Pub Date : 2024-05-28DOI: 10.1016/j.bjao.2024.100287
Callum Kaye , Jonathan Rhodes , Pauline Austin , Matthew Casey , Richard Gould , James Sira , Shaun Treweek , Graeme MacLennan
Introduction
Severe traumatic brain injury affects ∼4500 per year across the UK. Most patients undergo a period of sedation to prevent secondary brain injury, however the optimal sedation target is unclear. This study aimed to assess the relationship between the electroencephalogram (EEG)-based Bispectral Index™ (BIS™) value and the clinical sedation score, along with other clinical outcomes.
Methods
Patients with severe traumatic brain injury in four UK ICUs were recruited to have blinded BIS data collected for a 24-h period while sedated on the ICU. Drug, physiological, and outcome data were recorded from the ICU record. Sedation management was at the discretion of the ICU clinical team.
Results
Twenty-six participants were recruited to the study. The mean BIS was 38 (inter-quartile range 29–44) and there was poor correlation between BIS and sedation score as a group (correlation coefficient 0.17, 95% confidence interval 0.08–0.26), however the spread in BIS values increased with decreasing sedation score. There was no statistically significant relationship between BIS and intracranial pressure, vasopressor use, osmotherapy use, or need for an additional sedative.
Conclusion
This study supports previous work showing that BIS decreases with decreasing sedation score. However, the variation in BIS values increased with deeper levels of clinical sedation. Patients may not be benefiting from the full potential of sedation in traumatic brain injury and further studies of sedation titrated to an EEG-based parameter are needed.
{"title":"Assessment of depth of sedation using Bispectral Index™ monitoring in patients with severe traumatic brain injury in UK intensive care units","authors":"Callum Kaye , Jonathan Rhodes , Pauline Austin , Matthew Casey , Richard Gould , James Sira , Shaun Treweek , Graeme MacLennan","doi":"10.1016/j.bjao.2024.100287","DOIUrl":"https://doi.org/10.1016/j.bjao.2024.100287","url":null,"abstract":"<div><h3>Introduction</h3><p>Severe traumatic brain injury affects ∼4500 per year across the UK. Most patients undergo a period of sedation to prevent secondary brain injury, however the optimal sedation target is unclear. This study aimed to assess the relationship between the electroencephalogram (EEG)-based Bispectral Index™ (BIS™) value and the clinical sedation score, along with other clinical outcomes.</p></div><div><h3>Methods</h3><p>Patients with severe traumatic brain injury in four UK ICUs were recruited to have blinded BIS data collected for a 24-h period while sedated on the ICU. Drug, physiological, and outcome data were recorded from the ICU record. Sedation management was at the discretion of the ICU clinical team.</p></div><div><h3>Results</h3><p>Twenty-six participants were recruited to the study. The mean BIS was 38 (inter-quartile range 29<strong>–</strong>44) and there was poor correlation between BIS and sedation score as a group (correlation coefficient 0.17, 95% confidence interval 0.08–0.26), however the spread in BIS values increased with decreasing sedation score. There was no statistically significant relationship between BIS and intracranial pressure, vasopressor use, osmotherapy use, or need for an additional sedative.</p></div><div><h3>Conclusion</h3><p>This study supports previous work showing that BIS decreases with decreasing sedation score. However, the variation in BIS values increased with deeper levels of clinical sedation. Patients may not be benefiting from the full potential of sedation in traumatic brain injury and further studies of sedation titrated to an EEG-based parameter are needed.</p></div><div><h3>Clinical trial registration</h3><p>NCT03575169.</p></div>","PeriodicalId":72418,"journal":{"name":"BJA open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772609624000315/pdfft?md5=03923aeed549d2499f7deb3b3a755d54&pid=1-s2.0-S2772609624000315-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141164484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-22DOI: 10.1016/j.bjao.2024.100286
Imogen Fecher-Jones , Chloe Grimmett , Ben Ainsworth , Frances Wensley , Laura Rossiter , Michael P.W. Grocott , Denny Z.H. Levett
Background
Group preoperative education is becoming standard care for patients preparing for surgery, alongside optimisation of exercise, diet, and wellbeing. Although patient education is essential, the effectiveness of group education programmes or ‘surgery schools’ as a means of delivery is unclear. This review examines whether attending group preoperative education improves patient outcomes.
Methods
We systematically reviewed studies of group perioperative education before major elective surgery. Observational or intervention studies with a baseline group or control arm were included. All outcomes reported were collected and, where possible, effect estimates were summarised using random effects meta-analysis.
Results
Twenty-seven studies reported on 48 different outcomes after group education. Overall, there was a 0.7 (95% confidence interval 0.27–1.13) day reduction in mean length of stay. The odds ratio for postoperative complications after abdominal surgery was 0.56 (95% confidence interval 0.36–0.85; nine studies). Patient-centred outcomes were grouped into themes. Most studies reported a benefit from group education, but only postoperative physical impairment, pain, knowledge, activation, preoperative anxiety, and some elements of quality of life were statistically significant.
Conclusion
This review presents a summary of published evidence available for group preoperative education. While these data lend support for such programmes, there is a need for adequately powered prospective studies to evaluate the effectiveness of preoperative education on clinical outcomes and to evaluate whether behaviour change is sustained. Furthermore, the content, timing and mode of delivery, and evaluation measures of preoperative education require standardisation.
