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Sandra Kruszynski, Kornelijus Stanaitis, Janine Brandes, Christian F Poets, Henner Koch
Doxapram is a respiratory stimulant used for decades as a treatment option in apnea of prematurity (AOP) refractory to methylxanthine treatment. Its mode of action, however, is still poorly understood. We investigated direct effects of doxapram on the PreBötzinger complex (PreBötC) and on a downstream motor output system, the hypoglossal nucleus (XII), in the transverse brainstem slice preparation. While doxapram only a modest stimulatory effect on frequency of activity generated within the preBötC, a much more robust increase in the amplitude of population activity in the subsequent motor output generated in the XII was observed...
January 30, 2019: Journal of Neurophysiology
Mikala B Brown, Danielle R Dugat, Shane D Lyon, Laura A Nafe, Mark E Payton, Sarah K Peakheart, Rebecca S Salazar
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...
October 27, 2018: Veterinary Surgery: VS
Cornelia G de Waal, Gerard J Hutten, Juliette V Kraaijenga, Frans H de Jongh, Anton H van Kaam
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...
2019: Neonatology
Peadar B O'Donohoe, Nicky Huskens, Philip J Turner, Jaideep J Pandit, Keith J Buckler
Sensing of hypoxia and acidosis in arterial chemoreceptors is thought to be mediated through the inhibition of TASK and possibly other (e.g., BKC a ) 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 [Ca2+ ]i -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...
September 2018: Physiological Reports
Robert B Flint, Soma Bahmany, Bart C H van der Nagel, Birgit C P Koch
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...
October 2018: Biomedical Chromatography: BMC
Albert Dahan, Rutger van der Schrier, Terry Smith, Leon Aarts, Monique van Velzen, Marieke Niesters
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...
May 2018: Anesthesiology
Tomoyuki Shimokaze, Katsuaki Toyoshima, Jun Shibasaki, Yasufumi Itani
OBJECTIVE: We often encounter infants who developed hypokalaemia following low-dose doxapram for apnea of prematurity (AOP). AIMS: To determine changes in blood potassium (K+) levels after doxapram administration. STUDY DESIGN: We studied infants born before 30 weeks gestation. Doxapram (0.1-0.3 mg/kg/h) in addition to methylxanthines was used to treat AOP refractory to methylxanthines. RESULTS: Twenty-five infants received doxapram were studied...
June 2018: Journal of Perinatology: Official Journal of the California Perinatal Association
Denise I Radkey, Robert J Hardie, Lesley J Smith
OBJECTIVE: To compare the effects of alfaxalone and propofol, with and without acepromazine and butorphanol followed by doxapram, on laryngeal motion and quality of laryngeal examination in dogs. STUDY DESIGN: Randomized, crossover, blinded study. ANIMALS: Ten female Beagle dogs, aged 11-13 months and weighing 7.2-8.6 kg. METHODS: The dogs were administered four intravenous (IV) treatments: alfaxalone (ALF), alfaxalone+acepromazine and butorphanol (ALF-AB), propofol (PRO) and propofol+AB (PRO-AB)...
May 2018: Veterinary Anaesthesia and Analgesia
Jourdan A Andersson, Jian Sha, Michelle L Kirtley, Emily Reyes, Eric C Fitts, Sara M Dann, Ashok K Chopra
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 in vitro 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...
January 2018: Antimicrobial Agents and Chemotherapy
Isac Silva de Jesus, Milena Ferreira, Urbano Lopes Silva-Júnior, José Antônio Alves-Gomes
Considering the conserved nature of synaptic physiology among vertebrates, we tested the effects of three psychotropics (diazepam, doxapram, and nicotine) on Microsternarchus cf. bilineatus, measuring 10 parameters associated to the electric organ discharges rhythm and waveform before and after the administration of each drug and a control group. There were statistically significant differences (p < 0.005) among all the experimental groups, F (70, 22619.25) = 77.7, between the two experimental phases within their respective drug treatment, F (80, 24604...
December 2017: Zebrafish
Robert B Flint, Willem van Weteringen, Swantje Voller, Jarinda A Poppe, Birgit C P Koch, Ronald de Groot, Dick Tibboel, Catherijne A J Knibbe, Irwin K M Reiss, Sinno H P Simons, Dino Research Group
BACKGROUND: Drug effect evaluation is often based on subjective interpretation of a selection of patient data. Continuous analyses of high frequency patient monitor data are a valuable source to measuring drug effects. However, these have not yet been fully explored in clinical care. We aim to evaluate the usefulness and applicability of high frequency physiological data for analyses of pharmacotherapy. METHODS: As a proof of principle, the effects of doxapram, a respiratory stimulant, on the oxygenation in preterm infants were studied...
