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The Medical Letter on Drugs and... Jan 1970
Topics: Central Nervous System Stimulants; Doxapram; Humans; Morpholines; Pyrrolidinones
PubMed: 4393024
DOI: No ID Found -
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 -
The Journal of Pediatrics Sep 1986
Topics: Apnea; Doxapram; Humans; Infant, Newborn; Infant, Premature, Diseases
PubMed: 3746554
DOI: 10.1016/s0022-3476(86)80146-9 -
Anesthesia and Analgesia Nov 2005We determined the effects of doxapram on the major autonomic thermoregulatory responses in humans. Nine healthy volunteers were studied on 2 days: control and doxapram...
We determined the effects of doxapram on the major autonomic thermoregulatory responses in humans. Nine healthy volunteers were studied on 2 days: control and doxapram (IV infusion to a plasma concentration of 2.4 +/- 0.8, 2.5 +/- 0.9, and 2.6 +/- 1.1 microg/mL at the sweating, vasoconstriction, and shivering thresholds, respectively). Each day, skin and core temperatures were increased to provoke sweating, then reduced to elicit peripheral vasoconstriction and shivering. We determined the sweating, vasoconstriction, and shivering thresholds with compensation for changes in skin temperature. Data were analyzed with paired t-tests and presented as mean +/- sd; P < 0.05 was considered statistically significant. Doxapram did not change the sweating (control: 37.5 degrees +/- 0.4 degrees C, doxapram: 37.3 degrees +/- 0.4 degrees C; P = 0.290) or the vasoconstriction threshold (36.8 degrees +/- 0.7 degrees C versus 36.4 degrees +/- 0.5 degrees C; P = 0.110). However, it significantly reduced the shivering threshold from 36.2 degrees +/- 0.5 degrees C to 35.7 degrees +/- 0.7 degrees C (P = 0.012). No sedation or symptoms of panic were observed on either study day. The observed reduction in the shivering threshold explains the drug's efficacy for treatment of postoperative shivering; however, a reduction of only 0.5 degrees C is unlikely to markedly facilitate induction of therapeutic hypothermia as a sole drug.
Topics: Adult; Doxapram; Female; Humans; Male; Shivering; Sweating; Vasoconstriction
PubMed: 16243996
DOI: 10.1213/01.ANE.0000180198.13467.DF -
European Journal of Anaesthesiology Nov 2006To evaluate and compare the effect of two clinically available central nervous system stimulants, namely doxapram and aminophylline on arousal from sevoflurane... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND AND OBJECTIVE
To evaluate and compare the effect of two clinically available central nervous system stimulants, namely doxapram and aminophylline on arousal from sevoflurane anaesthesia and bispectral index.
METHODS
This randomized, double-blind, placebo-controlled, prospective study was conducted in 90 adult females, ASA I-II, scheduled for elective lower abdominal surgeries at Taipei Medical University Hospital. At 5 min before the completion of surgery, under sevoflurane anaesthesia, patients were divided into three groups to receive doxapram 1 mg kg(-1), aminophylline 2 mg kg(-1) or saline placebo intravenous. Standard vital signs, end-tidal CO(2), end-expiratory sevoflurane concentration, bispectral index and neuromuscular blockade were measured plus clinical parameters of recovery from general anaesthesia.
RESULTS
Compared with the control group, patients receiving doxapram or aminophylline showed a similarly faster recovery from sevoflurane anaesthesia correlated with increase in bispectral index.
CONCLUSION
Intravenous administration of doxapram 1 mg kg(-1) or aminophylline 2 mg kg(-1) hastened the early recovery from sevoflurane anaesthesia. The arousal effect of aminophylline and doxapram appears to be similar.
Topics: Adult; Aminophylline; Analysis of Variance; Anesthesia Recovery Period; Anesthesia, General; Anesthesia, Inhalation; Anesthetics, Inhalation; Arousal; Cardiotonic Agents; Central Nervous System Stimulants; Combined Modality Therapy; Double-Blind Method; Doxapram; Electroencephalography; Female; Humans; Methyl Ethers; Monitoring, Intraoperative; Prospective Studies; Psychomotor Performance; Sevoflurane
PubMed: 16895622
DOI: 10.1017/S0265021506001220 -
Developmental Pharmacology and... 1988To 18 premature apneic patients refractory to theophylline, doxapram (0.5-2.5 mg/kg/h) was administered in combination with therapeutic doses of theophylline. Doxapram...
