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Therapeutic Hypothermia and Temperature... Sep 2020Rapid induction and maintaining a target temperature of 32.0-36.0°C within a narrow range for <24 hours are essential, but those are very hard to perform in postcardiac...
Rapid induction and maintaining a target temperature of 32.0-36.0°C within a narrow range for <24 hours are essential, but those are very hard to perform in postcardiac arrest syndrome (PCAS) patients. We investigated the usability of an intravascular temperature management (IVTM) system with neurolept-anesthesia (NLA; droperidol and fentanyl). Single-arm, prospective multicenter trial was carried out in the seven university and the three affiliated hospitals. In the 24 comatose PCAS patients, the target temperature (33.0°C) was rapidly induced and maintained for 24 hours using an IVTM system with NLA. The rewarming speed was 0.1°C/h until 36.5°C and was maintained for 24 hours. The primary end point was the ability to achieve ≤34.0°C for <3 hours after starting cooling, and the secondary end points were the cooling rate, deviation from the target temperature, and adverse events. Cerebral Performance Category (CPC) score at 14 days was also evaluated. Statistical analyses were performed by SPSS software, using the intention-to-treat data sets. The target temperature of ≤34.0°C was reached by 45 minutes (35-73 minutes) and was within 3 hours in all patients. The cooling rate from 36.4°C to 33.0°C was 2.7°C/h (2.4-3.6°C/h). The temperature of 33.1°C (33.1-33.1°C) and 36.7°C (36.6-36.9°C) for 24 hours each was held during the maintenance and the after rewarming phases, respectively. Temperature deviations >0.2°C from 33.0°C in the maintenance phase occurred once each in two patients. The favorable neurological outcomes (CPC1, 2) were relatively good (50%). Five patients experienced serious adverse events; none was device related. We rapidly achieved therapeutic hypothermia within a narrow temperature range without major complications using the IVTM system with NLA in PCAS patients.
Topics: Body Temperature; Humans; Hypothermia, Induced; Post-Cardiac Arrest Syndrome; Prospective Studies; Rewarming; Temperature
PubMed: 32348714
DOI: 10.1089/ther.2019.0046 -
The Journal of Veterinary Medical... Aug 2019The present study used data from anesthetic records to analyze variables of intracranial pressure (ICP) during brain tumor surgery or in the early postoperative period...
The present study used data from anesthetic records to analyze variables of intracranial pressure (ICP) during brain tumor surgery or in the early postoperative period as prognostic indicators in dogs. Data from 17 dogs which were scheduled to undergo elective craniotomy for brain tumor surgery from 2009 to 2012 were included. Of these, five (29.4%) died during 14 days after the surgery because of respiratory failure following pneumonia (n=2), euthanasia due to difficulty in treatment of status epilepticus (n=1), tumor-bed hematoma (n=1), and unknown reason (n=1). In the 12 surviving dogs, neurological signs were improved or resolved at discharge. All dogs were administered midazolam and droperidol-fentanyl as premedication. General anesthesia was induced using propofol maintained on isoflurane and oxygen. Direct ICP was obtained via a Codman Microsensor strain gauge transducer. ICP hypertension (>13 mmHg) measured after 15 min of recovery from the moment after discontinuation of anesthesia by turning off the vaporizer dial was associated with poor prognosis (odds ratio, 20.00; 95% confidence interval, 1.39-287.60, P=0.028). This suggests that intracranial pressure influences the postoperative mortality rate in dogs undergoing brain tumor surgery.
Topics: Anesthesia, General; Animals; Brain Neoplasms; Craniotomy; Dog Diseases; Dogs; Intracranial Hypertension; Postoperative Period; Prognosis
PubMed: 30982789
DOI: 10.1292/jvms.18-0475 -
RSC Medicinal Chemistry Nov 2021Tuberculosis (TB), caused by (), is a deadly bacterial disease. Drug-resistant strains of make eradication of TB a daunting task. Overexpression of the enhanced...
Tuberculosis (TB), caused by (), is a deadly bacterial disease. Drug-resistant strains of make eradication of TB a daunting task. Overexpression of the enhanced intracellular survival (Eis) protein by confers resistance to the second-line antibiotic kanamycin (KAN). Eis is an acetyltransferase that acetylates KAN, inactivating its antimicrobial function. Development of Eis inhibitors as KAN adjuvant therapeutics is an attractive path to forestall and overcome KAN resistance. We discovered that an antipsychotic drug, haloperidol (HPD, ), was a potent Eis inhibitor with IC = 0.39 ± 0.08 μM. We determined the crystal structure of the Eis-haloperidol () complex, which guided synthesis of 34 analogues. The structure-activity relationship study showed that in addition to haloperidol (), eight analogues, some of which were smaller than , potently inhibited Eis (IC ≤ 1 μM). Crystal structures of Eis in complexes with three potent analogues and droperidol (DPD), an antiemetic and antipsychotic, were determined. Three compounds partially restored KAN sensitivity of a KAN-resistant strain K204 overexpressing Eis. The Eis inhibitors generally did not exhibit cytotoxicity against mammalian cells. All tested compounds were modestly metabolically stable in human liver microsomes, exhibiting 30-60% metabolism over the course of the assay. While direct repurposing of haloperidol as an anti-TB agent is unlikely due to its neurotoxicity, this study reveals potential approaches to modifying this chemical scaffold to minimize toxicity and improve metabolic stability, while preserving potent Eis inhibition.
