Zusammenfassung
Die venöse Thromboembolie ist eine häufige Komplikation bei kritisch kranken Patienten
und geht mit einer hohen Morbidität und Mortalität einher. Die meisten auf Intensivstation
(ITS) behandelten Patienten haben ein hohes Risiko für thromboembolische Komplikationen.
Es besteht die Notwendigkeit für gut definierte Strategien zur Verhinderung von Thrombosen
bei ITS-Patienten. Mechanische Methoden wie Kompressionsstrümpfe werden oft verwendet,
auch wenn die Evidenz für diese Maßnahmen bei ITS-Patienten begrenzt ist. Unfraktioniertes
Heparin (UFH) ist immer noch das führende Medikament zur Thromboseprophylaxe bei ITS-Patienten.
Pharmakokinetische Nachteile wie eine geringe Voraussagbarkeit des gerinnungshemmenden
Effekts sind besonders für ITS-Patienten relevant. Außerdem gibt es nur wenige klinische
Studien zur subkutanen oder intravenösen Prophylaxe mit UFH. Eine zumindest gleiche
Wirksamkeit und Sicherheit von subkutanem niedermolekularen Heparin (NMH) verglichen
mit subkutanem UFH ist in zahlreichen Studien gezeigt worden, die nicht-intensivmedizinische
Hochrisikokollektive untersuchten. Erste Studien zur Anwendung von NMH bei kritisch
kranken Patienten sind vielversprechend. Einige Schlüsse für den sicheren Gebrauch
von subkutanem NMH bei ITS-Patienten können gezogen werden. Intravenös appliziertes
NMH ist möglicherweise die optimale Prophylaxe für die meisten ITS-Patienten, wenngleich
geeignete Daten zur Dosierung fehlen. Vorsichtsmaßnahmen wie die Überwachung der Antikoagulation
bei Patienten mit Niereninsuffizienz sind die Voraussetzung, wenn NMH gegeben wird.
Weitere Untersuchungen zur Prophylaxe von venösen Thromboembolien bei ITS-Patienten
werden dringend benötigt.
Abstract
Venous thromboembolism is a common complication in critically ill patients, resulting
in high morbidity and mortality. Most patients treated in intensive care units (ICU)
face a high risk of thromboembolic complications. There is a need for well-defined
strategies for prevention of thrombosis in ICU patients. Mechanical methods such as
compression stockings are frequently used, even though evidence for these measures
in ICU patients is limited. Unfractionated heparin (UFH) is still the leading drug
for thromboprophylaxis in ICU patients, but pharmacokinetic disadvantages such as
low predictability of effect on anticoagulation are relevant, especially in ICU patients.
Additionally, there is no sufficient evidence from clinical trials to support subcutaneous
or intravenous prophylaxis with UFH. At least equivalent efficacy and safety of subcutaneous
low molecular weight heparin (LMWH) compared with subcutaneous UFH have been shown
in numerous studies investigating non-ICU high-risk groups. First studies on the use
of LMWH in critically ill patients are promising. Some conclusions for safe use of
subcutaneous LMWH in ICU patients can be drawn. Intravenous LMWH may be the optimal
prophylaxis in most ICU patients, but there is a lack of sufficient data on dosing.
Precautions such as monitoring of anticoagulation in patients with renal insufficiency
are fundamental if LMWH is given. Further investigations into prevention of venous
thromboembolism in ICU patients are urgently needed.
Schlüsselwörter
Thrombose - Intensivstation - Heparin - Enoxaparin - Nadroparin - Dalteparin
Key words
Thrombosis - intensive care unit - heparin - enoxaparin - nadroparin - dalteparin
Literatur
- 1
Attia J, Ray J G, Cook D J, Douketis D J, Ginsberg J S, Geerts W H.
Deep vein thrombosis and its prevention in critically ill patients.
Arch Intern Med.
2001;
161
1268-1279
- 2
Boldt J, Papsdorf M, Rothe A, Kumle B, Piper S.
Changes of the hemostatic network in critically ill patients - is there a difference
between sepsis, trauma, and neurosurgery patients?.
Crit Care Med.
2000;
28
445-450
- 3
Cade J F.
High risk of the critically ill for venous thromboembolism.
Crit Care Med.
1982;
10
448-450
- 4
Cook D, Attia J, Weaver B, McDonald E, Meade M, Crowther M.
Venous thromboembolic disease: An observational study in medical-surgical intensive
care unit patients.
J Crit Care.
2000;
15
127-132
- 5
Cook D, Laporta D, Skrobik Y, Peters S, Sharpe M, Murphy P, Chin D, Crowther M. for
the ICU Directors Group .
