Τόμος 22 (2004) – Τεύχος 3 – Άρθρο 6 – Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Ελληνική Έκδοση – Volume 22 (2004) – Issue 2 – Article 6 – Epitheorese Klinikes Farmakologias και Farmakokinetikes-Greek Edition

 

Τίτλος – Title

Σύνδρομο της Πολυοργανικής Δυσλειτουργίας/Πολυοργανικής Ανεπάρκειας

Multiple Organ Dysfunction / Multiple Organ Failure Syndrome

Συγγραφέας – Author

Ιωάννης Φλώρος*, Μαρία Μυρωνίδου-Τζουβελέκη**, Ανδρέας Πάγκαλης*, Κωνσταντίνος Καλούσης**, Βασίλης Κόκκας**

* Κλινική Εντατικής Θεραπείας του Πανεπιστημίου Αθηνών, Νοσοκομείο Ευαγγελισμός, Αθήνα, Ελλάς ** Εργαστήριο Φαρμακολογίας, Ιατρική Σχολή, Αριστοτέλειο Πανεπιστήμιο, Θεσσαλονίκη, Ελλάς

I. Floros*, M. Mironidou-Tzouveleki**, A. Pangalis*, K. Kalousis**, B. Kokkas**

* Intensive Care Clinic, Evangelismos Hospital, University of Athens, Athens, Greece ** Department of Pharmacology, Medical School, Aristotle University, Thessaloniki, Greece

Παραπομπή – Citation

  Φλώρος,Ι., Μυρωνίδου-Τζουβελέκη,Μ., Πάγκαλης,Α.,Καλούσης,Κ., Κόκκας,Β. : Σύνδρομο της Πολυοργανικής Δυσλειτουργίας/Πολυοργανικής Ανεπάρκειας, Επιθεώρηση Κλιν. Φαρμακολ. Φαρμακοκινητ. 22: 149-173 (2004)

Floros,I., Mironidou-Tzouveleki,M., Pangalis,A., Kalousis,K., Kokkas,B. : Multiple Organ Dysfunction / Multiple Organ Failure Syndrome, Epitheorese Klin. Farmakol. Farmakokinet. 22: 149-173 (2004)

Ημερομηνία Δημοσιευσης – Publication Date
10 Δεκεμβρίου 2004 – 2004-12-10
Γλώσσα Πλήρους Κειμένου –
Full Text Language

Ελληνικά – Greek

Παραγγελία – Αγορά –
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Λέξεις κλειδιά – Keywords
Πολυοργανική ανεπάρκεια, πολυοργανική δυσλειτουργία, σήψη, shock, συστηματική φλεγμονώδης αντίδραση, Μονάδα Εντατικής Θεραπείας (Μ.Ε.Θ.), κυτταροκίνες, αναπνευστική ανεπάρκεια, σύνδρομο αναπνευστικής δυσχέρειας ενηλίκων, κυκλοφορική ανεπάρκεια, ιστική αιμάτωση, ηπατική ανεπάρκεια, ανεπάρκεια πεπτικού συστήματος, οξεία νεφρική ανεπάρκεια, διάχυτη ενδαγγειακή πήξη, νευρολογική ανεπάρκεια
Multiple organ failure (MOF), Multiple organ dysfunction syndrome (MODS), sepsis, shock, systemic inflammatory reaction, Intensive Care Unit, cytokines, respira­tory insufficiency, adult respiratory distress syndrome (ARDS), circulatory insufficiency, tissue perfusion, hepatic insufficiency, gastrointestinal system insufficiency, acute renal failure, neurological insufficiency
Λοιποί Όροι – Other Terms