{"title":"Systematic review and narrative description of the outcomes of group preoperative education before elective major surgery","authors":"Imogen Fecher-Jones , Chloe Grimmett , Ben Ainsworth , Frances Wensley , Laura Rossiter , Michael P.W. Grocott , Denny Z.H. Levett","doi":"10.1016/j.bjao.2024.100286","DOIUrl":"https://doi.org/10.1016/j.bjao.2024.100286","url":null,"abstract":"<div><h3>Background</h3><p>Group preoperative education is becoming standard care for patients preparing for surgery, alongside optimisation of exercise, diet, and wellbeing. Although patient education is essential, the effectiveness of group education programmes or ‘surgery schools’ as a means of delivery is unclear. This review examines whether attending group preoperative education improves patient outcomes.</p></div><div><h3>Methods</h3><p>We systematically reviewed studies of group perioperative education before major elective surgery. Observational or intervention studies with a baseline group or control arm were included. All outcomes reported were collected and, where possible, effect estimates were summarised using random effects meta-analysis.</p></div><div><h3>Results</h3><p>Twenty-seven studies reported on 48 different outcomes after group education. Overall, there was a 0.7 (95% confidence interval 0.27–1.13) day reduction in mean length of stay. The odds ratio for postoperative complications after abdominal surgery was 0.56 (95% confidence interval 0.36–0.85; nine studies). Patient-centred outcomes were grouped into themes. Most studies reported a benefit from group education, but only postoperative physical impairment, pain, knowledge, activation, preoperative anxiety, and some elements of quality of life were statistically significant.</p></div><div><h3>Conclusion</h3><p>This review presents a summary of published evidence available for group preoperative education. While these data lend support for such programmes, there is a need for adequately powered prospective studies to evaluate the effectiveness of preoperative education on clinical outcomes and to evaluate whether behaviour change is sustained. Furthermore, the content, timing and mode of delivery, and evaluation measures of preoperative education require standardisation.</p></div><div><h3>Systematic review protocol</h3><p>PROSPERO (166297).</p></div>","PeriodicalId":72418,"journal":{"name":"BJA open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772609624000303/pdfft?md5=d440bc0878e59f38950ddd416ea1e870&pid=1-s2.0-S2772609624000303-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141083302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-08DOI: 10.1016/j.bjao.2024.100280
Teresa P. Nguyen , Brendan Carvalho , Hannah Sukhdeo , Kareem Joudi , Nan Guo , Marianne Chen , Jed T. Wolpaw , Jesse J. Kiefer , Melissa Byrne , Tatiana Jamroz , Allison A. Mootz , Sharon C. Reale , James Zou , Pervez Sultan
Background
Patients are increasingly using artificial intelligence (AI) chatbots to seek answers to medical queries.
Methods
Ten frequently asked questions in anaesthesia were posed to three AI chatbots: ChatGPT4 (OpenAI), Bard (Google), and Bing Chat (Microsoft). Each chatbot's answers were evaluated in a randomised, blinded order by five residency programme directors from 15 medical institutions in the USA. Three medical content quality categories (accuracy, comprehensiveness, safety) and three communication quality categories (understandability, empathy/respect, and ethics) were scored between 1 and 5 (1 representing worst, 5 representing best).
Results
ChatGPT4 and Bard outperformed Bing Chat (median [inter-quartile range] scores: 4 [3–4], 4 [3–4], and 3 [2–4], respectively; P<0.001 with all metrics combined). All AI chatbots performed poorly in accuracy (score of ≥4 by 58%, 48%, and 36% of experts for ChatGPT4, Bard, and Bing Chat, respectively), comprehensiveness (score ≥4 by 42%, 30%, and 12% of experts for ChatGPT4, Bard, and Bing Chat, respectively), and safety (score ≥4 by 50%, 40%, and 28% of experts for ChatGPT4, Bard, and Bing Chat, respectively). Notably, answers from ChatGPT4, Bard, and Bing Chat differed statistically in comprehensiveness (ChatGPT4, 3 [2–4] vs Bing Chat, 2 [2–3], P<0.001; and Bard 3 [2–4] vs Bing Chat, 2 [2–3], P=0.002). All large language model chatbots performed well with no statistical difference for understandability (P=0.24), empathy (P=0.032), and ethics (P=0.465).
Conclusions
In answering anaesthesia patient frequently asked questions, the chatbots perform well on communication metrics but are suboptimal for medical content metrics. Overall, ChatGPT4 and Bard were comparable to each other, both outperforming Bing Chat.
