The aim of this study was to describe and quantify pharmacokinetics of ampicillin used prophylactically in cardiac surgery both with and without cardiopulmonary bypass (CPB) using population pharmacokinetic analysis in order to propose an optimal dosing strategy. Adult patients undergoing cardiac surgery and treated with prophylactic dose of 2 g ampicillin were enrolled to this prospective study. Blood samples were collected according to the study protocol and ampicillin plasma concentrations were measured using HPLC/UV system. A three-stage population pharmacokinetic model using nonlinear mixed-effects modelling approach was developed. Totally 273 blood samples obtained from 20 patients undergoing cardiac surgery with the use of the CPB and 20 patients without CPB use were analyzed. Two-comparmental model best fits ampicillin concentration-time data. Mean ± SD body weight-normalized ampicillin central and peripheral volume of distribution was 0.12 ± 0.02 L/kg and 0.15 ± 0.03 L/kg, respectively, while mean ± SD ampicillin clearance in typical patient with eGFR of 1.5 mL/s/1.73 m2 was 1.17 ± 0.05 L/h. The use of CPB did not significantly affect the pharmacokinetics of ampicillin. When administering 2 g of ampicillin before surgery, an additional dose should be administered to reach the PK/PD target of fT > MIC = 50% if the operation lasts longer than 430 min in patients with moderate to severe renal impairment, 320 min in patients with mild renal impairment, 220 min in patients with normal renal function status or 140 min in patients with an augmented renal clearance.
- Klíčová slova
- Antibiotic prophylaxis, ampicillin, cardiac surgery patients, cardiopulmonary bypass, nonlinear mixed-effects modelling, pharmacokinetics,
- MeSH
- ampicilin MeSH
- antibakteriální látky * terapeutické užití MeSH
- dospělí MeSH
- kardiochirurgické výkony * MeSH
- kardiopulmonální bypass škodlivé účinky metody MeSH
- lidé MeSH
- prospektivní studie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ampicilin MeSH
- antibakteriální látky * MeSH
BACKGROUND: Cardiac surgery and cardiopulmonary bypass (CPB) have been shown to stimulate a systemic inflammatory response which has been associated with adverse postoperative outcomes. Adipose tissue, both epicardial (EAT) and subcutaneous (SAT), is a known source of inflammatory cytokines, but its role in the pathophysiology of surgery- and CPB-induced systemic inflammatory response has not been fully elucidated. Therefore, we conducted a study to establish levels of selected cytokines in EAT and SAT prior to and after surgery with CPB. METHODS: Adipose tissue samples were obtained from patients undergoing planned cardiac surgery on CPB. Samples from EAT and SAT were collected before and immediately after CPB. Levels of tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), adipocyte fatty acid-binding protein (AFABP), leptin and adiponectin were determined by ELISA, which were adjusted for a total concentration of proteins in the individual samples. RESULTS: Samples from 77 patients (mean age 67.68 ± 11.5 years) were obtained and analysed. Leptin, adiponectin, TNF-α and AFABP were shown to decrease their concentrations statistically significantly in the EAT after CPB while no statistically significant drop was observed in the SAT. On the contrary, IL-6 showed only a slight and statistically insignificant decrease in the EAT after CPB and it was in the SAT where a statistically significant drop was observed. DISCUSSION: One of the most relevant findings of this study was the marked decrease in EAT levels of TNF-α, AFABP, leptin and adiponectin after the CPB termination. Our results suggest that EAT might serve as a pool of cytokines which are released into the circulation in reaction to surgery with CPB. Should these novel findings be confirmed, new strategies to assess and possibly reduce EAT contribution on adverse outcomes of cardiac surgery may be developed.
