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Neonatology 2016Doxapram has been advocated as a treatment for persistent apnea of prematurity (AOP).
BACKGROUND
Doxapram has been advocated as a treatment for persistent apnea of prematurity (AOP).
OBJECTIVE
To evaluate the effect of doxapram on long-term neurodevelopmental outcome in preterm infants as its safety still needs to be established.
METHODS
From a retrospective cohort of preterm infants with a gestational age (GA) <30 weeks and/or a birth weight <1,250 g, born between 2000 and 2010, infants treated with doxapram (n = 142) and a nontreated control group were selected (n = 284). Patient characteristics and clinical and neurodevelopmental outcome data at 24 months' corrected age were collected. Neurodevelopmental delay (ND) was defined as having a Mental or Psychomotor Developmental Index (MDI/PDI) <-1 standard deviation (SD), cerebral palsy, or a hearing or visual impairment. Odds ratios (OR) were calculated using multiple logistic regression analyses adjusting for potential confounders.
RESULTS
Infants treated with doxapram had a lower GA compared to controls. The number of infants with a MDI or PDI <-1 SD was not different between the groups. The risk of the combined outcome death or ND was significantly lower in the doxapram group after adjusting for confounding factors (OR = 0.54, 95% CI: 0.37, 0.78). Doxapram-treated infants had a higher risk of bronchopulmonary dysplasia and patent ductus arteriosus, but a lower risk of spontaneous intestinal perforation. All other morbidities were not different between the groups.
CONCLUSIONS
This study suggests that doxapram is not associated with an increased risk of ND. These findings need to be confirmed or refuted by a large, well-designed, placebo-controlled randomized trial.
Topics: Apnea; Bronchopulmonary Dysplasia; Central Nervous System Stimulants; Child Development; Doxapram; Ductus Arteriosus, Patent; Female; Gestational Age; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Logistic Models; Male; Netherlands; Odds Ratio; Retrospective Studies; Treatment Outcome
PubMed: 26967910
DOI: 10.1159/000444006 -
American Journal of Perinatology Oct 2014The aim of the article is to provide an update on medication use in infants admitted to the neonatal intensive care unit (NICU) in the United States and examine how use...
OBJECTIVE
The aim of the article is to provide an update on medication use in infants admitted to the neonatal intensive care unit (NICU) in the United States and examine how use has changed over time.
STUDY DESIGN
We performed a retrospective review (2005-2010) of a large prospectively collected administrative database.
RESULT
Medications most commonly administered during the study period were ampicillin, gentamicin, caffeine citrate, vancomycin, beractant, furosemide, fentanyl, dopamine, midazolam, and calfactant (56-681 exposures per 1,000 infants). Those with the greatest relative increase in use included azithromycin, sildenafil, and milrinone. Medications with the greatest relative decrease in use included theophylline, metoclopramide, and doxapram.
CONCLUSION
Medication use in the NICU has changed substantially over time, and only 35% of the most commonly prescribed medications are Food and Drug Administration -approved in infants.
Topics: Drug Therapy; Drug Utilization; Female; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Intensive Care, Neonatal; Male; Retrospective Studies; United States
PubMed: 24347262
DOI: 10.1055/s-0033-1361933 -
European Journal of Anaesthesiology Jun 2020Bariatric surgery is a well established treatment of the obese. Postoperative respiratory failure and airway obstruction after bariatric surgery can often be attributed... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Bariatric surgery is a well established treatment of the obese. Postoperative respiratory failure and airway obstruction after bariatric surgery can often be attributed to the residual depressant effects of anaesthetics, sedatives and opioids. Peri-operative management of morbidly obese patients is still a concern for operating room professionals.
OBJECTIVE
The evaluation of the effects of doxapram on the outcomes of general anaesthesia following bariatric surgical procedures in the morbidly obese.
DESIGN
A single-blind randomised controlled trial with two parallel arms.
SETTING
A tertiary care teaching hospital, Tehran, Iran, from 2017 to 2018.
PARTICIPANTS
In total, 100 patients (69 women) with at least class two obesity were included in two groups of equal sizes and underwent bariatric surgery.
MAIN OUTCOME MEASURES
The primary outcome was the time from the administration of doxapram to tracheal extubation. Secondary outcomes included vital signs and variables including peak expiratory flow rate, time to return to spontaneous breathing, time to eye-opening and hand-squeezing on the commands, and time to recovery.
