微创心脏直视手术中肺功能变化的研究

目的 :探讨微创心内直视手术期间肺通气功能的变化。方法 :对 15例择期心脏手术患者在麻醉手术期间及体外循环前后 ,采用旁气流呼吸监测的方法测定通气功能的变化。结果 :气道峰压 (Ppeak)在体外循环 (CPB)前 5 m in始增高 (P<0 .0 1) ;胸肺顺应性在 CPB前 5 min开始下降 ((P<0 .0 5 ) ,手术结束时恢复至基础值水平。结论 :微创心脏直神手术后肺通气功能有一定程度损伤     

心血管手术术中经食管超声监测的价值

目的 探讨心血管手术术中麻醉医生行经食管超声心动图(TEE)监测的临床价值.方法 326例患者行体外循环心血管手术,全麻诱导插管后由麻醉医师行围术期 TEE监测,与术前经胸壁超声心动图(TTE)比较,及时调整手术方式,术中实时监测判断手术效果,术后判断心脏功能,指导血管活性药物应用.结果 经TEE提示,15例(4.60%)更改了手术方式,8例(2.45%)及时再次手术处理,26例(7.98%)停体外循环保留经食管探头监测心脏功能及指导用药至拔除气管导管.结论 麻醉医师在体外循环术中行TEE监测有助于手术的成功实施.     

Effect of cardiopulmonary bypass on plasma concentrations of diltiazem and its two active metabolites

Abstract— Diltiazem is often used to prevent myocardial ischaemia during the perioperative period of coronary artery bypass surgery. The purpose of this study was to investigate the effect of cardiopulmonary bypass (CPB) on plasma concentrations of diltiazem and of its two main and active metabolites (N-monodemethyldiltiazem (N-desmethyldiltiazem) and desacetyldiltiazem). The patients were administered their usual treatment during the preoperative days. The last dose was administered immediately before anaesthesia. At the onset of CPB, a significant decrease in the plasma concentrations of diltiazem and its metabolites was observed, whereas the variation was slight and not significant when the plasma concentrations were corrected for haemodilution. These results confirm that the decrease observed at the initiation of the bypass procedure can be ascribed to the haemodilution induced by the CPB. During CPB, the concentrations of diltiazem and its metabolites remained constant suggesting that the rate of metabolism and excretion of the drug was altered during the bypass procedure. At the end of CPB, there was no increase of drug plasma concentrations suggesting that no redistribution of diltiazem from tissues to plasma occurred. Furthermore, this study shows that only 33% of subjects have therapeutic levels of diltiazem before anaesthesia, and that all subjects have subtherapeutic levels during and after the CPB. These results suggest that a higher chronic oral dose of the drug should be given in patients undergoing cardiac surgery with CPB.     

Evaluation of Altered Drug Pharmacokinetics in Critically Ill Adults Receiving Extracorporeal Membrane Oxygenation

Extracorporeal membrane oxygenation (ECMO) is a life‐support modality used in patients with refractory cardiac and/or respiratory failure. A significant resurgence in the use ECMO has been seen in recent years as a result of substantial improvements in technology and survival benefit. With expanding ECMO use, a better understanding of how ECMO affects drug pharmacokinetics (PK) is necessary. The vast majority of PK studies in patients receiving ECMO have been conducted within neonatal or pediatric populations or within a controlled environment (e.g., in vitro or ex vivo). Because of significant differences in absorption, distribution, metabolism, and excretion, it may be inappropriate to extrapolate these PK data to adults. Thus, the aims of this review are to evaluate the changes in drug PK during ECMO and to summarize the available PK data for common drugs used in the adult critically ill patients during ECMO support. A search of the PubMed (1965–July 2016), EMBASE (1965–July 2016), and Cochrane Controlled Trial Register databases was performed. All relevant studies describing PK alterations during ECMO in ex vivo experiments and in adults were included. Evaluation of the data indicated that drug PK in adults receiving ECMO support may be significantly altered. Factors influencing these alterations are numerous and have intricate relationships with each other but can generally be classified as ECMO circuit factors, drug factors, and patient factors. Commonly used drugs in these patients include antimicrobials, sedatives, and analgesics. PK data for most of these drugs are generally lacking; however, recent research efforts in this patient population have provided some limited guidance in drug dosing. With an improved understanding of altered drug PK secondary to ECMO therapy, optimization of pharmacotherapy within this critically ill population continues to move forward.     