PubMed: 34825186
DOI: 10.1039/d1md00239b -
Mediators of Inflammation 2018Lung fibrosis is characterized by abnormal accumulation of Thy-deficient fibroblasts in the interstitium of the alveolar space. We have previously shown in...
Lung fibrosis is characterized by abnormal accumulation of Thy-deficient fibroblasts in the interstitium of the alveolar space. We have previously shown in bleomycin-treated chimeric Thy1-deficient mice with wild-type lymphocytes that Thy1-deficient fibroblasts accumulate and promote fibrosis and an "inflammation-free" environment. Here, we aimed to identify the critical effects of Thy1, or the absence of Thy1, in lung myofibroblast profibrotic functions, particularly proliferation and collagen deposition. Using specific Thy1 siRNA in Thy1-positive cells, Thy1 knockout cells, Thy1 cDNA expression vector in Thy1-deficient cells, and Thy1 cross-linking, we evaluated cell proliferation (assessed by cell mass and BrdU uptake), differentiation (using immunofluorescence), and collagen deposition (using Sircol assay). We found that myofibroblast Thy1 cross-linking and genetic manipulation modulate cell proliferation and expression of Fgf (fibroblast growth factor) and Angtl (angiotensin) receptors (using qPCR) that are involved in myofibroblast proliferation, differentiation, and collagen deposition. In conclusion, lung myofibroblast downregulation of Thy1 expression is critical to increase proliferation, differentiation, and collagen deposition.
Topics: Animals; Bleomycin; Cell Cycle; Cell Proliferation; Cell Survival; Cells, Cultured; Droperidol; Flow Cytometry; Ketamine; Lung; Male; Mice; Mice, Inbred C57BL; Microscopy, Confocal; Myofibroblasts; Thy-1 Antigens
PubMed: 30002599
DOI: 10.1155/2018/4638437 -
JA Clinical Reports 2017Hyperventilation syndrome (HVS) sometimes occurs in patients under stressful conditions and may provoke severe complications such as myocardial infarction and death. The...
BACKGROUND
Hyperventilation syndrome (HVS) sometimes occurs in patients under stressful conditions and may provoke severe complications such as myocardial infarction and death. The authors report a case of HVS following general anesthesia, where a continuous intravenous infusion of dexmedetomidine was effective for HVS.
CASE PRESENTATION
A 23-year-old male patient with recurrent tongue cancer was scheduled to undergo partial glossectomy and neck dissection. Emergence from general anesthesia was prompt. Twenty-two minutes after extubation, the patient complained of unbearable distress caused by the urinary catheter. He began to cry, with an increased respiratory rate of over 40 breaths per minute. Intravenous infusion of flurbiprofen, droperidol, and morphine was not effective. Electrocardiography and laryngofiberscopy indicated the absence of acute coronary syndrome and airway obstruction, respectively. An arterial blood gas determination showed pH 7.63, PaCO 18.2 mmHg, PaO 143 mmHg on O mask 4 L/min, Ca 4.29 mmol/L, and lactate 3.4 mmol/L. The patient was diagnosed with HVS. Dexmedetomidine infusion 2.0 μg/kg/h for 10 min followed by 0.7 μg/kg/h reduced respiratory rate, suppressed arousal, and disappeared the complaint of bladder distension. One hour after extubation, an arterial blood gas determination showed pH 7.33, PaCO 51.3 mmHg, PaO 196 mmHg on O mask 4 L/min, Ca 4.70 mmol/L, and lactate 1.5 mmol/L. After admission to the intensive care unit, dexmedetomidine infusion was maintained at the rate of 0.2 to 0.7 μg/kg/h until the following morning, and he did not complain of distress caused by the urinary catheter.
CONCLUSIONS
HVS can occur after emergence from general anesthesia, and dexmedetomidine infusion was effective for HVS.
PubMed: 29457066
DOI: 10.1186/s40981-017-0101-x -
Journal of Orthopaedic Surgery and... Aug 2022Insufficient pain control after lower limb arthroplasty results in delayed recovery and increased risk for pain chronicization. The ideal kind of analgesia is still...
