Apnea Flashcards
Methylxanthines were first reported as effective in what decade?
1970’s
What 2 Methylxanthines are 1st line treatment for Neonatal Apnea?
Caffeine
Theophylline
What are the MOA’s of Methylxanthines?
- Respiratory Center Stimulation
- Improvement in Respiratory Muscle Contraction –the above 2 are the biggest-
- Altered Sleep States
- Metabolic Rate
- Cardiac Output
- Metabolic Homeostasis (increased oxygenation and glucose–>decreased Apnea)
- Potentiation of Catecholamine effect (increased oxygenation)
- May provide an anti-inflammatory action in the immature lung
How does Improvement respiratory muscle contraction work to decrease Apnea?
- Increased Respiratory Muscle Fxn
- Improved Diaphragmatic Efficiency
- Increased Force Production w/electrical stimulation
- Decreased recovery time of fatigued muscles (fatigue a/w Apnea)
- Increase in Neuromuscular transmission–>Increased muscle tone–>r/t increased FRC & better oxygenation
How does Respiratory center stimulation work to decrease Apnea?
- Increased minute ventilation
- Decreased PaCO2 by increasing CO2 sensitivity
- Increasing in most indices of neurorespiratory drive (Vt)
- Optimal ventilatory responses (doses 10 mg/kg)
- Antagonize depressive effects of Narcotics (Codeine, MsO4, Niperidine)
Even in Methylxanthine doses as low as 2.5 mg/kg, what will be noted in the NB?
Increased Vt
Pharmacokinetics =
The study of the action of drugs within the body.
what the body does with the drug
What does Pharmacokinetics include?
Absorption Distribution Metabolism Excretion Onset of Action Duration of Effect Biotransformation Effects of routes of excretion of drug metabolites
Plasma clearance and elimination are ________ in newborns
Prolonged
Why can Caffeine be given more sparingly?
Why is drug monitoring not so critical w/Caffeine vs. Theophylline?
Because Caffeine’s T2 is 100 hrs (vs. 30 hrs in Theophylline
~25% of Theophylline is methylated to Caffeine. The plasma level at steady state fluctuates.
What is the desired plasma level of Caffeine?
Theophylline?
5-20 mg/L
5-15 mg/L
What is the dosing interval for Theophylline?
1-3 times/day
What is the dosing interval for Caffeine?
1 time/day
What is the preferred alternative in infants with Apnea of prematurity?
Why?
Caffeine
- Longer T2
- Wider therapeutic range (w/lower toxicity risk)
- Decreased rate adverse effects
- Ease of change from IV to PO (equivalent bioavailability
Both Caffeine and Theophylline can lead to what side effect?
Increased urinary excretion of Ca++
Theophylline concentrations > 15mg/L may be a/w?
So, what should you do?
Tachycardia
Consider holding the med w/HR >180 bp
What are the signs of Toxicity in Aminophylline/Theophylline?
Sinus tachycardia Failure to gain wt Vomiting Jittery Hyperreflexia Seizures
Numerous studies and clinical trials have documented what benefits of Methylxanthines?
- Decreasing # A’s & B’s
- Decreasing Cyanotic spells
- Possible improvement in the coordination between upper airway and respiratory muscles
- Less use of Mechanical ventilation
- Improved weaning from mechanical vent
Many practices will use Caffeine or Theophylline as ________ prior to extubation
Adjunct
What are the effects of methylxanthine use?
Improved: Lung function -animal studies: better fxn, higher compliance, decrease in vent support PDA Cardiac Fxn (inc. SV, HR, B/P) Other
What are the other effects a/w methylxanthine use?
CNS stim, smooth muscle relax, systemic blood vessel dilation, cerebral blood vasoconstriction, diuresis, augmentation of metabolic rate, bronchodilation, shortened blood coag time, stim. of insulin release, stim of glucagon release, inc. catecholamine release, inc. BS, inc. cortisol secretion, inc. plasma free-fatty acids, inc O2 consumption, dec. wt gain, a/w NEC (although not in CAP study)
Are Apnea w/hypoxemic episodes a/w NEC?
Yes
Small studies in infants w/BPD showed what within 1 hr of Caffeine Tx?
Decreased Airway resistance
Improved Lung mechanics
Did the CAP trial (caffeine for Apnea) show a statistically significant difference in the rate of BPD?
Did it show statistically significant decrease in PDA incidence in <1250 gms and surgical ligation?
Yes
Yes
Are there any long-term effects w/Methylxanthine use?
- Animal studies–yes
- Human infants–no independent adverse effect on long-term outcome.
- Several studies demonstrated no long-term effects
What is Doxapram?
CNS stimulant (not Methylxanthine)
Have long-term outcomes been measured in Doxapram use?
When is Doxapram used?
No.
It’s reserved for cases where Methylxanthines are not effective and only before considering more aggressive tx (i.e. mechanical ventilation)
Why isn’t Doxapram used more consistenly?
Because of proven safety & efficacy of methylxanthines & uncertainty of s/e’s of Doxapram
Apnea r/t premature is a Dx of ________?
Exclusion
Apnea can be ___________ from:
Multicausal: Metabolic Infectious Neurologic Other (risk factors)