- Klíčová slova
- cardiopulmonary bypass, cytokines, epicardial adipose tissue, inflammation, subcutaneous adipose tissue, systemic inflammatory response,
- MeSH
- cytokiny metabolismus MeSH
- kardiopulmonální bypass metody MeSH
- lidé MeSH
- perikard metabolismus MeSH
- podkožní tuk metabolismus MeSH
- senioři MeSH
- tuková tkáň metabolismus MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- cytokiny MeSH
OBJECTIVE: Cardiac surgery is known to trigger a systemic inflammatory response. While the use of conventional cardiopulmonary bypass (CPB) results in profound inflammation, modified mini-CPB is considered less harmful. We evaluated the impact of cardiac surgery on the expression of CD162, CD166, CD195 molecules and their association with the type of CPB used. METHODS AND RESULTS: Twenty-four patients were enrolled in our study. Twelve of them were operated using conventional CPB while the other twelve patients underwent surgery with mini-CPB. Blood samples were analysed by flow cytometry. We observed a significant increase in median fluorescence intensity of CD162 and CD195 that peaked instantly after surgery and normalized to the baseline value on the 1st day post surgery, whereas CD166 was initially down-regulated and its median fluorescence intensity (MFI) value increased to the baseline in the next few days. CONCLUSION: We observed immediate changes in the expression of CD162, CD166, and CD195 molecules on the neutrophils after surgery in both study groups of patients. The intensity of the observed changes was significantly greater in the group of patients who underwent conventional CPB compared to patients who underwent mini-CPB cardiac surgery.
- Klíčová slova
- CD162, CD166, CD195, cardiopulmonary bypass, inflammation,
- MeSH
- CD antigeny analýza imunologie MeSH
- fetální proteiny analýza imunologie MeSH
- kardiopulmonální bypass škodlivé účinky přístrojové vybavení metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- membránové glykoproteiny analýza imunologie MeSH
- miniinvazivní chirurgické výkony škodlivé účinky přístrojové vybavení metody MeSH
- molekuly buněčné adheze neuronové analýza imunologie MeSH
- neutrofily imunologie MeSH
- receptory CCR5 analýza imunologie MeSH
- senioři MeSH
- zánět etiologie imunologie prevence a kontrola MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- ALCAM protein, human MeSH Prohlížeč
- CCR5 protein, human MeSH Prohlížeč
- CD antigeny MeSH
- fetální proteiny MeSH
- membránové glykoproteiny MeSH
- molekuly buněčné adheze neuronové MeSH
- P-selectin ligand protein MeSH Prohlížeč
- receptory CCR5 MeSH
OBJECTIVES: The systemic inflammatory response syndrome (SIRS) after cardiac surgery with cardiopulmonary bypass (CPB) exacerbates organ dysfunction and increases postoperative mortality. The aim of this study was to reduce SIRS after CPB in a pig model by profoundly decreasing all blood defence factors (complement, coagulation and fibrinolytic and contact systems, leukocytes and thrombocytes) using pre‑operative aphaeresis. METHODS: Thirty-three pigs underwent 3 h of hypothermic CPB with 2 h of cardioplegic arrest, followed by 4 days of observation. One half of the sample underwent prebypass plasma-thrombo-leukocyte aphaeresis with the adjuvant leukofiltration. RESULTS: In the control group, there were classical signs of SIRS (tachycardia, tachypnea and leukocytosis) postoperatively. There was also myocardial ischaemia and the need for inotropic support in 90% of the control animals. Neutrophils showed an increase in superoxide anion production (P < 0.001), and surface neutral protease activity (P < 0.001) and blood endotoxin levels increased (P < 0.01) compared with preoperative levels. In contrast, in the aphaeretic group, there were no classical signs of SIRS; no myocardial ischaemia; minimum neutrophil production of the superoxide anion and protease activity were recorded (P < 0.001); and endotoxin levels were also decreased (P < 0.05) compared with the controls. In the control group, the haemodynamic problems associated with disconnecting from CPB correlated with the histologic findings in the myocardium (leukocyte endothelial adhesion and leukodiapedesis). CONCLUSIONS: Pre‑operative plasma‑thrombo-leukocyte aphaeresis significantly reduces the major symptoms of SIRS and organ dysfunction after 3 h of CPB without adverse effects, such as bleeding and infection, during the postoperative course.