The effects of alcoholism pharmacotherapy on immune responses in alcohol-dependent patients

Chronic alcohol use has profound modulatory effects on the immune system. Both the innate and the acquired immunity are compromised. The use of pharmacotherapy is increasingly applied to enhance the percentage of success in maintaining alcoholic patients in remission. Disulfiram, naltrexone and gamma hydroxybutiric acid are the drugs used for this purpose in Italian Addiction Services. In this study we analyze the effect of pharmacotherapy of alcohol dependence on immune responses in alcoholics. Six groups were studied. Group A included 10 patients who were still using alcohol. Group B consisted of 10 patients abstinent from alcohol in treatment only with group therapy. Groups C, D and E were composed of 10 patients each, treated for at least 6 months with oral doses of gamma hydroxybutiric acid, naltrexone or disulfiram respectively. Ten age- and sex-matched healthy volunteers who never misused alcohol were included as a control group. Lymphoproliferation and peripheral mononuclear cell production of the Th1 cytokines IL-2 and IFN-gamma, the Th2 cytokine IL-4, and of the pro-inflammatory cytokines IL-1 and TNF-alpha were evaluated in all the patients and controls. The level of activity of the hypothalamus pituitary adrenal axis was assessed. Both ACTH and cortisol levels in plasma were elevated in alcoholic patients with no treatment. In this group a significant alteration of cytokine production was observed. TNF and IFN-gamma were lower than controls, while the Th2 cytokine IL-4 was increased. These altered levels state for a Th1/Th2 unbalance characterized by decreased Th1 response in the presence of Th2 predominance. In patients undergoing pharmacological treatment, none of the immune parameters were different from those observed in healthy controls, independently of the type of drug administered. These data indicate that pharmacotherapy more than group therapy treatment is able to ameliorate the immune system functioning in alcoholic patients.     

Papaverine disposition in cardiac surgery patients and the effect of cardiopulmonary bypass

Summary Cardiac surgery involving cardiopulmonary bypass (CPB) causes substantial physiologic changes which may potentially alter the pharmacokinetic properties of drugs used during and after the procedure. Studies with fentanyl have implied a relationship between prolonged elimination half-lives following CPB and decreased liver perfusion during and after the procedure. To further test this hypothesis, the effects of CPB on the pharmacokinetics of papaverine, a coronary vasodilator currently being added to the cardioplegic solution to prevent vasospasm, were studied. The drug was given to two groups of patients, one (n=6) undergoing surgery with and one (n=5) without CPB, the latter serving as controls. Plasma papaverine concentrations declined biexponentially in the control patients with a mean elimination half-life of 1.30±0.25 h, total plasma clearance of 13.8±3.75 ml/min/kg, volume of distribution of 1.52±0.45 l/kg and volume of distribution, steady-state, of 0.992±0.530 l/kg. For the CPB group, only half-life was estimated, and averaged 2.77±0.28 h, significantly greater (p<0.01) than that in the controls. These results further confirm the increased half-lives seen with other hepatically cleared drugs following CPB and have implications in the clinical management of patients given drugs eliminated in this manner.     

Alteration of vancomycin pharmacokinetics during cardiopulmonary bypass in patients undergoing cardiac surgery.

The alteration of vancomycin pharmacokinetics during cardiopulmonary bypass (CPB) in patients undergoing cardiac surgery was studied. Eighteen patients were enrolled in the study. Vancomycin (1 g) was intravenously infused one to two hours before surgery. Blood samples were taken before, during, and after CPB. Serum drug concentrations were determined by an automated fluorescence polarization immunoassay and adjusted, with a bayesian analysis, to a bi-compartmental model implemented in a pharmacokinetic system program. Serum creatinine, hematocrit, and plasma proteins were also measured before, during, and after CPB. During CPB, serum creatinine, hematocrit, and plasma protein values all decreased significantly (p < 0.05). Serum vancomycin concentration also diminished abruptly with CPB (7.04 micrograms/mL; 95% confidence interval, 5.70-8.38 micrograms/mL) but increased moderately during the next 30 minutes, probably attributable to redistribution into plasma from tissue stores. Vancomycin's apparent volume of distribution showed an important increase during CPB (58.8%) (p < 0.0005), and its systemic clearance also increased significantly after CPB (19.7%) (p < 0.0005). The decrease in serum vancomycin concentration seems mediated by the hemodilution associated with the pump prime volume. Vancomycin's mean +/- S.D. nadir serum concentration before the next dose was 7.13 +/- 2.1 micrograms/mL. In patients undergoing cardiac surgery and treated prophylactically with a 1-g preoperative i.v. dose of vancomycin, the onset of CPB was associated with a drop in serum vancomycin concentration.     

