scholarly journals P31 No interaction between doxapram and caffeine for the treatment of preterm neonates with apnea

2019 ◽  
Vol 104 (6) ◽  
pp. e29.3-e30
Author(s):  
A Engbers ◽  
N Dia ◽  
S Völler ◽  
CAJ Knibbe ◽  
IKM Reiss ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Pharmacokinetic Interaction ◽  
Reference Population ◽  
Absolute Bioavailability ◽  
Preterm Neonates ◽  
Therapeutic Drug ◽  
Inadequate Response ◽  
List Type ◽  
Limited Information ◽  
Caffeine Citrate

BackgroundIn preterm neonates with apneas, co-administration with doxapram is often initiated in case of inadequate response to caffeine alone. While doxapram is exclusively registered for adults, there is limited information on its use in preterm infants. To examine whether the observed effects of doxapram are actually due to doxapram itself, and not a pharmacokinetic interaction between both respiratory stimulants, we studied the pharmacokinetics (PK) of caffeine in a population of preterm neonates receiving both caffeine and doxapram.MethodsCaffeine concentrations from patients in the DINO study (NCT02421068) who received both caffeine and doxapram were analyzed using NONMEM V7.3. A PK model of caffeine in preterm neonates was used as a basis to estimate the PK parameters of caffeine when co-administered with doxapram with F fixed to 1 and ka fixed to 1.48 h-1.1 The results of the current study were compared to those of the reference population published by Charles et al.1ResultsIn 15 preterm infants 58 samples were collected in which caffeine plasma levels were determined. Median gestational age (GA) was 26.3 (range 24–28) weeks, postnatal age (PNA) was 25 (0–63) days and current weight was 1100 (600–2140) grams. Caffeine CL and Vd for an individual with a PNA of 12 days were estimated 0.2 L/h/70kg (RSE 28%) and 68.2 L/70kg (RSE 73%), respectively. Maturation of CL was best described by a power function with an exponent of 0.404 (RSE 89%). These results seem in good agreement with the reference population of preterm neonates receiving caffeine without doxapram with values of 0.167 L/kg/70 kg, 58.6 L/70kg and 0.358.1ConclusionIn this pharmacokinetic study in preterm neonates receiving both caffeine and doxapram, we found similar values for CL, Vd and maturation of CL with PNA compared to literature values obtained in preterm neonates receiving caffeine alone.ReferencesBG C. et al. Caffeine citrate treatment for extremely premature infants with apnea: population pharmacokinetics, absolute bioavailability, and implications for therapeutic drug monitoring. Ther. Drug Monit 2008;30:709–716.Disclosure(s)Nothing to disclose

scholarly journals O11 Characterising the pharmacokinetics of phenobarbitone in neonates to facilitate future individualised dosing

2019 ◽  
Vol 104 (6) ◽  
pp. e5.1-e5 ◽  
Author(s):  
A Williams ◽  
T Donovan ◽  
B Charles ◽  
C Staatz
Keyword(s):  
Oral Bioavailability ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Volume Of Distribution ◽  
Absolute Bioavailability ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
List Type ◽  
Young Infants ◽  
Intravenous And Oral Administration

BackgroundPhenobarbitone is commonly used as a first-line drug in the treatment of neonatal seizures. Previous studies, with small subject numbers, have identified covariates that may influence the pharmacokinetics of phenobarbitone but results have been inconsistent. In particular, oral bioavailability is poorly described with doses reported as being identical for intravenous and oral administration, however, 2 recent studies have reported oral bioavailability of 49% and 59% respectively.1,2MethodsA population pharmacokinetic model was built based on routine therapeutic drug monitoring data from 112 infants at the Royal Brisbane and Women’s Hospital Neonatal Intensive Care Unit. Population modelling was performed using NONMEM 7.3 and PsN 4.7 with assistance from R studio and the packages Xpose and VPC. Body weight with allometric scaling on Clearance (CL) and Volume of Distribution (V) were included a priori in the structural model. Covariates tested included age (post-menstrual, gestational and post-natal), Apgar scores, concomitant phenytoin treatment, infection and method of nutrition.ResultsA one-compartment model provided an adequate fit to the data. Typical clearance increased with patient post-natal age (PNA) and was best modelled using the equation CL = 5.1 *WT0.75 * (PNA/6.25)0.43 (mL/h) were weight is in kg, PNA in days and 6.25 is the median post-natal age. Volume of distribution (V) was best modelled using the equation V = 799 * WT1.0 (mL). Oral bioavailability (F) was 85%. Between-subject variability was 25% and 30% respectively for CL and V.ConclusionThis study describes the largest population pharmacokinetic model of phenobarbitone developed to date with estimates of CL and V similar to previously published models. Estimated F is higher than previously reported but still lower than the implied F of 100% in most recommended dosing regimens. The model could be used to assist with future individualisation of dosing in this cohort.ReferencesMarsot A, et al. Pharmacokinetics and absolute bioavailability of phenobarbital in neonates and young infants, a population pharmacokinetic modelling approach. Fundam Clin Pharmacol 2014;28(4):465–71.Voller S, et al. Model-based clinical dose optimization for phenobarbital in neonates: An illustration of the importance of data sharing and external validation. Eur J Pharm Sci 2017;109s:S90–S97.Disclosure(s)Nothing to disclose

