Zusammenfassung
Fragestellung: In verschiedenen Studien wurde der positive Effekt von Clonidin im Rahmen der Prämedikation
belegt (Verminderung der perioperativen Stressantwort, analgetischer Effekt, anästhetikasparender
Effekt, Shiveringprophylaxe). Wichtigster Gesichtspunkt der pharmakologischen Prämedikation
ist jedoch unbestritten die Anxiolyse. Diesbezüglich wird der Wert von Clonidin unterschiedlich
diskutiert. In der vorliegenden Untersuchung überprüften wir die anxiolytische Wirkung
von Clonidin im Vergleich zu Midazolam. Methode: 50 Patienten der ASA-Klassen 1 - 3 wurden in unsere prospektive, doppelblinde Studie
einbezogen. Die Patienten wurden am Vortag der Operation mit 1 mg Flunitrazepam und
am OP-Tag 60 - 90 min präoperativ mit 5 µg/kg-1 Clonidin bzw. 100 µg/kg..1 Midazolam p. o. prämediziert. Mittels des Spielberger State-Trait Anxiety Inventory
(STAI-G X1) wurde das Ausmaß der Zustandsangst (State-Angst) vor und nach der Prämedikation
erfasst. Ergebnisse: Sowohl Clonidin als auch Midazolam führten zu einer signifikanten Reduktion des präoperativen
Angstempfindens über die Zeit (p < 0,001). Zwischen den Gruppen bestanden bezüglich
der mit dem STAI-G X1 ermittelten Punktwerte zu keinem Zeitpunkt signifikante Unterschiede
(p > 0,05). Das Ausmaß der Angstreduktion war zwischen den Gruppen vergleichbar. Schlussfolgerung: Clonidin besitzt neben den o. g. positiven Wirkungen im Rahmen der Prämedikation
eine der Midazolam entsprechenden anxiolytische Wirkung. Es stellt eine interessante
Alternative zu den in der Prämedikation als Goldstandard angesehenen Benzodiazepinen
(hier Midazolam) dar.
Abstract
Objective: Many investigations described a positive effect of clonidine for premedication (reduction
of perioperative stress response, analgetic effect, anaesthetic-saving effect, prophylaxis
of postoperative shivering). The most important objective in premedication is undisputed
anxiolysis. The anxiolytic effect of clonidine is differently discussed. Therefore
we investigated the anxiolytic effect of clonidine in comparison to midazolam. Methods: 50 patients (ASA 1 - 3) were included in the present doubleblinded, prospective study.
These patients got an oral premedication with 1 mg flunitrazepam in the evening before
surgery and 5 µg/kg-1 clonidine or 100 µg/kg-1 midazolam 60 - 90 minutes before surgery. By using Spielbergers State-Trait Anxiety
Inventory (STAI-G X1) we registered the degree of state-anxiety before and after premedication.
Results: Both clonidine as well as midazolam showed a significant reduction of the state-anxiety
over time (p < 0,001). Between the groups there were no differences in the STAI-scores
at any time (p > 0,05). The degree of reduction in the state-anxiety were comparable
between the groups. Conclusion: In addition to the higher up listed effects clonidine showed a anxiolytic effect,
which is comparable to midazolam. Therefore clonidine is an interesting alternative
to benzodiazepines, which are commonly used drugs for premedication.
Schlüsselwörter
Prämedikation - Anxiolyse - Clonidin - Midazolam
Key words
Premedication - Anxiolysis - Clonidine - Midazolam
Literatur
1
Bernard J M, Bourréli B, Homméril J L, Pinaud M.
Effects of oral clonidine premedication and postoperative i. v. infusion on haemodynamics
and adrenergic responses during recovery from anaesthesia.
Acta Anaesthesiol Scand.
1991;
35
54-59
2
Carabine U A, Milligan K R, Moore J A.
Adrenergic modulation of preoperative anxiety: a comparison of temazepam, clonidine
and timolol.
Anesth Analg.
1991;
73
633-637
3
Carabine U A, Wright P M, Moore J.
Preanaesthetic medication with clonidine: a dose-response study.
Br J Anaesth.
1991;
67
79-83
4
Davies D S, Wing L MH, Reid J L, Neill E, Tippett P, Dollery C T.
Pharmacokinetics and concentration-effect relationships of intravenous and oral clonidine.
Clin Pharmacol Ther.
1977;
21
593-601
5
De Kock M.
Alpha-2 adrenoceptor agonists: clonidine, dexmetomidine, mivazerol.
Curr Opin Anaesth.
1996;
9
295-299
6
De Kock M, Versailles H, Colinet B, Karthaeuser R, Scholtes J L.
Epidemiology of the adverse hemodynamic effects occurring during “Clonidine Anesthesia”:
A prospective open trial of intraoperative intravenous clonidine.
A Clin Anesth.
1995;
7
403-410
7
De Sarro G B, Ascotti C, Froio F, Kobri V, Nistico G.
Evidence that locus coeruleus is the site, where clonidine and drugs acting alpha1-
and alpha2-adrenoceptors affect sleep and arausal mechanism.
Brit J Pharmacol.
1987;
90
675-685
8
Doenicke A.
Editorial.
Anaesthesiol Intensivmed Notfallmed Schmerzther.
1997;
32
(3)
309-312
9
Eberhart L HJ, Novatchkov N, Schricker T, Georgieff M, Baur C P.
Clonidin im Vergleich zu Midazolam zur intravenösen Prämedikation vor ambulanten Eingriffen.
