Caffeine Therapy in Preterm Infants: The Dose (and Timing) Make the Medicine

2019 ◽  
Vol 38 (6) ◽  
pp. 365-374
Author(s):  
Sara E. Rostas ◽  
Christopher McPherson
Keyword(s):  
Preterm Infants ◽  
Current Evidence ◽  
High Dose ◽  
Dosing Regimens ◽  
Continued Use ◽  
Initiation Of Therapy ◽  
Timing Of Initiation ◽  
Apnea Of Prematurity ◽  
Robust Evidence

Caffeine is one of the most commonly utilized medications in the NICU. In preterm infants, short-term and long-term pulmonary and neurodevelopmental benefits of therapy are well documented in the literature. While robust evidence supports the use of standard doses of caffeine for apnea of prematurity or to facilitate successful extubation, much remains unknown regarding the boundaries of efficacy and safety for this common therapeutic agent. Escalating dosing regimens seem to provide additional benefit in select infants, but grave toxicity has also been documented with early utilization of high-dose caffeine. Conflicting data exist surrounding the ideal timing of initiation of therapy. Even the widely adhered to discontinuation point has been challenged by data supporting continued use. Until robust data definitively support change, practice should align with current evidence defining clear, safe, and efficacious dosing and timing of caffeine therapy.

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.

Caffeine dosing regimens in preterm infants with or at risk for apnea of prematurity

2021 ◽  
Author(s):  
Matteo Bruschettini ◽  
Petter Brattström ◽  
Chiara Russo ◽  
Wes Onland ◽  
Peter G Davis ◽  
...  
Keyword(s):  
At Risk ◽  
Preterm Infants ◽  
Dosing Regimens ◽  
Apnea Of Prematurity

scholarly journals Fifteen-minute consultation: Management of the infant born to a mother with toxoplasmosis in pregnancy

2020 ◽  
Vol 105 (5) ◽  
pp. 262-269 ◽  
Author(s):  
Anja Saso ◽  
Alasdair Bamford ◽  
Karen Grewal ◽  
Muna Noori ◽  
James Hatcher ◽  
...  
Keyword(s):  
Congenital Toxoplasmosis ◽  
Congenital Infection ◽  
Careful Consideration ◽  
Current Evidence ◽  
Clinical Consequences ◽  
Initiation Of Therapy ◽  
The Uk ◽  
Key Aspects

Congenital toxoplasmosis occurs following transplacental transfer of Toxoplasma gondii. Irrespective of symptom status at birth, infants with congenital infection may develop serious long-term sequelae, including learning disability, seizures, hydrocephalus, motor and hearing deficits, chorioretinitis and retinal scarring with impaired vision. Timely diagnosis facilitates early initiation of therapy, aimed at prevention or amelioration of adverse clinical consequences. Diagnosis can be difficult, however, since acutely infected mothers are often asymptomatic and laboratory testing can be complex. Moreover, any decision to start treatment in the newborn must include careful consideration of the benefits and risks. This paper outlines a structured approach for managing an infant born to a woman with possible or confirmed T. gondii infection during pregnancy, including key aspects of the antenatal history, interpretation and timing of investigations, treatment and appropriate follow-up. Our recommendations are based on current evidence in the literature, consensus from two UK paediatric infectious disease centres and the UK specialist Toxoplasma Reference Unit.

Effect of cumulative dexamethasone dose in preterm infants on neurodevelopmental and growth outcomes: a Western Australia experience

2020 ◽  
Vol 106 (1) ◽  
pp. 69-75
Author(s):  
Ashok Kumar Buchiboyina ◽  
Chi Seong Andrew Yip ◽  
Rolland Kohan ◽  
Elizabeth A Nathan ◽  
Damber Shrestha ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Western Australia ◽  
Cumulative Dose ◽  
System Level ◽  
High Dose ◽  
Z Score ◽  
Lower Growth ◽  
Growth Measurement ◽  
Growth Outcomes