scholarly journals Early oxygen levels contribute to brain injury in extremely preterm infants

2021 ◽  
Author(s):  
Krista Rantakari ◽  
Olli-Pekka Rinta-Koski ◽  
Marjo Metsäranta ◽  
Jaakko Hollmén ◽  
Simo Särkkä ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Brain Structures ◽  
High Oxygen ◽  
List Type ◽  
Neurodevelopmental Outcomes ◽  
Oxygen Levels ◽  
Arterial Blood ◽  
Extremely Preterm ◽  
Extremely Preterm Infants

Abstract Background Extremely low gestational age newborns (ELGANs) are at risk of neurodevelopmental impairments that may originate in early NICU care. We hypothesized that early oxygen saturations (SpO2), arterial pO2 levels, and supplemental oxygen (FiO2) would associate with later neuroanatomic changes. Methods SpO2, arterial blood gases, and FiO2 from 73 ELGANs (GA 26.4 ± 1.2; BW 867 ± 179 g) during the first 3 postnatal days were correlated with later white matter injury (WM, MRI, n = 69), secondary cortical somatosensory processing in magnetoencephalography (MEG-SII, n = 39), Hempel neurological examination (n = 66), and developmental quotients of Griffiths Mental Developmental Scales (GMDS, n = 58). Results The ELGANs with later WM abnormalities exhibited lower SpO2 and pO2 levels, and higher FiO2 need during the first 3 days than those with normal WM. They also had higher pCO2 values. The infants with abnormal MEG-SII showed opposite findings, i.e., displayed higher SpO2 and pO2 levels and lower FiO2 need, than those with better outcomes. Severe WM changes and abnormal MEG-SII were correlated with adverse neurodevelopment. Conclusions Low oxygen levels and high FiO2 need during the NICU care associate with WM abnormalities, whereas higher oxygen levels correlate with abnormal MEG-SII. The results may indicate certain brain structures being more vulnerable to hypoxia and others to hyperoxia, thus emphasizing the role of strict saturation targets. Impact This study indicates that both abnormally low and high oxygen levels during early NICU care are harmful for later neurodevelopmental outcomes in preterm neonates. Specific brain structures seem to be vulnerable to low and others to high oxygen levels. The findings may have clinical implications as oxygen is one of the most common therapies given in NICUs. The results emphasize the role of strict saturation targets during the early postnatal period in preterm infants.

scholarly journals Carbon dioxide levels in neonates: what are safe parameters?

2021 ◽  
Author(s):  
Sie Kei Wong ◽  
M. Chim ◽  
J. Allen ◽  
A. Butler ◽  
J. Tyrrell ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Systematic Review ◽  
Side Effects ◽  
Preterm Infants ◽  
Periventricular Leukomalacia ◽  
List Type ◽  
Permissive Hypercapnia ◽  
Prisma Statement ◽  
Carbon Dioxide Levels ◽  
Online Software

Abstract There is no consensus on the optimal pCO2 levels in the newborn. We reviewed the effects of hypercapnia and hypocapnia and existing carbon dioxide thresholds in neonates. A systematic review was conducted in accordance with the PRISMA statement and MOOSE guidelines. Two hundred and ninety-nine studies were screened and 37 studies included. Covidence online software was employed to streamline relevant articles. Hypocapnia was associated with predominantly neurological side effects while hypercapnia was linked with neurological, respiratory and gastrointestinal outcomes and Retinpathy of prematurity (ROP). Permissive hypercapnia did not decrease periventricular leukomalacia (PVL), ROP, hydrocephalus or air leaks. As safe pCO2 ranges were not explicitly concluded in the studies chosen, it was indirectly extrapolated with reference to pCO2 levels that were found to increase the risk of neonatal disease. Although PaCO2 ranges were reported from 2.6 to 8.7 kPa (19.5–64.3 mmHg) in both term and preterm infants, there are little data on the safety of these ranges. For permissive hypercapnia, parameters described for bronchopulmonary dysplasia (BPD; PaCO2 6.0–7.3 kPa: 45.0–54.8 mmHg) and congenital diaphragmatic hernia (CDH; PaCO2 ≤ 8.7 kPa: ≤65.3 mmHg) were identified. Contradictory findings on the effectiveness of permissive hypercapnia highlight the need for further data on appropriate CO2 parameters and correlation with outcomes. Impact There is no consensus on the optimal pCO2 levels in the newborn. There is no consensus on the effectiveness of permissive hypercapnia in neonates. A safe range of pCO2 of 5–7 kPa was inferred following systematic review.

