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Trials Jun 2024Critically ill patients are exposed to several physical and emotional stressors, needing analgesic and sedative drugs to tolerate invasive procedures and the harsh...
BACKGROUND
Critically ill patients are exposed to several physical and emotional stressors, needing analgesic and sedative drugs to tolerate invasive procedures and the harsh intensive care unit (ICU) environment. However, this pharmacological therapy presents several side effects: guidelines suggest using a light sedation target, keeping critically ill patients calm, conscious, and cooperative. Personalized music therapy (MT) can reduce stress and anxiety, decreasing the need for drugs. The aim of the current investigation is to compare different approaches for MT in the ICU: a personalized approach, with music selected by patients/families and listened through headphones, or a generalized approach, with ambient music chosen by a music therapist and transmitted through speakers.
PRIMARY OUTCOME
number of days "free from neuroactive drugs" in the first 28 days after ICU admission.
SECONDARY OUTCOMES
total amount of neuroactive drugs (midazolam, propofol, morphine, fentanyl, haloperidol), stress during ICU stay (sleep at night, anxiety and agitation, use of physical restraints, stressors evaluated at discharge), the feasibility of generalized MT (interruptions requested by staff members and patients/families).
METHODS
Randomized, controlled trial with three groups of critically ill adults: a control group, without MT; a personalized MT group, with music for at least 2 h per day; a generalized MT group, with music for 12.5 h/day, subdivided into fifteen 50-min periods.
DISCUSSION
One hundred fifty-three patients are expected to be enrolled. This publication presents the rationale and the study methods, particularly the strategies used to build the generalized MT playlist. From a preliminary analysis, generalized MT seems feasible in the ICU and is positively received by staff members, critically ill patients, and families.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03280329. September 12, 2017.
Topics: Humans; Music Therapy; Critical Illness; Randomized Controlled Trials as Topic; Time Factors; Hypnotics and Sedatives; Treatment Outcome; Intensive Care Units; Stress, Psychological; Critical Care; Analgesics
PubMed: 38867317
DOI: 10.1186/s13063-024-08220-8 -
Nursing in Critical Care Jun 2024Healthcare's carbon footprint contributes to 4.4% of global net emissions and intensive care units (ICUs) are very resource intensive. Existing studies on environmental...
BACKGROUND
Healthcare's carbon footprint contributes to 4.4% of global net emissions and intensive care units (ICUs) are very resource intensive. Existing studies on environmental sustainability in ICUs focused on carbon footprint generated from energy and electricity consumption, use of medical consumables and equipment, but few studies quantified carbon footprint generated from pharmaceuticals used in ICUs.
AIM
To evaluate carbon footprint arising from sedation practices in the ICUs.
STUDY DESIGN
A pilot, prospective observational study was conducted in two ICUs from 1 August to 22 September 2022 in Singapore General Hospital. Adult patients who were consecutively sedated, intubated and expected to be mechanically ventilated for at least 24 h were included. Total amount of analgesia and sedatives used and wasted in eligible patients were collected. Carbon emission from ICU sedation practices were then quantified using available life cycle assessment data.
RESULTS
A total of 31 patients were recruited. Top analgesia and sedative used in both ICUs were fentanyl and propofol, respectively. Carbon footprint from sedative usage and wastage across 7 weeks in both ICUs were 2.206 kg CO-e and 0.286 g CO-e, respectively. In total, this equates to driving 15.8 km by car. Proportion of drug wasted ranged from 5.1% to 25.0%, with the top reason for wastage being the drug was no longer clinically indicated. Recommendations to reduce carbon footprint include choosing sedatives with lower carbon emissions where possible and having effective communication among doctors and nurses regarding management plans to minimize unnecessary wastage.
CONCLUSION
Our study quantified carbon footprint arising from sedation practices, mainly drug usage and wastage in two ICUs in Singpore General Hospital.
RELEVANCE TO CLINICAL PRACTICE
Adopting a holistic approach to environmental sustainability in the ICU, sedation practices also contribute to generating greenhouse gases, albeit small, and can be targeted to reduce unnecessary carbon footprint.
PubMed: 38866584
DOI: 10.1111/nicc.13092 -
Drug Metabolism and Disposition: the... Jun 2024The role of the kidney as an excretory organ for exogenous and endogenous compounds is well recognized, but there is a wealth of data demonstrating that the kidney has...
