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Downar J, Lapenskie J, Kanji S, Watpool I, Haines J, Saeed U, Porteous R, Polskaia N, Burry L, Himed S, Anderson K, Fox-Robichaud A. Propranolol As an Anxiolytic to Reduce the Use of Sedatives for Critically Ill Adults Receiving Mechanical Ventilation (PROACTIVE): An Open-Label Randomized Controlled Trial. Crit Care Med 2025; 53:e257-e268. [PMID: 39982178 PMCID: PMC11801419 DOI: 10.1097/ccm.0000000000006534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/22/2025]
Abstract
OBJECTIVES Surges in demand for sedatives for mechanical ventilation during the COVID-19 pandemic caused shortages of sedatives globally. Propranolol, a nonselective beta-adrenergic blocker, has been associated with reduced agitation and sedative needs in observational studies. We aimed to test whether propranolol could reduce the dose of sedatives needed in mechanically ventilated patients. DESIGN Open-label randomized controlled trial. SETTING Three academic hospitals. SUBJECTS Any nonparalyzed patient receiving mechanical ventilation and requiring high-dose sedatives. INTERVENTIONS Enteral propranolol 20-60 mg every 6 hours titrated to effect in the intervention group; all participants received protocol-titrated sedation with propofol or midazolam. MEASUREMENTS AND MAIN RESULTS Mean change in 24 hours dose of sedative from baseline to day 3, proportion of sedation scores within target, and occurrence rate of adverse events. We enrolled a planned 72 patients between January 2021 and October 2022. Sixty-nine percent were male with a mean (sd) age of 54 years (15.91 yr). Most were admitted for COVID or non-COVID pneumonia. Intervention participants received propranolol for a mean of 10 days (mean daily dose, 90 mg). There was a significantly larger decrease in sedative dose from baseline (54% vs. 34%; p = 0.048) and more sedation assessments within target range (48% vs. 35%; p < 0.0001) in the intervention group compared with controls. There were no differences in mortality or adverse events. CONCLUSIONS Propranolol is an inexpensive drug that effectively lowered the need for sedatives in critically ill patients managed in the COVID-19 pandemic. Propranolol may help preserve limited supplies of sedatives while achieving target sedation.
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Affiliation(s)
- James Downar
- Department of Medicine, University of Ottawa, Ottawa, ON, Canada
- Bruyere Research Institute, Ottawa, ON, Canada
- Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | | | - Salmaan Kanji
- Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | - Irene Watpool
- Ottawa Hospital Research Institute, Ottawa, ON, Canada
| | | | - Uzma Saeed
- Hamilton Health Sciences, Hamilton, ON, Canada
| | | | | | - Lisa Burry
- Sinai Health System, Toronto, ON, Canada
| | | | | | - Alison Fox-Robichaud
- Hamilton Health Sciences, Hamilton, ON, Canada
- Department of Medicine, McMaster University, Hamilton, ON, Canada
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Jung B, Fosset M, Amalric M, Baedorf-Kassis E, O'Gara B, Sarge T, Moulaire V, Brunot V, Bourdin A, Molinari N, Matecki S. Early and late effects of volatile sedation with sevoflurane on respiratory mechanics of critically ill COPD patients. Ann Intensive Care 2024; 14:91. [PMID: 38888818 PMCID: PMC11189368 DOI: 10.1186/s13613-024-01311-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 05/12/2024] [Indexed: 06/20/2024] Open
Abstract
BACKGROUND The objective was to compare sevoflurane, a volatile sedation agent with potential bronchodilatory properties, with propofol on respiratory mechanics in critically ill patients with COPD exacerbation. METHODS Prospective study in an ICU enrolling critically ill intubated patients with severe COPD exacerbation and comparing propofol and sevoflurane after 1:1 randomisation. Respiratory system mechanics (airway resistance, PEEPi, trapped volume, ventilatory ratio and respiratory system compliance), gas exchange, vitals, safety and outcome were measured at inclusion and then until H48. Total airway resistance change from baseline to H48 in both sevoflurane and propofol groups was the main endpoint. RESULTS Sixteen patients were enrolled and were sedated for 126 h(61-228) in the propofol group and 207 h(171-216) in the sevoflurane group. At baseline, airway resistance was 21.6cmH2O/l/s(19.8-21.6) in the propofol group and 20.4cmH2O/l/s(18.6-26.4) in the sevoflurane group, (p = 0.73); trapped volume was 260 ml(176-290) in the propofol group and 73 ml(35-126) in the sevoflurane group, p = 0.02. Intrinsic PEEP was 1.5cmH2O(1-3) in both groups after external PEEP optimization. There was neither early (H4) or late (H48) significant difference in airway resistance and respiratory mechanics parameters between the two groups. CONCLUSIONS In critically ill patients intubated with COPD exacerbation, there was no significant difference in respiratory mechanics between sevoflurane and propofol from inclusion to H4 and H48.
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Affiliation(s)
- Boris Jung
- Medical Intensive Care Unit, Montpellier University and Montpellier University Health Care Center, Montpellier, 34295, France.
- PhyMedExp laboratory, Montpellier University, INSERM, CNRS, CHRU Montpellier, Montpellier, 34295, France.
- Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center Harvard Medical School, Boston, MA, USA.
- Division of Pulmonary, Sleep and Critical Care Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School Boston, Boston, MA, USA.