Pain levels and patient comfort after lower limb arthroplasty comparing i.v. patient-controlled analgesia, continuous peripheral nerve block and neuraxial analgesia: a retrospective cohort analysis of clinical routine data.
BACKGROUND
Insufficient pain control after lower limb arthroplasty results in delayed recovery and increased risk for pain chronicization. The ideal kind of analgesia is still discussed controversially. We conducted a retrospective analysis of single-center routine data from a German university hospital, including patients receiving either total hip (THA) or knee arthroplasty (TKA).
METHODS
All patients received general anesthesia. Patients undergoing THA received either continuous epidural ropivacaine infusion (0.133%, Epi) or patient-controlled analgesia (PCA) with the Wurzburg Pain Drip (tramadol, metamizole and droperidol, WPD) or with piritramide (Pir). After TKA, patients received either continuous femoral nerve block (ropivacaine 0.2%, PNB) or Pir.
RESULTS
The analyzed cohort comprised 769 cases. Use of WPD after THA (n = 333) resulted in significantly reduced Numeric Rating Scale (NRS) values at rest, compared to Epi (n = 48) and Pir (n = 72) (.75 [IQR 1.14] vs. 1.17 [1.5], p = .02 vs. 1.47 [1.33], p < .0001) as well as maximum NRS scores (2.4 [1.7] vs. 3.29 [1.94], p < .001 vs. 3.32 [1.76], p < .0001). Positive feedback during follow-up visits was significantly increased in patients with a WPD PCA (p < .0001), while negative feedback (senso-motoric weakness/technical problems/nausea/dizziness/constipation) was particularly increased in Epi patients and lowest in those with WPD (p < .0001). After TKA, Pir (n = 131) resulted in significantly reduced NRS values at rest, compared to PNB (n = 185) (1.4 [1.4] vs. 1.6 [1.68], p = .02). Positive feedback was increased in patients with a Pir PCA in comparison with PNB (p = .04), while negative feedback was increased in PNB patients (p = .04). Overall, WPD presented with the lowest rate of any complications (8.7%), followed by Pir (20.2%), PNB (27.6%) and Epi (31.3%) (p < .001).
CONCLUSIONS
In the assessed population, the use of a WPD PCA after THA offered better pain control and patient comfort in comparison with continuous epidural or piritramide-based analgesia. After TKA, the use of a Pir PCA provided superior analgesia and a lower complication rate compared to continuous PNB.
Topics: Analgesia, Patient-Controlled; Anesthetics, Local; Arthroplasty, Replacement, Knee; Femoral Nerve; Humans; Lower Extremity; Nerve Block; Pain, Postoperative; Patient Comfort; Peripheral Nerves; Pirinitramide; Retrospective Studies; Ropivacaine
PubMed: 35962409
DOI: 10.1186/s13018-022-03277-0 -
Annals of Cardiac Anaesthesia 2018The role of prophylaxis for postoperative nausea and vomiting (PONV) in cardiac surgery is under debate. (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
The role of prophylaxis for postoperative nausea and vomiting (PONV) in cardiac surgery is under debate.
AIMS
To study the risk factors for PONV after cardiac surgery and the role of betamethasone with or without droperidol for its prevention.
SETTING AND DESIGN
Randomized open-label controlled study comparing standard care with PONV prophylaxis from February to November 2016.
METHODS
Five hundred and two patients with planned nonemergent cardiac surgery were included.
INTERVENTIONS
In the intervention arm, PONV prophylaxis (4 mg betamethasone with/without 0.625 mg droperidol) was administered in high-risk patients (two or more risk factors). Patients in the control arm were treated as per routine hospital practices.
RESULTS
Female sex, past history of PONV, and migraines were associated with a significantly increased risk of PONV, while motion sickness, smoking status, and volatile anesthetics were not. Pain and treatment with nefopam or ketoprofen were associated with an increased risk of PONV. PONV was less frequent in the active arm compared to controls (45.5% vs. 54.0%, P = 0.063; visual analogic scale 10.9 vs. 15.3 mm, P = 0.043). Among the 180 patients (35.6%) with ≥2 risk factors, prophylaxis was associated with reduced PONV (intention-to-treat: 46.8% vs. 67.8%, P = 0.0061; per-protocol: 39.2% vs. 69%, P = 0.0002). In multivariate analysis, prophylaxis was independently associated with PONV (odds ratio [OR]: 0.324, 95% confidence interval: 0.167-0.629, P = 0.0009), as were female sex, past history of PONV, and migraines (OR: 3.027, 3.031, and 2.160 respectively). No drug-related side effects were reported.
