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Journal of Intensive Care Medicine Jun 2024Patients in the intensive care unit (ICU) often experience poor sleep quality. Pharmacologic sleep aids are frequently used as primary or adjunctive therapy to improve... (Review)
Review
Patients in the intensive care unit (ICU) often experience poor sleep quality. Pharmacologic sleep aids are frequently used as primary or adjunctive therapy to improve sleep, although their benefits in the ICU remain uncertain. This review aims to provide a comprehensive assessment of the objective and subjective effects of medications used for sleep in the ICU, as well as their adverse effects. PubMed, Web of Science, Scopus, Embase, and Cochrane Central Register of Controlled Trials were systematically searched from their inception until June 2023 for comparative studies assessing the effects of pharmacologic sleep aids on objective and subjective metrics of sleep. Thirty-four studies with 3498 participants were included. Medications evaluated were melatonin, ramelteon, suvorexant, propofol, and dexmedetomidine. The majority of studies were randomized controlled trials. Melatonin and dexmedetomidine were the best studied agents. Objective sleep metrics included polysomnography (PSG), electroencephalography (EEG), bispectral index, and actigraphy. Subjective outcome measures included patient questionnaires and nursing observations. Evidence for melatonin as a sleep aid in the ICU was mixed but largely not supportive for improving sleep. Evidence for ramelteon, suvorexant, and propofol was too limited to offer definitive recommendations. Both objective and subjective data supported dexmedetomidine as an effective sleep aid in the ICU, with PSG/EEG in 303 ICU patients demonstrating increased sleep duration and efficiency, decreased arousal index, decreased percentage of stage N1 sleep, and increased absolute and percentage of stage N2 sleep. Mild bradycardia and hypotension were reported as side effects of dexmedetomidine, whereas the other medications were reported to be safe. Several ongoing studies have not yet been published, mostly on melatonin and dexmedetomidine. While definitive conclusions cannot be made for most medications, dexmedetomidine improved sleep quantity and quality in the ICU. These benefits need to be balanced with possible hemodynamic side effects.
PubMed: 38881385
DOI: 10.1177/08850666241255345 -
International Journal of Gynaecology... Jun 2024To analyze the success rate of external cephalic version (ECV) in pregnant women with a history of previous cesarean section, as well as to describe the rate of...
OBJECTIVE
To analyze the success rate of external cephalic version (ECV) in pregnant women with a history of previous cesarean section, as well as to describe the rate of complications associated with the procedure.
METHODS
A retrospective cohort study of women who were offered an ECV at "Virgen de la Arrixaca" Clinic University Hospital (Murcia, Spain) between January 2014 and December 2023. We collected data for previous cesarean delivery, obstetric history, fetal presentation, amniotic fluid volume, ECV success rate, complications related to ECV, mode of delivery, and neonatal outcomes. The study confidently performed ECV under sedation with propofol and tocolysis with ritodrine. Univariate and multivariate analyses were conducted to compare the success rate of ECV, ECV complications, and mode of delivery between women with and without previous cesarean sections.
RESULTS
Of 1116 pregnant women who were offered ECV, 911 were included in the study, with 42 having a previous cesarean section. The success rate of ECV in pregnant women with a previous cesarean section was 78.6% (adjusted odds ratio 1.18; 95% confidence interval 0.49-2.86; P = 0.708), with a low complication rate of 9.5%, such as non-reassuring fetal heart rate (7.1%) or major vaginal bleeding (2.4%). Of the women who attempted a vaginal delivery after ECV, 80.8% were successful.
CONCLUSIONS
These findings support that ECV is a safe and effective option for women with a previous cesarean section, with success rates comparable to those in women without a previous cesarean section.
PubMed: 38881234
DOI: 10.1002/ijgo.15738 -
Perioperative Medicine (London, England) Jun 2024Remimazolam is a short-acting benzodiazepine newly approved for the induction and maintenance of general anesthesia. Remimazolam emerges as an ideal drug for the...
BACKGROUND
Remimazolam is a short-acting benzodiazepine newly approved for the induction and maintenance of general anesthesia. Remimazolam emerges as an ideal drug for the neurosurgical population due to its rapid emergence, enabling early neurological assessment, and its ability to maintain perfusion pressure, which is crucial for preventing cerebral ischemia. However, the use of benzodiazepine has been associated with an increased risk of postoperative delirium (POD). There is currently limited evidence about the relationship between remimazolam-based total intravenous anesthesia (TIVA) and POD.
METHODS
In this double-blind, randomized, non-inferiority trial, we plan to include 696 adult patients with American Society of Anesthesiologists physical status class I to III, undergoing elective neurovascular surgery under general anesthesia. After informed consent, the patients will be randomized to receive either remimazolam or propofol-based TIVA with a 1:1 ratio. The primary outcome is the incidence of POD within 5 days after surgery. Secondary outcomes include subtypes, number of positive assessments and severity of POD, emergence agitation, intraoperative awareness and undesirable patient movement, intraoperative hypotension, and postoperative cognitive function. The data will be analyzed in modified intention to treat.
