α2-Agonisten spielen heute eine wichtige Rolle in
der Anästhesie und Intensivmedizin. Bei sachgemäßem Einsatz
sind die Nebenwirkungen substanzspezifisch und vorhersehbar. Die Kombination
aus sedierenden und analgetischen Eigenschaften bei gleichzeitig fehlender
Atemdepression und einer Glättung der hämodynamischen Schwankungen
durch sympatholytische Eigenschaften weisen auf die günstigen Wirkungen
dieser Substanzklasse hin. Überdies induziert Dexmedetomidin eine
einzigartige, dem natürlichen Schlaf ähnliche Sedierung und kann die
Delir-Prävalenz beatmeter Patienten reduzieren.
Dexmedetomidin ist zugelassen zur Sedierung erwachsener
Intensivpatienten, die eine Sedierungstiefe benötigen, welche ein Erwecken
durch verbale Stimulation noch erlaubt (RASS 0 bis –3). Anders als
Clonidin, das bisher meist primär als Adjuvans eingesetzt wird und keine
Zulassung als Monosedativum hat, kann man Dexmedetomidin in solchen Situationen
daher als primäres Sedativum verwenden – ergänzt durch
Analgetika und ggf. zusätzliche Sedativa.
Die spezifischen Anwendungsgebiete bei kritisch kranken
Intensivpatienten unter Berücksichtigung der Grunderkrankung müssen
sicher noch durch weitere Untersuchungen und Erfahrungen in der klinischen
Praxis genauer definiert werden. Ebenso muss sich zeigen, ob die bisher in
Studien gefundenen günstigen Effekte bezüglich der
Delirhäufigkeit und der Reduktion der Beatmungsdauer bestätigt werden
können [10]
[39]
[40]. Nach bisherigen Daten kann Dexmedetomidin potenziell
eine wichtige Bereicherung des pharmakologischen Armamentariums in der
Anästhesie und Intensivmedizin sein. Weitere Untersuchungen sind aber
notwendig, um abschließend eine Nutzen-Risiko-Analyse vornehmen zu
können.
Literatur
1 Stähle H. A historical perspective: development of clonidine.. In: Scholz J, Tonner P H, Hrsg α2-adrenoceptor agonists in anaesthesia
and intensive care.. London: Balliere Tindall; 2000: 237-246
5
Martin J, Franck M, Sigel S et al.
Changes in sedation management in German intensive care units
between 2002 and 2006: a national follow-up survey.
Crit Care.
2007;
11
R124
6 Karol M, Maze M. Pharmacokinetics and interaction pharmacodynamics of
dexmedetomidine in humans.. In: Scholz J, Tonner P H, Hrsg α2-adrenoceptor agonists in anaesthesia
and intensive care.. London: Balliere Tindall; 2000: 261-269
9
Paris A, Mantz J, Tonner P H et al.
The effects of dexmedetomidine on perinatal excitotoxic brain
injury are mediated by the α2A-adrenoceptor subtype.
Anesth Analg.
2006;
102
456-461
10
Pandharipande P P, Pun B T, Herr D L et al.
Effect of sedation with dexmedetomidine vs lorazepam on acute
brain dysfunction in mechanically ventilated patients: the MENDS randomized
controlled trial.
Jama.
2007;
298
2644-2653
12
Nelson L E, Lu J, Guo T et al.
The α2-adrenoceptor agonist dexmedetomidine
converges on an endogenous sleep-promoting pathway to exert its sedative
effects.
Anesthesiology.
2003;
98
428-436
13
Huupponen E, Maksimow A, Lapinlampi P et al.
Electroencephalogram spindle activity during dexmedetomidine
sedation and physiological sleep.
Acta Anaesthesiol Scand.
2008;
52
289-294
17
Paris A, Hein L, Brede M et al.
The anesthetic effects of etomidate: species-specific
interaction with α2-adrenoceptors.
Anesth Analg.
2007;
105
1644-1649
18
Paris A, Ohlendorf C, Marquardt M et al.
The effect of meperidine on thermoregulation in mice:
involvement of α2-adrenoceptors.
Anesth Analg.
2005;
100
102-106
20
Brede M, Philipp M, Knaus A et al.
α2-adrenergic receptor subtypes –
novel functions uncovered in gene-targeted mouse models.
Biol Cell.
2004;
96
343-348
21
Gilsbach R, Hein L.
Are the pharmacology and physiology of
α2-adrenoceptors determined by
α2-heteroreceptors and autoreceptors, respectively?.