- Klíčová slova
- cardiopulmonary bypass, plasma‑thrombo-leukocyte aphaeresis, systemic inflammatory response syndrome,
- MeSH
- ischemická choroba srdeční etiologie MeSH
- kardiopulmonální bypass metody MeSH
- krevní plazma MeSH
- leukaferéza metody MeSH
- leukocyty fyziologie MeSH
- miniaturní prasata MeSH
- modely nemocí na zvířatech MeSH
- plazmaferéza metody MeSH
- prasata MeSH
- předoperační období MeSH
- separace krevních složek metody MeSH
- syndrom systémové zánětlivé reakce prevence a kontrola MeSH
- terapeutická hypotermie metody MeSH
- trombocyty MeSH
- vyvolaná zástava srdce metody MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: There is some controversy as to whether there is a benefit from the use of a centrifugal pump compared with a roller pump during cardiopulmonary bypass to facilitate cardiac surgery. We compared the two pumps, with the primary aim of determining any difference in the effects on inflammation after pulmonary endarterectomy surgery which required prolonged cardiopulmonary bypass and deep hypothermic circulatory arrest. METHODS: Between September 2010 and July 2013, 58 elective patients undergoing pulmonary endarterectomy were included in this prospective, randomised, controlled study; 30 patients were randomly allocated to the control group, which used a roller pump, and 28 patients to the treatment group, which used a centrifugal pump. Interleukin-6, procalcitonin, C-reactive protein, thromboelastographic parameters, P-selectin, international normalised ratio, activated prothrombin time, free haemoglobin, haematocrit, red blood cell count, white blood cell count, platelet count and protein S100β were recorded during and after the procedure. We also recorded the length of intensive care unit stay, blood loss and transfusion, neurological outcomes and respiratory and renal failure. RESULTS: There was a significant difference in the primary outcome measure: Interleukin-6 was significantly higher in the roller pump group (587 ± 38 ng · l(-1) vs. 327 ± 37 ng · l(-1); p<0.001) 24 hours after surgery, which we interpreted as an increased inflammatory response. This was confirmed by a significant rise in the procalcitonin level in the roller pump group 48 hours following surgery (0.79 (0.08-25.25) ng · ml(-1) vs. 0.36 (0.02-5.83) ng · ml(-1); p<0.05). There were, however, no significant differences in clinical outcome data. CONCLUSIONS: We have shown that the use of a centrifugal pump during prolonged cardiopulmonary bypass and deep hypothermic circulatory arrest is associated with a reduced inflammatory response compared to the standard roller pump. Larger multi-centre trials in this area of practice are required.
- Klíčová slova
- cardiac surgical procedure, cardiopulmonary bypass, centrifugal pump, inflammatory mediators, pulmonary endarterectomy, roller pump,
- MeSH
- dospělí MeSH
- kardiopulmonální bypass přístrojové vybavení metody MeSH
- krevní proteiny metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- počet leukocytů MeSH
- podpůrné srdeční systémy * MeSH
- zánět krev etiologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
- Názvy látek
- krevní proteiny MeSH
Coronary artery bypass grafting (CABG) is performed with the use of cardiopulmonary bypass (CPB) and cardioplegic arrest (CA) of the heart. The advantage of this technique, alternatively referred to as "on-pump" surgery, resides, for the surgeon, in relatively easy access to and manipulation with the non-beating, bloodless heart. However, the advantage that is, thereby, gained by the patient is paid off by an increased susceptibility to postoperative systemic inflammatory response syndrome (SIRS). Under unfavorable conditions, the inflammatory syndrome may develop into life-threatening forms of MODS (multiple organ dysfunction syndrome) or even MOFS (multiple organ failure syndrome). Deliberate avoidance of CPB, also known as "off-pump" surgery, attenuates early postoperative inflammation throughout its trajectory of SIRS→MODS→MOFS, but, in the long run, there appears to be no substantial difference in the overall mortality rates. In the last years, our knowledge of the pathophysiology of surgical inflammation has increased considerably. Recent findings, highlighting the as yet rather obscure role of pentraxin 3 (PTX3) in these processes, are discussed in this review article.
