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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 -
Academic Emergency Medicine : Official... Jan 2019Acute agitation secondary to alcohol intoxication frequently requires parenteral sedatives for patient and caregiver safety. Antipsychotics play a prominent role;...
BACKGROUND
Acute agitation secondary to alcohol intoxication frequently requires parenteral sedatives for patient and caregiver safety. Antipsychotics play a prominent role; however, no consensus exists regarding the ideal agent. One important consideration when evaluating the choice of antipsychotic is its association with emergency department (ED) length of stay (LOS).
OBJECTIVES
We sought to determine the median ED LOS for patients receiving a single parenteral dose of an antipsychotic for acute agitation secondary to alcohol intoxication in an urban Level I trauma center.
METHODS
This was a retrospective review of patients receiving a single parenteral dose of droperidol, haloperidol, or olanzapine who were acutely intoxicated on alcohol from 2011 to 2016. Patients needing psychiatric assessment in our ED are discharged to a geographically separate department; thus, ED LOS is minimally impacted by waits for psychiatric assessment. Data were abstracted from the electronic medical record and are presented descriptively.
RESULTS
A total of 40,601 patients were identified and screened; 24,319 patients were intoxicated but received no sedation. Of those remaining 4,495 received multiple drugs and/or benzodiazepines leaving 11,787 for analysis. Median age was 42 years, 76% were male, and 5% of patients were admitted. Mean breath ethanol concentration was 227 mg/dL. Antipsychotics administered were as follows: droperidol (n = 3,790), haloperidol (n = 1,449), and olanzapine (n = 6,548). Median ED LOS was shortest for droperidol (499 minutes, 95% confidence interval [CI] = 493-506 minutes), which was significantly shorter than both haloperidol (524 minutes, 95% CI = 515-537 minutes) and olanzapine (533 minutes, 95% CI = 528-539 minutes). No cases of sudden cardiac death occurred.
CONCLUSION
Droperidol, when given as monotherapy for sedation of acute agitation secondary to alcohol intoxication, was associated with significantly shorter ED LOS than either parenteral haloperidol or parenteral olanzapine. No difference in ED LOS was observed between haloperidol and olanzapine.
Topics: Adult; Alcoholic Intoxication; Antipsychotic Agents; Droperidol; Drug Delivery Systems; Emergency Service, Hospital; Female; Haloperidol; Humans; Length of Stay; Male; Middle Aged; Olanzapine; Psychomotor Agitation; Retrospective Studies
PubMed: 29851193
DOI: 10.1111/acem.13486 -
Ci Ji Yi Xue Za Zhi = Tzu-chi Medical... 2018Droperidol is a short-acting, potent dopamine D2 antagonist that can pass through the blood-brain barrier. A black box warning was issued for droperidol by the United... (Review)
Review
Droperidol is a short-acting, potent dopamine D2 antagonist that can pass through the blood-brain barrier. A black box warning was issued for droperidol by the United States Food and Drug Administration in 2001 because of a risk of development of torsades de pointes induced by QT prolongation. Many experts feel that the incidence of arrhythmia is overestimated, and low-dose droperidol is almost always used by anesthesiologists for postoperative nausea and vomiting. In this review, we used evidence-based analysis to appraise high-quality studies with a low risk of bias published after 2001 on the use of droperidol in the emergency department (ED). Droperidol appears not only efficacious but also safe to treat patients with nausea/vomiting, acute psychosis, and migraine in the ED. For these conditions, droperidol may be an option for shared decision-making.
PubMed: 29643708
DOI: 10.4103/tcmj.tcmj_195_17 -
PharmacoEconomics - Open Jun 2018The combination of midazolam and droperidol has proven superior to droperidol or olanzapine monotherapy in the management of acute agitation in emergency departments...
Economic Evaluation of Midazolam-Droperidol Combination, Versus Droperidol or Olanzapine for the Management of Acute Agitation in the Emergency Department: A Within-Trial Analysis.
BACKGROUND
The combination of midazolam and droperidol has proven superior to droperidol or olanzapine monotherapy in the management of acute agitation in emergency departments (EDs).
OBJECTIVE
This is the first economic analysis to evaluate the cost-benefit and cost effectiveness of the midazolam-droperidol combination compared with droperidol or olanzapine for the management of acute agitation in EDs.
METHODS
This analysis used data derived from a randomised, controlled, double-blind clinical trial conducted in two metropolitan Australian EDs between October 2014 and August 2015. The economic evaluation was from the perspective of Australian public hospital EDs. The main outcomes included agitation management time and the agitation-free time gained. Sensitivity analyses were undertaken.