Br J Pharmacol.
2012;
165
90-102
22 Gilsbach R, Albarrán-Juárez J, Hein L. Pre-versus postsynaptic signaling by
α2-adrenoceptors.. In: Qin Wang, Hrsg Current topics in membranes.. Salt Lake City (UT): Academic Press; 2011. 67: 139-160
24
Sawamura S, Kingery W S, Davies M F et al.
Antinociceptive action of nitrous oxide is mediated by
stimulation of noradrenergic neurons in the brainstem and activation of
α2B-adrenoceptors.
J Neurosci.
2000;
20
9242-9251
25
Dahmani S, Paris A, Jannier V et al.
Dexmedetomidine increases hippocampal phosphorylated
extracellular signal-regulated protein kinase 1 and 2 content by an
α2-adrenoceptor-independent mechanism: evidence for the
involvement of imidazoline I1 receptors.
Anesthesiology.
2008;
108
457-466
26 Dexdor 100 Mikrogramm/ml Konzentrat zur Herstellung einer
Infusionslösung,. Fachinformation Orion Pharma GmbH. Hamburg;
27
Iirola T, Aantaa R, Laitio R et al.
Pharmacokinetics of prolonged infusion of high-dose
dexmedetomidine in critically ill patients.
Crit Care.
2011;
15
R257
28
Tan J A, Ho K M.
Use of dexmedetomidine as a sedative and analgesic agent in
critically ill adult patients: a meta-analysis.
Intensive Care Med.
2010;
36
926-939
29
Pichot C, Ghignone M, Quintin L.
Dexmedetomidine and Clonidine: From Second-to-First-Line
Sedative Agents in the Critical Care Setting?.
J Intensive Care Med.
2011;
[Epub ahead of print]
30
Chrysostomou C, Sanchez De Toledo J, Avolio T et al.
Dexmedetomidine use in a pediatric cardiac intensive care
unit: can we use it in infants after cardiac surgery?.
Pediatr Crit Care Med.
2009;
10
654-660
35
Karhuvaara S, Kallio A, Salonen M et al.
Rapid reversal of α2-adrenoceptor agonist
effects by atipamezole in human volunteers.
Br J Clin Pharmacol.
1991;
31
160-165
36
Philbin K E, Bateman R J, Mendelowitz D.
Clonidine, anα2-receptor agonist, diminishes
GABAergic neurotransmission to cardiac vagal neurons in the nucleus
ambiguus.
Brain Res.
2010;
1347
65-70
37
Hogue Jr. C W, Talke P, Stein P K et al.
Autonomic nervous system responses during sedative infusions
of dexmedetomidine.
Anesthesiology.
2002;
97
592-598
38
Ebert T J, Hall J E, Barney J A et al.
The effects of increasing plasma concentrations of
dexmedetomidine in humans.
Anesthesiology.
2000;
93
382-394
39
Riker R R, Shehabi Y, Bokesch P M et al.
Dexmedetomidine vs midazolam for sedation of critically ill
patients: a randomized trial.
JAMA.
2009;
301
489-499
40
Shehabi Y, Grant P, Wolfenden H et al.
Prevalence of delirium with dexmedetomidine compared with
morphine based therapy after cardiac surgery: a randomized controlled trial
(DEXmedetomidine COmpared to Morphine-DEXCOM Study).
Anesthesiology.
2009;
111
1075-1084
41 Jaakola M. Intra-operative use of α2-adrenoceptor
agonists.. In: Scholz J, Tonner P H, Hrsg α2-adrenoceptor agonists in anaesthesia
and intensive care.. London: Balliere Tindall; 2000: 335-345
44
Gerlach A T, Murphy C V.
Dexmedetomidine-associated bradycardia progressing to
pulseless electrical activity: case report and review of the literature.
Pharmacotherapy.
2009;
29
1492
48
Pandharipande P, Sanders R, Girard T et al.
Effect of dexmedetomidine versus lorazepam on outcome in
patients with sepsis: an a priori-designed analysis of the MENDS randomized
controlled trial.
Crit Care.
2010;
14
R38
50
Infarct S urvival.
Randomised trial of intravenous atenolol among 16 027 cases
of suspected acute myocardial infarction: ISIS-1. First International Study of
Infarct Survival Collaborative Group.
Lancet.
1986;
2
57-66
51
Devereaux P J, Yang H, Yusuf S et al.
