New Approaches in Intravenous Anesthesia and Anesthetics—Part III

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Anesthesiology".

Deadline for manuscript submissions: closed (15 December 2023) | Viewed by 14834

Special Issue Editor


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Guest Editor
Dept. of Anesthesiology, Critical Care and Pain Medicine, Harvard Medical School, Boston Children’s Hospital, 300 Longwood Ave., Boston, MA 02115, USA
Interests: anesthesia and safety outside the operating room; dental sedation; sedation; target-controlled infusion (TCI)
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Special Issue Information

Dear Colleagues,

In August 2020, we launched our Special Issue "New Approaches in Intravenous Anesthesia and Anesthetics"—Part 1” (https://www.mdpi.com/journal/jcm/special_issues/Intravenous_Anesthesia). Then, in October 2021, we launched the second part of the same Special Issue (https://www.mdpi.com/journal/jcm/special_issues/Anesthesia_and_Anesthetics_Part_II), publishing many manuscripts concerning different topics related to anesthesia. Both Special Issues included manuscripts focusing on pharmacokinetics and pharmacodynamics of sedative anesthetics, important findings on opiate use and surgical practice, recent developments in sedation in the pediatric intensive care unit, and state-of-the-art intraoperative neuromonitoring in children.

Given the enormous success of Parts I and II, I believe that it is time to move forward to creating Special Issue Part III, with the aim of collecting additional insight into anesthesia and anesthetics. The JCM journal is very keen to attract a global audience, welcoming any contributions on this subject from around the world.

We particularly welcome papers providing insight into:

  1. The pharmacokinetics and pharmacodynamics of sedatives and anesthetics;
  2. Recent developments in perioperative care;
  3. Future insights into anesthesia practice over the next decade.

We welcome both solicited and unsolicited submissions contributing to our goal.

Dr. Keira P. Mason
Guest Editor

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Keywords

  • sedation
  • safety
  • intravenous
  • target-controlled infusions
  • adverse events
  • future
  • regional anesthesia

Published Papers (10 papers)