{"title":"Comparison of artificial intelligence large language model chatbots in answering frequently asked questions in anaesthesia","authors":"Teresa P. Nguyen , Brendan Carvalho , Hannah Sukhdeo , Kareem Joudi , Nan Guo , Marianne Chen , Jed T. Wolpaw , Jesse J. Kiefer , Melissa Byrne , Tatiana Jamroz , Allison A. Mootz , Sharon C. Reale , James Zou , Pervez Sultan","doi":"10.1016/j.bjao.2024.100280","DOIUrl":"https://doi.org/10.1016/j.bjao.2024.100280","url":null,"abstract":"<div><h3>Background</h3><p>Patients are increasingly using artificial intelligence (AI) chatbots to seek answers to medical queries.</p></div><div><h3>Methods</h3><p>Ten frequently asked questions in anaesthesia were posed to three AI chatbots: ChatGPT4 (OpenAI), Bard (Google), and Bing Chat (Microsoft). Each chatbot's answers were evaluated in a randomised, blinded order by five residency programme directors from 15 medical institutions in the USA. Three medical content quality categories (accuracy, comprehensiveness, safety) and three communication quality categories (understandability, empathy/respect, and ethics) were scored between 1 and 5 (1 representing worst, 5 representing best).</p></div><div><h3>Results</h3><p>ChatGPT4 and Bard outperformed Bing Chat (median [inter-quartile range] scores: 4 [3–4], 4 [3–4], and 3 [2–4], respectively; <em>P</em><0.001 with all metrics combined). All AI chatbots performed poorly in accuracy (score of ≥4 by 58%, 48%, and 36% of experts for ChatGPT4, Bard, and Bing Chat, respectively), comprehensiveness (score ≥4 by 42%, 30%, and 12% of experts for ChatGPT4, Bard, and Bing Chat, respectively), and safety (score ≥4 by 50%, 40%, and 28% of experts for ChatGPT4, Bard, and Bing Chat, respectively). Notably, answers from ChatGPT4, Bard, and Bing Chat differed statistically in comprehensiveness (ChatGPT4, 3 [2–4] <em>vs</em> Bing Chat, 2 [2–3], <em>P</em><0.001; and Bard 3 [2–4] <em>vs</em> Bing Chat, 2 [2–3], <em>P</em>=0.002). All large language model chatbots performed well with no statistical difference for understandability (<em>P</em>=0.24), empathy (<em>P</em>=0.032), and ethics (<em>P</em>=0.465).</p></div><div><h3>Conclusions</h3><p>In answering anaesthesia patient frequently asked questions, the chatbots perform well on communication metrics but are suboptimal for medical content metrics. Overall, ChatGPT4 and Bard were comparable to each other, both outperforming Bing Chat.</p></div>","PeriodicalId":72418,"journal":{"name":"BJA open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772609624000248/pdfft?md5=3069a1d67d9065d3c6a3fb1ea7230c29&pid=1-s2.0-S2772609624000248-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140880538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-07DOI: 10.1016/j.bjao.2024.100285
York Jiao , Thomas Kannampallil
Background
Accurate real-time prediction of intraoperative duration can contribute to improved perioperative outcomes. We implemented a data pipeline for extraction of real-time data from nascent anaesthesia records and silently deployed a predictive machine learning (ML) algorithm.
Methods
Clinical variables were retrieved from the electronic health record via a third-party clinical decision support platform and contemporaneously ingested into a previously developed ML model. The model was trained using 3 months data, and performance was subsequently evaluated over 10 months using continuous ranked probability score.
Results
The ML model made 6 173 435 predictions on 62 142 procedures. Mean continuous ranked probability score for the ML model was 27.19 (standard error 0.016) min compared with 51.66 (standard error 0.029) min for the bias-corrected scheduled duration. Linear regression did not demonstrate performance drift over the testing period.
Conclusions
We implemented and silently deployed a real-time ML algorithm for predicting surgery duration. Prospective evaluation showed that model performance was preserved over a 10-month testing period.
{"title":"Implementation and prospective performance evaluation of an intraoperative duration prediction model using high throughput real-time data","authors":"York Jiao , Thomas Kannampallil","doi":"10.1016/j.bjao.2024.100285","DOIUrl":"https://doi.org/10.1016/j.bjao.2024.100285","url":null,"abstract":"<div><h3>Background</h3><p>Accurate real-time prediction of intraoperative duration can contribute to improved perioperative outcomes. We implemented a data pipeline for extraction of real-time data from nascent anaesthesia records and silently deployed a predictive machine learning (ML) algorithm.</p></div><div><h3>Methods</h3><p>Clinical variables were retrieved from the electronic health record via a third-party clinical decision support platform and contemporaneously ingested into a previously developed ML model. The model was trained using 3 months data, and performance was subsequently evaluated over 10 months using continuous ranked probability score.</p></div><div><h3>Results</h3><p>The ML model made 6 173 435 predictions on 62 142 procedures. Mean continuous ranked probability score for the ML model was 27.19 (standard error 0.016) min compared with 51.66 (standard error 0.029) min for the bias-corrected scheduled duration. Linear regression did not demonstrate performance drift over the testing period.</p></div><div><h3>Conclusions</h3><p>We implemented and silently deployed a real-time ML algorithm for predicting surgery duration. Prospective evaluation showed that model performance was preserved over a 10-month testing period.</p></div>","PeriodicalId":72418,"journal":{"name":"BJA open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772609624000297/pdfft?md5=49f333345f70ce50da62ada51e35d356&pid=1-s2.0-S2772609624000297-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140880539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-05DOI: 10.1016/j.bjao.2024.100283
Julia K. Gundersen , Ela Chakkarapani , David A. Menassa , Lars Walløe , Marianne Thoresen
Background
Hypothermia is neuroprotective after neonatal hypoxic-ischaemic brain injury. However, systemic cooling to hypothermic temperatures is a stressor and may reduce neuroprotection in awake pigs. We compared two experiments of global hypoxic-ischaemic injury in newborn pigs, in which one group received propofol–remifentanil and the other remained awake during post-insult hypothermia treatment.