Prevention of venous thromboembolism in critically ill surgery patients: A cross sectional
study.
J Crit Care.
2001;
16
161-166
- 6
de Angelis G A, McIlhenny J, Willson D F, Vittone S, Dwyer S J, Gibson J C, Alford B A.
Prevalence of deep venous thrombosis in the lower extremities of children in the intensive
care unit.
Pediatr Radiol.
1996;
26
821-824
- 7
Dörffler-Melly J, de Jonge E, Pont A C, Meijers J, Vroom M B, Buller H R, Levi M.
Bioavailability of subcutaneous low-molecular-weight heparin to patients on vasopressors.
Lancet.
2002;
359
849-850
- 8 Encke A, Haas S, Krauspe R, Riess H, Stürmer K M. Aktualisierte Leitlinie: Stationäre
und ambulante Thromboembolie-Prophylaxe in der Chirurgie und der perioperativen Medizin.
AWMF Leitlinien: http://www.uni-duesseldorf.de/WWW/AWMF/ll/chall001.htm, Stand der
letzten Aktualisierung: 24. April 2003.
- 9
Eriksson B, Kälebo P, Anthmyr B A, Wadenvik H, Tengborn L, Risberg B.
Prevention of deep-vein thrombosis and pulmonary embolism after total hip replacement.
J Bone Joint Surg.
1991;
73A
484-493
- 10
Eriksson B, Söderberg K, Widlung L, Wandeli B, Tengborn L, Risberg B.
A comparative study of three low-molecular weight heparins (LMWH) and unfractionated
heparine (UH) in healthy volunteers.
Thromb Haemost.
1995;
73
398-401
- 11
Fraisse E, Holzapfel L, Couland J M, Simonneau G, Bedock B, Feissel M, Herbecq P,
Pordes R, Poussel J F, Roux L. and the association of non-university affiliated intensive
care specialist physicians of France .
Nadroparin in the prevention of deep venous thrombosis in acute decompensated COPD.
Am J Respir Crit Care Med.
2000;
161
1109-1114
- 12
Ganzer D, Gutezeit A, Mayer G, Greinacher A, Eichler P.
Thromboembolieprophylaxe als Auslöser thromboembolischer Komplikationen. Eine Untersuchung
zur Inzidenz der Heparin-induzierten Thrombozytopenie (HIT) Typ II.
Z Orthop.
1997;
135
543-549
- 13
Geerts W H, Code K I, Jay R M, Chen E, Szalai J P.
A prospective study of venous thromboembolism after major trauma.
N Engl J Med.
1994;
331
1601-1606
- 14
Geerts W H, Richard M J, Code K I, Chen E, Szalai J P, Eric A, Saibil M D, Hamilton P A.
A comparison of low-dose heparin with low-molecular-weight heparin as prophylaxis
against venous thromboembolism after major trauma.
N Engl J Med.
1996;
335
701-707
- 15
Geerts W H, Heit J A, Clagett G P, Pineo G F, Colwell C W, Anderson F A, Wheeler H B.
Sixth ACCP consensus conference. Prevention of venous thromboembolism.
Chest.
2001;
119
132-175
- 16
Geerts W H, Cook D, Selby R, Echells E.
Venous thromboembolism and its prevention in critical care.
J Crit Care.
2002;
17
95-104
- 17
Giannadiakis K, Leppek R, Gotzen L, Stiletto R.
Thromboembolism complications in multiple trauma patients: an underestimated problem?
Results of a clinical observational study of 50 patients.
Chirurg.
2001;
72
710-716
- 18
Gogarten W, van Aken H, Büttner J, Riess H, Wulf H, Buerkle H.
Leitlinien der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin (DGAI):
Rückenmarknahe Regionalanästhesien und Thromboembolieprophylaxe/Antikoagulation.
Anästhesiol Intensivmed.
2003;
44
218-230
- 19
Greenfield L J, Proctor M C, Rodriguez J L, Luchette F A, Cipolle M D, Cho J.
Posttrauma thromboembolism prophylaxis.
J Trauma.
1997;
42
100-103
- 20
Greinacher A, Lubenow N, Hinz P, Ekkernkamp A.
Die Heparin-induzierte Thrombozytopenie.
Dtsch Ärztebl.
2003;
100
A 2220-2229
- 21
Harenberg J, Giese C H, Knödler A, Zimmermann R, Schettler G.
Neutralisierung von niedermolekularem Heparin Kabi 2165 mit Protaminchlorid.
Klin Wschr.
1986;
64
1171-1175
- 22
Harris L M, Curl G R, Booth F V, Hassett J M, Leney G, Ricotta J J.
Screening for asymptomatic deep vein thrombosis in surgical intensive care patients.