INTERVENTIONS
Both groups underwent general anaesthesia. The intervention group received a single dose of doxapram 1 mg kg ideal body weight, immediately after reversal of neuromuscular blockade and after discontinuation of all anaesthetics.
RESULTS
Doxapram decreased time to extubation, time to eye-opening and hand-squeezing, shortened recovery time and lowered end-tidal CO2 significantly (all P < 0.001). Moreover, it increased peak expiratory flow rate, oxygen saturation, temperature, heart rate and blood pressure (all P < 0.001). The two groups were similar in the bispectral index and mean arterial pressure (both P > 0.05). None of our participants had complications attributable to doxapram.
CONCLUSION
The postoperative use of doxapram improves peak expiratory flow rate, and decreases respiratory complications of anaesthesia during recovery in the morbidly obese undergoing bariatric surgery. Doxapram is well tolerated in young ASA physical status classes 1 to 2 morbidly obese patients; however, the anaesthesiologist should cautiously evaluate the vital signs for at least half an hour following the administration of doxapram.
REGISTRATION
Iranian Registry of Clinical Trials (IRCT) http://www.irct.ir/ number IRCT2017060712203N9.
Topics: Airway Extubation; Bariatric Surgery; Doxapram; Female; Humans; Iran; Obesity, Morbid; Single-Blind Method
PubMed: 31842026
DOI: 10.1097/EJA.0000000000001144 -
Acta Paediatrica (Oslo, Norway : 1992) Sep 2014The aim of this study was to measure the brain activity of preterm infants treated with caffeine citrate and doxapram for preterm apnoea, using amplitude-integrated...
AIM
The aim of this study was to measure the brain activity of preterm infants treated with caffeine citrate and doxapram for preterm apnoea, using amplitude-integrated electroencephalography (aEEG), to identify any adverse effects on cerebral function.
METHODS
We analysed the aEEG tracings of 13 preterm infants <30 weeks of gestation before, during and after doxapram treatment, with regard to background activity (percentages of continuous and discontinuous patterns), occurrence of sleep-wake cycling and appearance of electrographic seizure activity. They were also compared with 61 controls without doxapram treatment.
RESULTS
During doxapram treatment, aEEG tracings showed an increase in continuous background activity (19 ± 30% before treatment, 38 ± 35% during treatment) and a decrease in discontinuous patterns. In addition, they showed more frequent electrographic seizure activity (0% before treatment, 15 ± 37% during treatment) and less frequent sleep-wake cycling (92 ± 27% before treatment, 85 ± 37% during treatment) could be observed. These results were confirmed when compared to the control group.
CONCLUSION
Doxapram treatment influences aEEG in preterm infants, showing higher percentages of continuous activity as well as more electrographic seizure activity and less sleep-wake cycling. It should, therefore, be used with caution in very preterm infants.
Topics: Apnea; Brain; Doxapram; Electroencephalography; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Respiratory System Agents; Retrospective Studies
PubMed: 24813556
DOI: 10.1111/apa.12681 -
Pediatric Research Mar 2023An oxygen saturation (SpO) histogram classification system has been shown to enable quantification of SpO instability into five types, based on histogram distribution...
BACKGROUND
An oxygen saturation (SpO) histogram classification system has been shown to enable quantification of SpO instability into five types, based on histogram distribution and time spent at SpO ≤ 80%. We aimed to investigate this classification system as a tool to describe response to doxapram treatment in infants with severe apnea of prematurity.
METHODS
This retrospective study included 61 very-low-birth-weight infants who received doxapram. SpO histograms were generated over the 24-h before and after doxapram start. Therapy response was defined as a decrease of ≥1 histogram types after therapy start.
RESULTS
The median (IQR) histogram type decreased from 4 (3-4) before to 3 (2-3) after therapy start (p < 0.001). The median (IQR) FiO remained constant before (27% [24-35%]) and after (26% [22-35%]) therapy. Thirty-six infants (59%) responded to therapy within 24 h. In 34/36 (94%) of the responders, invasive mechanical ventilation (IMV) was not required during the first 72 h of therapy, compared to 15/25 (60%) of non-responders (p = 0.002). Positive and negative predictive values of the 24-h response for no IMV requirement within 72 h were 0.46 and 0.94, respectively.