2017: Current Pharmaceutical Design
Roseanne J S Vliegenthart, Wes Onland, Aleid G van Wassenaer-Leemhuis, Anne P M De Jaegere, Cornelieke S H Aarnoudse-Moens, Anton H van Kaam
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...
2017: Neonatology
Jun Tamura, Makio Yanagisawa, Yusuke Endo, Keiichi Ueda, Haruka Koga, Yasuharu Izumisawa, Kazuto Yamashita
This report describes the anesthetic management of a 14-yr-old, 160-kg, female Indo-Pacific bottlenose dolphin ( Tursiops aduncus ) that underwent surgical debridement for a refractory subcutaneous abscess twice within a 6-mo interval. The animal was otherwise in good physical condition at each anesthetic procedure. Following premedication with intramuscular midazolam and butorphanol, anesthesia was induced with propofol and maintained with sevoflurane by intubation. During surgery ventilation was controlled...
March 2017: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
Yuki Suzuki, Noboru Kamada, Hitoshi Ohno, Yoshikazu Abe, Takuro Endo, Mamoru Kobayashi
AIM: Doxapram, a respiratory stimulant, is used to treat apnea. A reliable method of determining doxapram in blood is required for monitoring purposes. RESULTS: Doxapram, keto-doxapram (active metabolite) and propranolol (internal standard) were extracted from human serum by protein precipitation and plate filtration. Molecular ions were generated by electrospray ionization in positive ion mode, and the ions were analyzed using a triple-quadrupole mass spectrometer...
March 2017: Bioanalysis
Robert Flint, Nienke Halbmeijer, Naomi Meesters, Joost van Rosmalen, Irwin Reiss, Monique van Dijk, Sinno Simons
AIM: Using doxapram to treat neonates with apnoea of prematurity might avoid the need for endotracheal intubation and invasive ventilation. We studied whether doxapram prevented the need for intubation and identified the predictors of the success. METHODS: This was a retrospective study of preterm infants born from January 2006 to August 2014 who received oral or intravenous doxapram. Success was defined as no need for endotracheal intubation, due to apnoea, during doxapram therapy...
May 2017: Acta Paediatrica
M Roozekrans, E Olofsen, R van der Schrier, M Boom, R Mooren, A Dahan
Doxapram is an analeptic that induces ventilatory stimulation and increases blood pressure and cardiac output (CO). Its mechanism of action is the blockade of background K+ -channels expressed on type 1 carotid body cells. In the randomized controlled trial, the authors explored the role of the increase in CO by doxapram (plasma concentration (Cp) 1,000-3,500 ng/mL) on the pharmacokinetics (PKs) and pharmacodynamics (PDs) of the potent opioid alfentanil (Cp 100-200 ng/mL). Population PK-PD analyses were performed on the doxapram PK-CO data and the alfentanil PK-antinociception data...
December 21, 2016: Clinical Pharmacology and Therapeutics
Roseanne J S Vliegenthart, Christine H Ten Hove, Wes Onland, Anton H L C van Kaam
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...
2017: Neonatology
John R Richards, M Thais Davis, Mark R Curry, John H Tsushima, Howard E McKinney
No abstract text is available yet for this article.
March 2017: American Journal of Emergency Medicine
E Greze, M Benard, I Hamon, C Casper, F E Haddad, M-J Boutroy, J-M Hascoët
INTRODUCTION: Doxapram is used as a third-line treatment for apnea unresponsive to caffeine and continuous positive airway pressure (CPAP) in preterm infants. OBJECTIVES: The objectives of this study were to compare the effects of dosing adjusted for gender and postmenstrual age (PMA) (GrA) versus infants' weight alone (GrW) on doxapram plasma levels, clinical efficacy, and side effects. METHODS: This was a randomized, double-blind study, including premature infants for whom optimized caffeine and CPAP therapy for apnea of prematurity had failed...
December 2016: Paediatric Drugs
Anna J Haw, Leith Cr Meyer, John J Greer, Andrea Fuller
OBJECTIVES: To determine whether CX1942 reverses respiratory depression in etorphine-immobilized goats, and to compare its effects with those of doxapram hydrochloride. STUDY DESIGN: A prospective, crossover experimental trial conducted at 1753 m.a.s.l. ANIMALS: Eight adult female Boer goats (Capra hircus) with a mean ± standard deviation mass of 27.1 ± 1.6 kg. METHODS: Following immobilization with 0.1 mg kg(-1) etorphine, goats received one of doxapram, CX1942 or sterile water intravenously, in random order in three trials...
September 2016: Veterinary Anaesthesia and Analgesia
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