艾司洛尔对常温不停跳心内直视手术期间心肌损伤标志物的影响

目的 探讨艾司洛尔对常温不停跳心内直视手术期间心肌损伤标志物的影响。方法选择48例择期二尖瓣置换术病人随机分为对照组(C组)和艾司洛尔组(E组),每组各24例,常规建立心肺转流(CPB),平行循环后不降温及不主动复温,阻断腔静脉,不阻断主动脉,平均动脉压(MAP)维持在50～70mmHg,在心脏跳动下进行手术。E组在心内直视手术开始前予艾司洛尔1～2mg/kg静脉注射后,以0.3％的浓度静滴维持心率在30～50次/分。分别于手术前、术后即刻、术后6小时、12小时、24小时、48小时取动脉血测定血清C—反应蛋白(CRP)、肌酸激酶同工酶(CK—MB)、肌钙蛋白T(cTnT)和肌钙蛋白I(cTnI)浓度变化。结果 两组病人性别、年龄、心功能、心胸比值(C/T)差异无显著意义;术前两组间CRP、CK—MB、cTnT、cTnI差异无显著意义(P>0.05),两组患者血清CRP、CK—MB、cTnT、cTnI浓度在CPB后即刻显著升高(P<0.01),E组于术后6小时达峰值,术后24小时降至正常水平,C组于术后12小时达峰值,术后48小时降至正常值,同一时点比较,E组明显低于C组(P<0.05 or 0.01)。结论 艾司洛尔用于常温不停跳心内直视手术中可显著降低心肌损伤标志物升高程度,使酶峰提前,促进术后心功能恢复,具有良好的心肌保护作用。     

Cefamandole pharmacokinetics during standard and pulsatile cardiopulmonary bypass

The pharmacokinetics of cefamandole during standard or pulsatile cardiopulmonary bypass were studied in 13 adult cardiac surgery patients. All patients received 20 mg/kg of cefamandole intravenously at midnight before surgery, 6 AM on the morning of surgery and just prior to the initiation of cardiopulmonary bypass (CPB) surgery. Serum, skeletal muscle, and fat samples were taken at the beginning of CPB and at 30-minute intervals thereafter and assayed for cefamandole concentration. The average elimination rate constant and elimination half-life for cefamandole in patients undergoing standard CPB were 0.73 +/- 0.09 hour-1 and 0.94 +/- 0.11 hour, respectively. In contrast patients undergoing pulsatile CPB had significantly slower elimination rate constants (0.50 +/- 0.1 hour-1 and 1.4 +/- 0.28 hours, respectively; P less than or equal to .05). Area under the curve (AUC) values for cefamandole in fat and muscle tissue were higher in patients undergoing pulsatile CPB, but the differences were not statistically significant. Prolonged elimination from the serum, skeletal muscle, and adipose tissue, as compared with normal subjects, is seen with both pulsatile and standard CPB but is greater for the pulsatile method. Intraoperative dosing of cefamandole is required to maintain adequate serum and tissue levels for operations lasting longer than 4 or 6 hours in which standard or pulsatile CPB, respectively, are used.     

Alcuronium kinetics in patients undergoing cardiopulmonary bypass surgery.

1 The disposition of alcuronium was investigated in 10 patients undergoing surgery involving cardiopulmonary bypass (CPB) and compared with results from a group of non-cardiac patients studied previously. 2 After intravenous administration of a combined bolus and infusion dosage regimen, plasma concentrations fell in a bi-exponential fashion to a mean value of 0.55 micrograms/ml immediately before the start of extracorporeal circulation. 3 During CPB an apparent steady-state of alcuronium was reached immediately after commencement of CPB, however plasma concentrations were some 50% higher than those noted prior to commencement of CPB and those predicted using previous pharmacokinetic data from normal surgical patients. 4 Once CPB was completed and the alcuronium infusion terminated, post-infusion alcuronium plasma concentrations again appeared to decline bi-exponentially with time. 5 Of the pharmacokinetic parameters which were calculated model-independently, the apparent volume of distribution (Vss) was unchanged (329 vs 313 ml/kg) and the elimination half-life (t1/2,z) (532 vs 199 min) was prolonged and the plasma clearance (CL) (0.8 vs 1.34 ml min-1kg-1) markedly reduced in these patients compared to non-cardiac surgical patients. 6 As a result of these changes in alcuronium concentration during CPB and the diminished elimination of alcuronium following CPB, a closer monitoring of neuromuscular function may be necessary in cardiac patients undergoing CPB.     