| | - Maxime Fosset
- Medical Intensive Care Unit, Montpellier University and Montpellier University Health Care Center, Montpellier, 34295, France
- IMAG, CNRS, Montpellier University and Montpellier University Health Care Center, Montpellier, 34295, France
| | - Matthieu Amalric
- Medical Intensive Care Unit, Montpellier University and Montpellier University Health Care Center, Montpellier, 34295, France
| | - Elias Baedorf-Kassis
- Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center Harvard Medical School, Boston, MA, USA
- Division of Pulmonary, Sleep and Critical Care Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School Boston, Boston, MA, USA
| | - Brian O'Gara
- Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center Harvard Medical School, Boston, MA, USA
| | - Todd Sarge
- Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center Harvard Medical School, Boston, MA, USA
| | - Valerie Moulaire
- Medical Intensive Care Unit, Montpellier University and Montpellier University Health Care Center, Montpellier, 34295, France
| | - Vincent Brunot
- Medical Intensive Care Unit, Montpellier University and Montpellier University Health Care Center, Montpellier, 34295, France
| | - Arnaud Bourdin
- PhyMedExp laboratory, Montpellier University, INSERM, CNRS, CHRU Montpellier, Montpellier, 34295, France
- Department of Respiratory Diseases, Montpellier University and Montpellier University Health Care Center, Montpellier, 34295, France
| | - Nicolas Molinari
- IMAG, CNRS, Montpellier University and Montpellier University Health Care Center, Montpellier, 34295, France
| | - Stefan Matecki
- PhyMedExp laboratory, Montpellier University, INSERM, CNRS, CHRU Montpellier, Montpellier, 34295, France
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Flinspach AN, Herrmann E, Raimann FJ, Zacharowski K, Adam EH. Evaluation of volatile sedation in the postoperative intensive care of patients recovering from heart valve surgery: protocol for a randomised, controlled, monocentre trial. BMJ Open 2022; 12:e057804. [PMID: 35197356 PMCID: PMC8867344 DOI: 10.1136/bmjopen-2021-057804] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
INTRODUCTION Patients undergoing heart valve surgery are predominantly transferred postoperatively to the intensive care unit (ICU) under continuous sedation. Volatile anaesthetics are an increasingly used treatment alternative to intravenous substances in the ICU. As subject to inhalational uptake and elimination, the resulting pharmacological benefits have been repeatedly demonstrated. Therefore, volatile anaesthetics appear suitable to meet the growing demands of fast-track cardiac surgery. However, their use requires special preparation at the bedside and trained medical and nursing staff, which might limit the pharmacological benefits. The aim of our work is to assess whether the temporal advantages of recovery under volatile sedation outweigh the higher effort of special preparation. METHODS AND ANALYSIS The study is designed to evaluate the differences between intravenous sedatives (n=48) and volatile sedatives (n=48) in continued intensive care sedation. This study will be conducted as a prospective, randomised, controlled, single-blinded, monocentre trial at a German university hospital in consenting adult patients undergoing heart valve surgery at a university hospital. This observational study will examine the necessary preparation time, staff consultation and overall feasibility of the chosen sedation method. For this purpose, the continuation of sedation in the ICU with volatile sedatives is considered as one study arm and with intravenous sedatives as the comparison group. Due to rapid elimination and quick awakening after the termination of sedation, closer consultation between the attending physician and the ICU nursing staff is required, in addition to a prolonged setup time. Study analysis will include the required setup time, time from admission to extubation as primary outcome and neurocognitive assessability. In addition, possible operation-specific (blood loss, complications), treatment parameters (catecholamine dosages, lung function) and laboratory results (acute kidney injury, acid base balance (lactataemia), liver failure) as influencing factors will be collected. The study-relevant data will be extracted from the continuous digital records of the patient data management system after the patient has been discharged from the ICU. For statistical evaluation, 95% CIs will be calculated for the median time to extubation and neurocognitive assessability, and the association will be assessed with a Cox regression model. In addition, secondary binary outcome measures will be evaluated using Fisher's exact tests. Further descriptive and exploratory statistical analyses are also planned. ETHICS AND DISSEMINATION The study was approved by the Institutional Ethics Board of the University of Frankfurt, Germany (#20-1050). Informed consent of all individual patients will be obtained before randomisation. Results will be disseminated via publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER Clinical trials registration (NCT04958668) was completed on 1 July 2021.
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Affiliation(s)
- Armin Niklas Flinspach
- Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe University Frankfurt, Germany, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Frankfurt am Main, Hessen, Germany
| | - Eva Herrmann
- Department of Biostatistic and Mathematic Modeling, Goethe University, Frankfurt, Germany, Goethe-Universitat Frankfurt am Main, Frankfurt am Main, Hessen, Germany
| | - Florian Jürgen Raimann
- Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe University Frankfurt, Germany, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Frankfurt am Main, Hessen, Germany
| | - Kai Zacharowski
- Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe University Frankfurt, Germany, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Frankfurt am Main, Hessen, Germany
| | - Elisabeth Hannah Adam
- Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe University Frankfurt, Germany, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Frankfurt am Main, Hessen, Germany
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Gorsky K, Cuninghame S, Chen J, Jayaraj K, Withington D, Francoeur C, Slessarev M, Jerath A. Use of inhalational anaesthetic agents in paediatric and adult patients for status asthmaticus, status epilepticus and difficult sedation scenarios: a protocol for a systematic review. BMJ Open 2021; 11:e051745. [PMID: 34758996 PMCID: PMC8587357 DOI: 10.1136/bmjopen-2021-051745] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
INTRODUCTION Inhaled volatile anaesthetics have a long tradition of use as hypnotic agents in operating rooms and are gaining traction as sedatives in intensive care units (ICUs). However, uptake is impeded by low familiarity with volatiles, unique equipment and education needs. Inhaled anaesthetics are often reserved in ICUs as therapies for refractory and life threatening status asthmaticus, status epilepticus, high and difficult sedation need scenarios given they possess unique pharmacological properties to manage these medical conditions while providing sedation to acutely ill patients. The objective of this systematic review is to collate evidence regarding the efficacy, safety and feasibility of volatile anaesthetics in adult and paediatric ICU patients for these three emergency conditions. METHODS AND ANALYSIS We will conduct a systematic review of the primary studies in adult and paediatric ICU patients with status asthmaticus, status epilepticus and high/difficult sedation needs. We will include observational and interventional studies published from 1970 to 2021 in English or French investigating patients who have received a volatile inhalational agent for the above indications. We will evaluate the efficacy, safety, feasibility and implementation barriers for the volatile anaesthetics for each of three specified indications. Included studies will not be limited by necessity of a comparator arm. We will also evaluate clinical characteristics, patient demographics and provider attitudes towards volatile anaesthetic administration in defined critical care scenarios. Data will be extracted and analysed across these domains. The databases MEDLINE, EMBASE, the Science Citation Index as well as the Cochrane Central Controlled Trials Register will be queried with our search strategy.Descriptive and statistical analysis will be employed where appropriate. Data extraction and quality assessment will be performed in duplicate using a standardised tool. A narrative approach and statistical analyses will be used to describe patient characteristics, volatile efficacy, safety concerns, technical administration, attitudes towards administration and other implementation barriers. ETHICS AND DISSEMINATION No ethics board approval will be necessary for this systematic review. This research is independently funded. Results will be disseminated in a peer-reviewed journal and conference presentation. PROSPERO NUMBER CRD42021233083.
