-
Veterinary Surgery : VS Jan 2019To determine the influence of propofol or methohexital, with and without doxapram, on the examination of laryngeal function in dogs. (Comparative Study)
Comparative Study
OBJECTIVE
To determine the influence of propofol or methohexital, with and without doxapram, on the examination of laryngeal function in dogs.
STUDY DESIGN
Experimental study.
ANIMALS
Forty healthy dogs randomly assigned to 4 groups: propofol with saline (n = 10), propofol with doxapram (n = 10), methohexital with saline (n = 10), or methohexital with doxapram (n = 10).
METHODS
Propofol and methohexital were administered to effect. Investigators examined laryngeal function (initial) simultaneously with video laryngoscopy. Doxapram or saline was administered, and laryngeal function was reevaluated (second). Laryngeal motion, quality of laryngeal exposure, and the degree of swallowing, laryngospasm, and jaw tone were scored at each evaluation. Adverse events were recorded. Initial and second videos were evaluated by a masked observer, and still images obtained from both evaluations were evaluated for change in rima glottidis size by 2 masked observers.
RESULTS
Administration of doxapram and saline was delayed with propofol (P = .001). Laryngeal function did not differ between dogs receiving propofol or methohexital, irrespective of doxapram administration. Doxapram improved breathing scores in both groups (P < .001). Jaw tone increased with propofol during the second evaluation (P = .049). Swallowing was more prevalent at initial examination (P = .020). Methohexital resulted in an increased heart rate (P < .001) compared with propofol. Twenty-five percent of dogs receiving methohexital developed seizure-like activity (n = 5/20).
CONCLUSION
Evaluation of laryngeal function did not differ between healthy dogs anesthetized with propofol or methohexital. Methohexital provided shorter examination times with less jaw tone but was associated with adverse events.
CLINICAL SIGNIFICANCE
This study provides evidence to recommend propofol over methohexital as an induction agent for laryngeal function examination.
Topics: Anesthetics, Intravenous; Animals; Dogs; Doxapram; Female; Larynx; Male; Methohexital; Physical Examination; Propofol; Random Allocation; Respiratory System Agents; Treatment Outcome
PubMed: 30367699
DOI: 10.1111/vsu.13110 -
Neonatology 2019Doxapram is a treatment option for severe apnea of prematurity (AOP). However, the effect of doxapram on the diaphragm, the main respiratory muscle, is not known. (Observational Study)
Observational Study
BACKGROUND
Doxapram is a treatment option for severe apnea of prematurity (AOP). However, the effect of doxapram on the diaphragm, the main respiratory muscle, is not known.
OBJECTIVES
To investigate the effect of doxapram on diaphragmatic activity measured with transcutaneous electromyography of the diaphragm (dEMG).
METHODS
A pilot study was conducted in a tertiary neonatal intensive care unit. Diaphragmatic activity was measured from 30 min before up to 3 h after the start of doxapram treatment. dEMG parameters were compared to baseline (5 min before doxapram treatment) and at 15, 60, 120 and 180 min after the start of doxapram infusion.
RESULTS
Eleven preterm infants were included with a mean gestational age of 25.5 ± 1.2 weeks and birth weight of 831 ± 129 g. The amplitudedEMG, peakdEMG and tonicdEMG values did not change in the 3 h after the start of doxapram infusion compared to baseline. Clinically, the number of apnea episodes in the 24 h after doxapram treatment decreased significantly.
CONCLUSION
Doxapram infusion does not alter diaphragmatic activity measured with transcutaneous dEMG in preterm infants with AOP, indicating that its working mechanism is primarily on respiratory drive and not on respiratory muscle activity.
Topics: Apnea; Birth Weight; Diaphragm; Doxapram; Electromyography; Female; Gestational Age; Humans; Infant, Extremely Low Birth Weight; Infant, Extremely Premature; Infant, Newborn; Infant, Premature, Diseases; Intensive Care Units, Neonatal; Male; Netherlands; Pilot Projects; Prospective Studies; Respiratory System Agents
PubMed: 30352445
DOI: 10.1159/000493359 -
Physiological Reports Sep 2018Sensing of hypoxia and acidosis in arterial chemoreceptors is thought to be mediated through the inhibition of TASK and possibly other (e.g., BK ) potassium channels...