ObjectiveComparing the long-term neurodevelopmental and growth outcomes of lower and higher cumulative dexamethasone exposure in preterm infants ventilated for a minimum cumulative duration of 7 days.DesignA retrospective cohort medical chart review of infants born in Western Australia <29 weeks’ gestation between January 2007 and May 2016 who were mechanically ventilated >7 days.InterventionNo dexamethasone (controls) or a total cumulative dexamethasone dose of <2 mg/kg (lower) and ≥2 mg/kg (higher).Main outcome measuresLong-term disability at 2 and 5 years and growth measurement outcomes at 2 years of age.ResultsDexamethasone was given to 104 infants (66 with cumulative dose <2 mg/kg; 38 with cumulative dose ≥2 mg/kg), and 324 infants were controls. There was no difference in odds of long-term disability in infants with any dexamethasone exposure compared with controls (aOR: 0.90, 95% CI 0.34 to 2.02, p=0.784). No difference in long-term disability was found between the lower and higher groups (p=0.494). The prevalence of cerebral palsy (Gross Motor Functional Classification System level ≥2) between the control, lower and high-dose groups did not differ significantly (5.8% vs 4.0% vs 0%). The higher dose group had lower mean weight z-score (mean effect: −0.83, 95% CI: −1.54 to −0.01, p=0.023), height z-score (mean effect: −0.63, 95% CI: −12.5 to −0.01, p=0.048) and head circumference z-score (mean effect: −0.65, 95% CI: −1.25 to −0.05, p=0.035) compared with controls.ConclusionsIn our cohort, dexamethasone use was not associated with increased odds of long-term disability. Dexamethasone use was associated with lower growth measurements compared with controls.

Pharmacological Neuroprotection of the Preterm Brain: Current Evidence and Perspectives

2020 ◽  
Author(s):  
Tania Siahanidou ◽  
Christina Spiliopoulou
Keyword(s):  
Preterm Infants ◽  
Adverse Outcomes ◽  
Current Evidence ◽  
Omega 3 ◽  
Neurodevelopmental Outcomes ◽  
Neuroprotective Effects ◽  
Pharmacological Agents ◽  
Increased Risk ◽  
Long Term Follow Up

Despite improvements in viability, the long-term neurodevelopmental outcomes of preterm babies remain serious concern as a significant percentage of these infants develop neurological and/or intellectual impairment, and they are also at increased risk of psychiatric illnesses later in life. The current challenge is to develop neuroprotective approaches to improve adverse outcomes in preterm survivors. The purpose of this review was to provide an overview of the current evidence on pharmacological agents targeting the neuroprotection of the preterm brain. Among them, magnesium sulfate, given antenatally to pregnant women with imminent preterm birth before 30 to 34 weeks of gestation, as well as caffeine administered to preterm infants after birth, exhibited neuroprotective effects for human preterm brain. Erythropoietin treatment of preterm infants did not result in neuroprotection at 2 years of age in two out of three published large randomized controlled trials; however, long-term follow-up of these infants is needed to come to definite conclusions. Further studies are also required to assess whether melatonin, neurosteroids, inhaled nitric oxide, allopurinol, or dietary supplements (omega-3 fatty acids, choline, curcumin, etc.) could be implemented as neuroprotectants in clinical practice. Furthermore, other pharmacological agents showing promising signs of neuroprotective efficacy in preclinical studies (growth factors, hyaluronidase inhibitors or treatment, antidiabetic drugs, cannabidiol, histamine-H3 receptor antagonists, etc.), as well as stem cell- or exosomal-based therapies and nanomedicine, may prove useful in the future as potential neuroprotective approaches for human preterm brain. Key Points

scholarly journals A review on thimerosal: an irreplaceable element of long-term immunisation strategy in low income countries

2017 ◽  
Vol 6 (8) ◽  
pp. 1846
Author(s):  
Ritika Singla ◽  
Anita K. Gupta ◽  
Anjleen Kaur
Keyword(s):  
Low Income ◽  
Causal Relation ◽  
Low Cost ◽  
Positive Association ◽  
Low Income Countries ◽  
Current Evidence ◽  
Minamata Convention On Mercury ◽  
Continued Use ◽  
Dose Vaccine