- Klíčová slova
- alarmins, cardiopulmonary bypass, coronary artery bypass grafting, interleukin-10, pentraxin 3, sterile inflammation,
- MeSH
- antiflogistika imunologie MeSH
- ateroskleróza imunologie MeSH
- C-reaktivní protein genetika imunologie MeSH
- infarkt myokardu imunologie MeSH
- interleukin-10 imunologie MeSH
- kardiopulmonální bypass škodlivé účinky metody MeSH
- koronární bypass škodlivé účinky metody MeSH
- lidé MeSH
- sérový amyloidový protein genetika imunologie MeSH
- syndrom systémové zánětlivé reakce etiologie genetika imunologie MeSH
- transkriptom MeSH
- vyvolaná zástava srdce škodlivé účinky metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- antiflogistika MeSH
- C-reaktivní protein MeSH
- interleukin-10 MeSH
- PTX3 protein MeSH Prohlížeč
- sérový amyloidový protein MeSH
AIM: The aim of this study was to compare the impact of standard cardiopulmonary bypass (CPB) with mini CPB on peripheral tissue perfusion. METHODS: 24 patients with ischemic heart disease scheduled for CPB were randomised to two groups: Group A (12 patients, standard CPB) and Group B (12 patients, mini CPB). Oxygen tension was measured with an optical multiparametric sensor inserted into the patient's deltoid muscle. RESULTS: Lower priming in Group B (870 ± 221 mL) vs. Group A (1502 ± 48 mL) and significantly reduced hemodilution during mini CPB (Group B 25.3 ± 1.1% vs. Group A 30.1 ± 2.3%) were recorded. Higher and continuous blood flow during perfusion was analysed in Group A (4.58 ± 0.34 L.min(-1)) and lower than calculated blood flow was found in Group B (3.49 ± 0.51 L.min(-1) vs. 4.66 ± 0.38 L.min(-1)). There was a direct correlation between mean arterial pressure (MAP) and ptO2 in Group A during CPB and a direct correlation between pump blood flow and MAP during CPB in Group B. Higher levels of ptO2 during CPB and surgery after CPB in comparison with initial levels were found in Group B. Decreased ptO2 levels after surgery were found in both groups. CONCLUSION: Mini CPB enables perfusion with a relatively low flow. The results of this study suggest that a flow decrease in mini CPB is well tolerated by the organism.
- MeSH
- arteriální tlak MeSH
- elektivní chirurgické výkony metody MeSH
- hodnocení rizik MeSH
- ischemická choroba srdeční krev patofyziologie chirurgie MeSH
- kardiopulmonální bypass přístrojové vybavení metody MeSH
- kyslík krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikrocirkulace * MeSH
- musculus deltoideus krevní zásobení MeSH
- oxymetrie přístrojové vybavení metody MeSH
- pilotní projekty MeSH
- reprodukovatelnost výsledků MeSH
- rizikové faktory MeSH
- senioři MeSH
- spotřeba kyslíku MeSH
- vzorkové studie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- kyslík MeSH
Interleukin-10 (IL-10) is considered to be a cytokine with potent anti-inflammatory properties, which have been previously linked to increased incidence of sepsis. The level of IL-10 is elevated by cardiac surgery when cardiopulmonary bypass (CPB) and methylprednisolone are used. In our study, we compare the level of IL-10, IL-10 Receptor (IL-10R), and percentage of neutrophils between two groups of cardiac surgical patients undergoing Coronary Artery Bypass Grafting, both of which were not given methylprednisolone. The first group was operated with conventional CPB, while the second group was operated with minimally invasive CPB (mini-CPB). We detected enhanced level of IL-10 during surgery and at the end of surgery in both groups of patients. While no correlation between IL-10 and IL10R was found, IL-10 was positively correlated with increased percentage of neutrophils at the time points when the level of IL-10 peaked.