The role of the kidney as an excretory organ for exogenous and endogenous compounds is well recognized, but there is a wealth of data demonstrating that the kidney has significant metabolizing capacity for a variety of exogenous and endogenous compounds that in some cases surpass the liver. The induction of drug-metabolizing enzymes by some chemicals can cause drug-drug interactions and intraindividual variability in drug clearance. In this study, we evaluated the expression and induction of cytochrome P450 (P450) and UDP-glucuronosyltransferase (UGT) isoforms in 3D-cultured primary human renal proximal tubule epithelial cells (RPTEC) to elucidate their utility as models of renal drug metabolism. CYP2B6, CYP2E1, CYP3A4, CYP3A5, and all detected UGTs (UGT1A1, UGT1A4, UGT1A6, UGT1A9, and UGT2B7) mRNA levels in 3D-RPTEC were significantly higher than those in 2D-RPTEC and HK-2 cells and were close to the levels in the human kidney cortex. CYP1B1 and CYP2J2 mRNA levels in 3D-RPTEC were comparable to those in 2D-RPTEC, HK-2 cells, and the human kidney cortex. Midazolam 1'-hydroxylation, trifluoperazine N-glucuronidation, serotonin O-glucuronidation, propofol O-glucuronidation, and morphine 3-glucuronidation in the 3D-RPTEC were significantly higher than the 2D-RPTEC and comparable to those in the HepaRG cells, although bupropion, ebastine, and calcitriol hydroxylations were not different between the 2D- and 3D-RPTEC. Treatment with ligands of the aryl hydrocarbon receptor and farnesoid X receptor induced CYP1A1 and UGT2B4 expression, respectively, in 3D-RPTEC compared to 2D-RPTEC. We provided information on the expression, activity, and induction abilities of P450s and UGTs in 3D-RPTEC as an in vitro human renal metabolism model. This study demonstrated that the expression of P450s and UGTs in 3D-RPTEC was higher than those in 2D-RPTEC and HK-2 cells. The results were comparable to that in the human kidney cortex. 3D-RPTEC are useful for evaluating the induction of kidney P450s, UGTs, and human renal drug metabolism .
PubMed: 38866474
DOI: 10.1124/dmd.124.001685 -
Upsala Journal of Medical Sciences 2024Standard dosages of analgesic and sedative drugs are given to intensive care patients. The resulting range of blood concentrations and corresponding clinical responses...
BACKGROUND
Standard dosages of analgesic and sedative drugs are given to intensive care patients. The resulting range of blood concentrations and corresponding clinical responses need to be better examined. The purpose of this study was to describe daily dosages, measured blood concentrations, and clinical responses in critically ill patients. The purpose was also to contribute to establishing whole blood concentration reference values of the drugs investigated.
METHODS
A descriptive study of prospectively collected data from 302 admissions to a general intensive care unit (ICU) at a university hospital. Ten drugs (clonidine, fentanyl, morphine, dexmedetomidine, ketamine, ketobemidone, midazolam, paracetamol, propofol, and thiopental) were investigated, and daily dosages recorded. Blood samples were collected twice daily, and drug concentrations were measured. Clinical responses were registered using Richmond agitation-sedation scale (RASS) and Numeric rating scale (NRS).
RESULTS
Drug dosages were within recommended dose ranges. Blood concentrations for all 10 drugs showed a wide variation within the cohort, but only 3% were above therapeutic interval where clonidine (57 of 122) and midazolam (38 of 122) dominated. RASS and NRS were not correlated to drug concentrations.
CONCLUSION
Using recommended dose intervals for analgesic and sedative drugs in the ICU setting combined with regular monitoring of clinical responses such as RASS and NRS leads to 97% of concentrations being below the upper limit in the therapeutic interval. This study contributes to whole blood drug concentration reference values regarding these 10 drugs.