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Affiliation(s)
- Kevin Gorsky
- Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Sean Cuninghame
- Department of Medicine, University of Western Ontario, London, Ontario, Canada
| | - Jennifer Chen
- Department of Medical Biophysics, University of Western Ontario, London, Ontario, Canada
| | - Kesikan Jayaraj
- University of Toronto Faculty of Medicine, Toronto, Ontario, Canada
| | - Davinia Withington
- Department of Anesthesiology, McGill University Faculty of Medicine, Montreal, Quebec, Canada
| | - Conall Francoeur
- Department of Pediatrics, Laval University Faculty of Medicine, Quebec, Canada
| | - Marat Slessarev
- Department of Medicine, University of Western Ontario, London, Ontario, Canada
- The Brain Institute, Western University, London, Ontario, Canada
| | - Angela Jerath
- Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, Ontario, Canada
- Department of Anesthesia, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
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Park SH, Lu Y, Shao Y, Prophete C, Horton L, Sisco M, Lee HW, Kluz T, Sun H, Costa M, Zelikoff J, Chen LC, Cohen MD. Longitudinal impact on rat cardiac tissue transcriptomic profiles due to acute intratracheal inhalation exposures to isoflurane. PLoS One 2021; 16:e0257241. [PMID: 34648499 PMCID: PMC8516213 DOI: 10.1371/journal.pone.0257241] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Accepted: 08/26/2021] [Indexed: 12/13/2022] Open
Abstract
Isoflurane (ISO) is a widely used inhalation anesthetic in experiments with rodents and humans during surgery. Though ISO has not been reported to impart long-lasting side effects, it is unknown if ISO can influence gene regulation in certain tissues, including the heart. Such changes could have important implications for use of this anesthetic in patients susceptible to heart failure/other cardiac abnormalities. To test if ISO could alter gene regulation/expression in heart tissues, and if such changes were reversible, prolonged, or late onset with time, SHR (spontaneously hypertensive) rats were exposed by intratracheal inhalation to a 97.5% air/2.5% ISO mixture on two consecutive days (2 hr/d). Control rats breathed filtered air only. On Days 1, 30, 240, and 360 post-exposure, rat hearts were collected and total RNA was extracted from the left ventricle for global gene expression analysis. The data revealed differentially-expressed genes (DEG) in response to ISO (compared to naïve control) at all post-exposure timepoints. The data showed acute ISO exposures led to DEG associated with wounding, local immune function, inflammation, and circadian rhythm regulation at Days 1 and 30; these effects dissipated by Day 240. There were other significantly-increased DEG induced by ISO at Day 360; these included changes in expression of genes associated with cell signaling, differentiation, and migration, extracellular matrix organization, cell-substrate adhesion, heart development, and blood pressure regulation. Examination of consistent DEG at Days 240 and 360 indicated late onset DEG reflecting potential long-lasting effects from ISO; these included DEG associated with oxidative phosphorylation, ribosome, angiogenesis, mitochondrial translation elongation, and focal adhesion. Together, the data show acute repeated ISO exposures could impart variable effects on gene expression/regulation in the heart. While some alterations self-resolved, others appeared to be long-lasting or late onset. Whether such changes occur in all rat models or in humans remains to be investigated.
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Affiliation(s)
- Sung-Hyun Park
- Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, United States of America
- * E-mail:
| | - Yuting Lu
- Departments of Population Health & Environmental Medicine, New York University Grossman School of Medicine, New York, NY, United States of America
| | - Yongzhao Shao
- Departments of Population Health & Environmental Medicine, New York University Grossman School of Medicine, New York, NY, United States of America
| | - Colette Prophete
- Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, United States of America
| | - Lori Horton
- Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, United States of America
| | - Maureen Sisco
- Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, United States of America
| | - Hyun-Wook Lee
- Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, United States of America
| | - Thomas Kluz
- Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, United States of America
| | - Hong Sun
- Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, United States of America
| | - Max Costa
- Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, United States of America
| | - Judith Zelikoff
- Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, United States of America
| | - Lung-Chi Chen
- Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, United States of America
| | - Mitchell D. Cohen
- Department of Environmental Medicine, New York University Grossman School of Medicine, New York, NY, United States of America
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Li Y, Wang Y, Chang H, Cheng B, Miao J, Li S, Hu H, Huang L, Wang Q. Inhibitory Effects of Dexmedetomidine and Propofol on Gastrointestinal Tract Motility Involving Impaired Enteric Glia Ca 2+ Response in Mice. Neurochem Res 2021; 46:1410-1422. [PMID: 33656693 DOI: 10.1007/s11064-021-03280-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2020] [Revised: 02/20/2021] [Accepted: 02/20/2021] [Indexed: 12/31/2022]
Abstract
Propofol and dexmedetomidine are popular used for sedation in ICU, however, inadequate attention has been paid to their effect on gastrointestinal tract (GIT) motility. Present study aimed to compare the effect of propofol and dexmedetomidine on GIT motility at parallel level of sedation and explore the possible mechanism. Male C57BL/6 mice (8-10 weeks) were randomly divided into control, propofol and dexmedetomidine group. After intraperitoneal injection of propofol or dexmedetomidine, comparable sedative level was confirmed by sedative score, physiological parameters and electroencephalogram (EEG). Different segments of GIT motility in vivo (gastric emptying, small intestine transit, distal colon bead expulsion, stool weight and number of fecal pellets, gastrointestinal transit and whole gut transit time) and colonic migrating motor complexes (CMMCs) pattern in vitro were evaluated. The Ca2+ response of primary enteric glia was examined under the treatment of propofol or dexmedetomidine. There is little difference in physiological parameters and composite permutation entropy index (CPEI) between administration of 50 mg/kg propofol and 40 μg/kg dexmedetomidine, indicated that parallel level of sedation was reached. Data showed that propofol and dexmedetomidine had significantly inhibitory effect on GIT motility while dexmedetomidine was stronger. Also, the amplitude (ΔF/F0) of Ca2+ response in primary enteric glia was attenuated after treated with the sedatives while the effect of dexmedetomidine was greater than propofol. These findings demonstrated that dexmedetomidine caused stronger inhibitory effects on GIT motility in sedative mice, which may involve impaired Ca2+ response in enteric glia. Hence, dexmedetomidine should be carefully applied especially for potential GIT dysmotility patient.
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Affiliation(s)
- Yansong Li
- Department of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
| | - Yubo Wang
- School of Life Science and Technology, Xidian University, Xi'an, 710061, Shaanxi, China
| | - Haiqing Chang
- Department of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
| | - Bo Cheng
- Department of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
| | - Jiwen Miao
- Department of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
| | - Shuang Li
- Department of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
| | - Hao Hu
- Department of Pharmacology, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
| | - Liyu Huang
- School of Life Science and Technology, Xidian University, Xi'an, 710061, Shaanxi, China
| | - Qiang Wang
- Department of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
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Temesgen N, Chekol B, Tamirie T, Eshetie D, Simeneh N, Feleke A. Adult sedation and analgesia in a resource limited intensive care unit - A Systematic Review and evidence based guideline. Ann Med Surg (Lond) 2021; 66:102356. [PMID: 34035907 PMCID: PMC8138481 DOI: 10.1016/j.amsu.2021.102356] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 04/15/2021] [Accepted: 04/25/2021] [Indexed: 12/04/2022] Open
Abstract
Background Sedation and analgesia are essential in the intensive care unit in order to promote control of pain, anxiety, prevent loss of materials, accidental extubation and improve the synchrony of patients with ventilator. However, excess of these medications leads to an increased morbidity and mortality, and thus demands protocol. Methods Preferred Reporting Items for Systematic Reviews and the Meta-Analysis Protocol have been used to undertake this review. Pub Med, Cochrane Library, and Google Scholar search engines were used to find up-to-date evidence that helps to draw recommendations and conclusions. Results In this Guideline and Systematic Review, we have used 16 Systemic Review and Meta-Analysis, 3 Evidence-Based Guidelines and 10 RCT Meta-Analysis, 6 Systemic Reviews of Non-randomized Studies, 8 Randomized Clinical Trials, 11 Cohort Studies, 5 Cross-Sectional Studies and 1 Case Report with their respective study descriptions. Discussion Analgesia, which as a sedation basement can reduce sedative use, is key aspect of treatment in ICU patients, and we can also conclude that an analgesic sedation regimen can reduce the occurrence of delirium by reducing sedatives. The aim of this guideline and the systematic review is to write up and formulate analgesia-based sedation for limited resource settings. Conclusions Analgesia and sedation are effective in critically ill patients; however, too much sedation is associated with longer periods of mechanical ventilation and longer duration of ICU stay. Poorly managed ICU patients have a delirium rate of up to 80%, increased mortality, longer hospital stays, higher hospital costs and bad long-term outcomes.