DISCUSSION
This trial will evaluate the effect of remimazolam on the development of POD compared to propofol anesthesia. The results of this trial will provide evidence regarding the choice of optimal anesthetics to minimize the risk of POD in neurosurgical patients.
TRIAL REGISTRATION
The study protocol was prospectively registered at the Clinical trials ( https://clinicaltrials.gov , NCT06115031, principal investigator: Jiseon Jeong; date of first registration: November 2, 2023, before the recruitment of the first participant.
PubMed: 38877533
DOI: 10.1186/s13741-024-00415-6 -
Neuropharmacology Jun 2024We previously showed that the PDE4 inhibitor apremilast reduces ethanol consumption in mice by protein kinase A (PKA) and GABAergic mechanisms. Preventing PKA...
We previously showed that the PDE4 inhibitor apremilast reduces ethanol consumption in mice by protein kinase A (PKA) and GABAergic mechanisms. Preventing PKA phosphorylation of GABA β3 subunits partially blocked apremilast-mediated decreases in drinking. Here, we produced Gabrb1-S409A mice to render GABA β1 subunits resistant to PKA-mediated phosphorylation. Mass spectrometry confirmed the presence of the S409A mutation and lack of changes in β1 subunit expression or phosphorylation at other residues. β1-S409A male and female mice did not differ from wild-type C57BL/6J mice in expression of Gabrb1, Gabrb2, or Gabrb3 subunits or in behavioral characteristics. Apremilast prolonged recovery from ethanol ataxia to a greater extent in Gabrb1-S409A mice but prolonged recovery from zolpidem and propofol to a similar extent in both genotypes. Apremilast shortened recovery from diazepam ataxia in wild-type but prolonged recovery in Gabrb1-S409A mice. In wild-type mice, the PKA inhibitor H89 prevented apremilast modulation of ataxia by ethanol and diazepam, but not by zolpidem. In Gabrb1-S409A mice, inhibiting PKA or EPAC2 (exchange protein directly activated by cAMP) partially reversed apremilast potentiation of ethanol, diazepam, and zolpidem ataxia. Apremilast prevented acute tolerance to ethanol ataxia in both genotypes, but there were no genotype differences in ethanol consumption before or after apremilast. In contrast to results in Gabrb3-S408A/S409A mice, PKA phosphorylation of β1-containing GABA receptors is not required for apremilast's effects on acute tolerance or on ethanol consumption but is required for its ability to decrease diazepam intoxication. Besides PKA we identified EPAC2 as an additional cAMP-dependent mechanism by which apremilast regulates responses to GABAergic drugs.
PubMed: 38876310
DOI: 10.1016/j.neuropharm.2024.110035 -
Journal of Zoo and Wildlife Medicine :... Jun 2024The marbled crayfish () is a parthenogenetic invasive species across much of the world, and when found, euthanasia is often recommended to reduce spread to naïve...
The marbled crayfish () is a parthenogenetic invasive species across much of the world, and when found, euthanasia is often recommended to reduce spread to naïve ecosystems. Euthanasia recommendations in crustaceans includes a two-step method: first to produce nonresponsiveness and then to destroy central nervous tissue. Minimal data exist on adequate anesthetic or immobilization methods for crayfish. A population of 90 marbled crayfish was scheduled for euthanasia due to invasive species concerns. The population was divided into six treatment groups to evaluate whether immersion in emulsified isoflurane or propofol solutions could produce nonresponsiveness. Each group was exposed to one of six treatments for 1 h: isoflurane emulsified at 0.1%, 0.5%, 2%, 5%, and 15% or propofol at 10 mg/L and then increased to 100 mg/L. Crayfish from all treatment groups were moved to nonmedicated water after completion of 1 h and observed for an additional 4 h. All crayfish treated with isoflurane showed lack of a righting reflex at 5 min and loss of movement after 30 min. By 240 min (4 h), none of the crayfish from the isoflurane treatment groups regained movement. None of the crayfish in the propofol treatment achieved loss of reflexes or responsiveness, and all remained normal upon return to nonmedicated water. Isoflurane emulsified in water produces nonresponsiveness that is appropriate for the first step of euthanasia, while propofol was insufficient at these treatment doses.