Sensing of hypoxia and acidosis in arterial chemoreceptors is thought to be mediated through the inhibition of TASK and possibly other (e.g., BK ) potassium channels which leads to membrane depolarization, voltage-gated Ca-entry, and neurosecretion. Here, we investigate the effects of pharmacological inhibitors on TASK channel activity and [Ca ] -signaling in isolated neonatal rat type-1 cells. PK-THPP inhibited TASK channel activity in cell attached patches by up to 90% (at 400 nmol/L). A1899 inhibited TASK channel activity by 35% at 400 nmol/L. PK-THPP, A1899 and Ml 365 all evoked a rapid increase in type-1 cell [Ca ] . These [Ca ] responses were abolished in Ca -free solution and greatly attenuated by Ni (2 mM) suggesting that depolarization and voltage-gated Ca -entry mediated the rise in [Ca ] Doxapram (50 μmol/L), a respiratory stimulant, also inhibited type-1 cell TASK channel activity and increased [Ca ] . We also tested the effects of combined inhibition of BK and TASK channels. TEA (5 mmol/L) slightly increased [Ca ] in the presence of PK-THPP and A1899. Paxilline (300 nM) and iberiotoxin (50 nmol/L) also slightly increased [Ca ] in the presence of A1899 but not in the presence of PK-THPP. In general [Ca ] responses to TASK inhibitors, alone or in combination with BK inhibitors, were smaller than the [Ca ] responses evoked by hypoxia. These data confirm that TASK channel inhibition is capable of evoking membrane depolarization and robust voltage-gated Ca -entry but suggest that this, even with concomitant inhibition of BK channels, may be insufficient to account fully for the [Ca ] -response to hypoxia.
Topics: Animals; Animals, Newborn; Benzamides; Benzeneacetamides; Calcium Signaling; Carotid Body; Doxapram; HEK293 Cells; Humans; Nerve Tissue Proteins; Potassium Channels, Tandem Pore Domain; Rats; Rats, Sprague-Dawley; Respiratory System Agents
PubMed: 30284397
DOI: 10.14814/phy2.13876 -
Biomedical Chromatography : BMC Oct 2018A simple and specific UPLC-MS/MS method was developed and validated for simultaneous quantification of fentanyl, sufentanil, cefazolin, doxapram and its active... (Observational Study)
Observational Study
A simple and specific UPLC-MS/MS method was developed and validated for simultaneous quantification of fentanyl, sufentanil, cefazolin, doxapram and its active metabolite keto-doxapram. The internal standard was fentanyl-d5 for all analytes. Chromatographic separation was achieved with a reversed-phase Acquity UPLC HSS T3 column with a run-time of only 5.0 min per injected sample. Gradient elution was performed with a mobile phase consisting of ammonium acetate or formic acid in Milli-Q ultrapure water or in methanol with a total flow rate of 0.4 mL min . A plasma volume of only 50 μL was required to achieve adequate accuracy and precision. Calibration curves of all five analytes were linear. All analytes were stable for at least 48 h in the autosampler. The method was validated according to US Food and Drug Administration guidelines. This method allows quantification of fentanyl, sufentanil, cefazolin, doxapram and keto-doxapram, which is useful for research as well as therapeutic drug monitoring, if applicable. The strength of this method is the combination of a small sample volume, a short run-time, a deuterated internal standard, an easy sample preparation method and the ability to simultaneously quantify all analytes in one run.