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Research

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10 pages, 668 KiB  
Article
The Effect of Dexmedetomidine Sedation on Lower Gastrointestinal Motility in Children—Is It Suitable for Anorectal Manometry?
by Tal David Berger, Karina Lukovits, David Cavanaugh, Samuel Nurko and Keira Mason
J. Clin. Med. 2023, 12(23), 7494; https://doi.org/10.3390/jcm12237494 - 04 Dec 2023
Viewed by 717
Abstract
Anorectal manometry is one of the most frequently performed gastrointestinal motility studies in children. It is an important study in diagnosing Hirschsprung disease (HD). These procedures can be uncomfortable, painful and emotionally distressing. Nitrous oxide or midazolam are the only pharmacologic options available, [...] Read more.
Anorectal manometry is one of the most frequently performed gastrointestinal motility studies in children. It is an important study in diagnosing Hirschsprung disease (HD). These procedures can be uncomfortable, painful and emotionally distressing. Nitrous oxide or midazolam are the only pharmacologic options available, as clinical experience suggests that they do not alter manometry readings. Our study was designed to determine whether Dexmedetomidine (DEX) could provide adequate sedation without disrupting anal and rectal pressure. The effect of DEX on anorectal function has never been studied in children. This prospective study recorded anorectal manometry (ARM) measurements prior to the administration of DEX and then repeated the measurements at 1 and 5 min after DEX. The main ARM measurements included resting intra-anal sphincter pressure (IASP) and the presence and characteristics of the recto-anal inhibitory reflex (RAIR). DEX was administered as a bolus followed by a continuous infusion. Twenty patients were included (60% female; mean age 10.8 ± 4.6 years). The RAIR became absent in 2/16 (12.5%) patients after DEX administration. DEX may alter physiologic ARM and IASP recordings necessary to diagnose gastrointestinal medical conditions. Full article
(This article belongs to the Special Issue New Approaches in Intravenous Anesthesia and Anesthetics—Part III)
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12 pages, 824 KiB  
Article
Remimazolam Pilot for Office-Based Dental Sedation: Adverse Events, Awareness and Outcomes
by Rudi Swart, Sabine S. A. Maes, David Cavanaugh and Keira P. Mason
J. Clin. Med. 2023, 12(23), 7308; https://doi.org/10.3390/jcm12237308 - 25 Nov 2023
Cited by 1 | Viewed by 735
Abstract
In recent years, remimazolam has gained approval for use in adult procedural sedation in both the United Kingdom and the United States, potentially offering an alternative to conventional sedatives like propofol and midazolam for procedural sedation. However, there is a limited body of [...] Read more.
In recent years, remimazolam has gained approval for use in adult procedural sedation in both the United Kingdom and the United States, potentially offering an alternative to conventional sedatives like propofol and midazolam for procedural sedation. However, there is a limited body of literature that systematically reviews the outcomes of a remimazolam-alfentanil combination protocol for routine office-based dental procedures. The primary objective of this pilot study was to assess the occurrence of significant adverse events associated with the use of a remimazolam-alfentanil sedation protocol for adult dental procedures. Secondary outcomes included evaluating physiological responses, sedation effectiveness, patient and clinician satisfaction and the incidence of intraprocedural awareness. Notably, no significant adverse events were reported among the 25 adult subjects who received remimazolam and alfentanil, and all dental procedures were successfully completed. Patients and clinicians expressed high levels of satisfaction, and patients did not report any distressing memories associated with the dental procedure. These findings suggest that in a limited cohort, the remimazolam-alfentanil regimen appears to be well tolerated and effective for office-based dental procedures in adult patients, with a low risk of adverse events, acceptable hemodynamic effects, rapid onset and recovery and minimal intraoperative awareness. This study provides valuable insights into the potential use of the remimazolam-alfentanil combination in dental sedation practice. Full article
(This article belongs to the Special Issue New Approaches in Intravenous Anesthesia and Anesthetics—Part III)
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14 pages, 744 KiB  
Article
Implementation of an Enhanced Recovery after Surgery Pathway for Transgender and Gender-Diverse Individuals Undergoing Chest Reconstruction Surgery: An Observational Cohort Study
by Nelson J. Aquino, Susan M. Goobie, Steven J. Staffa, Elizabeth Eastburn, Oren Ganor and Cathie T. Jones
J. Clin. Med. 2023, 12(22), 7083; https://doi.org/10.3390/jcm12227083 - 14 Nov 2023