Thimerosal, an organic-mercury (Hg) compound containing 49.55% Hg by weight, is added to vaccines as a preservative permitting formulation of multi-dose vaccine vials. Being a derivative of ethylmercury, it has been linked with autism as a possible risk factor based on the assumption that exposure to ethylmercury would have similar neurotoxic effects as another mercurial compound, methylmercury. In 1999, AAP issued a joint statement emphasising the removal of thimerosal from vaccines. Subsequently, several studies have been conducted; those showing positive association between thimerosal exposure and autism have been recognised to be fraught with methodological flaws. On the other hand, many well controlled studies have failed to find any such causal relation and there are others that have clearly demonstrated a much favourable kinetic profile of ethylmercury as compared to methylmercury. Owing to the lack of data, AAP retired its original statement in 2002. Recently, thimerosal has been exempted from regulation by Minamata Convention on Mercury resulting in the continued use of low cost thimerosal containing vaccines in low income countries which cannot afford to run their immunisation program using single dose thimerosal free vaccines, that comparatively cost much higher, as is the case in high income countries. Some bodies view this as a discrimination on the basis of wealth of a nation and have opposed this decision. This review presents various studies regarding the causal association between thimerosal containing vaccines and autism. The current evidence fails to support any such association. Hence this review supports the exemption of thimerosal from regulation and also justifies its use in LICs for uninterrupted vaccination of the most vulnerable population.

scholarly journals Role of neuraxial drug delivery in cancer pain therapy

2020 ◽  
Vol 2 (4) ◽  
pp. FDD49
Author(s):  
Edgar Ross ◽  
Roshni Ramachandran ◽  
Jason D Ross ◽  
Ashish Bhandari ◽  
Patrick W Mantyh ◽  
...  
Keyword(s):  
Cancer Pain ◽  
Pain Treatment ◽  
Current Evidence ◽  
Oncologic Surgery ◽  
Cancer Pain Therapy ◽  
Continued Use ◽  
Long Term Prognosis ◽  
New Treatment

Opioids have long been the mainstay of cancer pain treatment and have been used without any consideration for their effect on cancer growth and long-term prognosis. There is now growing evidence that the continued use of opioids for this indication should be reviewed and even reconsidered. Although current evidence and literature covering this subject is mixed and does not yet allow for a clear determination to be made about safety, there is enough data to support the search for new treatment paradigms, beginning with anesthesia for oncologic surgery and management of cancer pain over the disease course.

scholarly journals Midazolam in Subarachnoid Block: Current Evidence

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Anirban Chattopadhyay ◽  
Souvik Maitra ◽  
Suvadeep Sen
Keyword(s):  
Clinical Studies ◽  
Animal Studies ◽  
Current Evidence ◽  
High Dose ◽  
Subarachnoid Block ◽  
Perioperative Analgesia ◽  
Clinically Significant ◽  
Gaba Receptor Complex

Midazolam, despite of being the commonest benzodiazepine used in anaesthesia and perioperative care, is a relatively newer addition to the list of adjuvant used in subarachnoid block. Midazolam causes spinally mediated analgesia and the segmental analgesia produced by intrathecal midazolam is mediated by the benzodiazepine-GABA receptor complex. Initial animal studies questioned the safety of intrathecal midazolam in terms of possible neurotoxicity. However subsequent clinical studies also failed to show any neurotoxicity of high dose midazolam even on long-term use. Addition of intrathecal midazolam to bupivacaine significantly improves the duration and quality of spinal anaesthesia and provides prolonged perioperative analgesia without any significant side effects. Clinical studies also reported its safety and efficacy in pregnant women, but some studies also reported mild sedation with intrathecal midazolam. It is also reported to decrease the incidence of PONV. Intrathecal midazolam does not have any clinically significant effect on perioperative hemodynamics.