Critically ill patients shall be awake, alert without pain, anxiety and delirium. Analgesia and sedation in the ICU shall be given as per needed after determined they are in need of. Sedation breaks are paramount important as equal as spontaneous breathing trials. Unnecessary deep sedations will increase hospital and personnel costs by increasing length of ICU stay.
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Affiliation(s)
- Netsanet Temesgen
- Debre Tabor University, College of Health Sciences, School of Medicine, Department of Anesthesia, Ethiopia
| | - Bsazinew Chekol
- Debre Tabor University, College of Health Sciences, School of Medicine, Department of Anesthesia, Ethiopia
| | - Tadesse Tamirie
- Debre Tabor University, College of Health Sciences, School of Medicine, Department of Anesthesia, Ethiopia
| | - Denberu Eshetie
- Debre Tabor University, College of Health Sciences, School of Medicine, Department of Anesthesia, Ethiopia
| | - Nigussie Simeneh
- University of Gondar, College of Medicine and Health Sciences, Department of Anesthesia and Critical Care, Ethiopia
| | - Abatneh Feleke
- University of Gondar, College of Medicine and Health Sciences, Department of Anesthesia and Critical Care, Ethiopia
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Bailly P, Egreteau PY, Ehrmann S, Thille AW, Guitton C, Grillet G, Reizine F, Huet O, Jaber S, Nowak E, L'her E. Inased (inhaled sedation in ICU) trial protocol: a multicentre randomised open-label trial. BMJ Open 2021; 11:e042284. [PMID: 33608400 PMCID: PMC7896597 DOI: 10.1136/bmjopen-2020-042284] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION The use of sedation in intensive care units (ICUs) is necessary and ubiquitous. The impact of sedation strategy on outcome, particularly when delivered early after initiation of mechanical ventilation, is unknown. Evidence is increasing that volatile anaesthetic agents could be associated with better outcome. Their use in delirium prevention is unknown. METHODS AND ANALYSIS This study is an investigator-initiated, prospective, multicentre, two-arm, randomised, control, open-trial comparing inhaled sedation strategy versus intravenous sedation strategy in mechanically ventilated patients in ICU. Two hundred and fifty patients will be randomly assigned to the intravenous sedation group or inhaled sedation group, with a 1:1 ratio in two groups according to the sedation strategy. The primary outcome is the occurrence of delirium assessed using two times a day confusion assessment method for the ICU (CAM-ICU). Secondary outcomes include cognitive and functional outcomes at 3 and 12 months. ETHICS AND DISSEMINATION The study has been approved by the Regional Ethics Committee (CPP Ouest) and national authorities (ANSM). The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER NCT04341350.
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Affiliation(s)
- Pierre Bailly
- Médecine Intensive et Réanimation, CHRU de Brest, Brest, Bretagne, France
| | - Pierre-Yves Egreteau
- Réanimation polyvalente, Centre Hospitalier des Pays de Morlaix, Morlaix, France
| | - Stephan Ehrmann
- Médecine Intensive et Réanimation, Centre Hospitalier Régional Universitaire de Tours, Tours, Centre, France
| | - Arnaud W Thille
- Médecine Intensive et Réanimation, CHU de Poitiers, Poitiers, France
- INSERM CIC 1402 Alive Research Group, Université de Poitiers, Poitiers, Poitou-Charentes, France
| | - Christophe Guitton
- Service de Réanimation Médico- Chirurgicale & USC, Centre Hospitalier de Mans, Le Mans, France
| | - Guillaume Grillet
- Réanimation polyvalente, Centre Hospitalier de Lorient, Lorient, Bretagne, France
| | - Florian Reizine
- Médecine Intensive et Réanimation, Centre Hospitalier Universitaire de Rennes, Rennes, Bretagne, France
| | - Olivier Huet
- Réanimation chirurgicale, Centre Hospitalier Régional et Universitaire de Brest, Brest, Bretagne, France
| | - S Jaber
- Anesthesia and Critical Care, Montpellier Univ Hosp, Montpellier, France
| | | | - Erwan L'her
- Médecine Intensive et Réanimation, CHRU de Brest, Brest, NA, France
- LATIM INSERM UMR 1101, Université de Bretagne Occidentale, Brest, NA, France
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Wenzel M, Leunig A, Han S, Peterka DS, Yuste R. Prolonged anesthesia alters brain synaptic architecture. Proc Natl Acad Sci U S A 2021; 118:e2023676118. [PMID: 33568534 PMCID: PMC7924219 DOI: 10.1073/pnas.2023676118] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Prolonged medically induced coma (pMIC) is carried out routinely in intensive care medicine. pMIC leads to cognitive impairment, yet the underlying neuromorphological correlates are still unknown, as no direct studies of MIC exceeding ∼6 h on neural circuits exist. Here, we establish pMIC (up to 24 h) in adolescent and mature mice, and combine longitudinal two-photon imaging of cortical synapses with repeated behavioral object recognition assessments. We find that pMIC affects object recognition, and that it is associated with enhanced synaptic turnover, generated by enhanced synapse formation during pMIC, while the postanesthetic period is dominated by synaptic loss. Our results demonstrate major side effects of prolonged anesthesia on neural circuit structure.