Cited by 1 | Viewed by 1134
Abstract
Enhanced Recovery After Surgery (ERAS) protocols are associated with improved clinical outcomes in cisgender breast surgery patients. However, a paucity of research exists regarding transgender and gender-diverse individuals (TGD) in the ERAS framework. The primary objective of this observational cohort study is to [...] Read more.
Enhanced Recovery After Surgery (ERAS) protocols are associated with improved clinical outcomes in cisgender breast surgery patients. However, a paucity of research exists regarding transgender and gender-diverse individuals (TGD) in the ERAS framework. The primary objective of this observational cohort study is to describe the implementation of a gender-affirming ERAS protocol and its relationship to hospital length of stay (LOS) in TGD patients following chest reconstruction surgery. The secondary aim is to identify intraoperative predictors of LOS and define variables associated with adverse outcomes. We identified 362 patients in three epochs: a traditional group (n = 144), a partial ERAS implementation group (n = 92), and an ERAS group (n = 126). Exploratory multivariable median regression modeling was performed to identify independent predictors of LOS. We report that the traditional group’s median hospital LOS was 1.1 days compared to 0.3 days in the ERAS group. Intraoperative tranexamic acid administration was associated with significantly shorter LOS (p < 0.001), reduced postoperative drainage (p < 0.001), and fewer returns to the operating room within 24 h (p = 0.047). Our data suggest that implementing a multimodal ERAS gender-affirming pathway was associated with improved patient-centered surgical outcomes such as decreased return to the operating room for hematoma evacuation, higher rates of discharge home, and reduced postoperative drainage output. Full article
(This article belongs to the Special Issue New Approaches in Intravenous Anesthesia and Anesthetics—Part III)
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11 pages, 1070 KiB  
Article
Remimazolam for Pediatric Procedural Sedation: Results of an Institutional Pilot Program
by Tatsuya Hirano, Yoshitaka Kimoto, Norifumi Kuratani, David Cavanaugh and Keira P. Mason
J. Clin. Med. 2023, 12(18), 5937; https://doi.org/10.3390/jcm12185937 - 13 Sep 2023
Cited by 1 | Viewed by 1216
Abstract
Remimazolam, an ultra-short-acting benzodiazepine sedative, was first approved in 2020 in Japan as a general anesthetic for adults. However, its utilization in pediatric settings remains unexplored and, to date, is confined to isolated case reports due to a lack of specific pediatric labeling. [...] Read more.
Remimazolam, an ultra-short-acting benzodiazepine sedative, was first approved in 2020 in Japan as a general anesthetic for adults. However, its utilization in pediatric settings remains unexplored and, to date, is confined to isolated case reports due to a lack of specific pediatric labeling. The primary objective of our study was to evaluate the safety profile of remimazolam when used for procedural sedation in children following dosages established in adult protocols. Additional parameters, including dosage per kg of body weight, duration of the procedure, efficacy (measured as successful completion of the procedure), the necessity for supplemental medications, and changes in physiological parameters, such as the heart rate (HR) and mean arterial blood pressure (MAP), were assessed. Our study encompassed 48 children with an average age of 7.0 years. The objective Tracking and Reporting Outcomes of Procedural Sedation tool indicated no adverse events. In our cohort, propofol and ketamine were used as adjunctive treatments in 8 and 39 patients, respectively, with successful completion of all procedures. Notable hemodynamic variability was observed, with 88.4% of patients experiencing a ≥20% change (increase or decrease) and 62.8% experiencing a ≥30% change in MAP. Additionally, a ≥20% change in HR was observed in 54.3% of patients, and a ≥30% change was observed in 34.8% of patients. Nevertheless, none of the patients required pharmacological intervention to manage these hemodynamic fluctuations. Our findings suggest that remimazolam, when supplemented with propofol or ketamine, could offer a safe and effective pathway for administering procedural sedation in pediatric populations. Full article
(This article belongs to the Special Issue New Approaches in Intravenous Anesthesia and Anesthetics—Part III)
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16 pages, 2490 KiB  
Article
Desktop Virtual Reality Offers a Novel Approach to Minimize Pain and Anxiety during Burn Wound Cleaning/Debridement in Infants and Young Children: A Randomized Crossover Pilot Study
by Taima Alrimy, Wadee Alhalabi, Areej Malibari, Fatma Alzahrani, Sharifah Alrajhi, Ayman Yamani, Halah Ahmed, Amro Abduljawad, Essam Nasser, Samar ALattar, Buthinah Alharby, Hasna Khalid, Mohammed Alhalabi, Hunter G. Hoffman and Keira P. Mason
