Zusammenfassung.
Anatomisch-physiologische Veränderungen von Neugeborenen und Säuglingen können die
Pharmakokinetik anästhesierelevanter Medikamente deutlich beeinflussen. Zudem stellt
die Neugeborenenphase die Lebensphase mit den schnellsten und ausgeprägtesten Veränderungen
bezüglich wichtiger Organfunktionen dar. Änderungen der Körperzusammensetzung und
des Proteingehaltes beeinflussen das Verteilungsvolumen, die Distribution zwischen
den Kompartimenten und die freie Plasmafraktion einiger Pharmaka wie z. B. Relaxanzien
oder Lokalanästhetika. Durch die Unreife hepatischer mikrosomaler Enzymsysteme kommt
es zu einer verminderten Metabolisierung v. a. von Substanzen mit einer niedrigen
hepatisch-metabolischen Clearance wie beispielsweise Diazepam, Morphin oder einige
Lokalanästhetika. Die Entwicklung der Enzymsysteme im ersten Lebensjahr führt zu einer
Steigerung der Clearance, die z. T. über das Erwachsenenniveau hinaus geht. Zudem
treten Veränderungen der Pharmakodynamik bei diesen Kindern im Sinne einer veränderten
Sensibilität gegenüber Pharmaka auf. So nimmt die MAC volatiler Anästhetika mit zunehmendem
Alter ab. Da es sich in dieser Altersgruppe um ein sehr heterogenes Patientenklientel
mit großen interindividuellen Differenzen handelt, ist eine individuell angepaßte
Dosierung erforderlich, um einen optimalen pharmakodynamischen Effekt ohne toxische
Nebenwirkungen zu erzielen.
Physiologic changes influence the pharmacokinetics of drugs relevant to anesthesia
in neonates and infants. The neonatal phase is the phase of life with the most rapid
and dramatic changes of organ-functions responsible for pharmacokinetics of most anesthetics.
Changes in body composition and the content of plasma proteins influence volume of
distribution, the drug distribution to different compartments and the amount of free
fraction in plasma. Due to the immaturity of hepatic microsomal enzyme systems there
is a decreased metabolism particular of agents which undergo low hepatic extraction
like Diazepam, Morphine or some local anesthetics. In the first year of life capacity
of the enzymatic systems increases and also clearance increases. Until puberty the
clearance of some drugs is greater than the adult level. There are also pharmacodynamic
changes like modified sensitivity to some drugs like volatile anesthetics or neuromuscular
blocking agents. In summary neonates and infants are a highly heterogenous group with
large interindividual differences. Therefore the dosage of anesthetic agents must
be individualized to achieve optimal pharmacodynamic effects without toxicity in this
age group.
Schlüsselwörter:
Pharmakokinetik - Neugeborene & - Säuglinge - Pädiatrische Anästhesie - Pharmakodynamik
Key words:
Pharmacokinetics - Neonates - Infants - Pediatric anesthesia - Pharmacodynamics
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Dr. A. Röper
Klinik für Anästhesie und operative Intensivmedizin Städtische Kliniken Bielefeld
gem.GmbH
Teutoburger Straße 50
33604 Bielefeld
Email: roeper@sk-bielefeld.de