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Affiliation(s)
- Michael Wenzel
- Neurotechnology Center, Department of Biological Sciences, Columbia University, New York, NY 10027
| | - Alexander Leunig
- Neurotechnology Center, Department of Biological Sciences, Columbia University, New York, NY 10027
| | - Shuting Han
- Neurotechnology Center, Department of Biological Sciences, Columbia University, New York, NY 10027
| | - Darcy S Peterka
- Neurotechnology Center, Department of Biological Sciences, Columbia University, New York, NY 10027
| | - Rafael Yuste
- Neurotechnology Center, Department of Biological Sciences, Columbia University, New York, NY 10027
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10
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Sedating Mechanically Ventilated COVID-19 Patients with Volatile Anesthetics: Insights on the Last-Minute Potential Weapons. Sci Pharm 2021. [DOI: 10.3390/scipharm89010006] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Coronavirus Disease 2019 (COVID-19) has spread globally with the number of cases exceeding seventy million. Although trials on potential treatments of COVID-19 Acute Respiratory Distress Syndrome (ARDS) are promising, the introduction of an effective therapeutic intervention seems elusive. In this review, we explored the potential therapeutic role of volatile anesthetics during mechanical ventilation in the late stages of the disease. COVID-19 is thought to hit the human body via five major mechanisms: direct viral damage, immune overactivation, capillary thrombosis, loss of alveolar capillary membrane integrity, and decreased tissue oxygenation. The overproduction of pro-inflammatory cytokines will eventually lead to the accumulation of inflammatory cells in the lungs, which will lead to ARDS requiring mechanical ventilation. Respiratory failure resulting from ARDS is thought to be the most common cause of death in COVID-19. The literature suggests that these effects could be directly countered by using volatile anesthetics for sedation. These agents possess multiple properties that affect viral replication, immunity, and coagulation. They also have proven benefits at the molecular, cellular, and tissue levels. Based on the comprehensive understanding of the literature, short-term sedation with volatile anesthetics may be beneficial in severe stages of COVID-19 ARDS and trials to study their effects should be encouraged.
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11
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Use of Inhaled Volatile Anesthetics for Longer Term Critical Care Sedation: A Pilot Randomized Controlled Trial. Crit Care Explor 2020. [DOI: 10.1097/cce.0000000000000281] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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12
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Flinspach AN, Zacharowski K, Ioanna D, Adam EH. Volatile Isoflurane in Critically Ill Coronavirus Disease 2019 Patients-A Case Series and Systematic Review. Crit Care Explor 2020; 2:e0256. [PMID: 33134946 PMCID: PMC7587445 DOI: 10.1097/cce.0000000000000256] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
OBJECTIVES The ongoing coronavirus pandemic is challenging, especially in severely affected patients who require intubation and sedation. Although the potential benefits of sedation with volatile anesthetics in coronavirus disease 2019 patients are currently being discussed, the use of isoflurane in patients with coronavirus disease 2019-induced acute respiratory distress syndrome has not yet been reported. DESIGN We performed a retrospective analysis of critically ill patients with hypoxemic respiratory failure requiring mechanical ventilation. SETTING The study was conducted with patients admitted between April 4 and May 15, 2020 to our ICU. PATIENTS We included five patients who were previously diagnosed with severe acute respiratory syndrome coronavirus 2 infection. INTERVENTION Even with high doses of several IV sedatives, the targeted level of sedation could not be achieved. Therefore, the sedation regimen was switched to inhalational isoflurane. Clinical data were recorded using a patient data management system. We recorded demographical data, laboratory results, ventilation variables, sedative dosages, sedation level, prone positioning, duration of volatile sedation and outcomes. MEASUREMENTS & MAIN RESULTS Mean age (four men, one women) was 53.0 (± 12.7) years. The mean duration of isoflurane sedation was 103.2 (± 66.2) hours. Our data demonstrate a substantial improvement in the oxygenation ratio when using isoflurane sedation. Deep sedation as assessed by the Richmond Agitation and Sedation Scale was rapidly and closely controlled in all patients, and the subsequent discontinuation of IV sedation was possible within the first 30 minutes. No adverse events were detected. CONCLUSIONS Our findings demonstrate the feasibility of isoflurane sedation in five patients suffering from severe coronavirus disease 2019 infection. Volatile isoflurane was able to achieve the required deep sedation and reduced the need for IV sedation.
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Affiliation(s)
- Armin Niklas Flinspach
- All authors: Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe-University Frankfurt, Frankfurt/Main, Germany
| | - Kai Zacharowski
- All authors: Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe-University Frankfurt, Frankfurt/Main, Germany
| | - Deligiannis Ioanna
- All authors: Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe-University Frankfurt, Frankfurt/Main, Germany
| | - Elisabeth Hannah Adam
- All authors: Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe-University Frankfurt, Frankfurt/Main, Germany
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13
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Fernandez-Lizarbe S, Civera-Tregón A, Cantarero L, Herrer I, Juarez P, Hoenicka J, Palau F. Neuroinflammation in the pathogenesis of axonal Charcot-Marie-Tooth disease caused by lack of GDAP1. Exp Neurol 2019; 320:113004. [PMID: 31271761 DOI: 10.1016/j.expneurol.2019.113004] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2018] [Revised: 06/17/2019] [Accepted: 06/28/2019] [Indexed: 01/17/2023]
Abstract
Mutations in the GDAP1 mitochondrial outer membrane gene cause Charcot-Marie-Tooth (CMT) neuropathy. Reduction or absence of GDAP1 has been associated with abnormal changes in the mitochondrial morphology and dynamics, oxidative stress and changes in calcium homeostasis. Neuroinflammation has been described in rodent models of genetic demyelinating CMT neuropathies but not in CMT primarily associated with axonopathy. Inflammatory processes have also been related to mitochondrial changes and oxidative stress in central neurodegenerative disorders. Here we investigated the presence of neuroinflammation in the axonal neuropathy of the Gdap1-/- mice. We showed by transcriptome profile of spinal cord and the in vivo detection of activated phagocytes that the absence of GDAP1 is associated with upregulation of inflammatory pathways. We observed reactive gliosis in spinal cord with increase of the astroglia markers GFAP and S100B, and the microglia marker IBA1. Additionally, we found significant increase of inflammatory mediators such as TNF-α and pERK, and C1qa and C1qb proteins of the complement system. Importantly, we observed an increased expression of CD206 and CD86 as M2 and M1 microglia and macrophage response markers, respectively, in Gdap1-/- mice. These inflammatory changes were also associated with abnormal molecular changes in synapses. In summary, we demonstrate that inflammation in spinal cord and sciatic nerve, but not in brain and cerebellum, is part of the pathophysiology of axonal GDAP1-related CMT.
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Affiliation(s)
| | - Azahara Civera-Tregón
- Laboratory of Neurogenetics and Molecular Medicine - IPER, Institut de Recerca Sant Joan de Déu, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain
| | - Lara Cantarero
- Laboratory of Neurogenetics and Molecular Medicine - IPER, Institut de Recerca Sant Joan de Déu, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain
| | - Isabel Herrer
- Centro de Investigación Príncipe Felipe, Valencia, Spain
| | - Paula Juarez
- Centro de Investigación Príncipe Felipe, Valencia, Spain
| | - Janet Hoenicka
- Laboratory of Neurogenetics and Molecular Medicine - IPER, Institut de Recerca Sant Joan de Déu, Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBESAM), Barcelona, Spain
| | - Francesc Palau
- Laboratory of Neurogenetics and Molecular Medicine - IPER, Institut de Recerca Sant Joan de Déu, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain; Department of Genetic and Molecular Medicine - IPER, Hospital Sant Joan de Déu, Barcelona, Spain; Clinic Institute of Medicine and Dermatology (ICMiD), Hospital Clínic, Barcelona, Spain; Division of Pediatrics, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain.