Topics: Cefazolin; Chromatography, High Pressure Liquid; Doxapram; Drug Stability; Fentanyl; Humans; Infant, Newborn; Limit of Detection; Linear Models; Prospective Studies; Reproducibility of Results; Tandem Mass Spectrometry
PubMed: 29768657
DOI: 10.1002/bmc.4290 -
Anesthesiology May 2018The ventilatory control system is highly vulnerable to exogenous administered opioid analgesics. Particularly respiratory depression is a potentially lethal complication... (Review)
Review
The ventilatory control system is highly vulnerable to exogenous administered opioid analgesics. Particularly respiratory depression is a potentially lethal complication that may occur when opioids are overdosed or consumed in combination with other depressants such as sleep medication or alcohol. Fatalities occur in acute and chronic pain patients on opioid therapy and individuals that abuse prescription or illicit opioids for their hedonistic pleasure. One important strategy to mitigate opioid-induced respiratory depression is cotreatment with nonopioid respiratory stimulants. Effective stimulants prevent respiratory depression without affecting the analgesic opioid response. Several pharmaceutical classes of nonopioid respiratory stimulants are currently under investigation. The majority acts at sites within the brainstem respiratory network including drugs that act at α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (ampakines), 5-hydroxytryptamine receptor agonists, phospodiesterase-4 inhibitors, D1-dopamine receptor agonists, the endogenous peptide glycyl-glutamine, and thyrotropin-releasing hormone. Others act peripherally at potassium channels expressed on oxygen-sensing cells of the carotid bodies, such as doxapram and GAL021 (Galleon Pharmaceuticals Corp., USA). In this review we critically appraise the efficacy of these agents. We conclude that none of the experimental drugs are adequate for therapeutic use in opioid-induced respiratory depression and all need further study of efficacy and toxicity. All discussed drugs, however, do highlight potential mechanisms of action and possible templates for further study and development.
Topics: Analgesia; Analgesics, Opioid; Animals; Carotid Body; Dipeptides; Humans; Phosphodiesterase 4 Inhibitors; Receptors, Dopamine D1; Respiratory Insufficiency; Respiratory System Agents
PubMed: 29553984
DOI: 10.1097/ALN.0000000000002184 -
Antimicrobial Agents and Chemotherapy Jan 2018Earlier, we reported that three Food and Drug Administration-approved drugs, trifluoperazine (TFP; an antipsychotic), amoxapine (AXPN; an antidepressant), and doxapram...
Earlier, we reported that three Food and Drug Administration-approved drugs, trifluoperazine (TFP; an antipsychotic), amoxapine (AXPN; an antidepressant), and doxapram (DXP; a breathing stimulant), identified from an murine macrophage cytotoxicity screen, provided mice with 40 to 60% protection against pneumonic plague when administered at the time of infection for 1 to 3 days. In the present study, the therapeutic potential of these drugs against pneumonic plague in mice was further evaluated when they were administered at up to 48 h postinfection. While the efficacy of TFP was somewhat diminished as treatment was delayed to 24 h, the protection of mice with AXPN and DXP increased as treatment was progressively delayed to 24 h. At 48 h postinfection, these drugs provided the animals with significant protection (up to 100%) against challenge with the agent of pneumonic or bubonic plague when they were administered in combination with levofloxacin. Likewise, when they were used in combination with vancomycin, all three drugs provided mice with 80 to 100% protection from fatal oral infection when they were administered at 24 h postinfection. Furthermore, AXPN provided 40 to 60% protection against respiratory infection with when it was administered at the time of infection or at 24 h postinfection. Using the same cytotoxicity assay, we identified an additional 76/780 nonantibiotic drugs effective against For , 121 nonantibiotic drugs were identified to inhibit bacterium-induced cytotoxicity in murine macrophages. Of these 121 drugs, 13 inhibited the macrophage cytotoxicity induced by two additional multiple-antibiotic-resistant strains. Six of these drugs decreased the intracellular survival of all three strains in macrophages. These results provided further evidence of the broad applicability and utilization of drug repurposing screening to identify new therapeutics to combat multidrug-resistant pathogens of public health concern.
