The Comparative Amnestic Effects of Midazolam, Propofol, Thiopental, and Fentanyl at Equisedative Concentrations 

1997 ◽  
Vol 87 (4) ◽  
pp. 749-764 ◽  
Author(s):  
Robert A. Veselis ◽  
Ruth A. Reinsel ◽  
Vladimir A. Feshchenko ◽  
Marek Wronski
Keyword(s):  
Memory Impairment ◽  
Pharmacodynamic Modeling ◽  
Target Concentration ◽  
Double Blind ◽  
Regression Methods ◽  
Drug Concentrations ◽  
Computer Controlled ◽  
Double Blind Design ◽  
To Receive ◽  
Relative Potencies

Background The authors evaluated the effects of midazolam, propofol, thiopental, and fentanyl on volunteer participants' memory for words and pictures at equisedative concentrations. Methods Sixty-seven healthy volunteers were randomized to receive intravenous infusions of midazolam (n = 11), propofol (n = 11), thiopental (n = 10), fentanyl with ondansetron pretreatment (n = 11), ondansetron alone (n = 8), or placebo (n = 16) in a double-blind design. Three increasing and then two decreasing sedative concentrations were achieved by computer-controlled infusion in each volunteer. Measures of sedation, memory, and drug concentration were obtained at each target concentration. Drug concentrations were normalized to equisedative effects using both Emax and logistic regression methods of pharmacodynamic modeling. The serum concentrations at 50% memory effect (Cp50s) were determined using four different memory end points. The relative potencies compared with midazolam for memory impairment were determined. Results Equisedative concentrations were midazolam, 64.5 +/- 9.4 ng/ml; propofol, 0.7 +/- 0.2 microg/ml; thiopental, 2.9 /- 1.0 microg/ml; and fentanyl, 0.9 +/- 0.2 ng/ml. The Cp50s for 50% loss of memory for words were midazolam, 56 +/- 4 ng/ml; propofol, 0.62 +/- 0.04 microg/ml; thiopental, 4.5 +/- 0.3 microg/ml; and fentanyl, 3.2 +/- 0.4 ng/ml. Compared with midazolam, relative potencies (with 95% confidence intervals) were propofol, 0.96 (0.44-1.78); thiopental, 0.76 (0.52-0.94); and fentanyl, 0.34 (0.05-0.76). Large effects on memory were only produced by propofol and midazolam. Conclusions At equal sedation, propofol produces the same degree of memory impairment as midazolam. Thiopental has mild memory effects whereas fentanyl has none. Ondansetron alone has no sedative or amnesic effects.

scholarly journals The Composition and Diversity of the Gut Microbiota in Children Is Modifiable by the Household Dogs: Impact of a Canine-Specific Probiotic

2021 ◽  
Vol 9 (3) ◽  
pp. 557
Author(s):  
Carlos Gómez-Gallego ◽  
Mira Forsgren ◽  
Marta Selma-Royo ◽  
Merja Nermes ◽  
Maria Carmen Collado ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Home Environment ◽  
Double Blind ◽  
Before And After ◽  
Probiotic Intervention ◽  
Probiotic Product ◽  
Acid Producing Bacteria ◽  
Double Blind Design ◽  
To Receive ◽  
Gut Microbiota Composition

The development of the infant gut microbiota is initiated during pregnancy and continued through early life and childhood, guided by the immediate environment of the child. Our aim was to characterize the shared microbiota between dogs and children as well as to determine whether introduction to dogs of a dog-specific probiotic combination modifies the transfer process. We studied 31 children from allergic families with pet dog(s) and 18 control families without a dog. Altogether 37 dogs were randomized for a 4-week period in a double-blind design to receive canine-derived probiotic product containing a mixture of L. fermentum, L. plantarum, and L. rhamnosus, or placebo. Fecal samples from children and dogs were taken before and after the treatment. Distinctive gut microbiota composition was observed in children with dogs compared to those without a dog, characterized by higher abundance of Bacteroides and short-chain fatty acid producing bacteria such as Ruminococcus and Lachnospiraceae. Probiotic intervention in dogs had an impact on the composition of the gut microbiota in both dogs and children, characterized by a reduction in Bacteroides. We provide evidence for a direct effect of home environment and household pets on children microbiota and document that modification of dog microbiota by specific probiotics is reflected in children’s microbiota.