CONCLUSIONS
Classification of SpO histograms provides an objective bedside measure to assess response to doxapram therapy and can serve as a tool to detect changes in oxygenation status around respiratory interventions.
IMPACT
The SpO histogram classification system provides a tool for quantifying response to doxapram therapy. The classification system allowed estimation of the probability of invasive mechanical ventilation requirement, already within a few hours of treatment. The SpO histogram classification system allows an objective bedside assessment of the oxygenation status of the preterm infant, making it possible to assess the changes in oxygenation status in response to respiratory interventions.
Topics: Infant; Infant, Newborn; Humans; Doxapram; Infant, Premature; Respiratory System Agents; Retrospective Studies; Oxygen Saturation; Infant, Premature, Diseases; Oxygen
PubMed: 35739260
DOI: 10.1038/s41390-022-02158-w -
Journal of Veterinary Emergency and... Jul 2022To describe circumstances and outcomes following cardiopulmonary arrest (CPA) in hospitalized birds.
OBJECTIVE
To describe circumstances and outcomes following cardiopulmonary arrest (CPA) in hospitalized birds.
DESIGN
Retrospective case study.
SETTING
Academic medical center.
METHODS
The hospital medical records system was searched for avian cases that underwent CPR. Medical records were reviewed; data retrieved included association of CPA with anesthesia or handling, use of external compressions and intubation, drug administration, rates of return of spontaneous circulation (ROSC), and outcome. Cases with incomplete medical records were excluded.
RESULTS
Forty-one cases of avian CPR were identified. Anesthesia-related arrest was reported in 26 of 41 cases. The remainder of CPA events occurred during an examination (6/41) or were observed during hospitalization for treatment of disease or injury (11/41). Compressions were performed in 14 birds and manual ventilation performed in 21 of 41 cases via intubation (19/21), tight-fitting face mask (1/21), or air sac cannulation (1/21). Vascular access was achieved in 24 of 41 cases. Emergency drug administration was documented in 22 of 41 cases and included epinephrine (20/22), atropine (19/22), glycopyrrolate (3/22), doxapram (2/22), dextrose (3/22), mannitol (1/22), and furosemide (1/22). Fluid therapy was administered in 24 of 41 cases. There were 3 documented cases of ROSC (7%), all in patients under general anesthesia, and 1 (2%) CPA survivor.
CONCLUSIONS
There was no standardized approach to avian CPR in this study, and ROSC was rare. When ROSC was achieved, birds were under general anesthesia with direct monitoring by a clinician, were ventilated, and were administered anesthetic reversals and anticholinergic or catecholamine emergency medications. These poor outcomes suggest that further research and an updated standardized approach to avian CPR, with special consideration of the physiological differences from mammals, are needed.
Topics: Animals; Birds; Cardiopulmonary Resuscitation; Heart Arrest; Hospitalization; Mammals; Retrospective Studies
PubMed: 35318792
DOI: 10.1111/vec.13191 -
International Journal of Toxicology Dec 2021Respiratory monitoring, using impedance with implanted telemetry in socially housed animals, was not possible until the recent development of digital signal...
Combined Cardiopulmonary Assessments Using Impedance and Digital Implants in Conscious Freely Moving Cynomolgus Monkeys, Beagle Dogs, and Göttingen Minipigs: Pharmacological Characterization and Social Housing Effects.
Respiratory monitoring, using impedance with implanted telemetry in socially housed animals, was not possible until the recent development of digital signal transmission. The objective of this study was to evaluate digital telemetry monitoring of cardiopulmonary parameters (respiratory rate, tidal volume, minute volume, electrocardiography (DII), systemic arterial blood pressure, physical activity, and body temperature) in conscious, single-housed, non-rodent species commonly used in toxicology studies following administration of positive/negative controls (saline, dexmedetomidine, morphine, amphetamine, and doxapram), and also, the effects of various social housing arrangements in untreated female and/or male cynomolgus monkeys, Beagle dogs, and Göttingen minipigs (n = 4 per species). Aggressions were observed in socially housed male minipigs, however, which prevented pair-housed assessments in this species. All tested pharmacological agents significantly altered more than one organ system, highlighting important inter-organ dependencies when analyzing functional endpoints. Stress-related physiological changes were observed with single-housing or pair-housing with a new cage mate in cynomolgus monkeys and Beagle dogs, suggesting that stable social structures are preferable to limit variability, especially around dosing. Concomitant monitoring of cardiovascular and respiratory parameters from the same animals may help reduce the number of animals (3 Rs) needed to fulfill the S7A guidelines and allows for identification of organ system functional correlations. Globally, the data support the use of social housing in non-rodents for safety pharmacology multi-organ system (heart and lungs) monitoring investigations.