J. Clin. Med. 2023, 12(15), 4985; https://doi.org/10.3390/jcm12154985 - 28 Jul 2023
Cited by 1 | Viewed by 1089
Abstract
Although most scald burn injuries involve children under six, because of the challenges of using head mounted displays with young children there is very little research exploring the use of VR in children under six. The current clinical pilot study measured the analgesic [...] Read more.
Although most scald burn injuries involve children under six, because of the challenges of using head mounted displays with young children there is very little research exploring the use of VR in children under six. The current clinical pilot study measured the analgesic effectiveness of our new desktop VR system (with no VR helmet) in children under six during burn wound care (a within-subjects design with randomized treatment order). Between December 2021–April 2022, nine children with burn injuries (10 months to 5 years age, mean = 18 months) participated. The mean burn size was 10% Total Body Surface Area, range 2–22%. Using nurse’s ratings, VR significantly reduced children’s pain during burn wound care by 40% on the observational Faces, Legs, Activity, Crying, and Consolability (FLACC) pain scale. Specifically, non-parametric within-subject sign tests compared nurse’s ratings of the young patients’ pain during burn wound care using usual pain medications with no VR = 6.67, (SD = 2.45) vs. adjunctive Animal Rescue World VR (VR = 4.00, SD = 2.24, p < 0.01). The observational Procedure–Behavior Checklist (PBCL) nurse’s scale measured a 34% reduction in anxiety with VR as compared to pharmacologic treatment alone (p < 0.005). Similarly, when using single graphic rating scales the patients’ parents reported a significant 36% decrease in their child’s pain during VR (p < 0.05), a 38% (p < 0.005) decrease in their child’s anxiety during VR, and a significant increase in patients’ joy during VR. It can be concluded that during burn wound care with no distraction (traditional pain medications), children under 6 years old experienced severe pain during a 10 min burn wound cleaning session. During burn wound care combining desktop virtual reality and traditional pain medications, the same pediatric patients experienced only mild pain during burn wound cleaning/debridement. VR significantly reduced the children’s pain and anxiety during burn wound care. Full article
(This article belongs to the Special Issue New Approaches in Intravenous Anesthesia and Anesthetics—Part III)
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11 pages, 913 KiB  
Article
Remimazolam as an Adjunct to General Anesthesia in Children: Adverse Events and Outcomes in a Large Cohort of 418 Cases
by Yoshitaka Kimoto, Tatsuya Hirano, Norifumi Kuratani, David Cavanaugh and Keira P. Mason
J. Clin. Med. 2023, 12(12), 3930; https://doi.org/10.3390/jcm12123930 - 08 Jun 2023
Cited by 1 | Viewed by 1363
Abstract
Remimazolam was first approved in 2020 as a general anesthetic for adults and still does not have pediatric labeling. Our study will be the first pilot program that administers remimazolam as an adjunct to a general endotracheal anesthetic in children. Between August 2020 [...] Read more.
Remimazolam was first approved in 2020 as a general anesthetic for adults and still does not have pediatric labeling. Our study will be the first pilot program that administers remimazolam as an adjunct to a general endotracheal anesthetic in children. Between August 2020 and December 2022, electronic medical records were collected for all children who received remimazolam during anesthesia. The remimazolam dosing regimen was extrapolated from the adult package insert, with intravenous induction doses of 12 mg/kg/h administered until the desired effect was achieved. Subsequent infusions were given at a rate of 1–2 mg/kg/h, accompanied by intermittent boluses of 0.2 mg/kg, with all dosing adjustments made according to the anesthesiologist’s clinical discretion. A total of 418 children (mean 4.6 yrs, 68.7% ASA 1 and 2) underwent surgeries which averaged 81.2 min. A total of 75.2% of patients had greater than a 20% change (increase or decrease) in MAP (lowest or highest) from baseline, and 203 (49.3%) patients had greater than a 30% change (increase or decrease) in MAP (lowest or highest) from baseline. A total of 5% received ephedrine to treat unanticipated hemodynamic variability. Discharge criteria were met within an average of 13.8 min after arrival at the post-anesthesia care unit. Remimazolam may offer the benefits of rapid recovery following general endotracheal anesthesia. The risk of hemodynamic variability which necessitates and responds to ephedrine should be anticipated. Full article
(This article belongs to the Special Issue New Approaches in Intravenous Anesthesia and Anesthetics—Part III)
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Review