RESULTS
The midazolam-droperidol combination was the least costly regimen (Australian dollars [AU$]46.25 per patient) compared with the droperidol and olanzapine groups (AU$92.18 and AU$110.45 per patient, respectively). The main cost driver for all groups was the cost of the labour required during the initial adequate sedation. The combination afforded an additional 10-13 min of mean agitation-free time gained, which can be translated to additional savings of AU$31.24-42.60 per patient compared with the droperidol and olanzapine groups. The benefit-cost ratio for the midazolam-droperidol combination was 12.2:1.0, or AU$122,000 in total benefit for every AU$10,000 spent on management of acute agitation. Sensitivity analyses over key variables indicated these results were robust.
CONCLUSIONS
The midazolam-droperidol combination may be a cost-saving and dominant cost-effective regimen for the treatment of acute agitation in EDs as it is more effective and less costly than either droperidol or olanzapine monotherapy.
PubMed: 29623620
DOI: 10.1007/s41669-017-0047-y -
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 -
SAGE Open Medicine 2018Minimally invasive epiduroscopy has recently been reported as an effective treatment procedure for chronic and intractable low back pain. However, no study has...
OBJECTIVES
Minimally invasive epiduroscopy has recently been reported as an effective treatment procedure for chronic and intractable low back pain. However, no study has determined safe anesthetics for monitored anesthesia care during epiduroscopy. We aimed to compare and evaluate conventional monitored anesthesia care drugs with dexmedetomidine.
METHODS
A retrospective study including all patients who underwent epiduroscopy at the JR Tokyo General Hospital from April 2011 to March 2016 was designed. The epiduroscopy procedures were performed under anesthesia with dexmedetomidine plus fentanyl (dexmedetomidine group) or droperidol plus fentanyl (neuroleptanalgesia group). Patients who received analgesics other than fentanyl, another analgesic combined with fentanyl, any sedative other than dexmedetomidine or droperidol, or who had incomplete data were excluded. We compared (1) the type and dose of medication during the epiduroscopy and (2) the incidence of postoperative nausea and vomiting.
RESULTS
We identified 45 patients (31 and 14 in the dexmedetomidine and neuroleptanalgesia groups, respectively) with a mean age of 69.0 years. The two groups had comparable characteristics, such as age, sex, body mass index, the American Society of Anesthesiologists Physical Status, analgesics used in the clinic, comorbidities, history of smoking, and the duration of anesthesia. The dexmedetomidine group received a significantly lower fentanyl dose during surgery (126 ± 14 vs 193 ± 21 µg, mean ± standard deviation, p = 0.014) and exhibited a significantly lower incidence of postoperative nausea and vomiting (1 vs 3, p = 0.047) than the neuroleptanalgesia group.
CONCLUSION
This study involved elderly patients, and the use of dexmedetomidine in monitored anesthesia care during epiduroscopy procedures in these patients may reduce the required fentanyl dose during surgery and the incidence of postoperative nausea and vomiting. This strategy may help prevent respiratory depression and aspiration.
PubMed: 29449944
DOI: 10.1177/2050312118756804 -
British Journal of Anaesthesia Jan 2018Poor adherence to guidelines aimed at reducing the incidence of postoperative nausea and vomiting (PONV) is well known. In a before-and-after study, we tested the...
BACKGROUND
Poor adherence to guidelines aimed at reducing the incidence of postoperative nausea and vomiting (PONV) is well known. In a before-and-after study, we tested the effectiveness of a simplified algorithm for PONV prophylaxis on the incidence of PONV.
METHODS
In the first audit, we examined the adherence to our institutional guidelines for PONV prevention. In response to the results of this audit, we introduced a simplified algorithm for PONV prevention [female patients receiving triple prophylaxis (dexamethasone and ondansetron plus either a target-controlled infusion with propofol or droperidol) and male patients receiving double prophylaxis, dexamethasone, and ondansetron]. The impact of the simplification of the PONV algorithm was evaluated in a second audit. In both audits, we reviewed the medical records of all adult patients undergoing elective non-cardiac non-day-case surgery under general anaesthesia and being admitted to our post-anaesthesia care unit during two arbitrarily chosen weeks. We assessed the incidence of nausea, vomiting, and PONV after 1 and 24 h, and the compliance with the departmental algorithm for PONV prophylaxis.
RESULTS
After simplification of the PONV algorithm, the overall incidence of PONV within 24 h after surgery was significantly lower than before the implementation of the simplified PONV algorithm (22% vs 33%, P=0.02). The PONV incidence within 1 h was comparable between the audits (11% vs 14%, P=0.45). The adherence to departmental guidelines for PONV prophylaxis was significantly higher after the implementation of the simplified PONV algorithm (46% vs 18%, P=0.0001).