Anästhesiol Intensivmed Notfallmed Schmerzther.
2000;
35
388-393
10
Ellis J E, Drijvers G, Pedlow S, Laff S P, Sorrentino M J, Foss J F, Shah M, Busse J R,
Mantha S, McKinsey J F, Osinski J, Thisted R A, Roizen M F.
Premedication with oral and transdermal clonidine provides safe an efficacious postoperative
sympatholysis.
Anesth Analg.
1994;
79
1133-1140
11
Flacke J W, Bloor B C, Flacke W E, Wong D, Dazza S, Stead S, Laks H.
Reduced narcotic requirement by clonidine with improved hemodynamic and adrenergic
stability in patients undergoing coronary bypass surgery.
Anesthesiology.
1987;
67
11-19
12
Frank T, Thieme V, Radow L.
Prämedikation im Rahmen einer TIVA bei kieferchirurgischen Operationen - Vergleich
der operierenden Verläufe nach Clonidin versus Midazolam.
Anästhesiol Intensivmed Notfallmed Schmerzther.
2000;
35
428-434
13
Ghignone M, Calvillo O, Quintin L.
Anesthesia and hypertension: the effect of clonidine on perioperative hemodynamics
and isoflurane requirements.
Anesthesiology.
1987;
67
3-10
14
Kindler C H, Harms C, Amsler F, Ihde-Scholl T, Scheidegger D.
The visual analog scale allows effective measurement of preoperative anxiety and detection
of patients' anesthetic concerns.
Anesth Analg.
2000;
90
706-712
15 Kulka P J, Tryba M.
Systemische Gabe von alpha2-Adrenozeptor-Agonisten zur Prämedikation und Anästhesie. In: Tryby M, Zenz M (Hrsg) Alpha2-Adrenozeptor-Agonisten in anästhesie, Intensiv-
und Schmerztherapie. Papst Science Publ 1996: 80-107
16
Kulka P J, Tryba M, Lang C, Kolhorst V, Vogt V.
Sedative and anxiolytic interactions of clonidine and benzodiazepines.
Br J Anaesth.
1994;
72
A156
17
Kulka P J, Tryba M, Zenz M.
Dose-response effects of intravenous clonidine on stress response during induction
of anesthesia in coronary artery bypass graft patients.
Anesth Analg.
1995;
80
263-268
18
Madler C, Schmidt T, Poloczek S.
Prämedikation.
Anesthesiol Intensivmed Notfallmed Schmerzther.
1996;
31
509-521
19
Millar K, Jelicic M, Bonke B, Asbury A J.
Assessment of properative anxiety: comparison of measures in patients awaiting surgery
for breast cancer.
Br J Anaesth.
1995;
74
180-183
20
Pittaluga A, Torelli R, Raiteri M.
Clonidine differentially modulates the release of endogenous GABA in varios rat brain
areas.
Pharmacol Res.
1991;
24
189-196
21
Pouttu J, Scheinin B, Rosenberg P H, Vinamäki O, Scheinin M.
Oral premedication with clonidin: effects on stress responses during general anaesthesia.
Acta Anaesthesiol Scand.
1987;
31
730-734
22
Quintin L, Roudot F, Roux C, Macquin I, Basmaciogullari A, Guyene T, Vaubourdolle M,
Viale J P, Bonnet F, Ghignone M.
Effect of clonidine on the circulation and vasoactive hormones after aortic surgery.
Br J Anaesth.
1991;
66
108-115
23
Scheinin H, Jaakola M L, Sjovall S, Ali-Melkkilä T, Kaukinen S, Turunen J, Kanto J.
Intramuscular dexmedetomidinee as premedication for general anaesthesia.
Anesthesiology.
1993;
78
1065-1075
24
Scheinin M, Schwinn D A.
The locus coeruleus. Site of hypnotic actions of alpha-2-adrenoceptor agonists.
Anesthesiology.
1992;
76
873-875
25
Schmidt T, Madler C.
Indikatoren präoperativer Angst und Anxiolyse aus anästhesiologischer Sicht.
Anästhesiol Intensivmed Notfallmed Schmerzther.
1997;
32
(3)
330-335
26 Spielberger C D, Gorsuch R L, Lushene R E.
Manual for the State-Trait Anxiety Inventory. Consulting Psychologists Press. Palo Alto, Calif; 1983
27
Spielberger C D, Auerbach S M, Wadsworth A P, Dunn T M, Taulbee E S.
Emotional reactions to surgery.
J Consult Clin Psych.
1973;
40
33-38
28
Tolksdorf W.
Der präoperative Streß. Forschungsansätze und Behandlungsmethoden.
Anästhesiol Intensivmed Notfallmed Schmerzther.
1997;
32
(3)
318-324
29
Tryba M, Schulte-Tamburen A, Kulka P J, Zenz M.
Premedication with dexmedetomidine a novel alpha2-adrenoceptor agonist: sedative and
anxiolytic effects.
Br J Anaesth.
1997;
72
A157
30
Weindler J, Kiefer R T, Rippa A, Wiech K, Ruprecht K W.
Low-dose oral clonidine as premedication before intraocular surgery in retrobulbar
anesthesia.
Eur J Ophthalmol.
2000;
10
248-256
31
Wright P MC, Carabine U A, McClune S, Orr D A, Moore J.
Preanaesthetic premedication with clonidine.
Br J Anaesth.
1990;
65
628-632
Dr. med. T. Frank
Abteilung für Anästhesiologie und Intensivtherapie, Paracelsus-Klinik Zwickau
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