scholarly journals Early High-dose Caffeine Improves Respiratory Outcomes in Preterm Infants

Children ◽  
2021 ◽  
Vol 8 (6) ◽  
pp. 501
Author(s):  
Vineet Lamba ◽  
Oscar Winners ◽  
Prem Fort
Keyword(s):  
Mechanical Ventilation ◽  
Preterm Infants ◽  
Regression Models ◽  
High Dose ◽  
Long Term Outcomes ◽  
Logistic Regression Models ◽  
Caffeine Citrate ◽  
Timing Of Initiation ◽  
Respiratory Outcomes

The objective of the study is to determine if early high-dose caffeine (HD) therapy is associated with shorter duration of mechanical ventilation, bronchopulmonary dysplasia (BPD), or decreased need for mechanical ventilation. We conducted a single center, retrospective cohort study of 273 infants less than 32 weeks gestational age (GA). Infants receiving early HD (10 mg/kg/day maintenance) caffeine citrate started within 24 h of life were compared with those receiving LD (6 mg/kg/day) with variable timing of initiation using linear and logistic regression models. The infants in the early HD group had 91.4 (95% confidence interval (CI): −166.6, −16.1; p = 0.018) less hours of mechanical ventilation up to 36 weeks PMA or discharge as compared with the LD group. Moreover, infants in the HD group had 0.37 (95% CI: 0.14, 0.97; p = 0.042) times lower odds of developing moderate/severe BPD compared with the LD group. Infants receiving early HD caffeine had improved respiratory outcomes with no increase in measured comorbidities. Large prospective studies are needed to determine the long-term outcomes of using high-dose caffeine prophylaxis for preterm infants.

scholarly journals Unwanted Hormonal and Metabolic Effects of Postoperative Adjuvant Mitotane Treatment for Adrenocortical Cancer

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2615 ◽  
Author(s):  
Vittoria Basile ◽  
Soraya Puglisi ◽  
Anna Calabrese ◽  
Anna Pia ◽  
Paola Perotti ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Pharmacokinetic Interaction ◽  
Metabolic Effects ◽  
Therapeutic Drug ◽  
Male Hypogonadism ◽  
Adrenocortical Cancer ◽  
Biochemical Alterations ◽  
Biochemical Assessment ◽  
Higher Doses

Mitotane is widely used for the treatment of adrenocortical cancer (ACC), although the drug-related toxicity complicates its use. The aim of this study is to assess comprehensively the different endocrine and metabolic unwanted effects of the drug, and to provide data on the supportive therapies. We retrospectively analyzed 74 ACC patients adjuvantly treated with mitotane for ≥12 months. During the treatment period (40 months, 12–195), 32.4% of patients needed replacement therapy for mineralocorticoid deficit, 36.2% for hypothyroidism and 34.3% for male hypogonadism. In fertile women, hypogonadism was uncommon, while 65.4% of women developed ovarian cysts. Although no significant change in low-density lipoprotein (LDL) was observed, statins were started in 50% of patients for a significant increase in total cholesterol and triglycerides. Dyslipidemia occurred early, after a median time of 6 months from mitotane start. Conversely, testosterone replacement was usually started after >2 years. In many cases, ranging from 29.4% to 50% according to the side effect, toxicity occurred well before the achievement of the target mitotane concentrations. Supportive therapies were able to revert the biochemical alterations induced by mitotane, although higher doses were needed for a likely pharmacokinetic interaction of exogenous steroids and statins with mitotane. In conclusion, adjuvant mitotane therapy is associated with a spectrum of unwanted effects encompassing the function of different endocrine glands and requires a careful clinical and biochemical assessment associated with the therapeutic drug monitoring.

scholarly journals Thyroid dysfunction in preterm neonates exposed to iodine

2017 ◽  
Vol 45 (1) ◽  
Author(s):  
Fiona L.R. Williams ◽  
Jennifer Watson ◽  
Chris Day ◽  
Aung Soe ◽  
Sateesh K. Somisetty ◽  
...  
Keyword(s):  
Caesarean Section ◽  
Contrast Media ◽  
Preterm Infants ◽  
Breast Feeding ◽  
Thyroid Dysfunction ◽  
Exposed Group ◽  
Preterm Neonates ◽  
Iodinated Contrast Media ◽  
Iodinated Contrast ◽  
Blood Spot