Treatment of neuroleptic-induced akathisia with the 5-HT2 antagonist mianserin

1999 ◽  
Vol 174 (3) ◽  
pp. 238-242 ◽  
Author(s):  
Michael Poyurovsky ◽  
Marina Shardorodsky ◽  
Camil Fuchs ◽  
Michael Schneidman ◽  
Abraham Weizman
Keyword(s):  
Placebo Group ◽  
Low Dose ◽  
Rating Scales ◽  
Therapeutic Option ◽  
Response To Treatment ◽  
Double Blind ◽  
Log Odds ◽  
Double Blind Design ◽  
To Receive ◽  
Barnes Akathisia Scale

BackgroundSerotonin (5-HT): dopamine imbalance may underlie neuroleptic-induced akathisia.AimTo evaluate the efficacy of the 5-HT2 antagonist, mianserin in neuroleptic-induced akathisia.MethodsThirty neuroleptic-treated patients with schizophrenia were randomly allocated in a double-blind design to receive either mianserin (15 mg/day) or placebo for five days. Patients were assessed at baseline and on Days 3 and 5 by the Barnes Akathisia Scale (BARS), as well as by other relevant clinical rating scales.ResultsCompared with the placebo group, the mianserin-treated patients showed a significant reduction in all four BARS subscales by Day 5, with mean reductions in the BARS global score of 9.9% and 52.2%, respectively (P=0.006). Response to treatment (a reduction of at least two points on the BARS global subscale), was noted in six patients (40%) in the mianserin group and only one patient (9.1%) in the placebo group (P=0.04, log odds ratio 2.23).ConclusionsMianserin at a low dose may be a promising therapeutic option for patients with acute neuroleptic-induced akathisia.

Withdrawal of Long-Term Phenothiazines from Chronically Hospitalized Psychiatric Patients

1964 ◽  
Vol 9 (4) ◽  
pp. 290-298 ◽  
Author(s):  
G. Marjerrison ◽  
D. Irvine ◽  
C. N. Stewart ◽  
R. Williams ◽  
H. Matheu ◽  
...  
Keyword(s):  
Urinary Excretion ◽  
Time Course ◽  
Psychiatric Patients ◽  
Behavioural Change ◽  
Control Group ◽  
Double Blind ◽  
Single Measure ◽  
Double Blind Design ◽  
To Receive

A study was conducted of the effect of substituting placebo medication for active phenothiazine medication under double-blind conditions, in a population of chronically hospitalized psychotic patients who had all been undergoing long-term phenothiazine treatment. Behavioural change was assessed monthly by psychiatric nurses using a ward behaviour inventory, which had been specially constructed to be sensitive to kinds of behaviour likely to affect the clinical prescription of phenothiazines. At the fifth month of the study, differences were noted between the placebo-substituted group and a control group continuing to receive their originally-prescribed phenothiazine compounds. Significant worsening in the Placebo group did not appear until the fifth monthly rating, and at that time significant improvement in the control (medication unchanged) group also first became evident. These results support the hypothesis that the continued long-term use of phenothiazine compounds in chronically-hospitalized psychotics is effective in the sustained reduction of psychopathological behaviour. An investigation of trifluoperazine and chlorprothixene within the same double-blind design indicated that both were significantly more effective than placebo in maintaining the behavioural level typical of the prior long-term medication with phenothiazines. Using the FPN test as one measure of the time course of urinary excretion of some of the phenothiazine metabolites, no relationship was demonstrated in the placebo-substituted group between FPN changes and behavioural worsening. The FPN test, rated blind, was able to discriminate the placebo-substituted group from the group continuing to receive their usual phenothiazines; as a single measure of the time course of urinary excretion of phenothiazine metabolites, however, FPN changes were not related to behavioural worsening within the placebo-substituted group.

Hyperbaric Spinal Ropivacaine 

1999 ◽  
Vol 90 (4) ◽  
pp. 971-977 ◽  
Author(s):  
Susan B. McDonald ◽  
Spencer S. Liu ◽  
Dan J. Kopacz ◽  
Carol A. Stephenson
Keyword(s):  
Spinal Anesthesia ◽  
Low Dose ◽  
Isometric Force ◽  
Double Blind ◽  
Response Characteristics ◽  
High Incidence ◽  
Discharge Criteria ◽  
To Receive ◽  
Dose Dependent ◽  
Relative Potencies