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14
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Blum JM, Groff RF. Turning of the Page. Crit Care Med 2019; 45:1580-1581. [PMID: 28816848 DOI: 10.1097/ccm.0000000000002504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Affiliation(s)
- James M Blum
- Division of Critical Care Medicine, Department of Anesthesiology, Emory University School of Medicine, Atlanta, GA
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15
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Koutsogiannaki S, Shimaoka M, Yuki K. The Use of Volatile Anesthetics as Sedatives for Acute Respiratory Distress Syndrome. ACTA ACUST UNITED AC 2019; 6:27-38. [PMID: 30923729 PMCID: PMC6433148 DOI: 10.31480/2330-4871/084] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Acute respiratory distress syndrome (ARDS) remains to pose a high morbidity and mortality without any targeted therapies. Sedation, usually given intravenously, is an important part of clinical practice in intensive care unit (ICU), and the effect of sedatives on patients’ outcomes has been studied intensively. Although volatile anesthetics are not routine sedatives in ICU, preclinical and clinical studies suggested their potential benefit in pulmonary pathophysiology. This review will summarize the current knowledge of ARDS and the role of volatile anesthetic sedation in this setting from both clinical and mechanistic standpoints. In addition, we will review the infrastructure to use volatile anesthetics.
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Affiliation(s)
- Sophia Koutsogiannaki
- Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts, USA.,Department of Anesthesiology, Critical Care and Pain Medicine, Cardiac Anesthesia Division, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Motomu Shimaoka
- Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Tsushi, Mie, Japan
| | - Koichi Yuki
- Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts, USA.,Department of Anesthesiology, Critical Care and Pain Medicine, Cardiac Anesthesia Division, Boston Children's Hospital, Boston, Massachusetts, USA
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16
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Herling SF, Greve IE, Vasilevskis EE, Egerod I, Bekker Mortensen C, Møller AM, Svenningsen H, Thomsen T, Cochrane Emergency and Critical Care Group. Interventions for preventing intensive care unit delirium in adults. Cochrane Database Syst Rev 2018; 11:CD009783. [PMID: 30484283 PMCID: PMC6373634 DOI: 10.1002/14651858.cd009783.pub2] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Delirium is defined as a disturbance in attention, awareness and cognition with reduced ability to direct, focus, sustain and shift attention, and reduced orientation to the environment. Critically ill patients in the intensive care unit (ICU) frequently develop ICU delirium. It can profoundly affect both them and their families because it is associated with increased mortality, longer duration of mechanical ventilation, longer hospital and ICU stay and long-term cognitive impairment. It also results in increased costs for society. OBJECTIVES To assess existing evidence for the effect of preventive interventions on ICU delirium, in-hospital mortality, the number of delirium- and coma-free days, ventilator-free days, length of stay in the ICU and cognitive impairment. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, BIOSIS, International Web of Science, Latin American Caribbean Health Sciences Literature, CINAHL from 1980 to 11 April 2018 without any language limits. We adapted the MEDLINE search for searching the other databases. Furthermore, we checked references, searched citations and contacted study authors to identify additional studies. We also checked the following trial registries: Current Controlled Trials; ClinicalTrials.gov; and CenterWatch.com (all on 24 April 2018). SELECTION CRITERIA We included randomized controlled trials (RCTs) of adult medical or surgical ICU patients receiving any intervention for preventing ICU delirium. The control could be standard ICU care, placebo or both. We assessed the quality of evidence with GRADE. DATA COLLECTION AND ANALYSIS We checked titles and abstracts to exclude obviously irrelevant studies and obtained full reports on potentially relevant ones. Two review authors independently extracted data. If possible we conducted meta-analyses, otherwise we synthesized data narratively. MAIN RESULTS The electronic search yielded 8746 records. We included 12 RCTs (3885 participants) comparing usual care with the following interventions: commonly used drugs (four studies); sedation regimens (four studies); physical therapy or cognitive therapy, or both (one study); environmental interventions (two studies); and preventive nursing care (one study). We found 15 ongoing studies and five studies awaiting classification. The participants were 48 to 70 years old; 48% to 74% were male; the mean acute physiology and chronic health evaluation (APACHE II) score was 14 to 28 (range 0 to 71; higher scores correspond to more severe disease and a higher risk of death). With the exception of one study, all participants were mechanically ventilated in medical or surgical ICUs or mixed. The studies were overall at low risk of bias. Six studies were at high risk of detection bias due to lack of blinding of outcome assessors. We report results for the two most commonly explored approaches to delirium prevention: pharmacologic and a non-pharmacologic intervention.Haloperidol versus placebo (two RCTs, 1580 participants)The event rate of ICU delirium was measured in one study including 1439 participants. No difference was identified between groups, (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.87 to 1.17) (moderate-quality evidence). Haloperidol versus placebo neither reduced or increased in-hospital mortality, (RR 0.98, 95% CI 0.80 to 1.22; 2 studies; 1580 participants (moderate-quality evidence)); the number of delirium- and coma-free days, (mean difference (MD) -0.60, 95% CI -1.37 to 0.17; 2 studies, 1580 participants (moderate-quality of evidence)); number of ventilator-free days (mean 23.8 (MD -0.30, 95% CI -0.93 to 0.33) 1 study; 1439 participants, (high-quality evidence)); length of ICU stay, (MD 0.18, 95% CI -0.60 to 0.97); 2 studies, 1580 participants; high-quality evidence). None of the studies measured cognitive impairment. In one study there were three serious adverse events in the intervention group and five in the placebo group; in the other there were five serious adverse events and three patients died, one in each group. None of the serious adverse events were judged to be related to interventions received (moderate-quality evidence).Physical and cognitive therapy interventions (one study, 65 participants)The study did not measure the event rate of ICU delirium. A physical and cognitive therapy intervention versus standard care neither reduced nor increased in-hospital mortality, (RR 0.94, 95% CI 0.40 to 2.20, I² = 0; 1 study, 65 participants; very low-quality evidence); the number of delirium- and coma-free days, (MD -2.8, 95% CI -10.1 to 4.6, I² = 0; 1 study, 65 participants; very low-quality evidence); the number of ventilator-free days (within the first 28/30 days) was median 27.4 (IQR 0 to 29.2) and 25 (IQR 0 to 28.9); 1 study, 65 participants; very low-quality evidence, length of ICU stay, (MD 1.23, 95% CI -0.68 to 3.14, I² = 0; 1 study, 65 participants; very low-quality evidence); cognitive impairment measured by the MMSE: Mini-Mental State Examination with higher scores indicating better function, (MD 0.97, 95% CI -0.19 to 2.13, I² = 0; 1 study, 30 participants; very low-quality evidence); or measured by the Dysexecutive questionnaire (DEX) with lower scores indicating better function (MD -8.76, 95% CI -19.06 to 1.54, I² = 0; 1 study, 30 participants; very low-quality evidence). One patient experienced acute back pain accompanied by hypotensive urgency during physical therapy. AUTHORS' CONCLUSIONS There is probably little or no difference between haloperidol and placebo for preventing ICU delirium but further studies are needed to increase our confidence in the findings. There is insufficient evidence to determine the effects of physical and cognitive intervention on delirium. The effects of other pharmacological interventions, sedation, environmental, and preventive nursing interventions are unclear and warrant further investigation in large multicentre studies. Five studies are awaiting classification and we identified 15 ongoing studies, evaluating pharmacological interventions, sedation regimens, physical and occupational therapy combined or separately, and environmental interventions, that may alter the conclusions of the review in future.