AbstractBackground:Infants <32 weeks’ gestation should not be exposed to topical iodine and its avoidance is recommended during pregnancy and breast feeding. Exposure to contrast media and topical iodine is frequently used in many preterm neonates.Aim:To determine whether thyrotropin levels in preterm infants are affected by exposure to intrapartum/neonatal topical iodine and/or the use of iodinated contrast media.Design:Infants <32 weeks’ gestation were recruited. Maternal and neonatal exposures to iodinated contrast media and topical iodine were recorded; levels of thyrotropin and thyroxine were measured from blood-spot cards on postnatal days 7, 14, 28 and the equivalent of 36 weeks’ gestation.Results:One hundred and twenty-five infants were exposed to topical iodine/contrast media and 48 infants were unexposed. No infants were treated for hypothyroidism; three infants (exposed group) had transient hyperthyrotropinaemia. Mean thyrotropin levels were significantly higher on postnatal days 7, 14 and 28 in infants exposed to topical iodine prior to caesarean section compared to unexposed infants, a relationship which persisted after adjustment.Conclusions:In the context of this study, neonatal thyroid dysfunction was seen following exposure to iodine via caesarean section but not via exposure to contrast media.

scholarly journals IV Paracetamol for closure of patent ductus arteriosus in preterm neonates admitted to a tertiary care centre

2018 ◽  
Vol 5 (2) ◽  
pp. 294 ◽  
Author(s):  
Sunil B. ◽  
Shruthi Patel ◽  
Girish N.
Keyword(s):  
Side Effects ◽  
Preterm Infants ◽  
Ductus Arteriosus ◽  
Treatment Options ◽  
Tertiary Care ◽  
Current Treatment ◽  
Preterm Neonates ◽  
Tertiary Care Centre ◽  
Vascular Connection ◽  
Intravenous Paracetamol

Background: Ductus arteriosus is a vascular connection between the pulmonary artery and descending aorta. The incidence is inversely related to birth weight and gestational age (GA). In preterm infants it varies between 40% and 60% on the third day of life. At present, the choice of treatment of clinically significant PDA is with either ibuprofen or indomethacin, but they carry many contraindications and potential side effects. Hence it is important to consider that paracetamol may be used as an alternative to other non steroidal anti-inflammatory drugs and is effective in ductal closure with minimal side effects.Methods:Thirty six preterm infants with hemodynamically significant PDA(hs-PDA) were treated with intravenous paracetamol and subsequent closure was evaluated clinically and by follow-up 2D-Echo.Results: PDA closure following intravenous paracetamol was evident in 27 babies (75%). There were no significant side effects noted with paracetamol therapy.Conclusions: This study shows that paracetamol could offer favourable safety profile in comparison to current treatment options. Therefore, paracetamol may be accepted as a first-line drug treatment for PDA in preterm infants. 

scholarly journals The Usefulness of Saliva in Therapeutic Drug Monitoring of Caffeine in Preterm Infants.

2021 ◽  
Author(s):  
Ana García-Robles ◽  
Álvaro Solaz-García ◽  
Jorge Verdú-Andrés ◽  
José Luis Poveda-Andrés ◽  
Antonio José Cañada-Martínez ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Gestational Age ◽  
Solid Phase ◽  
Newborn Infants ◽  
Capillary Liquid Chromatography ◽  
Therapeutic Drug ◽  
Paired Samples ◽  
Postmenstrual Age ◽  
On Line ◽  
Array Detection

Abstract Aim To verify if the concentrations of caffeine in saliva are comparable to the serum concentrations in preterm infants treated with caffeine for apnoea of prematurity. Methods Prospective observational study. Eligible patients were newborn infants < 37 weeks of gestational age treated with oral or intravenous caffeine for apnoea of prematurity. Two paired samples of saliva-blood were collected per patient. Tube solid phase microextraction coupled on-line to capillary liquid chromatography with diode array detection were used for analysis. Results A total of 47 newborns with a median gestational age 28 [26–30] weeks and mean of 1.11 ± 0.4 kg of birth weight. Median postmenstrual age, when samples were collected, was 31 [29–33] weeks. Serum caffeine median levels of 19.30 µg/mL [1.9–53.90]and salivary caffeine median levels of 16.36 µg/mL [2.20–56.90] were obtained. There was a strong positive Pearson’s correlation between the two variables r = 0.83 (p < 0.001). Conclusion The measurement of caffeine salivary concentrations after intravenous or oral administration offers an alternative to serum caffeine monitoring in apnoea of prematurity.

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