Background Ropivacaine is a newly introduced local anesthetic that may be a useful alternative to low-dose bupivacaine for outpatient spinal anesthesia. However, its relative potency to bupivacaine and its dose-response characteristics are unknown. This double-blind, randomized, crossover study was designed to determine relative potencies of low-dose hyperbaric spinal ropivacaine and bupivacaine and to assess the suitability of spinal ropivacaine for outpatient anesthesia. Methods Eighteen healthy volunteers were randomized into three equal groups to receive one spinal administration with bupivacaine and a second with ropivacaine, of equal-milligram doses (4, 8, or 12 mg) of 0.25% drug with 5% dextrose. The duration of blockade was assessed with (1) pinprick, (2) transcutaneous electrical stimulation, (3) tolerance to high tourniquet, (4) electromyography and isometric force dynamometry, and (5) achievement of discharge criteria. Differences between ropivacaine and bupivacaine were assessed with linear and multiple regression. P < 0.05 was considered significant. Results Ropivacaine and bupivacaine provided dose-dependent prolongation of sensory and motor block and time until achievement of discharge criteria (R2 ranges from 0.33-0.99; P values from < 0.001 through 0.01). Spinal anesthesia with ropivacaine was significantly different from bupivacaine and was approximately half as potent for all criteria studied. A high incidence of back pain (28%; P = 0.098) was noted after intrathecal ropivacaine was given. Conclusion Ropivacaine is half as potent and in equipotent doses has a similar profile to bupivacaine with a higher incidence of side effects. Low-dose hyperbaric spinal ropivacaine does not appear to offer an advantage over bupivacaine for use in outpatient anesthesia.

A Controlled Trial with Diclofensine, a New Psychoactive Drug, in the Treatment of Depression

1981 ◽  
Vol 9 (5) ◽  
pp. 324-329 ◽  
Author(s):  
C Cherpillod ◽  
L M O Omer
Keyword(s):  
Controlled Trial ◽  
Dose Range ◽  
Severe Depression ◽  
Controlled Study ◽  
Clinical Effects ◽  
Double Blind ◽  
Reference Drug ◽  
Efficacy Index ◽  
Double Blind Design ◽  
To Receive

Diclofensine inhibits the uptake of serotonin, noradrenaline and dopamine. In a controlled study, out-patients suffering from moderate to severe depression were treated with the objective of assessing the new drug's therapeutically effective dose range. Maprotiline was used as a reference drug: fourteen patients were assigned to receive diclofensine and thirteen to receive maprotiline in a double-blind design. Depending on tolerance and efficacy, they were treated for periods ranging from 5 to 150 days. Doses were titrated to the optimum. Findings suggest that a 50 mg daily dose of diclofensine would be sufficient for the majority of the patients. The dosage can be safely increased up to 150 mg daily but this offers few therapeutic advantages. While the efficacy index of the two drugs was similar (approximately 60%), they differed greatly in their profile of side-effects. No signs of abrupt dissipation of the achieved clinical effects were observed during continued treatment, and no withdrawal reactions were observed when the treatment was stopped. The new drug may be more effective in treating patients in whom a psycho-energizing and mood alleviating effect is desired.

The Pharmacodynamic Interaction of Propofol and Alfentanil during Lower Abdominal Surgery in Women

1995 ◽  
Vol 83 (1) ◽  
pp. 8-22. ◽  
Author(s):  
Jaap Vuyk ◽  
Toine Lim ◽  
Frank H. M. Engbers ◽  
Anton G. L. Burm ◽  
Arie A. Vletter ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Abdominal Surgery ◽  
Skin Incision ◽  
Target Concentration ◽  
Double Blind ◽  
Pharmacodynamic Interaction ◽  
End Points ◽  
Arterial Blood ◽  
Computer Controlled ◽  
The Individual