- MeSH
- aktivace neutrofilů MeSH
- cytokiny metabolismus MeSH
- interleukin-10 metabolismus MeSH
- kardiopulmonální bypass metody MeSH
- koronární bypass metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- methylprednisolon farmakologie MeSH
- miniinvazivní chirurgické výkony MeSH
- neutrofily cytologie metabolismus MeSH
- receptory interleukinu-1 biosyntéza MeSH
- regulace genové exprese * MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cytokiny MeSH
- interleukin-10 MeSH
- methylprednisolon MeSH
- receptory interleukinu-1 MeSH
AIMS: To follow the IFNγ receptor expression on monocytes and granulocytes of cardiac surgical patients with respect to the type of cardiopulmonary bypass (CPB). METHODS: Expression of IFNγ receptor on monocytes and granulocytes of 26 cardiac surgical patients operated with the use of either "standard" or "miniaturised" CPB was determined by flow cytometry. RESULTS: The significant increase in IFNγ receptor expression on monocytes on the 1(st) and on the 3(rd) postoperative days was revealed in both groups of patients (p<0.001) irrespective of the type of CPB used, being non-significantly different between groups. In contrast, the expression of IFNγ on granulocytes displayed significant differences in terms of the CPB used. Whereas, in "standard" CPB patients, granulocyte INFγ receptor expression reached its maximum immediately after surgery (p<0.01), in "miniivasive" CPB patients, the peak in INFγ receptor expression was postponed to the 1(st) postoperative day (p<0.05). Statistically significantly higher IFNγ receptor expression on granulocytes was found in "standard" CPB patients (p<0.05). CONCLUSION: Compared to "miniaturised" CPB patients, the significantly higher IFNγ receptor expression on granulocytes was found in "standard" CPB patients (p<0.05) on the 1(st) postoperative day.
- MeSH
- granulocyty metabolismus MeSH
- kardiochirurgické výkony * MeSH
- kardiopulmonální bypass klasifikace metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- miniaturizace MeSH
- monocyty metabolismus MeSH
- pooperační období MeSH
- průtoková cytometrie MeSH
- receptor interferonu gama MeSH
- receptory interferonů metabolismus MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- receptory interferonů MeSH
BACKGROUND: Regional hypoperfusion has been associated with the development of postoperative organ dysfunction in cardiac surgery involving cardiopulmonary bypass (CPB). Direct tissue oxymetry is a potentially new method for monitoring the quality of the peripheral tissue perfusion during CPB. The aim of this study was to assess the effects of CPB in skeletal muscle oxygenation when measured in the deltoid muscle by direct oxymetry during perioperative period. METHOD: Seven patients underwent on-pump coronary artery bypass grafting. Direct oxymetry was performed by an optical cathether introduced into the deltoid muscle. Continuous measurement was made during the surgical procedure and the postoperative period. Mean arterial blood pressure, blood flow during CPB, laboratory markers of tissue hypoperfusion, blood gases and body temperature were also recorded. RESULTS: Interstitial muscle tissue oxygen tension (pO(2)) decreased after the introduction to anaesthesia and, more significantly, during CPB. After the disconnection from CPB at the end of the operation, the pO(2) returned to pre-anaesthetic values. During the first hours after admission of the patients to the intensive care unit, the pO(2) progressively decreased, reached a minimum value after four hours, and increased slowly thereafter. There was a significant correlation of pO(2) with mean arterial blood pressure and blood flow during that time. CONCLUSION: The result of this first measurement seems to demonstrate that the standard technique of conducting cardiopulmonary bypass produces low muscle oxygen tension and, thus, little perfusion of skeletal muscle. The data also indicate that both high mean arterial blood pressure and high flow are necessary during CPB to ensure skeletal muscle perfusion. The investigation is continuing.
- MeSH
- analýza krevních plynů MeSH
- kardiopulmonální bypass přístrojové vybavení metody MeSH
- koronární bypass přístrojové vybavení metody MeSH
- krevní tlak MeSH
- kyslík metabolismus MeSH
- lidé MeSH
- musculus deltoideus metabolismus MeSH
- oxymetrie přístrojové vybavení metody MeSH
- perfuze přístrojové vybavení metody MeSH
- předoperační období MeSH
- regionální krevní průtok MeSH
- senioři MeSH
- tělesná teplota MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- kyslík MeSH