Topics: Acinetobacter baumannii; Amoxapine; Animals; Anti-Bacterial Agents; Cell Line; Disease Models, Animal; Doxapram; Drug Repositioning; Drug Resistance, Multiple, Bacterial; Female; Klebsiella pneumoniae; Levofloxacin; Macrophages; Mice; Mice, Inbred C57BL; Plague; RAW 264.7 Cells; Trifluoperazine
PubMed: 29109161
DOI: 10.1128/AAC.01943-17 -
Neonatology 2017Restrictive use of invasive mechanical ventilation (IMV) in preterm infants reduces the risk of bronchopulmonary dysplasia (BPD). Our objective was to determine its... (Comparative Study)
Comparative Study
BACKGROUND AND OBJECTIVE
Restrictive use of invasive mechanical ventilation (IMV) in preterm infants reduces the risk of bronchopulmonary dysplasia (BPD). Our objective was to determine its effect on neurodevelopmental impairment (NDI) at 24 months' corrected age (CA).
METHODS
This retrospective single-center cohort study included all patients with a gestational age <30 weeks born in 2004/2005 (epoch 1) and 2010/2011 (epoch 2). In epoch 2, we introduced a policy of restriction on IMV and liberalized the use of respiratory stimulants in the delivery room and neonatal intensive care. Data on patient characteristics, respiratory management, short-term outcomes, mortality, BPD, and NDI at 24 months' CA were collected.
RESULTS
Four hundred and four preterm infants were included. Compared to those in epoch 1, infants in epoch 2 were less likely to be intubated and the duration of IMV was shorter. Other noninvasive adjuvant therapies such as caffeine, doxapram, and nasal ventilation were more often used during epoch 2. There was a trend to less BPD in epoch 2 compared to epoch 1 (17 vs. 23%, adjusted OR = 0.75, 95% CI: 0.48, 1.16). Mortality did not change over time. The combined outcome death or NDI at 24 months' CA was significantly lower in epoch 2 compared to epoch 1 (24.7 vs. 33.9%, adjusted OR = 0.71, 95% CI: 0.53, 0.97).
CONCLUSIONS
Restricted use of IMV is feasible in preterm infants and might be associated with a reduced risk of the combined outcome death or NDI at 24 months' CA. Larger studies are needed to confirm these findings.
Topics: Age Factors; Bronchopulmonary Dysplasia; Child Development; Child, Preschool; Continuous Positive Airway Pressure; Delivery Rooms; Feasibility Studies; Female; Gestational Age; High-Frequency Ventilation; Humans; Infant; Infant, Newborn; Infant, Premature; Intensive Care Units, Neonatal; Intubation, Intratracheal; Male; Nervous System; Netherlands; Neurodevelopmental Disorders; Noninvasive Ventilation; Pulmonary Surfactants; Respiration, Artificial; Retrospective Studies; Risk Factors; Treatment Outcome
PubMed: 28601870
DOI: 10.1159/000471841 -
Neonatology 2017Apnea of prematurity (AOP) is a common complication of preterm birth, for which caffeine is the first treatment of choice. In case of persistent AOP, doxapram has been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Apnea of prematurity (AOP) is a common complication of preterm birth, for which caffeine is the first treatment of choice. In case of persistent AOP, doxapram has been advocated as an additional therapy.
OBJECTIVE
To identify and appraise all existing evidence regarding efficacy and safety of doxapram use for AOP in infants born before 34 weeks of gestational age.
METHODS
All studies reporting on doxapram use for AOP were identified by searching electronic databases, references from relevant studies, and abstracts from the Societies for Pediatric Research. Two reviewers independently assessed study eligibility and quality, and extracted data on study design, patient characteristics, efficacy and safety outcomes.
RESULTS
The randomized controlled trials showed less apnea during doxapram treatment when compared to placebo, but no difference in treatment effect when compared to theophylline. No serious adverse effects were reported. We identified 28 observational studies consisting mainly of cohort studies and case series (n = 1,994). There was considerable heterogeneity in study design and quality. Most studies reported a positive effect of doxapram on apnea rate. A few studies reported on long-term outcomes with conflicting results. A range of possible doxapram-related short-term adverse effects were reported, sometimes associated with the use of higher doses.