CONCLUSION
Betamethasone with/without droperidol was effective in decreasing PONV in high risk cardiac surgical patients without any side effect.
Topics: Aged; Cardiac Surgical Procedures; Female; Humans; Male; Middle Aged; Pain Management; Pain, Postoperative; Postoperative Nausea and Vomiting; Risk Factors
PubMed: 29336385
DOI: 10.4103/aca.ACA_122_17 -
Anaesthesia Jul 2017We tested whether prophylactic droperidol and ondansetron, in combination with a moderate dose of dexamethasone, were equally effective in reducing nausea and vomiting... (Randomized Controlled Trial)
Randomized Controlled Trial
We tested whether prophylactic droperidol and ondansetron, in combination with a moderate dose of dexamethasone, were equally effective in reducing nausea and vomiting after tonsillectomy in children and that both were superior to saline with dexamethasone. We randomly allocated 300 children to intravenous saline, droperidol 10 μg.kg or ondansetron 150 μg.kg , after induction of anaesthesia and the administration of intravenous dexamethasone 250 μg.kg . The rates (95%CI) of nausea or vomiting within 24 postoperative hours were: 42/91 after saline, 46% (36%-57%); 43/87 after droperidol, 49% (39%-60%); reduced to 18/84 by ondansetron, 21% (13%-32%), p < 0.001. There were no differences in the rates of side-effects between groups. We conclude that ondansetron is more effective than saline in preventing nausea or vomiting after paediatric tonsillectomy when given with a moderate dose of dexamethasone, whereas droperidol was not.
Topics: Antiemetics; Child; Child, Preschool; Dexamethasone; Double-Blind Method; Droperidol; Female; Humans; Male; Ondansetron; Postoperative Nausea and Vomiting; Tonsillectomy
PubMed: 28449280
DOI: 10.1111/anae.13907 -
Cureus Dec 2023Background A preoperative sciatic nerve block (SNB) before total knee arthroplasty (TKA) frequently causes postoperative drop foot; however, this can also occur as an...
Background A preoperative sciatic nerve block (SNB) before total knee arthroplasty (TKA) frequently causes postoperative drop foot; however, this can also occur as an unintended result of surgical invasion. This study assessed the benefits of a postoperative SNB at the subgluteal space for patients who underwent TKA. Methodology This was a single-center, retrospective cohort study. Patients who underwent TKA under general anesthesia between May 2018 and June 2019 at the Teikyo University School of Medicine were screened for inclusion. They received either a preoperative femoral nerve block alone (control group; n = 87) or a preoperative femoral nerve block and postoperative SNB at the subgluteal space (post-SNB group; n = 40). The primary outcome was the pain-related Numerical Rating Scale (NRS) scores. The secondary outcomes were postoperative nausea and vomiting (PONV), intravenous patient-controlled analgesia (iv-PCA) suspension, and postoperative complications. Results No significant differences were observed in the characteristics, NRS scores, time to first drug use for pain, and iv-PCA suspension between groups. However, the incidence of PONV was significantly lower in the post-SNB group (p = 0.03). Logistic regression analysis revealed that droperidol doses of iv-PCA and the presence of postoperative SNB were independently associated with PONV occurrence [A1] {(p = 0.008, 95% confidence intervals (CI) [0.46, 0.89] and (p = 0.02, 95% CI [0.25, 0.88])}. Conclusions A postoperative SNB at the subgluteal space following TKA does not improve postoperative pain control; however, it may have contributed to reduced PONV.
PubMed: 38249241
DOI: 10.7759/cureus.50882 -
Chemical Research in Toxicology Aug 2022Molecular dynamics was used to optimize the droperidol-hERG complex obtained from docking. To accommodate the inhibitor, residues T623, S624, V625, G648, Y652, and F656...
Molecular dynamics was used to optimize the droperidol-hERG complex obtained from docking. To accommodate the inhibitor, residues T623, S624, V625, G648, Y652, and F656 did not move significantly during the simulation, while F627 moved significantly. Binding sites in cryo-EM structures and in structures obtained from molecular dynamics simulations were characterized using solvent mapping and Atlas ligands, which were negative images of the binding site, were generated. Atlas ligands were found to be useful for identifying human ether-á-go-go-related potassium channel (hERG) inhibitors by aligning compounds to them or by guiding the docking of compounds in the binding site. A molecular dynamics optimized structure of hERG led to improved predictions using either compound alignment to the Atlas ligand or docking. The structure was also found to be suitable to define a strategy for lowering inhibition based on the proposed binding mode of compounds in the channel.
Topics: Binding Sites; ERG1 Potassium Channel; Ether; Ether-A-Go-Go Potassium Channels; Humans; Ligands; Solvents
PubMed: 35895844
DOI: 10.1021/acs.chemrestox.2c00036