Methods
In both studies, newborn pigs were anaesthetised using halothane during a 45-min global hypoxic-ischaemic insult induced by reducing Fio2 and graded hypotension until a low-voltage <7 μV electroencephalogram was achieved. On reoxygenation, the pigs were randomly allocated to receive 24 h of normothermia or hypothermia. In the first study (n=18) anaesthesia was discontinued and the pigs' tracheas were extubated. In the second study (n=14) anaesthesia was continued using propofol and remifentanil. Brain injury was assessed after 72 h by classical global histopathology, Purkinje cell count, and apoptotic cell counts in the hippocampus and cerebellum.
Results
Global injury was nearly 10-fold greater in the awake group compared with the anaesthetised group (P=0.021). Hypothermia was neuroprotective in the anaesthetised pigs but not the awake pigs. In the hippocampus, the density of cleaved caspase-3-positive cells was increased in awake compared with anaesthetised pigs in normothermia. In the cerebellum, Purkinje cell density was reduced in the awake pigs irrespective of treatment, and the number of cleaved caspase-3-positive Purkinje cells was greatly increased in hypothermic awake pigs. We detected no difference in cleaved caspase-3 in the granular cell layer or microglial reactivity across the groups.
Conclusions
Our study provides novel insights into the significance of anaesthesia/sedation during hypothermia for achieving optimal neuroprotection.
{"title":"The effects of anaesthesia on cell death in a porcine model of neonatal hypoxic-ischaemic brain injury","authors":"Julia K. Gundersen , Ela Chakkarapani , David A. Menassa , Lars Walløe , Marianne Thoresen","doi":"10.1016/j.bjao.2024.100283","DOIUrl":"https://doi.org/10.1016/j.bjao.2024.100283","url":null,"abstract":"<div><h3>Background</h3><p>Hypothermia is neuroprotective after neonatal hypoxic-ischaemic brain injury. However, systemic cooling to hypothermic temperatures is a stressor and may reduce neuroprotection in awake pigs. We compared two experiments of global hypoxic-ischaemic injury in newborn pigs, in which one group received propofol–remifentanil and the other remained awake during post-insult hypothermia treatment.</p></div><div><h3>Methods</h3><p>In both studies, newborn pigs were anaesthetised using halothane during a 45-min global hypoxic-ischaemic insult induced by reducing <em>F</em>i<span>o</span><sub>2</sub> and graded hypotension until a low-voltage <7 μV electroencephalogram was achieved. On reoxygenation, the pigs were randomly allocated to receive 24 h of normothermia or hypothermia. In the first study (<em>n</em>=18) anaesthesia was discontinued and the pigs' tracheas were extubated. In the second study (<em>n</em>=14) anaesthesia was continued using propofol and remifentanil. Brain injury was assessed after 72 h by classical global histopathology, Purkinje cell count, and apoptotic cell counts in the hippocampus and cerebellum.</p></div><div><h3>Results</h3><p>Global injury was nearly 10-fold greater in the awake group compared with the anaesthetised group (<em>P</em>=0.021). Hypothermia was neuroprotective in the anaesthetised pigs but not the awake pigs. In the hippocampus, the density of cleaved caspase-3-positive cells was increased in awake compared with anaesthetised pigs in normothermia. In the cerebellum, Purkinje cell density was reduced in the awake pigs irrespective of treatment, and the number of cleaved caspase-3-positive Purkinje cells was greatly increased in hypothermic awake pigs. We detected no difference in cleaved caspase-3 in the granular cell layer or microglial reactivity across the groups.</p></div><div><h3>Conclusions</h3><p>Our study provides novel insights into the significance of anaesthesia/sedation during hypothermia for achieving optimal neuroprotection.</p></div>","PeriodicalId":72418,"journal":{"name":"BJA open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772609624000273/pdfft?md5=b9ef365c3f529eb8b09476831e938eae&pid=1-s2.0-S2772609624000273-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140825748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-05DOI: 10.1016/j.bjao.2024.100282
Anne Rüggeberg , Patrick Meybohm , Eike A. Nickel
In the early days of anaesthesia, the fasting period for liquids was kept short. By the mid-20th century ‘nil by mouth after midnight’ had become routine as the principles of the management of ‘full stomach’ emergencies were extended to include elective healthy patients. Back then, no distinction was made between the withholding of liquids and solids. Towards the end of the last century, recommendations of professional anaesthesiology bodies began to reduce the fasting time of clear liquids to 2 h. This reduction in fasting time was based on the understanding that gastric emptying of clear liquids is rapid, exponential, and proportional to the current filling state of the stomach. Furthermore, there was no evidence of a link between drinking clear liquids and the risk of aspiration. Indeed, most instances of aspiration are caused by failure to identify aspiration risk factors and adjust the anaesthetic technique accordingly. In contrast, long periods of liquid withdrawal cause discomfort and may also lead to serious postoperative complications. Despite this, more than two decades after the introduction of the 2 h limit, patients still fast for a median of up to 12 h before anaesthesia, mainly because of organisational issues. Therefore, some hospitals have decided to allow patients to drink clear liquids within 2 h of induction of anaesthesia. Well-designed clinical trials should investigate whether these concepts are safe in patients scheduled for anaesthesia or procedural sedation, focusing on both aspiration risk and complications of prolonged fasting.