CONCLUSIONS
A simplified algorithm for PONV prophylaxis resulted in a significant reduction in the PONV incidence and better compliance with the PONV algorithm.
Topics: Aged; Algorithms; Anesthesia, General; Antiemetics; Dexamethasone; Droperidol; Drug Therapy, Combination; Female; Guideline Adherence; Humans; Hypnotics and Sedatives; Male; Medical Audit; Middle Aged; Ondansetron; Postoperative Nausea and Vomiting; Propofol; Treatment Outcome
PubMed: 29397124
DOI: 10.1016/j.bja.2017.08.003 -
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 -
Anesthesiology Apr 2018Although midbrain dopaminergic pathways are known to contribute to arousal and emergence from anesthesia, few reports exist regarding the anesthetic effects of dopamine...
BACKGROUND
Although midbrain dopaminergic pathways are known to contribute to arousal and emergence from anesthesia, few reports exist regarding the anesthetic effects of dopamine D2 receptor antagonism in humans. This study examined the effect of the D2 receptor antagonist droperidol on sevoflurane anesthesia by examining α and slow wave electroencephalogram oscillations.
METHODS
Forty-five patients, age 20 to 60 yr, were enrolled. Frontal electroencephalograms were continuously collected for offline analysis via Bispectral Index monitoring. After induction of anesthesia, end-tidal sevoflurane concentration was deliberately maintained at 1%, and intravenous droperidol (0.05 mg/kg bolus) was administered. Electroencephalogram changes were examined in power spectrum and bicoherence, before and 10 min after droperidol injection, then compared using the Wilcoxon signed-ranks test and/or paired t test.
RESULTS
Droperidol significantly augmented the α-bicoherence peak induced by sevoflurane from 30.3% (24.2%, 42.4%) to 50.8% (41.7%, 55.2%) (median [25th, 75th percentiles]; P < 0.0001), Hodges-Lehman median difference, 15.8% (11.3 to 21.4%) (95% CI). The frequency of the α-bicoherence peak was simultaneously shifted to the lower frequency; from 11.5 (11.0, 13.0) to 10.5 (10.0, 11.0) Hz (median [25th, 75th percentiles], P < 0.0001). Averaged bicoherence in the δ-θ area increased conspicuously from 17.2% (15.6 to 18.7%) to 25.1% (23.0 to 27.3%) (mean [95% CI]; P < 0.0001), difference, 8.0% (6.0 to 9.9%).
CONCLUSIONS
Droperidol augments both α and δ-θ bicoherences while shifting the α-bicoherence peaks to lower frequencies, and enhances the effect of sevoflurane anesthesia on the electroencephalogram via γ-aminobutyric acid-mediated oscillatory network regulation.
Topics: Adjuvants, Anesthesia; Adult; Anesthetics, Inhalation; Brain Waves; Dopamine D2 Receptor Antagonists; Droperidol; Drug Synergism; Electrocardiography; Female; Humans; Male; Middle Aged; Sevoflurane; Young Adult
PubMed: 29251645
DOI: 10.1097/ALN.0000000000002046 -
Dementia & Neuropsychologia 2017Delirium is a common disorder associated with poor prognosis, especially in the elderly. The impact of different treatment approaches for delirium on morbimortality and...
UNLABELLED
Delirium is a common disorder associated with poor prognosis, especially in the elderly. The impact of different treatment approaches for delirium on morbimortality and long-term welfare is not completely understood.
OBJECTIVE
To determine the efficacy of pharmacological and non-pharmacological treatments in elderly patients with delirium.
METHODS
This systematic review compared pharmacological and non-pharmacological treatments in patients over 60 years old with delirium. Databases used were: MEDLINE (PubMed), EMBASE, Cochrane CENTRAL and LILACS from inception to January 6, 2016.
RESULTS
A total of ten articles were selected. The six non-pharmacological intervention studies showed no impact on duration of delirium, mortality or institutionalization, but a decrease in severity of delirium and improvement in medium-term cognitive function were observed. The most commonly used interventions were temporal-spatial orientation, orientation to self and others, early mobilization and sleep hygiene. The four studies with pharmacological interventions found that rivastigmine reduced the duration of delirium, improved cognitive function and reduced caregiver burden; olanzapine and haloperidol decreased the severity of delirium; droperidol reduced length of hospitalization and improved delirium remission rate.
CONCLUSION
Although the pharmacological approach has been used in the treatment of delirium among elderly, there have been few studies assessing its efficacy, involving a small number of patients. However, the improvements in delirium duration and severity suggest these drugs are effective in treating the condition. Once delirium has developed, non-pharmacological treatment seems less effective in controlling symptoms, and there is a lack of studies describing different non-pharmacological interventions.
PubMed: 29213524
DOI: 10.1590/1980-57642016dn11-030009