neonatal apnea Flashcards
what is a methylxanthine?
a purine base found in most human body tissues and fluids
what is the function of a methylxanthine?
respiratory center stimulant
what are the effects of caffeine and theophylline on the respiratory system?
increases TV, subsequent increase in MVe, decreases partial pressure of CO2 (by increasing CO2 sensitivity), increase in respiratory muscle contraction, inc O2 consumption, dec airway resistance (bronchodilation); net: increases most indices of neural respiratory drive (better lung fx, higher compliance, significantly decreases need for vent support)
what effects do methylxanthine have on respiratory muscles and systemic musculature?
improvement in diaphragmatic efficiency and increase in force production with electrical stimulation and decrease recovery time required of fatigued muscles; causes systemic smooth muscles to relax
what effects do methylxanthine on neurological system, specifically neuromuscular transport?
potentiates catecholamine effects, stimulates the CNS, alters sleep states and increases transport resulting in improved muscle tone and subsequent increase in functional residual capacity and better oxygenation
What are the effects of methylxanthines on the metabolism?
increases metabolic rate, facilitates metabolic homeostasis, inc insulin release, inc glucagon release (inc serum glu), inc cortisol secretion, inc free fatty acid levels, inc weight gain and decrease risk of NEC
Methylxanthines are the antagonist of what?
the depressive effects of codeine, morphine and meperedine (demerol)
at what doseage are optimal effects observed?
10 mg/kg
what is the plasma half life of caffeine?
100 hours
what is the plasma half life of theophylline?
30 hours
What is the desired plasma level of caffeine?
5-20 mg/L
what is the desired plasma level of theophylline?
5-15 mg/L
what percentage of theophylline is methalated to caffeine?
25%
what is the ratio of theophylline to caffeine in the blood plasma at steady state?
0.3-0.4
why is caffeine preferable to theophylline as a first line respiratory stimulant agent?
Caffeine can be given more sparingly (b/c of long half life Qd dosing) and therapeutic drug monitoring is not as critical, wider therapeutic range, decreased risk of toxicity (>50mg/kg), low rate of adverse side effects, easy transition to PO dose as with theophylline
what is a loading dose of theophylline?
5-6 mg/kg
what is the maintenance dose of theophylline?
2-4 mg/kg
theophylline toxicity is suspected when serum levels are found to be… what?
> 15mg/L
What is the drug clearance of caffeine v. theophylline?
caffeine is very slow (longer half life) and theophylline is slow
What are the plasma levels at a steady state of caffeine v theopylline?
caffeine levels are stable at a steady state; theopylline is fluctating
What is the dosing interval for caffeine v theophylline?
caffeine is Qd; theophylline is 1-3 times/d
What are signs and symptoms of theophylline toxicity?
tachycardia (sustained >180 bpm),diaphoresis, diarrhea, GERD, failure to gain weight, jittery, vomiting, seizures and hyperreflexia
Both methylxanthines can lead to increased excretion of which electrolyte?
calcium
How has the efficacy of methylxanthines been demonstrated?
decreased: # of apnea events, # of brady events, cyanotic spells, imporvement in the coordination between upper airway and respiratory muscles, less use of mech vent, improved weaning from vent
In clinical practice, methylxanthines are commonly used as adjunt therapies for what goal?
successful extubation and transition to less invasive means of respiratory support
Apnea with concurrent hypoxemia events can increase a patient’s risk for… what?
NEC
What are the effects of methylxanthines on the GU system?
diuresis
What is the effect of methylxanthines on the cardiac fx?
inc CO, inc SV, inc HR, inc BP, systemic vascular dilation, cerebrovascular constriction, shortens blood coagulation time; may decrease incidence of PDA and need for surgical closure
what is the effect of methylxanthines on the immune system?
may have an anti inflammatory effect on the immature lung
Pts with BPD demonstrate what effects how long after administration?
dec in airway resistance and improved lung mechanics within 1 hour after administration
In the CAP Trial what were the rates of BPD and O2 requirements in patients >36 weeks corrected GA?
36.3% compared to 49% in non tx peer group
Are the long term effects of methylxanthines in animal models?
research supports some long term effects
In human patients, are there long term effects of methylxanthine administration?
no independent adverse effects of caffeine on long term outcome; severl studies showed no long-term effects
What causes apnea in the newborn?
altered metabolism, infection, neurologic, etc…
What is doxapram?
dopram; respiratory stimulant
When would doxapram be considered as an intervention?
when a pt has had no demonstrated lung improvement and only before considering escalation in care/ more invasive interventions (ie intubation)
why is doxapram not considered a first line intervention?
lack of long term outcome studies in relation to the known efficacy and safety of methylxanthines
What system does theophylline affect the most?
CV first, then CNS- that is why toxicity symptoms first appear in the CV system
What system does caffeine affect the most?
CNS first, then CV
Which methylxanthine is most therapeutic in treating apenic spells in the first 1-3 days of administration?
theophylline; advantage disappears later