J Vasc Surg.
1997;
26
764-769
- 23
Hartl P, Brücke P, Dienstl E, Vinazzer H.
Prophylaxis of thromboembolism in general surgery: Comparison between standard heparin
and Fragmin.
Thromb Research.
1990;
57
577-584
- 24
Heidecke V, Rainov N G, Heidecke K, Burkert W.
Thromboembolische Komplikationen bei neurochirurgischen Patienten.
Zentralbl Chir.
1997;
122
367-373
- 25
Hill A B, Garber B, Dervin G, Howard A.
Heparin prophylaxis for deep venous thrombosis in a patient with multiple injuries:
an evidence-based approach to a clinical problem.
J Can Surg.
2002;
45
282-287
- 26
Hirsch D R, Ingenito E P, Goldhaber S Z.
Prevalence of deep venous thrombosis among patients in medical intensive care.
JAMA.
1995;
274
335-337
- 27
Ibrahim E H, Iregui M, Prentice D, Sherman G, Kollef M H, Shannon W.
Deep vein thrombosis during prolonged mechanical ventilation despite prophylaxis.
Crit Care Med.
2002;
30
771-774
- 28
Jorgensen P S, Knudsen J B, Broeng D L, Josephsen L, Bjerregaard P, Hagen D K, Jorgensen P K,
Torholm C.
The thromboprophylactic effect of a low-molecular-weight heparin (Fragmin) in hip
fracture surgery. A placebo-controlled study.
Clin Orth Rel Research.
1992;
278
95-100
- 29
Kakkar V V, Cohen A T, Edmonson R A, Phillips M J, Cooper D J, Das S K, Maher K T,
Sanderson R M, Ward V P, Kakkar S.
Low molecular weight versus standard heparin for prevention of venous thromboembolism
after major abdominal surgery.
Lancet.
1993;
341
259-265
- 30
Kapoor M, Kupfer Y Y, Tessler S.
Subcutaneous heparin prophylaxis significantly reduces the incidence of venous thromboembolic
events in the critically ill.
Crit Care Med.
1999;
27
A69
- 31
Keane M G, Ingenito E P, Goldhaber S Z.
Utilization of venous thrombosis prophylaxis in an intensive care unit.
Chest.
1994;
106
13-14
- 32
Koch A, Ziegler S, Breitscherdt H, Victor N.
Low molecular weight heparin and unfractionated heparin in thrombosis prophylaxis:
Meta-analysis based on original patient data.
Thromb Res.
2001;
102
295-309
- 33
Kollef M H, Zahid M, Eisenberg P R.
Predictive value of a rapid semiquantitative D-dimer assay in critically ill patients
with suspected venous thromboembolic disease.
Crit Care Med.
2000;
28
414-420
- 34
Kudsk K A, Fabian T C, Baum S, Gold R E, Mangiante E, Voeller G.
Silent deep vein thrombosis in immobilized multiple trauma patients.
Am J Surg.
1989;
158
515-519
- 35
Legere B M, Dweik R A, Arroliga A C.
Venous thromboembolism in the intensive care unit.
Clin Chest Med.
1999;
20
367-384
- 36 Leizorovicz A. Prospective evaluation of dalteparin efficacy for prevention of
venous thromboembolism in immobilized patients trial (PREVENT). Oral presentation
ISTH-congress, Birmingham 2003.
- 37
Lersch C, Paschalidis M, Theiss W.
Tiefe Venenthrombosen durch zentralvenöse Katheter.
VASA.
1999;
28
71-78
- 38
Lohmann U, Gläser E, Braun B E, Bötel U.
Thromboembolieprophylaxe bei Wirbelsäulenfrakturen mit Rückenmarkverletzungen.
Zentralbl Chir.
2001;
126
385-390
- 39
Marik P E, Andrews L, Maini B.
The incidence of deep venous thrombosis in ICU patients.
Chest.
1997;
111
661-664
- 40
Mayr A J, Dünser M, Jochberger S, Fries D, Klingler A, Joannidis M, Hasibeder W, Schobersberger W.
Antifactor Xa activity in intensive care patients receiving thromboembolic prophylaxis
with standard dose enoxaparin.
Thromb Res.
2002;
105
201-204
- 41
Merli G J, Herbison G J, Ditunno J F, Weitz H H, Henzes J H, Park C H, Jaweed M M.
Deep vein thrombosis: prophylaxis in acute spinal cord injured patients.
Arch Phys Med Rehabil.
1988;
69
661-664
- 42
Merrer J, de Jonghe B, Golliot F, Lefrant J Y, Raffay B, Barre E, Rigaud J P, Casciani D,
Misset B, Bosquet C, Outin H, Brun-Buisson C, Nitenberg G. for the french catheter
study group in intensive care .