To 18 premature apneic patients refractory to theophylline, doxapram (0.5-2.5 mg/kg/h) was administered in combination with therapeutic doses of theophylline. Doxapram concentrations in serum were measured 48 h after commencement of the infusion and then in 2-hour intervals during a 6-8 h withdrawal. Total body clearance (dose/Css) of the drug ranged from 0.20 to 0.56 liter/h in 13 patients and 1.14 to 1.75 liter/h in 4 patients suggesting a binomial distribution in the disposition kinetics of the drug. Other pharmacokinetic indices, although variable, did not exhibit binomial distribution. The mean volume of distribution and half-life of doxapram were 7.33 +/- 4.55 liter/kg and 8.17 +/- 4.13 h, respectively. Based on our calculations to accelerate the attainment of a steady-state plasma concentration (Css) of approximately 1.5 mg/l, a loading dose of 5.5 mg/kg and a maintenance dose of 1 mg/kg/h along with serum concentration monitoring are recommended.
Topics: Apnea; Doxapram; Drug Administration Schedule; Humans; Infant, Newborn; Infant, Premature, Diseases
PubMed: 3191816
DOI: 10.1159/000457699 -
Pediatrics International : Official... Apr 2001Doxapram is contraindicated for newborn infants in Japan because of its serious side effects. However, because of encouraging results of recent studies regarding the...
BACKGROUND
Doxapram is contraindicated for newborn infants in Japan because of its serious side effects. However, because of encouraging results of recent studies regarding the efficacy and safety of therapy for apnea of prematurity (AOP) with lower doses of doxapram than those previously proposed, approximately 60% of Japanese neonatologists continue to use doxapram at small doses. Caution is warranted because the sample sizes of the former studies are inadequate to evaluate doxapram for both its beneficial and harmful effects. Therefore, we conducted the present study in order to investigate the efficacy and harmful events of low-dose doxapram therapy for idiopathic AOP in very low-birth weight (VLBW) infants in a larger population.
METHODS
One hundred and six VLBW infants with idiopathic AOP were treated with doxapram at a dose of 0.2-1.0 mg/kg per h in combination with methylxanthines and the frequency of apnea and secondary outcomes were compared with a group of control infants.
RESULTS
An approximate 80% reduction in the frequency of apnea was found with only minimal side effects following low-dose doxapram. Although there were no significant differences in secondary outcomes between the doxapram-treated and control groups, mortality in doxapram-treated infants was significantly lower than that in control infants.
CONCLUSIONS
Patients with AOP unresponsive to treatment with methylxanthines may benefit from the addition of low-dose doxapram.
Topics: Apnea; Doxapram; Drug Therapy, Combination; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Recurrence; Respiratory System Agents; Treatment Outcome; Xanthines
PubMed: 11285061
DOI: 10.1046/j.1442-200x.2001.01359.x -
European Journal of Anaesthesiology Feb 2021
Topics: Airway Extubation; Bariatric Surgery; Delayed Emergence from Anesthesia; Doxapram; Humans; Neuromuscular Blockade; Obesity, Morbid
PubMed: 33394796
DOI: 10.1097/EJA.0000000000001338 -
American Journal of Perinatology Mar 1991Doxapram was administered orally to six premature babies (3 males, 3 females) with refractory apnea at a mean gestational age of 29 +/- 2.3 weeks, mean birthweight of...
Doxapram was administered orally to six premature babies (3 males, 3 females) with refractory apnea at a mean gestational age of 29 +/- 2.3 weeks, mean birthweight of 1142 +/- 359 gm and a mean postnatal age of 24 days. They received 12, 24, and 36 mg/kg/6 hr on day 1, 2, and 3, respectively, assuming a bioavailability of 50%. Serial plasma doxapram concentrations, determined by high-performance liquid chromatography, increased with incremental doses. The drug underwent oxidative metabolism, producing ketodoxapram, the plasma concentration of which remained stable during treatment. The ratio of plasma concentrations to oral doses ranged from 0.10 to 0.12, suggesting that doxapram is poorly absorbed in the newborn. Oral doxapram may replace the intravenous infusion but doses may have to be increased to, but not exceeding, 24 mg/kg/6 hr to achieve therapeutic plasma concentrations. Interpatient variability, poor absorption and gastrointestinal adverse effects caution against the routine use of oral doxapram.
Topics: Administration, Oral; Apnea; Blood Pressure; Dose-Response Relationship, Drug; Doxapram; Female; Humans; Infant, Newborn; Infant, Premature; Intestinal Absorption; Male; Metabolic Clearance Rate
PubMed: 2006935
DOI: 10.1055/s-2007-999357 -
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