Topics: Humans; Hypnotics and Sedatives; Analgesics; Male; Female; Middle Aged; Aged; Intensive Care Units; Prospective Studies; Adult; Midazolam; Critical Care; Dexmedetomidine; Fentanyl; Critical Illness; Propofol; Clonidine; Ketamine; Morphine; Aged, 80 and over; Dose-Response Relationship, Drug; Thiopental; Acetaminophen
PubMed: 38863729
DOI: 10.48101/ujms.v129.10560 -
Laboratory Animals Jun 2024Two healthy Landrace pigs anaesthetized with propofol suffered rapid onset of fatal sepsis. Clinical signs included severe arterial hypotension, loss of peripheral...
Two healthy Landrace pigs anaesthetized with propofol suffered rapid onset of fatal sepsis. Clinical signs included severe arterial hypotension, loss of peripheral oxygenation, low end-tidal CO, clinical onset of pulmonary oedema and cardiac dysfunction. Gross and histopathological examination revealed loss of vascular integrity with severe lung oedema and congestion, haemorrhages in several organs and fluid leakage into body cavities. Large numbers of Gram-negative bacteria, primarily sp., were present in the anaesthetic infusion containing propofol and were also cultured from internal organs of both pigs. The propofol was likely contaminated by bacteria after inappropriate handling and storage in the operating room. This report illustrates the potential for severe nosocomial infection when applying propofol in animals and humans and may serve as a reminder of the importance of strict aseptic practice in general, and specifically in the handling of this anaesthetic agent.
PubMed: 38863139
DOI: 10.1177/00236772231200524 -
BMC Geriatrics Jun 2024Myocardial injury after non-cardiac surgery (MINS) is a common and serious complication in older patients. This study investigates the impact of neuromuscular block on... (Randomized Controlled Trial)
Randomized Controlled Trial
Impact of neuromuscular block on myocardial injury after non-cardiac surgery (MINS) incidence in the early postoperative stage of older patients undergoing laparoscopic colorectal cancer resection: a randomized controlled study.
BACKGROUND
Myocardial injury after non-cardiac surgery (MINS) is a common and serious complication in older patients. This study investigates the impact of neuromuscular block on the MINS incidence and other cardiovascular complications in the early postoperative stage of older patients undergoing laparoscopic colorectal cancer resection.
METHODS
70 older patients who underwent laparoscopic colorectal cancer resection were separated into the deep neuromuscular block group and moderate neuromuscular block group for 35 cases in each group (n = 1:1). The deep neuromuscular block group maintained train of four (TOF) = 0, post-tetanic count (PTC) 1-2, and the moderate neuromuscular block group maintained TOF = 1-2 during the operation. Sugammadex sodium was used at 2 mg/kg or 4 mg/kg for muscle relaxation antagonism at the end of surgery. The MINS incidence was the primary outcome and compared with Fisher's exact test. About the secondary outcomes, the postoperative pain was analyzed with Man-Whitney U test, the postoperative nausea and vomiting (PONV) and the incidence of cardiovascular complications were analyzed with Chi-square test, intraoperative mean artery pressure (MAP) and cardiac output (CO) ratio to baseline, length of stay and dosage of anesthetics were compared by two independent samples t-test.
RESULTS
MINS was not observed in both groups. The highest incidence of postoperative cardiovascular complications was lower limbs deep vein thrombosis (14.3% in deep neuromuscular block group and 8.6% in moderate neuromuscular group). The numeric rating scale (NRS) score in the deep neuromuscular block group was lower than the moderate neuromuscular block group 72 h after surgery (0(1,2) vs 0(1,2), P = 0.018). The operation time in the deep neuromuscular block group was longer (356.7(107.6) vs 294.8 (80.0), min, P = 0.008), the dosage of propofol and remifentanil was less (3.4 (0.7) vs 3.8 (1.0), mg·kg·h, P = 0.043; 0.2 (0.06) vs 0.3 (0.07), μg·kg·min, P < 0.001), and the length of hospital stay was shorter than the moderate neuromuscular block group (18.4 (4.9) vs 22.0 (8.3), day, P = 0.028). The differences of other outcomes were not statistically significant.
CONCLUSIONS
Maintaining different degrees of the neuromuscular block under TOF guidance did not change the MINS incidence within 7 days after surgery in older patients who underwent laparoscopic colorectal cancer resection.
TRIAL REGISTRATION
The present study was registered in the Chinese Clinical Trial Registry (10/02/2021, ChiCTR2100043323).