CONCLUSION
Based on the limited number of studies and level of evidence, no firm conclusions on the efficacy and safety of doxapram in preterm infants can be drawn. For this reason, routine use cannot be recommended. A large multicenter randomized controlled trial is urgently needed to provide more conclusive evidence.
Topics: Apnea; Caffeine; Doxapram; Gestational Age; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Randomized Controlled Trials as Topic; Respiratory System Agents; Theophylline
PubMed: 27760427
DOI: 10.1159/000448941 -
Journal of the American Veterinary... Jul 2016OBJECTIVE To investigate the prevalence and type of laryngeal abnormalities in dogs examined because of cough that did not have signs of upper airway disease and to...
OBJECTIVE To investigate the prevalence and type of laryngeal abnormalities in dogs examined because of cough that did not have signs of upper airway disease and to compare the prevalence of those abnormalities among dogs with various respiratory tract diseases. DESIGN Prospective study. ANIMALS 138 dogs with cough that did not have signs of upper airway disease. PROCEDURES The study was conducted between July 2001 and October 2014 and included dogs examined for cough that had laryngoscopic and bronchoscopic examinations performed by 1 examiner. Laryngeal hyperemia and swelling were recorded, and laryngeal function was assessed before and after doxapram stimulation when indicated. Results were compared among dogs on the basis of cough duration (acute [< 2 weeks], subacute [2 weeks to 2 months], and chronic [> 2 months]) and disease diagnosed (inflammatory airway disease, airway collapse, lower respiratory tract infection, and eosinophilic bronchopneumopathy). RESULTS Laryngeal hyperemia was detected in 73 of 134 (54%) dogs with cough of subacute or chronic duration, and its prevalence did not vary significantly among dogs with various diseases. Thirteen dogs had laryngeal paresis, and 13 dogs had laryngeal paralysis; dysphonia (n = 2) and stridor (1) were uncommon findings in those dogs. The prevalence of laryngeal dysfunction (paresis or paralysis) did not differ significantly among diseases. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that 26 of 138 (19%) dogs examined because of cough alone had laryngeal dysfunction, which suggested that a complete laryngoscopic examination should be included in the diagnostic evaluation of dogs with cough.
Topics: Airway Obstruction; Animals; Constriction, Pathologic; Cough; Dog Diseases; Dogs; Laryngeal Diseases; Larynx
PubMed: 27379595
DOI: 10.2460/javma.249.2.195 -
Anesthesiology and Pain Medicine Feb 2016Postanaesthetic shivering is one of the most common unpleasant complications in patients.
BACKGROUND
Postanaesthetic shivering is one of the most common unpleasant complications in patients.
OBJECTIVES
The aim of this study was to compare the efficacy of doxapram, ketamine and meperidine in prevention of shivering after anaesthesia.
PATIENTS AND METHODS
In this randomized, double-blind clinical trial, 120 patients aged between 20 - 45 years old under general anaesthesia were enrolled. The patients were randomly allocated into one of three groups: group M received 20 mg meperidine (n = 40), group K received 0.25 mg/kg ketamine (n = 40) and group D received 0.25 mg/kg doxapram (n = 40). All of the drugs were administered intravenously. The core temperature, shivering, time of the first postoperative analgesic requirement, and some of the other side effects were recorded. Obtained data from the three groups were compared using one-way ANOVA and chi-square test.
RESULTS
Three patients (7.5%) of group K, four patients (10%) of group D and one patient (2.5%) of group M experienced shivering (P = 0.39). The interval to the first analgesic requirement significantly prolonged in the groups K and M compared to the group D (P < 0.001). No significant differences were identified in nausea and vomiting among the groups. No significant pharmaceutical adverse effects were observed in our study.
CONCLUSIONS
The results of this study showed that ketamine, doxapram and meperidine are equally effective in the prevention of postoperative shivering.
PubMed: 27110525
DOI: 10.5812/aapm.27515