Pharmacotherapy during pediatric extracorporeal membrane oxygenation: a review

Introduction: Pediatric critical illness and associated alterations in organ function can change drug pharmacokinetics (PK). Extracorporeal membrane oxygenation (ECMO), a life-saving therapy for severe cardiac and/or respiratory failure, causes additional PK alterations that affect drug disposition.

Areas covered: The purposes of this review are to discuss the PK changes that occur during ECMO, the associated therapeutic implications, and to review PK literature relevant to pediatric ECMO. We discuss various classes of drugs commonly used for pediatric patients on ECMO, including sedatives, analgesics, antimicrobials and cardiovascular drugs. Finally, we discuss future areas of research and recommend strategies for future pediatric ECMO pharmacologic investigations.

Expert opinion: Clinicians caring for pediatric patients treated with ECMO must have an understanding of PK alterations that could lead to either therapeutic failures or increased drug toxicity during this life-saving therapy. Limited data currently exist for optimal drug dosing in pediatric populations who are treated with ECMO. While there are clear challenges to conducting and analyzing data associated with clinical pharmacokinetic-pharmacodynamic studies of children on ECMO, we present techniques to address these challenges. Improved understanding of the physiology and drug disposition during ECMO combined with PK-PD modeling will allow for more adaptable and individualized dosing schemes.     

万汶用于体外循环对凝血功能的影响

目的 观察万汶和贺斯在体外循环(CPB)手术中对凝血功能的影响,明确万汶在体外循环中的应用价值.方法 选择40例先天性心脏病纠治术的患者,随机分为万汶组20例(A组)和贺斯组20例(B组)分别将2种胶体用于CPB预充液,术中监测心率(HR)、平均动脉压(MAP)、中心静脉压(CVP),并监测CPB前30 min和CPB后60min的红细胞压积(HCT)、血浆凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(Fib).结果 CPB后60min 2组PT均无明显变化(P＞0.05);APTT较体外循环前延长,且2组比较差异显著(P＜0.05);Fib均低于CPB前(P＜0.05),2组间差异无统计学意义(P＞0.05).结论 适量万汶和贺斯应用于CPB作为预充液一部分,对血流动力学和凝血功能均无明显影响,且万汶对机体凝血功能影响更小,是目前用于CPB的较好的新一代血浆代用品.     

Role of aprotinin in the management of patients during and after cardiac surgery

Management of patients undergoing cardiac surgery has evolved in recent years as more is understood about the physiological changes and responses that occur during and after cardiopulmonary bypass (CPB). In particular, our understanding of the mechanisms involved in haemostasis and in the inflammatory response to bypass surgery, has allowed significant refinements in patient management. Improvements in the pharmacological conservation of blood loss have been striking, particularly with the development of the serine protease inhibitor, aprotinin (Trasylol^®, Bayer). Aprotinin represents a significant improvement, especially for patients at high risk, since it reduces the need for allogeneic and (sometimes scarce) blood products. However, in view of its cost, making an appropriate selection of patients most at risk of serious blood loss is a major consideration in the use of aprotinin. While its mechanisms of action are not well understood, the use of aprotinin also appears to reduce inflammatory response to CPB.     

Role of aprotinin in the management of patients during and after cardiac surgery

Management of patients undergoing cardiac surgery has evolved in recent years as more is understood about the physiological changes and responses that occur during and after cardiopulmonary bypass (CPB). In particular, our understanding of the mechanisms involved in haemostasis and in the inflammatory response to bypass surgery, has allowed significant refinements in patient management. Improvements in the pharmacological conservation of blood loss have been striking, particularly with the development of the serine protease inhibitor, aprotinin (Trasylol, Bayer). Aprotinin represents a significant improvement, especially for patients at high risk, since it reduces the need for allogeneic and (sometimes scarce) blood products. However, in view of its cost, making an appropriate selection of patients most at risk of serious blood loss is a major consideration in the use of aprotinin. While its mechanisms of action are not well understood, the use of aprotinin also appears to reduce inflammatory response to CPB.     