Topics: Humans; Male; Female; Aged; Laparoscopy; Colorectal Neoplasms; Postoperative Complications; Neuromuscular Blockade; Incidence; Aged, 80 and over; Heart Injuries
PubMed: 38862916
DOI: 10.1186/s12877-024-05125-8 -
Neurological Sciences : Official... Jun 2024There is not a preferred medication for treating refractory status epilepticus (RSE) and intravenous ketamine is increasingly used. Ketamine efficacy, safety, dosage,...
BACKGROUND
There is not a preferred medication for treating refractory status epilepticus (RSE) and intravenous ketamine is increasingly used. Ketamine efficacy, safety, dosage, and influence of other variables on seizure cessation while on ketamine infusions are not well studied. We aimed to characterize ketamine effect on RSE, including interictal activity on electroencephalogram (EEG) and when done by Teleneurocritical care (TNCC).
METHODS
We conducted a multicenter, retrospective study from August 2017 to October 2022. Patients 18 years or older who had RSE and received ketamine were included. The primary outcome was effect of ketamine on RSE including interictal activity; secondary outcomes were effect of other variables on RSE, care by TNCC, ketamine infusion dynamics, adverse events, and discharge outcomes. Logistic regression was used.
RESULTS
Fifty-one patients from five hospitals met inclusion criteria; 30 patients had RSE and interictal activity on EEG. Median age was 56.8 years (IQR 18.2) and 26% had previously diagnosed epilepsy. Sixteen (31%) patients were treated virtually by TNCC. In those with RSE on EEG, ketamine was added as the fourth antiseizure medication (mean 4.4, SD 1.6). An initial bolus of ketamine was used in 24% of patients (95 mg, IQR 47.5), the median infusion rate was 30.8 mcg/kg/min (IQR 40.4), and median infusion duration was 40 h (IQR 37). Ketamine was associated with 50% cessation of RSE and interictal activity at 24 h in 84% of patients, and complete seizure cessation in 43% of patients. In linear regression, ASMs prior to ketamine were associated with seizure cessation (OR 2.6, 95% CI 0.9-6.9, p = 0.05), while the inverse was seen with propofol infusions (OR 0.02, 95% CI 0.001-0.43, p = 0.01). RSE management by in-person NCC versus virtual by TNCC did not affect rates of seizure cessation.
CONCLUSIONS
Ketamine infusions for RSE were associated with reduced seizure burden at 24 h, with 84% of patients having 50% seizure reduction. Similar efficacy and safety was observed irrespective of underlying RSE etiology or when done via TNCC vs in-person NCC.
PubMed: 38862653
DOI: 10.1007/s10072-024-07635-0 -
BMC Anesthesiology Jun 2024Laparoscopic partial hepatectomy inevitably decrease patient immune function. Propofol has been shown to have immunomodulatory effects but is associated with hemodynamic... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Comparison of the effects of remimazolam tosylate and propofol on immune function and hemodynamics in patients undergoing laparoscopic partial hepatectomy: a randomized controlled trial.
BACKGROUND
Laparoscopic partial hepatectomy inevitably decrease patient immune function. Propofol has been shown to have immunomodulatory effects but is associated with hemodynamic side effects. Despite studies showing a negligible impact of remimazolam tosylate on hemodynamics, it has not been reported for partial hepatectomy patients. Its influence on immune function also remains unexplored. This study sought to investigate the differences in immune function and intraoperative hemodynamics between patients who underwent laparoscopic partial hepatectomy with remimazolam tosylate and those who underwent laparoscopic partial hepatectomy with propofol.
METHODS
This was a single-center, randomized controlled trial involving 70 patients, who underwent elective laparoscopic partial hepatectomy. The patients were randomly divided into two groups: the remimazolam group (group R) and the propofol group (group P). In this study, the primary outcomes assessed included the patient's immune function and hemodynamic parameters, and the secondary outcomes encompassed the patient's liver function and adverse events.
RESULTS
Data from 64 patients (group R, n = 31; group P, n = 33) were analyzed. The differences in the percentages of CD3, CD4, CD8, and NK cells and the CD4/CD8 ratio between the two groups were not statistically significant at 1 day or 3 days after surgery. Compared with those in group P, the MAP and HR at T2 and the MAP at T1 in group R were significantly increased(P < 0.05). The differences in HR and MAP at T0, T3, T4, T5, T6, and T7 and HR at T1 between the two groups were not statistically significant. There were no differences in liver function or adverse effects between the two groups, suggesting that remimazolam tosylate is a safe sedative drug(P > 0.05).