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Affiliation(s)
- Suzanne Forsyth Herling
- Rigshospitalet, University of CopenhagenThe Neuroscience CentreBlegdamsvej 9CopenhagenDenmark2100
- Herlev and Gentofte Hospital, University of CopenhagenDepartment of AnaesthesiaHerlev Ringvej 75HerlevDenmark2730
| | - Ingrid E Greve
- Bispebjerg and Frederiksberg Hospitals, University of CopenhagenDepartment of Anaesthesia and Intensive careCopenhagenDenmark
| | - Eduard E Vasilevskis
- Division of General Internal Medicine and Public Health, Vanderbilt University and theTennessee Valley Geriatric Research, Education and Clinical Center (GRECC)Department of Medicine1215 21st Ave. S.6005 Medical Center East, NTNashvilleTNUSA37232‐8300
| | - Ingrid Egerod
- Rigshospitalet, University of CopenhagenIntensive Care Unit 4131Blegdamsvej 9Copenhagen ØDenmark2100
| | - Camilla Bekker Mortensen
- Zealand University HospitalIntensive Care Unit, Department of AnaesthesiologyLykkebækvej 1KøgeDenmark4600
| | - Ann Merete Møller
- Herlev and Gentofte Hospital, University of CopenhagenDepartment of AnaesthesiaHerlev Ringvej 75HerlevDenmark2730
- Herlev and Gentofte Hospital, University of CopenhagenCochrane AnaesthesiaHerlev RingvejHerlev Ringvej 75HerlevDenmark2730
- Herlev and Gentofte Hospital, University of CopenhagenCochrane Emergency and Critical CareHerlev Ringvej 75HerlevDenmark2730
| | - Helle Svenningsen
- VIA University CollegeFaculty of Health SciencesAarhus NDenmarkDK‐8200
| | - Thordis Thomsen
- Rigshospitalet, The Abdominal CentreDepartment of Nursing ResearchBlegdamsvej 9CopenhagenDenmark2200
- University of CopenhagenDepartment of Clinical MedicineCopenhagenDenmark
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17
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An Exploratory Study of Sevoflurane as an Alternative for Difficult Sedation in Critically Ill Children. Pediatr Crit Care Med 2018; 19:e335-e341. [PMID: 29557840 DOI: 10.1097/pcc.0000000000001538] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES To analyze the effectiveness of inhaled sevoflurane in critically ill children with challenging sedation. DESIGN Prospective case series. SETTING Two PICUs of university hospitals in Spain. INTERVENTIONS Prospective observational study and exploratory investigation conducted in two PICUs in Madrid, Spain, over a 6-year period. Children treated with inhaled sevoflurane due to difficult sedation were included. Sevoflurane was administered via the anesthetic conserving device (AnaConDa) connected to a Servo-I ventilator (Maquet, Solna, Sweden). A morphine infusion was added to sevoflurane for analgesia. Demographic and clinical data, oral and IV sedatives, Sedation and Analgesic Clinical scores, and Bispectral Index Score monitoring were registered. MEASUREMENTS AND MAIN RESULTS Twenty-three patients with a median age of 6 months old were included. Fifty percentage of the patients had critical heart diseases. Sedative and analgesic drugs used before starting sevoflurane were mainly midazolam (63%) and fentanyl (53%). Six patients (32%) also received muscle relaxants. Sevoflurane was administered for a median of 5 days (interquartile range, 5.5-8.5 d). Median end-tidal sevoflurane concentration was 0.8% (interquartile range, 0.7-0.85%), achieved with an infusion rate of 7.5 mL/hr (5.7-8.6 mL/hr). After 48 hours of treatment, some sedative drugs could be removed in 18 patients (78%). Median Bispectral Index Score value prior to sevoflurane administration was 61 (interquartile range, 49-62), falling to 42 (interquartile range, 41-47; p < 0.05) after 6 hours of treatment. Six patients (26%) presented withdrawal syndrome after sevoflurane suspension, and all of them had received sevoflurane at least for 6 days. The main side effect was moderate hypotension in seven patients (30%). CONCLUSIONS Inhaled sevoflurane appeared to be an effective sedative agent in critically ill children and can be useful in those patients on mechanical ventilation difficult to sedate with conventional drugs. It can be administered easily in the PICU with conventional ventilators using the AnaConDa system. Withdrawal syndrome may occur with prolonged treatment.
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18
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Staudacher DL, Hamilton SK, Duerschmied D, Biever PM, Zehender M, Bode C, Wengenmayer T. Isoflurane or propofol sedation in patients with targeted temperature management after cardiopulmonary resuscitation: A single center study. J Crit Care 2018; 45:40-44. [DOI: 10.1016/j.jcrc.2018.01.014] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2017] [Revised: 12/19/2017] [Accepted: 01/15/2018] [Indexed: 12/31/2022]
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19
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Jerath A, Parotto M, Wasowicz M, Ferguson ND. Opportunity Knocks? The Expansion of Volatile Agent Use in New Clinical Settings. J Cardiothorac Vasc Anesth 2017; 32:1946-1954. [PMID: 29449155 DOI: 10.1053/j.jvca.2017.12.035] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2017] [Indexed: 12/27/2022]
Affiliation(s)
- Angela Jerath
- Department of Anesthesia and Pain Medicine, Toronto General Hospital, Toronto, Ontario, Canada.