Role of Corticosteroids During Cardiopulmonary Bypass

Corticosteroids are commonly used in the peri-operative setting for patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). The inflammatory response to CPB is associated with organ dysfunction and increased mortality. Corticosteroids reduce biochemical inflammatory markers associated with CPB, however the impact on clinical outcomes is mixed. The purpose of this article is to evaluate the evidence of changes in clinical outcomes associated with the peri-operative administration of corticosteroids in patients undergoing cardiac surgery with CPB. Randomized, placebo-controlled trials and meta-analyses were reviewed for evidence evaluating the impact of corticosteroids on clinical outcomes including mortality, myocardial infarction, atrial fibrillation (AF), duration of intubation, length of intensive care unit (ICU) or hospital stay, hyperglycemia, and gastrointestinal complications. Most of the relevant studies are underpowered to assess major clinical outcomes. Although corticosteroids likely reduce the risk of AF, this needs to be evaluated when used in addition to or in lieu of other anti-arrhythmic agents. Evidence does not equivocally support the use of corticosteroids to improve clinical outcomes in cardiac surgery patients.Key Words: cardiac surgery, cardiopulmonary bypass, corticosteroidsAlthough commonly used in the peri-operative setting of cardiopulmonary bypass (CPB), corticosteroids have limited evidence of improving clinical patient outcomes. The anti-inflammatory effects of corticosteroids are well studied, but they do not necessarily correlate with improved clinical outcomes. In 2004, guidelines from the American Heart Association recommended “liberal prophylactic use” based on the reduction in systemic inflammation, however corticosteroids are no longer recommended in the 2011 guidelines.^1,2During CPB, blood is exposed to foreign materials causing the systemic release of inflammatory markers including tumor necrosis factor-α and interleukin-6.³ These substances have known cardio-depressant effects, although most patients recover normally postoperatively. For some, however, the inflammatory response can cause hypotension and organ dysfunction. Inflammation also causes impaired gas exchange and interstitial damage throughout the lungs.⁴ Thus CPB-induced inflammation could lead to worse outcomes including myocardial ischemia, cardiac arrhythmias, and prolonged respiratory failure.The physiologic effects of corticosteroids can predict the potential benefits and risks. Through multiple mechanisms, corticosteroids minimize the CPB-induced inflammatory response. They decrease capillary wall permeability, preventing migration of inflammatory mediators into the systemic circulation. Corticosteroids also prevent the release of intracellular cytokines and subsequent adhesion to cell surfaces. Conversely, hyperglycemia, a well-known side effect, could contribute to impaired immune function and delays in wound healing. Renal effects can cause electrolyte and fluid imbalances, leading to hemodynamic changes and cardiac instability. Gastrointestinal effects of corticosteroids could cause nausea, vomiting, and ulcerative bleeding. While the anti-inflammatory effects are desirable, evidence of improved clinical outcomes is needed before recommending corticosteroids in the peri-operative setting. This review will summarize evidence from randomized controlled studies and meta-analyses that evaluate the impact of peri-operative use of corticosteroids on clinical outcomes.     

常温与低温体外循环下婴幼儿心脏直视手术对细胞因子的影响

目的探讨常温及低温体外循环心脏直视手术对细胞因子的影响。方法方法选择先天性心脏病40例,随机分为常温组及低温组各20例,分别于术晨、体外循环结束时及术后6、12、24、48h抽取患者动脉血标本。测定血浆TNF-α、IL-6、IL-8。结果两组术前各项检查指标无显著差异。①常温体外循环下炎性因子升高水平低于中低温;②常温体外循环下炎性因子恢复时间比中低温明显缩短。结论常温体外循环心脏直视手术对细胞因子的影响显著轻于低温组,因而对术后机体的恢复优于低温方法。     

Alternative use of isoflurane and propofol confers superior cardioprotection than using one of them alone in a dog model of cardiopulmonary bypass