CONCLUSION
The effects of remimazolam tosylate on the immune function of patients after partial hepatectomy are comparable to those of propofol. Additionally, its minimal effect on hemodynamics significantly decreases the incidence of hypotension during anesthesia induction, thereby enhancing overall perioperative safety.
TRIAL REGISTRATION
The trial was registered on May 9, 2022 in the Chinese Clinical Trial Registry, registration number ChiCTR2200059715 (09/05/2022).
Topics: Humans; Male; Female; Hepatectomy; Middle Aged; Hemodynamics; Laparoscopy; Propofol; Benzodiazepines; Anesthetics, Intravenous; Adult; Aged; Hypnotics and Sedatives
PubMed: 38858649
DOI: 10.1186/s12871-024-02589-4 -
The Journal of ECT Jun 2024To compare seizure-related, hemodynamic, and recovery outcomes when using remimazolam for ECT with those of other anesthetics, specifically propofol and etomidate.
The Effect of Remimazolam on Seizure Profile, Hemodynamics, and Recovery in Patients With Electroconvulsive Therapy Comparison With Propofol and Etomidate: A Retrospective Study.
OBJECTIVES
To compare seizure-related, hemodynamic, and recovery outcomes when using remimazolam for ECT with those of other anesthetics, specifically propofol and etomidate.
METHODS
A total of 49 patients who underwent 405 ECT treatment sessions under general anesthesia were retrospectively analyzed. Remimazolam, propofol, and etomidate were used for 93, 138, and 174 ECT sessions, respectively. The primary outcome was durations of motor and electroencephalogram (EEG) seizure activity, whereas secondary outcomes included hemodynamics (ie, mean arterial pressure [MAP] and heart rate [HR] at various time points from induction to postanesthesia care unit [PACU] discharge), antihypertensive drugs administration after electrical stimulus, and recovery profiles (ie, length of PACU stay and incidence of postictal confusion).
RESULTS
Durations of motor and EEG seizures were shorter for remimazolam than etomidate (motor, P < 0.001; EEG, P = 0.003) but similar compared with propofol (motor, P = 0.191; EEG, P = 0.850). During seizure, remimazolam showed a comparable MAP and HR to etomidate (MAP: P = 0.806; HR: P = 0.116). The antihypertensive drug use was lowest for remimazolam (6.8%), followed by propofol (35.6%) and etomidate (65.6%), and the mean length of PACU stay was comparable for remimazolam (19.7 min), propofol (22.8 min), and etomidate (24.5 min). The occurrence of postictal confusion did not differ among the 3 agents (P > 0.050).
CONCLUSIONS
Remimazolam is a promising anesthetic option for ECT because of its comparable seizure profiles, stable hemodynamics, and comparable PACU stay when compared with propofol and etomidate without additional adverse events.
PubMed: 38857335
DOI: 10.1097/YCT.0000000000001025 -
Anesthesiology Jun 2024During the last 100 years, the role of anesthesiologists in psychiatry has focused primarily on facilitating electroconvulsive therapy and mitigating postoperative...
During the last 100 years, the role of anesthesiologists in psychiatry has focused primarily on facilitating electroconvulsive therapy and mitigating postoperative delirium and other perioperative neurocognitive disorders. The discovery of the rapid and sustained antidepressant properties of ketamine, and early results suggesting that other general anesthetic drugs (including nitrous oxide, propofol, and isoflurane) have antidepressant properties, has positioned anesthesiologists at a new frontier in the treatment of neuropsychiatric disorders. Moreover, shared interest in understanding the biologic underpinnings of anesthetic drugs as psychotropic agents is eroding traditional academic boundaries between anesthesiology and psychiatry. This article presents a brief overview of anesthetic drugs as novel antidepressants and identifies promising future candidates for the treatment of depression. The authors issue a call to action and outline strategies to foster collaborations between anesthesiologists and psychiatrists as they work toward the common goals of repurposing anesthetic drugs as antidepressants and addressing mood disorders in surgical patients.
PubMed: 38856663
DOI: 10.1097/ALN.0000000000005037