{"title":"Preoperative fasting and the risk of pulmonary aspiration—a narrative review of historical concepts, physiological effects, and new perspectives","authors":"Anne Rüggeberg , Patrick Meybohm , Eike A. Nickel","doi":"10.1016/j.bjao.2024.100282","DOIUrl":"https://doi.org/10.1016/j.bjao.2024.100282","url":null,"abstract":"<div><p>In the early days of anaesthesia, the fasting period for liquids was kept short. By the mid-20th century ‘nil by mouth after midnight’ had become routine as the principles of the management of ‘full stomach’ emergencies were extended to include elective healthy patients. Back then, no distinction was made between the withholding of liquids and solids. Towards the end of the last century, recommendations of professional anaesthesiology bodies began to reduce the fasting time of clear liquids to 2 h. This reduction in fasting time was based on the understanding that gastric emptying of clear liquids is rapid, exponential, and proportional to the current filling state of the stomach. Furthermore, there was no evidence of a link between drinking clear liquids and the risk of aspiration. Indeed, most instances of aspiration are caused by failure to identify aspiration risk factors and adjust the anaesthetic technique accordingly. In contrast, long periods of liquid withdrawal cause discomfort and may also lead to serious postoperative complications. Despite this, more than two decades after the introduction of the 2 h limit, patients still fast for a median of up to 12 h before anaesthesia, mainly because of organisational issues. Therefore, some hospitals have decided to allow patients to drink clear liquids within 2 h of induction of anaesthesia. Well-designed clinical trials should investigate whether these concepts are safe in patients scheduled for anaesthesia or procedural sedation, focusing on both aspiration risk and complications of prolonged fasting.</p></div>","PeriodicalId":72418,"journal":{"name":"BJA open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772609624000261/pdfft?md5=1835d3a376703ef20b66bf8e87f4e357&pid=1-s2.0-S2772609624000261-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140825750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-05DOI: 10.1016/j.bjao.2024.100284
Ahmed Abdelaatti , Donal J. Buggy , Thomas P. Wall
Background
Local anaesthetics are widely used for their analgesic and anaesthetic properties in the perioperative setting, including surgical procedures to excise malignant tumours. Simultaneously, chemotherapeutic agents remain a cornerstone of cancer treatment, targeting rapidly dividing cancer cells to inhibit tumour growth. The potential interactions between these two drug classes have drawn increasing attention and there are oncological surgical contexts where their combined use could be considered. This review examines existing evidence regarding the interactions between local anaesthetics and chemotherapeutic agents, including biological mechanisms and clinical implications.
Methods
A systematic search of electronic databases was performed as per Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Selection criteria were designed to capture in vitro, in vivo, and clinical studies assessing interactions between local anaesthetics and a wide variety of chemotherapeutic agents. Screening and data extraction were performed independently by two reviewers. The data were synthesised using a narrative approach because of the anticipated heterogeneity of included studies.
Results
Initial searches yielded 1225 relevant articles for screening, of which 43 met the inclusion criteria. The interactions between local anaesthetics and chemotherapeutic agents were diverse and multifaceted. In vitro studies frequently demonstrated altered cytotoxicity profiles when these agents were combined, with variations depending on the specific drug combination and cancer cell type. Mechanistically, some interactions were attributed to modifications in efflux pump activity, tumour suppressor gene expression, or alterations in cellular signalling pathways associated with tumour promotion. A large majority of in vitro studies report potentially beneficial effects of local anaesthetics in terms of enhancing the antineoplastic activity of chemotherapeutic agents. In animal models, the combined administration of local anaesthetics and chemotherapeutic agents showed largely beneficial effects on tumour growth, metastasis, and overall survival. Notably, no clinical study examining the possible interactions of local anaesthetics and chemotherapy on cancer outcomes has been reported.
Conclusions
Reported preclinical interactions between local anaesthetics and chemotherapeutic agents are complex and encompass a spectrum of effects which are largely, although not uniformly, additive or synergistic. The clinical implications of these interactions remain unclear because of the lack of prospective trials. Nonetheless, the modulation of chemotherapy effects by local anaesthetics warrants further clinical investigation in the context of cancer surgery where they could be used together.