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20 pages, 2196 KiB  
Review
Considerations for Intravenous Anesthesia Dose in Obese Children: Understanding PKPD
by James Denzil Morse, Luis Ignacio Cortinez and Brian Joseph Anderson
J. Clin. Med. 2023, 12(4), 1642; https://doi.org/10.3390/jcm12041642 - 18 Feb 2023
Cited by 1 | Viewed by 1728
Abstract
The intravenous induction or loading dose in children is commonly prescribed per kilogram. That dose recognizes the linear relationship between volume of distribution and total body weight. Total body weight comprises both fat and fat-free mass. Fat mass influences the volume of distribution [...] Read more.
The intravenous induction or loading dose in children is commonly prescribed per kilogram. That dose recognizes the linear relationship between volume of distribution and total body weight. Total body weight comprises both fat and fat-free mass. Fat mass influences the volume of distribution and the use of total body weight fails to recognize the impact of fat mass on pharmacokinetics in children. Size metrics alternative to total body mass (e.g., fat-free and normal fat mass, ideal body weight and lean body weight) have been proposed to scale pharmacokinetic parameters (clearance, volume of distribution) for size. Clearance is the key parameter used to calculate infusion rates or maintenance dosing at steady state. Dosing schedules recognize the curvilinear relationship, described using allometric theory, between clearance and size. Fat mass also has an indirect influence on clearance through both metabolic and renal function that is independent of its effects due to increased body mass. Fat-free mass, lean body mass and ideal body mass are not drug specific and fail to recognize the variable impact of fat mass contributing to body composition in children, both lean and obese. Normal fat mass, used in conjunction with allometry, may prove a useful size metric but computation by clinicians for the individual child is not facile. Dosing is further complicated by the need for multicompartment models to describe intravenous drug pharmacokinetics and the concentration effect relationship, both beneficial and adverse, is often poorly understood. Obesity is also associated with other morbidity that may also influence pharmacokinetics. Dose is best determined using pharmacokinetic–pharmacodynamic (PKPD) models that account for these varied factors. These models, along with covariates (age, weight, body composition), can be incorporated into programmable target-controlled infusion pumps. The use of target-controlled infusion pumps, assuming practitioners have a sound understanding of the PKPD within programs, provide the best available guide to intravenous dose in obese children. Full article
(This article belongs to the Special Issue New Approaches in Intravenous Anesthesia and Anesthetics—Part III)
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15 pages, 1609 KiB  
Review
The Emerging Role of Virtual Reality as an Adjunct to Procedural Sedation and Anesthesia: A Narrative Review
by Rita Hitching, Hunter G. Hoffman, Azucena Garcia-Palacios, Maheen M. Adamson, Esmeralda Madrigal, Wadee Alhalabi, Ahad Alhudali, Mariana Sampaio, Barry Peterson, Miles R. Fontenot and Keira P. Mason
J. Clin. Med. 2023, 12(3), 843; https://doi.org/10.3390/jcm12030843 - 20 Jan 2023
Cited by 11 | Viewed by 3235
Abstract
Over the past 20 years, there has been a significant reduction in the incidence of adverse events associated with sedation outside of the operating room. Non-pharmacologic techniques are increasingly being used as peri-operative adjuncts to facilitate and promote anxiolysis, analgesia and sedation, and [...] Read more.
Over the past 20 years, there has been a significant reduction in the incidence of adverse events associated with sedation outside of the operating room. Non-pharmacologic techniques are increasingly being used as peri-operative adjuncts to facilitate and promote anxiolysis, analgesia and sedation, and to reduce adverse events. This narrative review will briefly explore the emerging role of immersive reality in the peri-procedural care of surgical patients. Immersive virtual reality (VR) is intended to distract patients with the illusion of “being present” inside the computer-generated world, drawing attention away from their anxiety, pain, and discomfort. VR has been described for a variety of procedures that include colonoscopies, venipuncture, dental procedures, and burn wound care. As VR technology develops and the production costs decrease, the role and application of VR in clinical practice will expand. It is important for medical professionals to understand that VR is now available for prime-time use and to be aware of the growing body in the literature that supports VR. Full article
(This article belongs to the Special Issue New Approaches in Intravenous Anesthesia and Anesthetics—Part III)
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Other

