK. Etomidate as an Induction Agent for Endotracheal Intubation in Patients With Sepsis. Ann Emerg Med 2009; 53:405; author reply 406. [DOI: 10.1016/j.annemergmed.2008.08.041] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2008] [Revised: 08/05/2008] [Accepted: 08/18/2008] [Indexed: 11/15/2022]
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