Άρθρο

Article

Περίληψη – Summary

Το σύνδρομο της πολυοργανικής ανεπάρκειας είναι η παθολογική έκπτωση της λειτουργίας διαφόρων οργάνων ή οργανικών συστημάτων. Αυτό χαρακτηρίζεται από διαταραχή της λειτουργίας των πνευμόνων, των νεφρών, του ήπατος, του εγκεφάλου, της καρδιάς και της πεπτικής οδού, όπως και από γρήγορη απώλεια σωματικού βάρους και ελάττωση της μυϊκής μάζας των σκελετικών μυών. Το σύνδρομο ακολουθεί, συνήθως, τη σήψη, το βαρύ τραυματισμό, το παρατεταμένο shock, την οξεία παγκρεατίτιδα, τη διάχυτη ενδαγγειακή πήξη, τις πολλαπλές μεταγγίσεις και τις σοβαρές χειρουργικές επεμβάσεις. Η ακριβής συχνότητα εμφάνισης του συνδρόμου είναι άγνωστη, ωστόσο η επίπτωση και η θνησιμότητα φαίνεται ότι αυξάνονται σταθερά. Η προοδευτική πολυοργανική ανεπάρκεια είναι σήμερα η συνηθέστερη αιτία θανάτου στις ΜΕΘ. Επιπρόσθετα, οι ασθενείς παραμένουν επί μακρόν νοσηλευόμενοι και με τεράστιο οικονομικό κόστος. Τέσσερις βασικοί μηχανισμοί θεωρούνται σήμερα ως παθογενετικοί παράγοντες της συστηματικής βλάβης οργάνων, τα οποία δεν πάσχουν πρωτογενώς: (α) η μη ειδική ανοσολογική διαταραχή, (β) η κυκλοφορική ανεπάρκεια, η δυσλειτουργία ενδοθηλίου και η ανεπαρκής ιστική οξυγόνωση/ιστική αιμάτωση, (γ) οι διαταραχές του βλεννογονικού φραγμού του εντέρου και η μετατόπιση μικροβίων και μικρο-βιακών προϊόντων στην κυκλοφορία και στο λεμφικό σύστημα, (δ) η γενικευμένη διαταραχή κυτταρικών και υποκυτταρικών λειτουργιών και τελικά ο κυτταρικός θάνατος. Η κλινική εικόνα της πολυοργανικής ανεπάρκειας μεταβάλλεται ανάλογα με τα προσβαλλόμενα όργανα και το βαθμό δυσλειτουργίας τους. Η ανεπάρκεια του αναπνευστικού συστήματος εκδηλώνεται με την παρουσία ενός ή περισσοτέρων από τα ακόλουθα ευρήματα: συχνότητα αναπνοών £ 5/min ή ³ 49/min, PaCO2 ³50 mmHg, (A-a) DO2 ³350 mmHg (κυψελιδοτριχοειδική διαφορά Ο2), ανάγκη μηχανικού αερισμού με αναπνευστήρα. Η μηχανική υποστήριξη της αναπνοής στους ασθενείς με ARDS, έχει ως στόχο αφ’ ενός μεν την οξυγόνωση και την ελάττωση του πολύ αυξημένου αναπνευστικού έργου και αφ’ ετέρου την αποφυγή περαιτέρω πνευμονικής βλάβης από τον αναπνευστήρα. Η ανεπάρκεια του κυκλοφορικού εκδηλώνεται με την παρουσία ενός ή περισσοτέρων από τα ακόλουθα ευρήματα: υπόταση (μέση τιμή αρτηριακής πίεσης £49 mmHg), ανάγκη για αγγειοσυσπαστικά φάρμακα καρδιακή συχνότητα £54/min, αρρυθμίες (επεισόδιο κοιλιακής ταχυκαρδίας και/ή κοιλιακής μαρμαρυγής), pH αρτηριακού αίματος £ 7,24 με PaCO2 £49mmHg. H καρδιακή ανεπάρκεια είναι αποτέλεσμα, αφ’ ενός μεν μυοκαρδιακής καταστολής, αφ’ ετέρου δε βλάβης της περιφερικής αγγειακής κυκλοφορίας. Η δυσλειτουργία του κυκλοφορικού αντιμετωπίζεται με την επαρκή χορήγηση όγκου υγρών, αγγειοσυσταλτικών και ινότροπων για την διατήρηση επαρκούς αιμάτωσης. Η ηπατική ανεπάρκεια χαρακτηρίζεται από την αύξηση της χολερυθρίνης ³12 mg/100ml και/ή την αύξηση της αλκαλικής φωσφατάσης και της γαλακτικής δεϋδρογενάσης σε τιμές τριπλάσιες του φυσιολογικού. Σημαντικότερος θεραπευτικός στόχος είναι η αποκατάσταση της αιμάτωσης των σπλάχνων. Η ανεπάρκεια του πεπτικού εκδηλώνεται ως ανικανότητα των ασθενών να ανεχθούν την εντερική διατροφή, χωρίς την παρουσία μηχανικής απόφραξης, ως αλιθισιακή χολοκυστίτιδα, ή παγκρεατίτιδα απουσία χολόλιθων, τραύματος, ή αλκοόλης, ή ως αιμορραγία πεπτικού που απαιτεί για την αντιμετώπισή της περισσότερες από 2 μονάδες αίματος ανά 24h. Η άμεση εντερική διατροφή και η διαιτητική υποστήριξη παίζουν σημαντικό ρόλο στην αντιμετώπισή της. Η νεφρική ανεπάρκεια χαρακτηρίζεται την παρουσία ενός ή περισσοτέρων από τα ακόλουθα: ρυθμός διούρησης £ 500 ml/24h ή £ 160 ml/8h, άζωτο ουρίας αίματος ³100 mg/dl, κρεατινίνη αίματος ³ 3,5 mg/100ml. Βασικός χειρισμός για την πρόληψή της είναι η απόκατάσταση επαρκών πιέσεων πλήρωσης και αιμάτωσης, ενώ θεραπευτικά εφαρμόζονται μέθοδοι νεφρικής υποκατάστασης. Από το αιμοποιητικό σύστημα παρατηρείται ελάττωση του αριθμού των έμμορφων συστατικών του αίματος (λευκά αιμοσφαίρια £1000/mm3, αιμοπετάλια £ 20000/mm3, αιματοκρίτης £ 20%), καθώς και διαταραχές της πήξης που μπορούν να εκφράζονται με αιμορραγική διάθεση ή/και με υπερπηκτικότητα. Οι στρατηγικές για την επαναφορά της διαταραγμένης ισορροπίας μεταξύ προπηκτικών και αντιπηκτικών παραγόντων στον βαριά πάσχοντα περιλαμβάνουν τη χορήγηση αντιθρομβίνης ΙΙΙ, ανασυσταμένου TFPI και ενεργοποιημένης πρωτεΐνης C. Τέλος, μπορεί να παρατηρείται δυσλειτουργία του νευρικού συστήματος, η οποία εκφράζεται με τιμή της κλίμακας Γλασκώβης £8. Η κατανόηση των μηχανισμών που εμπλέκονται στο σύνδρομο της πολυοργανικής δυσλειτουργίας/πολύ-οργανικής ανεπάρκειας, αλλά και της χρονικής τους αλληλουχίας, θα αποτελέσουν τη βάση για την αποτελεσματικότερη αντιμετώπισή του και τη μείωση της θνησιμότητας στις Μονάδες Εντατικής Θεραπείας. Η θεραπεία του ήδη εγκατασταθέντος συνδρόμου είναι υποστηρικτική, για το λόγο αυτό η πρόληψη είναι καθοριστικής σημασίας.