Background Propofol and alfentanil are frequently combined to provide general anesthesia. The purpose of this study was to characterize the pharmacodynamic interaction between propofol and alfentanil for several clinically relevant end points. Methods Twenty-one women, aged 20-55 yr, scheduled for lower abdominal surgery, were randomly assigned in a double-blind manner to one of three groups to receive a computer-controlled infusion of propofol with target concentrations of 2, 4, or 6 micrograms/ml. In addition, all patients received computer-controlled infusion of alfentanil (initial target concentration 50 ng/ml). While the target concentration of propofol was maintained constant, the target concentration of alfentanil was varied in steps of 10-50 ng/ml according to the presence or absence of patient responses to perioperative stimuli. Arterial blood samples for alfentanil and propofol determination were taken at clinically relevant stimuli. Alfentanil-propofol interactions for laryngoscopy, intubation, skin incision, the opening of the peritoneum, and awakening were determined by logistic regression over the three groups (n = 21). The alfentanil concentrations associated with a 50% probability (EC50s) of suppression of responses to intraabdominal surgical stimuli, as determined by logistic regression in the individual patients, were related to corresponding mean blood propofol concentrations by nonlinear regression analysis. Results With blood propofol concentrations increasing from 2 to 10 micrograms/ml, the EC50 of alfentanil decreased from 170 to 25 ng/ml for laryngoscopy, from 280 to 23 ng/ml for intubation, from 259 to 9 ng/ml for the opening of the peritoneum, and from 209 to 16 ng/ml for the intraabdominal surgical stimuli. With plasma alfentanil concentrations increasing from 10 to 150 ng/ml, the EC50 of propofol for the regaining of consciousness decreased from 3.8 to 0.8 microgram/ml. Discussion We defined the pharmacodynamic interaction between propofol and alfentanil for suppression of responses to perioperative stimuli during lower abdominal surgery. We conclude that propofol reduces alfentanil requirements for all studied clinical end points. In addition, alfentanil decreases propofol concentrations at which patients regain consciousness.

The Effects of a Caffeine Placebo and Experimenter Expectation on Blood Pressure, Heart Rate, Well-Being, and Cognitive Performance

2001 ◽  
Vol 6 (1) ◽  
pp. 15-25 ◽  
Author(s):  
Harald Walach ◽  
Stefan Schmidt ◽  
Yvonne-Michelle Bihr ◽  
Susanne Wiesch
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cognitive Task ◽  
Well Being ◽  
Control Group ◽  
Double Blind ◽  
Main Effect ◽  
The Difference ◽  
Being There ◽  
To Receive

We studied the effect of experimenter expectations and different instructions in a balanced placebo design. 157 subjects were randomized into a 2 × 4 factorial design. Two experimenters were led to expect placebos either to produce physiological effects or not (pro- vs. antiplacebo). All subjects except a control group received a caffeine placebo. They were either made to expect coffee, no coffee, or were in a double-blind condition. Dependent measures were blood pressure, heart rate, well-being, and a cognitive task. There was one main effect on the instruction factor (p = 0.03) with the group “told no caffeine” reporting significantly better well-being. There was one main effect on the experimenter factor with subjects instructed by experimenter “proplacebo” having higher systolic blood pressure (p = 0.008). There was one interaction with subjects instructed by experimenter “proplacebo” to receive coffee doing worse in the cognitive task than the rest. Subjects instructed by experimenter “antiplacebo” were significantly less likely to believe the experimental instruction, and that mostly if they had been instructed to receive coffee. Contrary to the literature we could not show an effect of instruction, but there was an effect of experimenters. It is likely, however, that these experimenter effects were not due to experimental manipulations, but to the difference in personalities.

The Antiaggressive Action of Combined Haloperidol-Propranolol Treatment in Schizophrenia

2000 ◽  
Vol 5 (4) ◽  
pp. 312-325 ◽  
Author(s):  
Gadi Maoz ◽  
Daniel Stein ◽  
Sorin Meged ◽  
Larisa Kurzman ◽  
Joseph Levine ◽  
...  
Keyword(s):  
Rating Scales ◽  
Double Blind ◽  
Propranolol Group ◽  
Schizophrenic Patients ◽  
Propranolol Treatment ◽  
Simultaneous Decrease ◽  
The Mean ◽  
Haloperidol Treatment ◽  
To Receive ◽  
Drug Free

Psychopharmacological interventions for managing aggression in schizophrenia have thus far yielded inconsistent results. This study evaluates the antiaggressive efficacy of combined haloperidol-propranolol treatment. Thirty-four newly admitted schizophrenic patients were studied in a controlled double-blind trial. Following a 3-day drug-free period and 7 days of haloperidol treatment, patients were randomly assigned to receive either haloperidol-propranolol or haloperidol-placebo for eight consecutive weeks. Doses of medications were adjusted as necessary; biperiden was administered if required. Rating scales were applied to assess aggression, anger, psychosis, depression, anxiety and extrapyramidal symptoms. The mean daily dose of haloperidol was 21 mg (SD = 6.4) in the research group and 29 mg (SD = 6.9) in the controls. Mean and maximal daily doses of propranolol were 159 mg (SD = 61) and 192 mg (SD = 83), and of placebo, 145 mg (SD = 50) and 180 mg (SD = 70), respectively. Compared with the controls, the scores for the research patients decreased significantly from baseline, particularly after 4 weeks of treatment, for some dimensions of anger, psychosis, anxiety, and neuroleptic-induced parkinsonism. A tendency for reduced aggression was shown in the combined haloperidol-propranolol group for some dimensions but not others. These patients also required significantly less biperiden. The tendency toward elevated antiaggressive effect of combined haloperidol-propranolol treatment compared to haloperidol alone may be explained by a simultaneous decrease in aggression, psychotic symptomatology, and anxiety.