Topics: Animals; Astacoidea; Isoflurane; Propofol; Euthanasia, Animal; Anesthetics, Inhalation; Immersion; Dose-Response Relationship, Drug
PubMed: 38875198
DOI: 10.1638/2023-0137 -
BMC Anesthesiology Jun 2024Intra-operative anaesthesia management should be optimised to reduce the occurrence of postoperative nausea and vomiting in high-risk patients; however, a single... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
Intra-operative anaesthesia management should be optimised to reduce the occurrence of postoperative nausea and vomiting in high-risk patients; however, a single intervention may not effectively reduce postoperative nausea and vomiting in such patients. This study assessed the effect of an optimised anaesthetic protocol versus a conventional one on postoperative nausea and vomiting in patients who underwent laparoscopic sleeve gastrectomy.
METHODS
A single-centre randomised trial was conducted at Peking University Shenzhen Hospital from June 2021 to December 2022. Among 168 patients who underwent laparoscopic sleeve gastrectomy, 116 qualified, and 103 completed the study with available data. Patients were categorized into the conventional group (received sevoflurane and standard fluids) and the optimised group (underwent propofol-based anaesthesia and was administered goal-directed fluids). The primary endpoints were postoperative nausea and vomiting incidence and severity within 24 h.
RESULTS
Postoperative nausea and vomiting assessment at 0-3 h post-surgery revealed no significant differences between groups. However, at 3-24 h, the optimised anaesthetic protocol group showed lower postoperative nausea and vomiting incidence and severity than those of the conventional group (P = 0.005). In the conventional group, 20 (37.04%) patients experienced moderate-to-severe postoperative nausea and vomiting, compared to six (12.25%) patients in the optimised group (odds ratio = 0.237; 95% CI = 0.086, 0.656; P = 0.006). No significant differences were noted in antiemetic treatment, moderate-to-severe pain incidence, anaesthesia recovery, post-anaesthetic care unit stay, or postoperative duration between the groups. While the total intra-operative infusion volumes were comparable, the optimised group had a significantly higher colloidal infusion volume (500 mL vs. 0 mL, P = 0.014) than that of the conventional group.
CONCLUSIONS
The incidence and severity of postoperative nausea and vomiting 3-24 h postoperatively in patients who underwent laparoscopic sleeve gastrectomy were significantly lower with propofol-based total intravenous anaesthesia and goal-directed fluid therapy than with sevoflurane anaesthesia and traditional fluid management. Total intravenous anaesthesia is an effective multimodal antiemetic strategy for bariatric surgery.
TRIAL REGISTRATION
This trial was registered with the Chinese Clinical Trial Registry (ChiCTR-TRC- 2,100,046,534, registration date: 21 May 2021).
Topics: Humans; Postoperative Nausea and Vomiting; Male; Female; Laparoscopy; Gastrectomy; Adult; Propofol; Sevoflurane; Middle Aged; Anesthetics, Intravenous; Anesthetics, Inhalation; Anesthesia
PubMed: 38872117
DOI: 10.1186/s12871-024-02577-8 -
Journal of Clinical Anesthesia Jun 2024Elderly patients undergoing pathophysiological changes necessitate clinical tools for cerebral monitoring. This prospective randomized controlled study aimed to explore...
STUDY OBJECTIVE
Elderly patients undergoing pathophysiological changes necessitate clinical tools for cerebral monitoring. This prospective randomized controlled study aimed to explore how cerebral monitoring using ΔoHbi, ΔHHbi, and ΔcHbi manifests in elderly patients under either propofol or sevoflurane anesthesia.
DESIGN
Single-center, prospective, randomization.
SETTING
A single tertiary hospital (Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea).
PATIENTS
Enrolled 100 patients scheduled for urologic surgery under general anesthesia. Inclusion criteria were (a) age 70-80 years, (b) American Society of Anesthesiologists (ASA) physical status I-II.
INTERVENTION
Patients were double-blind randomized to receive propofol-based or sevoflurane anesthesia. Cerebral oximetry-related parameters were measured at 5, 10, 15, 20, and 30 min in a setting devoid of surgery-related factors.
MEASUREMENTS
The primary outcome focused on the ΔoHbi pattern in the left and right sides within the propofol and sevoflurane groups.
MAIN RESULTS
We analyzed 100 patients, 50 patients in each group. In the propofol group, the left ΔoHbi decreased from 1.4 (3.7) at 5 min to -0.1 (1.8) at 30 min (P < 0.0001), and the right ΔoHbi decreased from 2.9 (4.2) at 5 min to -0.06 (2.3) at 30 min (P < 0.0001). In the sevoflurane group, the left ΔoHbi decreased from 1.1 (3.4) at 5 min to -1.4 (4.4) at 30 min (P < 0.0001), and the right ΔoHbi decreased from 2.0 (3.2) at 5 min to -1.2 (3.9) at 30 min (P < 0.0001). There were no significant differences between the two groups. ΔHHbi did not exhibit significant changes after an initial decrease at 5 min and showed no significant differences between the two groups.