{"title":"Local anaesthetics and chemotherapeutic agents: a systematic review of preclinical evidence of interactions and cancer biology","authors":"Ahmed Abdelaatti , Donal J. Buggy , Thomas P. Wall","doi":"10.1016/j.bjao.2024.100284","DOIUrl":"https://doi.org/10.1016/j.bjao.2024.100284","url":null,"abstract":"<div><h3>Background</h3><p>Local anaesthetics are widely used for their analgesic and anaesthetic properties in the perioperative setting, including surgical procedures to excise malignant tumours. Simultaneously, chemotherapeutic agents remain a cornerstone of cancer treatment, targeting rapidly dividing cancer cells to inhibit tumour growth. The potential interactions between these two drug classes have drawn increasing attention and there are oncological surgical contexts where their combined use could be considered. This review examines existing evidence regarding the interactions between local anaesthetics and chemotherapeutic agents, including biological mechanisms and clinical implications.</p></div><div><h3>Methods</h3><p>A systematic search of electronic databases was performed as per Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Selection criteria were designed to capture <em>in vitro</em>, <em>in vivo</em>, and clinical studies assessing interactions between local anaesthetics and a wide variety of chemotherapeutic agents. Screening and data extraction were performed independently by two reviewers. The data were synthesised using a narrative approach because of the anticipated heterogeneity of included studies.</p></div><div><h3>Results</h3><p>Initial searches yielded 1225 relevant articles for screening, of which 43 met the inclusion criteria. The interactions between local anaesthetics and chemotherapeutic agents were diverse and multifaceted. <em>In vitro</em> studies frequently demonstrated altered cytotoxicity profiles when these agents were combined, with variations depending on the specific drug combination and cancer cell type. Mechanistically, some interactions were attributed to modifications in efflux pump activity, tumour suppressor gene expression, or alterations in cellular signalling pathways associated with tumour promotion. A large majority of <em>in vitro</em> studies report potentially beneficial effects of local anaesthetics in terms of enhancing the antineoplastic activity of chemotherapeutic agents. In animal models, the combined administration of local anaesthetics and chemotherapeutic agents showed largely beneficial effects on tumour growth, metastasis, and overall survival. Notably, no clinical study examining the possible interactions of local anaesthetics and chemotherapy on cancer outcomes has been reported.</p></div><div><h3>Conclusions</h3><p>Reported preclinical interactions between local anaesthetics and chemotherapeutic agents are complex and encompass a spectrum of effects which are largely, although not uniformly, additive or synergistic. The clinical implications of these interactions remain unclear because of the lack of prospective trials. Nonetheless, the modulation of chemotherapy effects by local anaesthetics warrants further clinical investigation in the context of cancer surgery where they could be used together.</p></div><div><h3>Clinical trial regis","PeriodicalId":72418,"journal":{"name":"BJA open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772609624000285/pdfft?md5=bbcd5c2c0f4210ef07591c9bee0cc2e4&pid=1-s2.0-S2772609624000285-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140825749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-29DOI: 10.1016/j.bjao.2024.100281
Maria B. Nielsen , Thomas L. Klitgaard , Ulla M. Weinreich , Frederik M. Nielsen , Anders Perner , Olav L. Schjørring , Bodil S. Rasmussen
Background
Oxygen supplementation is ubiquitous in intensive care unit (ICU) patients with chronic obstructive pulmonary disease (COPD) and acute hypoxaemia, but the optimal oxygenation target has not been established.
Methods
This was a pre-planned subgroup analysis of the Handling Oxygenation Targets in the ICU (HOT-ICU) trial, which allocated patients with acute hypoxaemia to a lower oxygenation target (partial pressure of arterial oxygen [Pao2] of 8 kPa) vs a higher target (Pao2 of 12 kPa) during ICU admission, for up to 90 days; the allocation was stratified for presence or absence of COPD. Here, we report key outcomes for patients with COPD.
Results
The HOT-ICU trial enrolled 2928 patients of whom 563 had COPD; 277 were allocated to the lower and 286 to the higher oxygenation group. After allocation, the median Pao2 was 9.1 kPa (inter-quartile range 8.7–9.9) in the lower group vs 12.1 kPa (11.2–12.9) in the higher group. Data for arterial carbon dioxide (Paco2) were available for 497 patients (88%) with no between-group difference in time-weighted average; median Paco2 6.0 kPa (5.2–7.2) in the lower group vs 6.2 kPa (5.4–7.3) in the higher group. At 90 days, 122/277 patients (44%) in the lower oxygenation group had died vs 132/285 patients (46%) in the higher (relative risk 0.98; 95% confidence interval 0.82–1.17; P=0.67). No statistically significant differences were found in any secondary outcome.
Conclusions
In ICU patients with COPD and acute hypoxaemia, a lower vs a higher oxygenation target did not reduce mortality. There were no between-group differences in Paco2 or in secondary outcomes.