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17 pages, 2915 KiB  
Systematic Review
Comparison of Remimazolam–Flumazenil versus Propofol for Recovery from General Anesthesia: A Systematic Review and Meta-Analysis
by Quantong Wu, Fuchao Xu, Jie Wang and Ming Jiang
J. Clin. Med. 2023, 12(23), 7316; https://doi.org/10.3390/jcm12237316 - 26 Nov 2023
Viewed by 1103
Abstract
(1) Purpose: to systematically evaluate the recovery following sedation and anesthesia with remimazolam combined with flumazenil in comparison to propofol. (2) Methods: Electronic databases, including PubMed, Embase, Web of Science, and the Cochrane Library, were systematically searched from their inception up to 22 [...] Read more.
(1) Purpose: to systematically evaluate the recovery following sedation and anesthesia with remimazolam combined with flumazenil in comparison to propofol. (2) Methods: Electronic databases, including PubMed, Embase, Web of Science, and the Cochrane Library, were systematically searched from their inception up to 22 October 2023. Included in this analysis were randomized controlled trials (RCT) that compared remimazolam–flumazenil with propofol for the recovery from sedation and anesthesia in adults. The risk of bias was assessed using the Cochrane risk of bias tool. Pooled risk ratios (RR) or mean differences (MD) along with their corresponding 95% confidence intervals (CI) were calculated using either fixed-effects or random-effects models, and the results were visualized in forest plots. (3) Results: Nine RCTs involving 745 patients who underwent general anesthesia in three different countries were included. Compared to propofol, the remimazolam–flumazenil combination shortened the emergence time (MD = −4.34 min, 95% CI = [−6.88, −1.81], p = 0.0008, low certainty), extubation time (MD = −4.26 min, 95% CI = [−6.81, −1.7], p = 0.0011, low certainty), and the post-anesthesia care unit (PACU) stay (MD = −4.42 min, 95% CI = [−7.45, −1.38], p = 0.0044, low certainty), while reducing the incidence of respiratory depression (RR = 0.2, 95% CI = [0.04, 0.89], p = 0.03, high certainty) after general anesthesia. However, this combination was associated with a higher incidence of re-sedation (RR = 4.15, 95% CI = [1.31, 13.13], p = 0.01, moderate certainty). (4) Conclusions: Based on the existing evidence, the combination of remimazolam and flumazenil accelerates recovery from general anesthesia and lowers the risk of respiratory depression compared to propofol. However, it is important to consider the higher risk of re-sedation when using this combination in clinical practice. Due to limitations in the quality of the evidence, it is advisable to interpret the results of meta-analyses with caution. Full article
(This article belongs to the Special Issue New Approaches in Intravenous Anesthesia and Anesthetics—Part III)
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11 pages, 2190 KiB  
Systematic Review
Opioid Free Anesthesia in Thoracic Surgery: A Systematic Review and Meta Analysis
by Filippo D’Amico, Gaia Barucco, Margherita Licheri, Gabriele Valsecchi, Luisa Zaraca, Marta Mucchetti, Alberto Zangrillo and Fabrizio Monaco
J. Clin. Med. 2022, 11(23), 6955; https://doi.org/10.3390/jcm11236955 - 25 Nov 2022
Cited by 7 | Viewed by 1880
Abstract
Introduction: Recent studies showed that balanced opioid-free anesthesia is feasible and desirable in several surgical settings. However, in thoracic surgery, scientific evidence is still lacking. Thus, we conducted the first systematic review and meta-analysis of opioid-free anesthesia in this field. Methods: The primary [...] Read more.
Introduction: Recent studies showed that balanced opioid-free anesthesia is feasible and desirable in several surgical settings. However, in thoracic surgery, scientific evidence is still lacking. Thus, we conducted the first systematic review and meta-analysis of opioid-free anesthesia in this field. Methods: The primary outcome was the occurrence of any complication. Secondary outcomes were the length of hospital stay, recovery room length of stay, postoperative pain at 24 and 48 h, and morphine equivalent consumption at 48 h. Results: Out of 375 potentially relevant articles, 6 studies (1 randomized controlled trial and 5 observational cohort studies) counting a total of 904 patients were included. Opioid-free anesthesia compared to opioid-based anesthesia, was associated with a lower rate of any complication (74 of 175 [42%] vs. 200 of 294 [68%]; RR = 0.76; 95% CI, 0.65–0.89; p < 0.001; I2 = 0%), lower 48 h morphine equivalent consumption (MD −14.5 [−29.17/−0.22]; p = 0.05; I2 = 95%) and lower pain at 48 h (MD −1.95 [−3.6/0.3]; p = 0.02, I = 98%). Conclusions: Opioid-free anesthesia in thoracic surgery is associated with lower postoperative complications, and less opioid demand with better postoperative analgesia at 48 h compared to opioid-based anesthesia. Full article
(This article belongs to the Special Issue New Approaches in Intravenous Anesthesia and Anesthetics—Part III)
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