scholarly journals Cerebellar rTMS in PSP: a Double-Blind Sham-Controlled Study Using Mobile Health Technology

2021 ◽  
Author(s):  
Andrea Pilotto ◽  
Maria Cristina Rizzetti ◽  
Alberto Lombardi ◽  
Clint Hansen ◽  
Michele Biggi ◽  
...  
Keyword(s):  
Digital Technology ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Health Technology ◽  
Controlled Study ◽  
Double Blind ◽  
Non Invasive ◽  
Lower Back ◽  
Before And After ◽  
Double Blind Design ◽  
Theta Burst

AbstractThere are no effective treatments in progressive supranuclear palsy (PSP). The aim of this study was to test the efficacy of theta burst repetitive transcranial magnetic stimulation (rTMS) on postural instability in PSP. Twenty PSP patients underwent a session of sham or real cerebellar rTMS in a crossover design. Before and after stimulation, static balance was evaluated with instrumented (lower back accelerometer, Rehagait®, Hasomed, Germany) 30-s trials in semitandem and tandem positions. In tandem and semitandem tasks, active stimulation was associated with increase in time without falls (both p=0.04). In the same tasks, device-extracted parameters revealed significant improvement in area (p=0.007), velocity (p=0.005), acceleration and jerkiness of sway (p=0.008) in real versus sham stimulation. Cerebellar rTMS showed a significant effect on stability in PSP patients, when assessed with mobile digital technology, in a double-blind design. These results should motivate larger and longer trials using non-invasive brain stimulation for PSP patients.

Frühgeborene unter maschineller Beatmung: Immunmodulatorischer Effekt der präventiven Gabe von Azithromycin

2020 ◽  
pp. 1-3
Author(s):  
Maximilian Jorczyk
Keyword(s):  
Very Low Birth Weight ◽  
Controlled Trial ◽  
Preterm Neonates ◽  
Double Blind ◽  
Mechanically Ventilated ◽  
Before And After ◽  
Anti Inflammatory ◽  
To Receive ◽  
Therapeutic Possibilities ◽  
Inflammatory Effect

<b>Introduction:</b> Macrolides have anti-inflammatory and immunomodulatory properties that give this class of antibiotics a role that differs from its classical use as an antibiotic, which opens new therapeutic possibilities. <b>Objective:</b> The aim of this study was to evaluate the anti-inflammatory effect of azithromycin in preventing mechanical ventilation (MV)-induced lung injury in very-low-birth-weight preterm neonates. <b>Methods:</b> This is a randomized, double-blind, placebo-controlled trial of preterm neonates who received invasive MV within 72 h of birth. Patients were randomized to receive intravenous azithromycin (at a dose of 10/mg/kg/day for 5 days) or placebo (0.9% saline) within 12 h of the start of MV. Two blood samples were collected (before and after intervention) for measurement of interleukins (ILs) and PCR for <i>Ureaplasma</i>. Patients were followed up throughout the hospital stay for the outcomes of death and bronchopulmonary dysplasia defined as need for oxygen for a period of ≥28 days of life (registered at ClinicalTrials.gov, No. NCT03485703). <b>Results:</b> Forty patients were analyzed in the azithromycin group and 40 in the placebo group. Five days after the last dose, serum IL-2 and IL-8 levels dropped significantly in the azithromycin group. There was a significant reduction in the incidence of death and O<sub>2</sub> dependency at 28 days/death in azithromycin-treated patients regardless of the detection of <i>Ureaplasma</i> in blood. <b>Conclusions:</b> Azithromycin has anti-inflammatory effects, with a decrease in cytokines after 5 days of use and a reduction in death and O<sub>2</sub> dependency at 28 days/death in mechanically ventilated preterm neonates.

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