{"title":"Effects of a lower versus a higher oxygenation target in intensive care unit patients with chronic obstructive pulmonary disease and acute hypoxaemic respiratory failure: a subgroup analysis of a randomised clinical trial","authors":"Maria B. Nielsen , Thomas L. Klitgaard , Ulla M. Weinreich , Frederik M. Nielsen , Anders Perner , Olav L. Schjørring , Bodil S. Rasmussen","doi":"10.1016/j.bjao.2024.100281","DOIUrl":"https://doi.org/10.1016/j.bjao.2024.100281","url":null,"abstract":"<div><h3>Background</h3><p>Oxygen supplementation is ubiquitous in intensive care unit (ICU) patients with chronic obstructive pulmonary disease (COPD) and acute hypoxaemia, but the optimal oxygenation target has not been established.</p></div><div><h3>Methods</h3><p>This was a pre-planned subgroup analysis of the Handling Oxygenation Targets in the ICU (HOT-ICU) trial, which allocated patients with acute hypoxaemia to a lower oxygenation target (partial pressure of arterial oxygen [<em>P</em>a<span>o</span><sub>2</sub>] of 8 kPa) <em>vs</em> a higher target (<em>P</em>a<span>o</span><sub>2</sub> of 12 kPa) during ICU admission, for up to 90 days; the allocation was stratified for presence or absence of COPD. Here, we report key outcomes for patients with COPD.</p></div><div><h3>Results</h3><p>The HOT-ICU trial enrolled 2928 patients of whom 563 had COPD; 277 were allocated to the lower and 286 to the higher oxygenation group. After allocation, the median <em>P</em>a<span>o</span><sub>2</sub> was 9.1 kPa (inter-quartile range 8.7–9.9) in the lower group <em>vs</em> 12.1 kPa (11.2–12.9) in the higher group. Data for arterial carbon dioxide (<em>P</em>a<span>co</span><sub>2</sub>) were available for 497 patients (88%) with no between-group difference in time-weighted average; median <em>P</em>a<span>co</span><sub>2</sub> 6.0 kPa (5.2–7.2) in the lower group <em>vs</em> 6.2 kPa (5.4–7.3) in the higher group. At 90 days, 122/277 patients (44%) in the lower oxygenation group had died <em>vs</em> 132/285 patients (46%) in the higher (relative risk 0.98; 95% confidence interval 0.82–1.17; <em>P</em>=0.67). No statistically significant differences were found in any secondary outcome.</p></div><div><h3>Conclusions</h3><p>In ICU patients with COPD and acute hypoxaemia, a lower <em>vs</em> a higher oxygenation target did not reduce mortality. There were no between-group differences in <em>P</em>a<span>co</span><sub>2</sub> or in secondary outcomes.</p></div><div><h3>Clinical trial registration</h3><p>NCT 03174002, EudraCT number 2017-000632-34.</p></div>","PeriodicalId":72418,"journal":{"name":"BJA open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S277260962400025X/pdfft?md5=85af0e0347b7c556d6035e0d378e2595&pid=1-s2.0-S277260962400025X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140813730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-20DOI: 10.1016/j.bjao.2024.100279
Mark Larsson , Ulrik Sartipy , Anders Franco-Cereceda , Anders Öwall , Jan Jakobsson
Background
We hypothesised that a continuous 72-h bilateral parasternal infusion of lidocaine at 2×35 mg h−1 would decrease pain and the inflammatory response after sternotomy for open heart surgery, subsequently improving quality of recovery.
Methods
We randomly allocated 45 participants to a 72-h bilateral parasternal infusion of lidocaine or saline commencing after wound closure. The primary outcome was the cumulative patient-controlled analgesia (PCA) morphine consumption at 72 h. Secondary outcomes included total morphine requirement, pain, peak expiratory flow, and serum interleukin-6 concentration. In addition, we used an eHealth platform for a 3-month follow-up of pain, analgesic use, and Quality of Recovery-15 scores.
Results
The 72-h PCA morphine requirement was significantly lower in the lidocaine than the saline group (10 mg [inter-quartile range: 5–19 mg] and 28.2 mg [inter-quartile range: 16–42.5 mg], respectively; P=0.014). The total morphine requirement (including morphine administered before the start of PCA) was significantly lower at 24, 48, and 72 h. Pain was well controlled with no difference in pain scores between treatment groups. The peak expiratory flow was lower in the lidocaine group at 72 h. Interleukin-6 concentrations showed no difference at 24, 48, or 72 h. Quality of Recovery-15 scores did not differ between treatment groups at any time during the 3-month follow-up.
Conclusions
After sternotomy for open heart surgery, a 72-h bilateral parasternal lidocaine infusion significantly decreased PCA and total morphine requirement. However, neither signs of decreased inflammatory response nor an improvement in recovery was seen.
{"title":"The effect of continuous bilateral parasternal block with lidocaine on patient-controlled analgesia opioid requirement and recovery after open heart surgery: a double-blind randomised controlled trial","authors":"Mark Larsson , Ulrik Sartipy , Anders Franco-Cereceda , Anders Öwall , Jan Jakobsson","doi":"10.1016/j.bjao.2024.100279","DOIUrl":"https://doi.org/10.1016/j.bjao.2024.100279","url":null,"abstract":"<div><h3>Background</h3><p>We hypothesised that a continuous 72-h bilateral parasternal infusion of lidocaine at 2×35 mg h<sup>−1</sup> would decrease pain and the inflammatory response after sternotomy for open heart surgery, subsequently improving quality of recovery.</p></div><div><h3>Methods</h3><p>We randomly allocated 45 participants to a 72-h bilateral parasternal infusion of lidocaine or saline commencing after wound closure. The primary outcome was the cumulative patient-controlled analgesia (PCA) morphine consumption at 72 h. Secondary outcomes included total morphine requirement, pain, peak expiratory flow, and serum interleukin-6 concentration. In addition, we used an eHealth platform for a 3-month follow-up of pain, analgesic use, and Quality of Recovery-15 scores.</p></div><div><h3>Results</h3><p>The 72-h PCA morphine requirement was significantly lower in the lidocaine than the saline group (10 mg [inter-quartile range: 5–19 mg] and 28.2 mg [inter-quartile range: 16–42.5 mg], respectively; <em>P</em>=0.014). The total morphine requirement (including morphine administered before the start of PCA) was significantly lower at 24, 48, and 72 h. Pain was well controlled with no difference in pain scores between treatment groups. The peak expiratory flow was lower in the lidocaine group at 72 h. Interleukin-6 concentrations showed no difference at 24, 48, or 72 h. Quality of Recovery-15 scores did not differ between treatment groups at any time during the 3-month follow-up.</p></div><div><h3>Conclusions</h3><p>After sternotomy for open heart surgery, a 72-h bilateral parasternal lidocaine infusion significantly decreased PCA and total morphine requirement. However, neither signs of decreased inflammatory response nor an improvement in recovery was seen.</p></div><div><h3>Clinical trial registration</h3><p>EudraCT number 2018-004672-35.</p></div>","PeriodicalId":72418,"journal":{"name":"BJA open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772609624000236/pdfft?md5=d1f87500618cab5e179e57980abf7be1&pid=1-s2.0-S2772609624000236-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140622454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-28DOI: 10.1016/j.bjao.2024.100276
S. Kendall Smith , MohammadMehdi Kafashan , Rachel L. Rios , Emery N. Brown , Eric C. Landsness , Christian S. Guay , Ben Julian A. Palanca
Background
The alpha-2 adrenergic agonist dexmedetomidine induces EEG patterns resembling those of non-rapid eye movement (NREM) sleep. Fulfilment of slow wave sleep (SWS) homeostatic needs would address the assumption that dexmedetomidine induces functional biomimetic sleep states.