CONCLUSIONS
In cerebral oximetry, ΔoHbi and ΔHHbi could emerge as a valuable approach for discerning changes in the underlying baseline status of the brain in elderly patients during anesthesia.
PubMed: 38870700
DOI: 10.1016/j.jclinane.2024.111519 -
Critical Care Medicine Jul 2024
Topics: Humans; Propofol; Intubation, Intratracheal; Critical Illness; Dose-Response Relationship, Drug; Anesthetics, Intravenous; Hypnotics and Sedatives
PubMed: 38869401
DOI: 10.1097/CCM.0000000000006276 -
Minerva Anestesiologica Jun 2024Major spine surgery is associated with severe postoperative pain and increased opioid consumption. Opioid-free anesthesia (OFA) is thought to provide adequate... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
Major spine surgery is associated with severe postoperative pain and increased opioid consumption. Opioid-free anesthesia (OFA) is thought to provide adequate intraoperative analgesia with reduced postoperative opioid consumption. The aim of this study is to compare the impact of intraoperative OFA approach to the conventional opioid-based anesthesia (OBA) on postoperative pain, opioid consumption, and related side effects in patients undergoing multilevel spinal fusion surgery.
METHODS
Forty-eight patients undergoing elective major spine surgery were randomly allocated to either receive intraoperative dexmedetomidine and lidocaine (OFA group) or fentanyl during induction and intraoperative remifentanil (OBA group). All patients received intraoperative sevoflurane, propofol, rocuronium, ketamine, dexamethasone, ondansetron and postoperative paracetamol and patient-controlled analgesia device set to deliver intravenous morphine for 48 hours after surgery. Postoperative pain was measured using numerical rating scale. Opioid side effects were documented, when present.
RESULTS
OFA group required less morphine in the first 24 hours post-surgery (17.28±12.25 mg versus 27.96±19.75 mg, P<0.05). The incidence of postoperative nausea and vomiting (PONV) was significantly lower in the OFA group. More patients in the OFA group required antihypertensive medications compared to patients in the OBA group (P<0.05). In the post anesthesia care unit, OFA patients had a significantly longer stay than OBA patients (114.1±49.33 min versus 89.96±30.71 min, P<0.05).
CONCLUSIONS
OFA can be an alternative to OBA in patients undergoing multilevel spine fusion surgery. OFA reduces opioids consumption in the first 24 hours and PONV.
Topics: Humans; Male; Female; Analgesics, Opioid; Middle Aged; Prospective Studies; Pain, Postoperative; Adult; Spine; Dexmedetomidine; Aged; Spinal Fusion; Postoperative Nausea and Vomiting; Remifentanil; Anesthesia
PubMed: 38869262
DOI: 10.23736/S0375-9393.24.17962-X -
Annals of Clinical and Translational... Jun 2024Epileptiform activity (EA), including seizures and periodic patterns, worsens outcomes in patients with acute brain injuries (e.g., aneurysmal subarachnoid hemorrhage...
BACKGROUND/OBJECTIVES
Epileptiform activity (EA), including seizures and periodic patterns, worsens outcomes in patients with acute brain injuries (e.g., aneurysmal subarachnoid hemorrhage [aSAH]). Randomized control trials (RCTs) assessing anti-seizure interventions are needed. Due to scant drug efficacy data and ethical reservations with placebo utilization, and complex physiology of acute brain injury, RCTs are lacking or hindered by design constraints. We used a pharmacological model-guided simulator to design and determine the feasibility of RCTs evaluating EA treatment.
METHODS
In a single-center cohort of adults (age >18) with aSAH and EA, we employed a mechanistic pharmacokinetic-pharmacodynamic framework to model treatment response using observational data. We subsequently simulated RCTs for levetiracetam and propofol, each with three treatment arms mirroring clinical practice and an additional placebo arm. Using our framework, we simulated EA trajectories across treatment arms. We predicted discharge modified Rankin Scale as a function of baseline covariates, EA burden, and drug doses using a double machine learning model learned from observational data. Differences in outcomes across arms were used to estimate the required sample size.
RESULTS
Sample sizes ranged from 500 for levetiracetam 7 mg/kg versus placebo, to >4000 for levetiracetam 15 versus 7 mg/kg to achieve 80% power (5% type I error). For propofol 1 mg/kg/h versus placebo, 1200 participants were needed. Simulations comparing propofol at varying doses did not reach 80% power even at samples >1200.
CONCLUSIONS
Our simulations using drug efficacy show sample sizes are infeasible, even for potentially unethical placebo-control trials. We highlight the strength of simulations with observational data to inform the null hypotheses and propose use of this simulation-based RCT paradigm to assess the feasibility of future trials of anti-seizure treatment in acute brain injury.
PubMed: 38867375
DOI: 10.1002/acn3.52059