Topics: Amphetamine; Analgesics, Opioid; Animals; Cardiovascular System; Central Nervous System Stimulants; Dexmedetomidine; Dogs; Doxapram; Electric Impedance; Electrocardiography; Macaca fascicularis; Morphine; Swine; Swine, Miniature
PubMed: 34610777
DOI: 10.1177/10915818211040487 -
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 2020Evaluation of pharmacotherapy during intensive care treatment is commonly based on subjective, intermittent interpretations of physiological parameters. Real-time... (Observational Study)
Observational Study
INTRODUCTION
Evaluation of pharmacotherapy during intensive care treatment is commonly based on subjective, intermittent interpretations of physiological parameters. Real-time visualization and analysis may improve drug effect evaluation. We aimed to evaluate the effects of the respiratory stimulant doxapram objectively in preterm infants using continuous physiological parameters.
METHODS
In this longitudinal observational study, preterm infants who received doxapram therapy were eligible for inclusion. Physiological data (1 Hz) were used to assess respiration and to evaluate therapy effects. The oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) ratio and the area under the 89% SpO2 curve (duration × saturation depth below target) were calculated as measures of hypoxemia. Regression analyses were performed in 1-h timeframes to discriminate therapy failure (intubation or death) from success (no intubation).
RESULTS
Monitor data of 61 patients with a median postmenstrual age (PMA) at doxapram initiation of 28.7 (IQR 27.6-30.0) weeks were available. The success rate of doxapram therapy was 56%. Doxapram pharmacodynamics were reflected in an increased SpO2 and SpO2/FiO2 ratio as well as a decrease in episodes with saturations below target (SpO2 <89%). The SpO2/FiO2 ratio, corrected for PMA and mechanical ventilation before therapy start, discriminated best between therapy failure and success (highest AUC ROC of 0.83).
CONCLUSION
The use of continuous physiological monitor data enables objective and detailed interpretation of doxapram in preterm infants. The SpO2/FiO2 ratio is the best predictive parameter for therapy failure or success. Further implementation of real-time data analysis and treatment algorithms would provide new opportunities to treat newborns.
Topics: Doxapram; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Oxygen; Respiratory System Agents
PubMed: 32841955
DOI: 10.1159/000509269 -
Frontiers in Veterinary Science 2021Sepsis is a frequent life-threatening condition in young calves, requiring rapid broad spectrum and bactericidal therapy to maximize survival chances. Few studies have...
Sepsis is a frequent life-threatening condition in young calves, requiring rapid broad spectrum and bactericidal therapy to maximize survival chances. Few studies have identified and characterized bacteria involved in sepsis in calves. This report demonstrates the involvement of a multidrug resistant , an emerging pathogen in human medicine, in a calf with suspected sepsis. was identified by MALDI-TOF MS from blood cultures of a critically ill calf. Susceptibility testing showed phenotypic resistance against ampicillin, gentamicin, potentiated sulphonamides, streptomycin, tetracyclines and intermediate susceptibility for enrofloxacin. Whole genome sequencing confirmed identification as and the multidrug resistant character of the isolate. Antimicrobial resistance genes acting against aminoglycosides, beta-lactam antibiotics, fosfomycin, quinolones, sulphonamides, trimethoprim and tetracyclines were found. The calf recovered after empirical parenteral therapy with enrofloxacin and sodium penicillin for seven days. Ancillary therapy consisted of fluid therapy, ketoprofen and doxapram hydrochloride. To the authors' knowledge, this is the first report characterizing a multidrug resistant isolate from blood culture in cattle. It is currently unknown whether animals and farms may act as reservoirs for multidrug resistant strains.
PubMed: 33842574
DOI: 10.3389/fvets.2021.631716