The Multiple Organ Failure Syndrome is the pathological failure of the function of various organs or organ systems. It is characterized by disturbance of the functionality of the lungs, the kidneys, the liver, the brain, the heart, the gastro­intestinal tract, as well as by quick weight loss and reduction of the skeletal muscles mass. It usually follows sepsis, heavy injuries, long-duration shock, acute pancreatitis, multiple organ transfusions and severe surgical operations.The exact frequency of the appearance of the syndrome is unknown, yet the incidence and the mortality seem to be steadily increasing. The pro­gressive multiple organ insufficiency is today the commonest cause of death in the Intensive Care Units. In addition, the patients remain in hospital for long and at very high cost.Four basic mechanisms are now considered re­sponsible for the systemic damage of organs that are not primarily affected: a) non-special immune disorder, caused by parts of the cell wall of gram-negative bacteria, ischemia and tissue damage, b) circulatory insufficiency, endothelial dysfunction and insufficient tissue oxygenation/perfusion, c) disturbance of the intestinal mucosal barrier, resulting in translocation of bacteria and their prod­ucts in the blood and lymph circulation, d) generalized disturbance of cellular and subcel­lular processes and, finally, cellular death. The clinical expression of the multiple organ fail­ure depends on the affected organs and the sever­ity of their dysfunction. The respiratory insufficiency is manifested by the presence of one or more of the following findings: frequency of breath £ 5/min or ³ 49/min, PaCO2 ³50 mmHg, (A-a) DO2 ³350 mmHg (alveolar-arte­rial oxygen difference), need for mechanical venti­lation. The mechanical support of breathing for pa­tients with ARDS aims at the oxygenation and the reduction of the increased respiratory work and also at the prevention of further lung damage from the ventilator (barotrauma). The circulatory insufficiency is characterised by one or more of the following findings: hypotension (mean arterial pressure £49mmHg), need for vaso­constrictive drugs, heart rate £54/min, arrhythmias (ventricular tachycardia and/or atrial fibrillation), arterial blood pH£7.24 with PaCO2£49mmHg. The cardiac failure is the consequence of the myocar­dial suppression and also of the peripheral circula­tion damage. The circulatory dysfunction is treated with the administration of a sufficient volume of liquids, vasopressors and inotropes in order to maintain sufficient tissue perfusion. The hepatic failure is characterised by an in­crease in bilirubin value ³12mg/100ml and/or an increase hepatic enzymes. The most important therapeutic target is the restoration of the visceral blood supply. The gastrointestinal insufficiency is shown as an inability of the patients to tolerate enteric feeding, without the presence of mechanical blocking, as non-lithiasic cholocystitis, pancreatitis with the ab­sence of bilestones, trauma or alcohol or as gas­trointestinal bleeding which requires >2 units of blood/24h. The prompt enteric feeding and the nu­tritional supplementation play a key role in its treat­ment. The renal failure is characterised by the presence of one or more of the following: urination rate £ 500ml/24h or 160ml/8h, blood urea nitrogen ³100 mg/dl, blood creatinine ³ 3.5mg/100ml. For its pre­vention it is basic to restore sufficient filling and perfusion pressures, while methods of renal re­placement are also applied. The dysfunction of the haemopoietic system is expressed with a reduction in the numbers of white blood cells, platelets and haematocrit, as well as by disturbance of the coagulation mechanism. The strategies for the restoration of the disturbed bal­ance between coagulant and anticoagulant factors in the critically ill patient include the administration of antithrombin III, recombinant TFPI and activated protein C. Finally, neurological insufficiency may also ap­pear, expressed with a Glascow Scale Score £8. The understanding of the mechanisms involved in the Multiple Organ Dysfunction/Multiple Organ Fail­ure Syndrome and their temporal sequence will be the basis for its effective treatment and the reduc­tion of the mortality in the Intensive Care Units.

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