Thiopentone levels during cardiopulmonary bypass

Plasma total and unbound concentrations of thiopentone were investigated during exponentially decreasing infusions in seven patients undergoing cardiopulmonary bypass. Total plasma thiopentone concentrations reached a plateau (10.2, SD 2.1 micrograms/ml) soon after the initial bolus dose and commencement of the infusion. Concentrations were maintained until the onset of cardiopulmonary bypass, whereupon total plasma thiopentone concentration fell abruptly to 50.0 (SD 5.8) percent of the prebypass level. The unbound fraction of thiopentone increased from 16.6 (SD 1.9) percent before bypass to a maximum of 29.3 (SD 5.6) percent during bypass (p less than 0.01), decreased to 22.9 (SD 3.3) percent at the end of bypass (p less than 0.01), but was still elevated 5-7 hours later (20.5, SD 2.5 percent). The result of the changes in binding was a smaller decline in unbound thiopentone concentration at the onset of bypass to 76.4 (SD 15.7) percent of the prebypass level. Also, unbound levels returned to the prebypass level by the end of bypass, whereas total levels remained low.     

Inclusion of sevoflurane in cardioplegia reduces neutrophil activity during cardiopulmonary bypass

OBJECTIVE: The purpose of this study was to examine the effects of sevoflurane cardioplegia on neutrophil response and complement activation after cardiopulmonary bypass (CPB). DESIGN: A prospective, randomized clinical investigation. SETTING: University-affiliated hospital; single institutional. PARTICIPANTS: Twenty-one male patients undergoing coronary bypass surgery using CPB. INTERVENTIONS: Eleven patients were randomly assigned to receive sevoflurane 2% as a part of the cardioplegic mixture (SEV). The control group (n = 10) received no sevoflurane in their cardioplegia (control). MEASUREMENTS AND MAIN RESULTS: Myeloperoxidase activity (MPO) was assayed in coronary sinus blood as a surrogate for neutrophilic response at the termination of CPB. MPO activity in the coronary sinus blood was lower in the patients who received sevoflurane compared with controls. MPO activity was higher in patients with cardiac events at 4-year follow-up when compared with asymptomatic patients. IL-8, C4b, C3d, C5a, and CH50 were assessed in coronary sinus and peripheral blood at time of CPB initiation (T0) and upon the termination of CPB (T2). Peripheral blood sampling occurred at the sixth hour after T0 (T6). IL-8 levels were significantly inhibited in the SEV group when compared with controls at T2 and T6. CH50 (an index of global activation of complement system) decreased 30% at T2 and 52% at T6. The classic component of the complement pathway (C4b) was effectively inhibited in the SEV group, whereas the common pathway (C3d and C5a) was similar in both groups. CONCLUSIONS: The addition of sevoflurane to cardioplegia is associated with an inhibition of neutrophils after CPB. A major component of the neutrophil response appears to be IL-8 mediated, although the classic complement pathway is also inhibited by sevoflurane.     

Propranolol binding in plasma during cardiopulmonary bypass

The effect of cardiopulmonary bypass on the plasma binding of propranolol was examined in seven patients. The fraction of propranolol free in plasma doubled, increasing from 6.6 to 13.5 per cent (P less than 0.001) following the administration of heparin, 400 IU/kg. Once cardiopulmonary bypass was concluded and protamine, 8 mg/kg, given, the free fraction decreased from 13.4 to 8.7 per cent (P less than 0.005). There was a further significant decrease to 6.5 per cent over the next 3.1 hours (SE +/- 0.3). Those alterations in the free fraction, which would result in more drug being available for binding to receptor sites and for exerting its pharmacologic effect, were due principally to the changes in free fatty acid levels produced by heparin and protamine, but also to the hemodilution produced by the pump prime.     

Dobutamine increases oxygen consumption during constant flow cardiopulmonary bypass

We have studied the effects of flow and dobutamine on systemic haemodynamic variables, oxygen delivery (DO2) and oxygen consumption (VO2) in 20 patients during cardiopulmonary bypass (CPB) with mild hypothermia (34 degrees C). In a subgroup of seven patients, we also studied the effects on gastric microcirculatory blood flow (MCF) using laser Doppler flowmetry. During CPB, measurements were made before and after two interventions: the first consisted of increasing flow from 2.4 to 3.0 litre min-1 m-2 for 10 min; the second consisted of an infusion of dobutamine at a rate of 6 micrograms kg-1 min-1 for 10 min during constant flow CPB. There were no significant differences in DO2, VO2 or haemodynamic variables between the two baseline measurements. The increase in flow raised DO2 (27%, P < 0.001), mean arterial pressure (P < 0.01) and MCF (P < 0.01), but failed to increase VO2. In contrast, dobutamine infusion increased VO2 (11%, P < 0.001) during constant flow CPB without significant changes in DO2, systemic haemodynamic variables or MCF. These results indicate that increases in VO2 during dobutamine may be flow-independent.      

Coronary artery bypass grafting by warm blood cardioplegia and normothermic cardiopulmonary bypass

Warm blood cardioplegia and normothermic cardiopulmonary bypass (CPB) have been used in coronary artery bypass grafting (CABG). The method of myocardial protection was intermittent combined antegrade and retrograde warm blood cardioplegia with terminal warm blood cardioplegia. We performed elective CABG in 30 patients above the age of 70 years (elderly group). These patients were compared with 30 patients below 70 years who underwent elective CABG (young group). No significant differences were observed about the preoperative data between two groups. No significant differences were obtained in the postoperative cardiac function, cerebral or renal complication between two groups. Warm blood cardioplegia and normothermic CPB were not associated with adverse effects on postoperative recovery in elderly as well as young patients. We may conclude that warm blood cardioplegia with normothermic CPB is a safe procedure for CABG in elderly as well as young patients.     