scholarly journals Corticosteroids for the prevention of bronchopulmonary dysplasia in preterm infants: a network meta-analysis

2018 ◽  
Vol 103 (6) ◽  
pp. F506-F511 ◽  
Author(s):  
Linan Zeng ◽  
Jinhui Tian ◽  
Fujian Song ◽  
Wenrui Li ◽  
Lucan Jiang ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Bronchopulmonary Dysplasia ◽  
Low Birthweight ◽  
Low Dose ◽  
Meta Analysis ◽  
Cochrane Library ◽  
High Dose ◽  
Extremely Preterm ◽  
Subgroup Analyses

ObjectiveTo determine the comparative efficacy and safety of corticosteroids in the prevention of bronchopulmonary dysplasia (BPD) in preterm infants.Study designWe systematically searched PubMed, EMBASE and the Cochrane Library. Two reviewers independently selected randomised controlled trials (RCTs) of postnatal corticosteroids in preterm infants. A Bayesian network meta-analysis and subgroup analyses were performed.ResultsWe included 47 RCTs with 6747 participants. The use of dexamethasone at either high dose or low dose decreased the risk of BPD (OR 0.29, 95% credible interval (CrI) 0.14 to 0.52; OR 0.58, 95% CrI 0.39 to 0.76, respectively). High-dose dexamethasone was more effective than hydrocortisone, beclomethasone and low-dose dexamethasone. Early and long-term dexamethasone at either high dose or low dose decreased the risk of BPD (OR 0.11, 95% CrI 0.02 to 0.4; OR 0.37, 95% CrI 0.16 to 0.67, respectively). There were no statistically significant differences in the risk of cerebral palsy (CP) between different corticosteroids. However, high-dose and long-term dexamethasone ranked lower than placebo and other regimens in terms of CP. Subgroup analyses indicated budesonide was associated with a decreased risk of BPD in extremely preterm and extremely low birthweight infants (OR 0.60, 95% CrI 0.36 to 0.93).ConclusionsDexamethasone can reduce the risk of BPD in preterm infants. Of the different dexamethasone regimens, aggressive initiation seems beneficial, while a combination of high-dose and long-term use should be avoided because of the possible adverse neurodevelopmental outcome. Dexamethasone and inhaled corticosteroids need to be further evaluated in large-scale RCTs with long-term follow-ups.

Patent Ductus Arteriosus in Preterm Infants, Part 1: Understanding the Pathophysiologic Link Between the Patent Ductus Arteriosus and Clinical Complications

2017 ◽  
Vol 36 (5) ◽  
pp. 265-272 ◽  
Author(s):  
Yasser N. Elsayed ◽  
Debbie Fraser
Keyword(s):  
Patent Ductus Arteriosus ◽  
Preterm Infants ◽  
Ductus Arteriosus ◽  
Neurodevelopmental Outcome ◽  
Neonatal Outcomes ◽  
Current Evidence ◽  
Clear Understanding ◽  
Compensatory Mechanisms ◽  
Patent Ductus

AbstractThe clinical guidelines for treating patent ductus arteriosus (PDA) have significantly evolved over the last decades from treating any ductal shunt to more conservative management where only the hemodynamically significant patent ductus arteriosus (HSPDA) is treated. This shift has resulted largely from a lack of evidence from randomized controlled trials supporting a relationship between treating a PDA and improving long-term neonatal outcomes. However, there are many unresolved issues. There is no consensus on the precise definition of HSPDA requiring treatment or a clear understanding of when to treat HSPDA. Moreover, the current evidence shows worsening of the long-term neurodevelopmental outcome for infants undergoing surgical PDA ligation.The presence of physiologic variability among preterm infants, and the presence of different compensatory mechanisms may make it difficult to establish a link between pathophysiology and long-term outcomes. That is, the physiologic variability cannot be simply assessed by randomly assigning infants into two arms of a study. Relying on research from animal and human studies, this article explains the link between the pathophysiology of a PDA and neonatal outcomes.

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