Complications of femoral and subclavian venous catheterization in critically ill patients:
a randomized controlled trial.
JAMA.
2001;
286
700-707
- 43
Mort T C, Yeston N S.
The relationship of premortem diagnoses and post mortem findings in a surgical intensive
care unit.
Crit Care Med.
1999;
27
299-303
- 44
Neuhaus A, Bentz R R, Weg J G.
Pulmonary embolism in respiratory failure.
Chest.
1978;
73
460-465
- 45
Partsch H, Blättler W.
Leitlinien zur Thromboembolie-Prophylaxe.
Phlebol.
2000;
29
106-113
- 46
Peters J T, Melillo N G, Pesin J L, Peters C E, Boni C M, Kennedy J F.
Analysis of deep venous thrombosis prophylaxis in an intensive care unit.
Chest.
1997;
112
155S
- 47
Randolph A G, Cook D J, Gonzales C A, Andrew M.
Benefit of heparin in central venous and pulmonary artery catheters. A meta-analysis
of randomized controlled trials.
Chest.
1998;
113
165-171
- 48
Roder J D, Weber R, Adolf J, van de Flierdt E.
Niedermolekulares Heparin (LMWH Kabi-2165) zur Thromboembolieprophylaxe in der viszeralchirurgischen
Intensivmedizin.
Intensivbehandlung.
1988;
13
149-153
- 49
Samama M M, Cohen A T, Darmon J Y.
A comparison of enoxaparin with placebo for the prevention of venous thromboembolism
in acutely ill medical patients.
N Engl J Med.
1999;
341
793-800
- 50
Schönhofer B, Köhler D.
Prevalence of deep vein thrombosis of the leg in patients with acute exacerbation
of chronic obstructive pulmonary disease.
Respiration.
1998;
65
173-177
- 51
Seemann S.
HIT II auf der Intensivstation.
Anästhesiol Intensivmed Notfallmed Schmerzther.
2002;
37 Suppl I
20-23
- 52
Timsit J F, Farkas J C, Boyer J M, Martin J B, Misset B, Renaud B, Carlet J.
Central vein catheter-related thrombosis in intensive care patients: incidence, risk
factors, and relationship with catheter-related sepsis.
Chest.
1998;
114
207-213
- 53
Torholm C, Broeng L, Seest Jorgensen P, Bjerregaard P, Josephsen L, Korsholm Jorgensen P,
Hagen K, Bjerre Knudsen J.
Thromboprophylaxis by low-molecular-weight heparin in elective surgery.
J Bone Joint Surg (Br).
1991;
73 B
434-438
- 54
Tuttle-Newhall J E, Rutledge R, Hultman C S, Fakhry S M.
Statewide, population-based, time-series analysis of the frequency and outcome of
pulmonary embolus in 318,554 trauma patients.
J Trauma.
1997;
42
90-99
- 55
Vaitkus P T, Leizorovicz A, Goldhaber S Z. PREVENT Investigator Group .
Rationale and design of a clinical trial of a low-molecular-weight heparin in preventing
clinically important venous thromboembolism in medical patients: the prospective evaluation
of dalteparin efficacy for prevention of venous thromboembolism in immobilized patients
trial (the PREVENT study).
Vasc Med.
2002;
7
269-273
- 56
Velmahos G C, Nigro J, Tatevossian R, Murray J A, Cornwell E E, Belzberg H, Asensio J A,
Berne T V, Demetriades D.
Inability of an aggressive policy of thromboprophylaxis to prevent deep venous thrombosis
(DVT) in critically injured patients: are current methods of DVT prophylaxis insufficient?.
J Am Coll Surg.
1998;
187
529-533
- 57
Vervloet M G, Thijs L G, Hack C E.
Derangements of coagulation and fibrinolysis in critically ill patients with sepsis
and septic shock.
Semin Thromb Haemost.
199;
24
33-44
- 58
Warkentin T E, Levine M N, Hirsh J, Horsewood P, Roberts R S, Gent M, Kelton J G.
Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin
or unfractionated heparin.
N Engl J Med.
1995;
332
1130-1335
- 59
Weilemann L S, Giesen H U, Swars H, Schinzel H, Hafner S, Ehrenthal W.
Einfluß von niedermolekularem Heparin auf die Gerinnungsaktivierung bei Sepsis.
Intensivmed.
1992;
29
162-165
Prof. Dr. med. A. Greinacher
Institut für Immunologie und Transfusionsmedizin · Ernst-Moritz-Arndt-Universität
Greifswald
Sauerbruchstraße · 17489 Greifswald
Email: greinach@uni-greifswald.de