Methods
In-home sleep EEG recordings were obtained from 13 healthy participants before and after dexmedetomidine sedation. Dexmedetomidine target-controlled infusions and closed-loop acoustic stimulation were implemented to induce and enhance EEG slow waves, respectively. EEG recordings during sedation and sleep were staged using modified American Academy of Sleep Medicine criteria. Slow wave activity (EEG power from 0.5 to 4 Hz) was computed for NREM stage 2 (N2) and NREM stage 3 (N3/SWS) epochs, with the aggregate partitioned into quintiles by time. The first slow wave activity quintile served as a surrogate for slow wave pressure, and the difference between the first and fifth quintiles as a measure of slow wave pressure dissipation.
Results
Compared with pre-sedation sleep, post-sedation sleep showed reduced N3 duration (mean difference of −17.1 min, 95% confidence interval −30.0 to −8.2, P=0.015). Dissipation of slow wave pressure was reduced (P=0.02). Changes in combined durations of N2 and N3 between pre- and post-sedation sleep correlated with total dexmedetomidine dose, (r=−0.61, P=0.03).
Conclusions
Daytime dexmedetomidine sedation and closed-loop acoustic stimulation targeting EEG slow waves reduced N3/SWS duration and measures of slow wave pressure dissipation on the post-sedation night in healthy young adults. Thus, the paired intervention induces sleep-like states that fulfil certain homeostatic NREM sleep needs in healthy young adults.
{"title":"Daytime dexmedetomidine sedation with closed-loop acoustic stimulation alters slow wave sleep homeostasis in healthy adults","authors":"S. Kendall Smith , MohammadMehdi Kafashan , Rachel L. Rios , Emery N. Brown , Eric C. Landsness , Christian S. Guay , Ben Julian A. Palanca","doi":"10.1016/j.bjao.2024.100276","DOIUrl":"https://doi.org/10.1016/j.bjao.2024.100276","url":null,"abstract":"<div><h3>Background</h3><p>The alpha-2 adrenergic agonist dexmedetomidine induces EEG patterns resembling those of non-rapid eye movement (NREM) sleep. Fulfilment of slow wave sleep (SWS) homeostatic needs would address the assumption that dexmedetomidine induces functional biomimetic sleep states.</p></div><div><h3>Methods</h3><p>In-home sleep EEG recordings were obtained from 13 healthy participants before and after dexmedetomidine sedation. Dexmedetomidine target-controlled infusions and closed-loop acoustic stimulation were implemented to induce and enhance EEG slow waves, respectively. EEG recordings during sedation and sleep were staged using modified American Academy of Sleep Medicine criteria. Slow wave activity (EEG power from 0.5 to 4 Hz) was computed for NREM stage 2 (N2) and NREM stage 3 (N3/SWS) epochs, with the aggregate partitioned into quintiles by time. The first slow wave activity quintile served as a surrogate for slow wave pressure, and the difference between the first and fifth quintiles as a measure of slow wave pressure dissipation.</p></div><div><h3>Results</h3><p>Compared with pre-sedation sleep, post-sedation sleep showed reduced N3 duration (mean difference of −17.1 min, 95% confidence interval −30.0 to −8.2, <em>P</em>=0.015). Dissipation of slow wave pressure was reduced (<em>P</em>=0.02). Changes in combined durations of N2 and N3 between pre- and post-sedation sleep correlated with total dexmedetomidine dose, (<em>r</em>=−0.61, <em>P</em>=0.03).</p></div><div><h3>Conclusions</h3><p>Daytime dexmedetomidine sedation and closed-loop acoustic stimulation targeting EEG slow waves reduced N3/SWS duration and measures of slow wave pressure dissipation on the post-sedation night in healthy young adults. Thus, the paired intervention induces sleep-like states that fulfil certain homeostatic NREM sleep needs in healthy young adults.</p></div><div><h3>Clinical trial registration</h3><p>ClinicalTrials.gov <span>NCT04206059</span><svg><path></path></svg>.</p></div>","PeriodicalId":72418,"journal":{"name":"BJA open","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2772609624000200/pdfft?md5=e7d6d12302990a8e911d449be4d1ec8c&pid=1-s2.0-S2772609624000200-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140309825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}