Effects of extended-release metoprolol succinate in patients
undergoing non-cardiac surgery (POISE trial): a randomised controlled trial.
POISE Study Group.
Lancet.
2008;
371
1839-1847
52
Wallace A W, Galindez D, Salahieh A et al.
Effect of clonidine on cardiovascular morbidity and mortality
after noncardiac surgery.
Anesthesiology.
2004;
101
284-293
53
Wijeysundera D N, Bender J S, Beattie W S.
α2 adrenergic agonists for the prevention of
cardiac complications among patients undergoing surgery.
Cochrane Database Syst Rev.
2009;
Oct 7 (4)
CD004126
54
Nishina K, Mikawa K, Uesugi T et al.
Efficacy of clonidine for prevention of perioperative
myocardial ischemia: a critical appraisal and meta-analysis of the
literature.
Anesthesiology.
2002;
96
323-329
55
Kress J P, Pohlman A S, O’Connor M F, Hall J B.
Daily interruption of sedative infusions in critically ill
patients undergoing mechanical ventilation.
N Engl J Med.
2000;
342
1471-1477
57
Girard T, Kress J, Fuchs B et al.
Efficacy and safety of a paired sedation and ventilator
weaning protocol for mechanically ventilated patients in intensive care
(Awakening and Breathing Controlled trial): a randomised controlled trial.
Lancet.
2008;
371
126-134
58
Schweickert W, Pohlman M, Pohlman A et al.
Early physical and occupational therapy in mechanically
ventilated, critically ill patients: a randomised controlled trial.
Lancet.
2009;
373
1874-1882
59
Venn R M, Grounds R M.
Comparison between dexmedetomidine and propofol for sedation
in the intensive care unit: patient and clinician perceptions.
Br J Anaesth.
2001;
87
684-690
60
Venn R M, Bradshaw C J, Spencer R et al.
Preliminary UK experience of dexmedetomidine, a novel agent
for postoperative sedation in the intensive care unit.
Anaesthesia.
1999;
54
1136-1142
61
Ruokonen E, Parviainen I, Jakob S M et al.
Dexmedetomidine versus propofol/midazolam for long-term
sedation during mechanical ventilation.
Intensive Care Med.
2009;
35
282-290
62
Pandharipande P, Shintani A, Peterson J et al.
Lorazepam is an independent risk factor for transitioning to
delirium in intensive care unit patients.
Anesthesiology.
2006;
104
21-26
63
Hughes C, Pandharipande P.
Review articles: the effects of perioperative and intensive
care unit sedation on brain organ dysfunction.
Anesth Analg.
2011;
112
64
Roche C ampo, Drouot X, Thille A et al.
Poor sleep quality is associated with late noninvasive
ventilation failure in patients with acute hypercapnic respiratory
failure.
Crit Care Med.
2010;
38
477-485
65
Figueroa-Ramos M, Arroyo-Novoa C, Lee K et al.
Sleep and delirium in ICU patients: a review of mechanisms
and manifestations.
Intensive Care Med.
2009;
53
781-795
67
Dahmani S, Rouelle D, Gressens P, Mantz J.
Characterization of the postconditioning effect of
dexmedetomidine in mouse organotypic hippocampal slice cultures exposed to
oxygen and glucose deprivation.
Anesthesiology.
2010;
112
373-383
69
Angst M S, Ramaswamy B, Davies M F, Maze M.
Comparative analgesic and mental effects of increasing plasma
concentrations of dexmedetomidine and alfentanil in humans.
Anesthesiology.
2004;
101
744-752
71
Dasta J F, Kane-Gill S L, Pencina M et al.
A cost-minimization analysis of dexmedetomidine compared with
midazolam for long-term sedation in the intensive care unit.
Crit Care Med.
2010;
38
497-503
72
Honey B L, Benefield R J, Miller J L, Johnson P N.
α2-receptor agonists for treatment and
prevention of iatrogenic opioid abstinence syndrome in critically ill
patients.
Ann Pharmacother.
2009;
43
1506-1511
73
Baddigam K, Russo P, Russo J, Tobias J D.
Dexmedetomidine in the treatment of withdrawal syndromes in
cardiothoracic surgery patients.
J Intensive Care Med.
2005;
20
118-123
76
Darnell C, Steiner J, Szmuk P, Sheeran P.
Withdrawal from multiple sedative agent therapy in an infant:
is dexmedetomidine the cause or the cure?.
Pediatr Crit Care Med.
2010;
11
e1-e3