Our previous clinical study reported that isoflurane preconditioning and high-dose propofol posttreatment attenuated myocardial ischemia/reperfusion injury of patients in surgery with cardiopulmonary bypass (CPB). This study was designed to confirm this cardiac protection by use of a dog CPB model and to elucidate the related mechanism. Adult mongrel male dogs undergoing standard CPB were assigned into 4 groups: Sham group, Propofol group, Isoflurane (Iso) group and isoflurane in combination of propofol (pre-Iso+P) group. After induction, anesthesia was maintained with propofol (Propofol group), isoflurane (Iso group) or isoflurane preconditioning in combination with propofol posttreatment (pre-Iso+P group). After 2 h cardiac arrest and CPB, aortic cross-clamping was released to allow 2 h reperfusion. The results demonstrated that joint use of isoflurane and propofol facilitated cardiac functional recovery, improved myocardial oxygen utilization and decreased cardiac enzyme release. Also, the oxidative damage caused by ischemia/reperfusion injury was remarkably attenuated. Linear regression analysis showed that cardiac function performance and oxidative stress status were inversely correlated, indicating the improved cardiac function was in closed association with the attenuation of oxidative stress. In addition, the cardiac oxygen consumption (VO(2)) was found to be significantly associated with the above cardiac function and oxidative stress parameters, suggesting VO(2) was predictive for the levels of cardiac damage and oxidative stress. Therefore, we conclude that alternative use of isoflurane and propofol confers superior cardioprotection against postischemic myocardial injury and dysfunction, and this protection was probably mediated by attenuation of cardiac oxidative damage.     

腺苷与双嘧达莫预适应在心肺转流中的心肌保护作用

目的 观察腺苷与核苷转运抑制剂双嘧达莫药理性预适应在心脏直视术心肺转流(CPB)中对心肌的保护作用.方法 53例心脏瓣膜置换术患者随机分为四组:腺苷组转流前微量泵入腺苷;联合组术前口服双嘧达莫,余同腺苷组;双嘧达莫组仅口服双嘧达莫;对照组泵入同体积生理盐水.分别于转流前、主动脉开放后2、6、16 h采集患者桡动脉血,测血清肌酸激酶同功酶(CK-MB)、肌钙蛋白I(cTn I)、丙二醛(MDA);观察术后机械通气时间及术后正性肌力药物的应用.结果 腺苷组术后多巴胺用量少,开放后2 h CK-MB、6 h MDA,开放后cTn I均较对照组显著降低,联合组开放后CK-MB、cTn I、MDA均降低.结论 外源性腺苷预适应有显著心肌保护作用,核苷转运抑制可增强这一作用,内源性腺苷对心肌保护的效果不明显.     

体外循环对血小板的影响及其与术后急性肺损伤的关系

目的探讨体外循环(CPB)对血小板的影响及其与术后急性肺损伤的关系。方法对20例体外循环下行心脏手术的患者,在肝素化前、转流30 min、体外循环停机时和术后24 h分别测定体外循环前后血小板计数(PLT)、血栓烷B2(TXB2)值变化;分别于术后用乌司他丁注射液20万U加入100 mL生理盐水中静脉滴注,参麦注射液30 mL加入5%葡萄糖注射液250 mL中静脉滴注,每日1次,连用14 d。并于手术后即刻、2 h和6 h行动脉血气分析、肺动态顺应性和氧合指数测定。观察术后不同时间点肺功能改变。结果与体外循环术前相比,血小板计数在术中和术后降低,血栓烷B2在术中明显增高,术后很快下降但仍高于术前(P<0.05或P<0.01)。肺动态顺应性和氧合指数在术后降低(P<0.05或P<0.01)。结论体外循环可导致血小板数量的改变和功能障碍,并在术后肺损伤中发挥重要作用。     

Cefazolin concentrations in serum during cardiopulmonary bypass surgery

The objective of the study was to investigate possible changes in cefazolin serum levels induced by cardiopulmonary bypass (CPB). Six cardiac male patients who underwent cardiac surgery requiring CPB took part in the study. Cefazolin 2 g was intravenously infused over 60 min before anesthesia and blood samples were taken at appropriate times after drug administration (0, 0.25, 0.5, 1, 4, 6, 8 h), 2 min before and 5 min after the beginning and 2 min before and 5 min after the end of CPB. Drug serum concentrations were determined by means of a microbiological method. Five minutes after the start of CPB, cefazolin serum levels decreased on average by 46.6% and remained steadily low until 5 min after the end of CPB. Then, they rose on average by 37.3% at 4 h and then declined slowly until the last sampling at 8 h. Cefazolin serum concentrations were low during CPB but remained in a potentially effective range for antimicrobial prophylaxis for this surgery.