| | - Matteo Parotto
- Department of Anesthesia and Pain Medicine, Toronto General Hospital, Toronto, Ontario, Canada
| | - Marcin Wasowicz
- Department of Anesthesia and Pain Medicine, Toronto General Hospital, Toronto, Ontario, Canada
| | - Niall D Ferguson
- Interdepartmental Division of Critical Care Medicine, University of Toronto, University Health Network, Toronto, Ontario, Canada
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20
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Karnjuš I, Mekiš D, Križmarić M. Uncontrolled delivery of liquid volatile anaesthetic when using the anaesthetic conserving device. J Clin Monit Comput 2017; 32:629-638. [PMID: 28567612 DOI: 10.1007/s10877-017-0022-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2016] [Accepted: 04/24/2017] [Indexed: 11/30/2022]
Abstract
During patient sedation with liquid volatile anaesthetic, some problems may occur through a process called auto-pumping, defined as an expansion of bubbles inside the syringe, which can lead to uncontrolled anaesthetic delivery. The study examined how the temperature of liquid volatile anaesthetics (sevoflurane and isoflurane) and the presence of gas bubbles in the syringe affect the occurrence of auto-pumping when using the anaesthetic conserving device (ACD, AnaConDa™, Sedana Medical, Uppsala, Sweden). Four different circumstances for each volatile anaesthetic were tested with a bench study: volatile anaesthetic at room temperature or precooled with and without the presence of gas bubbles in the syringe. Liquid volatile anaesthetic was infused into the ACD via a syringe pump at a fixed rate and heated gradually until the temperature of the syringe surface reached 50 °C. A main-stream gas monitor was used to measure the expired fraction of volatile anaesthetic (FE vol%). The occurrence of auto-pumping was observed only in the subgroups containing gas bubbles, with both anaesthetics. In these subgroups, the values of the expired anaesthetic gas fraction increased dramatically with the expansion of gas bubbles in the syringe (ΔFE ranged from +1.6 to 2.4 vol% for sevoflurane and +2.3 to 3.4 vol% for isoflurane). Furthermore, when the heat source was removed, a substantial decline in anaesthetic agent values below the baseline was observed with both anaesthetics. The presence of gas bubbles in the syringe, especially when exposed to a heat source, may provoke auto-pumping with uncontrolled excessive anaesthetic delivery. If auto-pumping is suspected, the syringe pump must be stopped and the ACD removed from the breathing circuit at once.
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Affiliation(s)
- Igor Karnjuš
- Department of Nursing, Faculty of Health Sciences, University of Primorska, Polje 42, 6310, Izola, Slovenia.
| | - Dušan Mekiš
- Department of Anaesthesiology, Intensive Care and Pain Management, University Medical Centre Maribor, Ljubljanska ulica 5, 2000, Maribor, Slovenia.,Department of Anaesthesiology and Reanimation, Faculty of Medicine, University of Maribor, Taborska 8, 2000, Maribor, Slovenia
| | - Miljenko Križmarić
- Department of Anaesthesiology and Reanimation, Faculty of Medicine, University of Maribor, Taborska 8, 2000, Maribor, Slovenia.,Department of Bioinformatics, Faculty of Health Sciences, University of Maribor, Žitna ulica 15, 2000, Maribor, Slovenia
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21
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Jerath A, Panckhurst J, Parotto M, Lightfoot N, Wasowicz M, Ferguson ND, Steel A, Beattie WS. Safety and Efficacy of Volatile Anesthetic Agents Compared With Standard Intravenous Midazolam/Propofol Sedation in Ventilated Critical Care Patients. Anesth Analg 2017; 124:1190-1199. [DOI: 10.1213/ane.0000000000001634] [Citation(s) in RCA: 62] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
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22
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Heytens K, De Bleecker J, Verbrugghe W, Baets J, Heytens L. Exertional rhabdomyolysis and heat stroke: Beware of volatile anesthetic sedation. World J Crit Care Med 2017; 6:21-27. [PMID: 28224104 PMCID: PMC5295166 DOI: 10.5492/wjccm.v6.i1.21] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2016] [Revised: 09/27/2016] [Accepted: 11/17/2016] [Indexed: 02/06/2023] Open
Abstract
In view of the enormous popularity of mass sporting events such as half-marathons, the number of patients with exertional rhabdomyolysis or exercise-induced heat stroke admitted to intensive care units (ICUs) has increased over the last decade. Because these patients have been reported to be at risk for malignant hyperthermia during general anesthesia, the intensive care community should bear in mind that the same risk of life-threatening rhabdomyolysis is present when these patients are admitted to an ICU, and volatile anesthetic sedation is chosen as the sedative technique. As illustrated by the three case studies we elaborate upon, a thorough diagnostic work-up is needed to clarify the subsequent risk of strenuous exercise, and the anesthetic exposure to volatile agents in these patients and their families. Other contraindications for the use of volatile intensive care sedation consist of known malignant hyperthermia susceptibility, congenital myopathies, Duchenne muscular dystrophy, and intracranial hypertension.
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23
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Muyldermans M, Jennes S, Morrison S, Soete O, François PM, Keersebilck E, Rose T, Pantet O. Partial Nephrogenic Diabetes Insipidus in a Burned Patient Receiving Sevoflurane Sedation With an Anesthetic Conserving Device—A Case Report. Crit Care Med 2016; 44:e1246-e1250. [DOI: 10.1097/ccm.0000000000001956] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Jerath A, Wąsowicz M. In reply: Anesthesia scavenging in critical care areas: beware of possible hazards and questionable efficacy. Can J Anaesth 2016; 64:98-99. [PMID: 27718055 DOI: 10.1007/s12630-016-0745-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2016] [Accepted: 09/21/2016] [Indexed: 11/29/2022] Open
Affiliation(s)
- Angela Jerath
- Department of Anesthesia & Pain Management, Toronto General Hospital, Toronto, ON, Canada.,Department of Anesthesia, University of Toronto, Toronto, ON, Canada
| | - Marcin Wąsowicz
- Department of Anesthesia & Pain Management, Toronto General Hospital, Toronto, ON, Canada. .,Department of Anesthesia, University of Toronto, Toronto, ON, Canada.
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Baarslag MA, Allegaert K, Knibbe CAJ, van Dijk M, Tibboel D. Pharmacological sedation management in the paediatric intensive care unit. J Pharm Pharmacol 2016; 69:498-513. [DOI: 10.1111/jphp.12630] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2016] [Accepted: 07/27/2016] [Indexed: 02/06/2023]
Abstract
Abstract
Objective
This review addresses sedation management on paediatric intensive care units and possible gaps in the knowledge of optimal sedation strategies. We present an overview of the commonly used sedatives and their pharmacokinetic and pharmacodynamic considerations in children, as well as the ongoing studies in this field. Also, sedation guidelines and current sedation strategies and assessment methods are addressed.
Key findings
This review shows that evidence and pharmacokinetic data are scarce, but fortunately, there is an active research scene with promising new PK and PD data of sedatives in children using new study designs with application of advanced laboratory methods and modelling. The lack of evidence is increasingly being recognized by authorities and legislative offices such as the US Food and Drug Administration (FDA) and European Medicines Agency (EMA).
Conclusion
The population in question is very heterogeneous and this overview can aid clinicians and researchers in moving from practice-based sedation management towards more evidence- or model-based practice. Still, paediatric sedation management can be improved in other ways than pharmacology only, so future research should aim on sedation assessment and implementation strategies of protocolized sedation as well.
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Affiliation(s)
- Manuel A Baarslag
- Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands
| | - Karel Allegaert
- Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands
- Department of development and regeneration, KU Leuven, Belgium
| | - Catherijne A J Knibbe
- Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, The Netherlands
- Division of Pharmacology, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands
| | - Monique van Dijk
- Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands
| | - Dick Tibboel
- Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands
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