PURPOSE: Bioavailability of clopidogrel in the form of crushed tablets administered via nasogastric tube (NGT) has not been established in patients after cardiopulmonary resuscitation. Therefore, we performed a study comparing pharmacokinetic and pharmacodynamic response to high loading dose of clopidogrel in critically ill patients after cardiopulmonary resuscitation (CPR) with patients scheduled for elective coronary angiography with stent implantation. METHODS: In the NGT group (nine patients, after cardiopulmonary resuscitation, mechanically ventilated, therapeutic hypothermia), clopidogrel was administered in the form of crushed tablets via NGT. Ten patients undergoing elective coronary artery stenting took clopidogrel per os (po) in the form of intact tablets. Pharmacokinetics of clopidogrel was measured with high-performance liquid chromatography (HPLC) before and at 0.5, 1, 6, 12, 24 h after administration of a loading dose of 600 mg. In five patients in each group, antiplatelet effect was measured with thrombelastography (TEG; Platelet Mapping) before and 24 h after administration. RESULTS: The carboxylic acid metabolite of clopidogrel was detected in all patients in the po group. In eight patients, the maximum concentration was measured in the range of 0.5-1 h after the initial dose. In four patients in the of NGT group, the carboxylic acid metabolite of clopidogrel was undetectable and in the remaining patients was significantly delayed (peak values at 12 h). All patients in the po group reached clinically relevant (>50 %) inhibition of thrombocyte adenosine diphosphate (ADP) receptor after 24 h compared with only two in the NGT group (p = 0.012). There was a close correlation between peak of inactive clopidogrel metabolite plasmatic concentration and inhibition of the ADP receptor (r = 0.79; p < 0.001). CONCLUSION: The bioavailability of clopidogrel in critically ill patients after cardiopulmonary resuscitation is significantly impaired compared with stable patients. Therefore, other drugs, preferentially administered intravenously, should be considered.
- MeSH
- antagonisté purinergního receptoru P2 aplikace a dávkování krev farmakokinetika MeSH
- aplikace orální MeSH
- biologická dostupnost MeSH
- gastrointestinální intubace MeSH
- inhibitory agregace trombocytů aplikace a dávkování krev farmakokinetika MeSH
- kardiopulmonální resuscitace * MeSH
- koronární angioplastika * přístrojové vybavení MeSH
- kritický stav MeSH
- lidé středního věku MeSH
- lidé MeSH
- purinergní receptory P2 účinky léků metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stenty MeSH
- tablety MeSH
- terapeutická hypotermie MeSH
- tiklopidin aplikace a dávkování analogy a deriváty krev farmakokinetika MeSH
- trombocyty účinky léků metabolismus MeSH
- tromboelastografie MeSH
- umělé dýchání MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: To validate a porcine model of ruptured abdominal aortic aneurysm (rAAA) repair. DESIGN: Experimental study. METHODS: Ten experimental and five sham-operated pigs were studied. Instrumentation for cardiac output (CO) measurement, regional blood flow (renal-REN and portal-PORT) and blood sampling (inferior vena cava (IVC), renal and portal vein) was done. Microcirculation was visualised sublingually and in ileostoma. Protocol: simulation of rAAA with bleeding (mean arterial pressure (MAP) 45 mmHg) and increased abdominal pressure (25 mmHg) for 4 h; 2 h of infrarenal clamp with shed blood retransfusion; 11 h of post-surgery care. RESULTS: Six experimental pigs completed the protocol and are presented. Bleeding decreased CO to 95%, PORT to 80% and REN to 10% of baseline. From clamping on CO and PORT increased above baseline whereas REN (47%) with creatinine clearance remained compromised till the end. Microcirculation was affected more in ileum than sublingually. Approximately threefold increase in cytokines (tumour necrosis factor-α (TNF-alpha), interleukin (IL)-6 and IL-10) and oxidative stress markers (thiobarbituric acid-reactive substances (TBARs) and 4-hydroxy-2-trans-nonenal (HNE) was observed. Only mild increase in IL-6 and TBARs was observed in sham-operated animals. Organ histology did not reveal differences between groups. CONCLUSIONS: This near-lethal model of rAAA induced expected severe deterioration of haemodynamics and metabolism accompanied with a moderate inflammatory and oxidative stress response.
- MeSH
- aneurysma břišní aorty krev etiologie patofyziologie chirurgie MeSH
- biologické markery krev MeSH
- časové faktory MeSH
- cytokiny krev MeSH
- hemodynamika MeSH
- hypertenze etiologie MeSH
- krvácení etiologie MeSH
- mediátory zánětu krev MeSH
- mikrocirkulace MeSH
- modely nemocí na zvířatech MeSH
- monitorování fyziologických funkcí MeSH
- oxidační stres MeSH
- reprodukovatelnost výsledků MeSH
- ruptura aorty krev etiologie patofyziologie chirurgie MeSH
- Sus scrofa MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- validační studie MeSH