Effect of cardiopulmonary bypass on plasma levels of nifedipine

Blood levels of many medications are acutely lowered by cardiopulmonary bypass (CPB). Because nifedipine is often used to provide protection from coronary ischemia, a determination of the effect of CPB on plasma nifedipine levels might help to determine the potential clinical benefit of nifedipine during and after bypass. Four samples of blood were drawn from each of eight patients undergoing cardiac surgery: one before, two during, and one after CPB. Although plasma levels of nifedipine declined during and after bypass (P less than 0.05, analysis of variance), the time-course and slope of the decline indicate that this was an effect of normal metabolism of the drug rather than an effect of physiologic changes occurring during CPB. An important additional finding was that the majority of patients had subtherapeutic levels of nifedipine before bypass, suggesting that additional nifedipine given during and after surgery might be of benefit. The effect of the CPB circuit itself was also examined in vitro by mixing nifedipine into a pump prime solution that was then recirculated with 2 U of outdated blood while levels of nifedipine were measured for 3 h. Plasma levels did not change in either a CPB circuit exposed to light or kept in a darkened room.     

心肺转流围术期血浆肝素浓度的变化

目的　心肺转流 (CPB)围术期血浆肝素浓度的变化及其与抗凝监测、肝素中和及肝素反跳的关系。方法　 10例成人CPB心脏手术病人 ,于麻醉后肝素前、肝素 1、2、3、4、5、10min、CPB前、CPB后 5、10、30min、停机、中和 1∶0 5、1∶0 75、1∶1、中和结束及术后 1～ 6h采血。分别测定血浆肝素浓度 (应用发色底物抗Xa方法 ) ,激活部分凝血致活酶时间 (APTT)、凝血酶时间 (TT)及激活全血凝固时间 (ACT)。结果　静注肝素 (4 0 0U/kg)后 1min血浆浓度达高峰为 (6 4 6± 1 0 5 )U/ml,到CPB开始时为 (4 2 8± 0 30 )U/ml,停机时为 (2 82± 0 4 1)U/ml。CPB前血浆肝素浓度与ACT显著相关 (r =0 896 ,P <0 0 1)。首次中和 (比值为 1∶0 5 )后肝素浓度为 (0 12± 0 10 )U/ml。术后 3～ 4h肝素浓度重新升高 (与基础值相比P <0 0 1) ,但与ACT、APTT及TT均无相关性 (P >0 0 5 )。结论　CPB前ACT能可靠监测肝素抗凝 ;CPB后鱼精蛋白首次按 1∶0 5已基本能中和游离的肝素 ;总比例 1∶1 5后 ,无肝素反跳     

Clinical evaluation of normothermic cardiopulmonary bypass and cold cardioplegia.

BACKGROUND: To evaluate the validity of normothermic cardiopulmonary bypass (CPB) associated with topical hypothermia and cold cardioplegia technique. METHODS: In a clinical prospective trial, a consecutive series of 100 patients, homogeneous for demographics, clinical and operative data, undergoing coronary artery bypass surgery were randomized for hypothermic CPB (rectal temperature 28-32 degrees C group A, 50 patients) and normothermic CPB (rectal temperature 35-37 degrees C, group B, 50 patients). In both groups of patients cold crystalloid cardioplegic solution and topical hypothermia was used. RESULTS: During CPB group B patients had lower systemic vascular resistance (p=0.0001); they needed a significant (p=0.0001) increase in vasocostrictive. At the removal of aortic cross-clamp, a spontaneous sinus rhythm resumed in 48% of patients in group A and in 95% of group B patients (p=0.001). To disconnect CPB, vasoconstrictive drugs were used in 10% of patients in group B and in none of patients in group A (p=0.0001); vasodilating drugs were infused in 96% of patients in group A and in 40% of patients in group B (p=0.0001). In the immediate postoperative period, positive inotropic agents were used in 67% of patients in group A and in 22% of patients in group B (p= 0.0003); group B patients showed a more physiological rewarming, reduced periods of mechanical ventilation and an easier regulation of the volemia. CONCLUSIONS: In our clinical experience the technique of cold heart and warm body proved to be safe and effective in simplifying surgical procedures and facilitating postoperative management.     

The effects of venous cannulation technique and cardioplegia type on plasma potassium concentration and arterial blood pressure during cardiopulmonary bypass.

The cannulation method and cardioplegia solution used during cardiopulmonary bypass (CPB) may both influence plasma potassium concentrations ([K+]) and mean arterial blood pressure (MAP). Bi-caval or right atrial cannulation methods are routinely used in conjunction with crystalloid or blood cardioplegia. We investigated the influence of cannulation method and cardioplegia solutions on plasma [K+] and MAP during cardiopulmonary bypass. Sixty consecutive patients undergoing elective coronary artery bypass grafting (CABG) using CPB were studied. They were randomly divided into three groups of 20 patients. Patients in Group A underwent bi-caval venous cannulation and received crystalloid cardioplegia. Group B patients underwent right atrial cannulation and received crystalloid cardioplegia. Group C patients underwent right atrial cannulation and received blood cardioplegia. In each case. cardioplegia was administered antegrade via the aortic root. Plasma [K+], MAP. and hemoglobin concentration (Hb) were measured over an 8-min period following cardioplegia administration (pilot studies indicated pressure changes occuring post cardioplegia administration up to this time). The combination of bi-caval cannulation and crystalloid cardioplegia (Group A) was associated with the least increase in plasma [K+] and no decrease in MAP. The maximum [K+] for this Group was 4.2 mmol/L (4.6% increase). The minimum mean pressure was 57 mmHg (13.6% increase). Both right atrial cannulation groups (B and C) showed a large rise in plasma [K+] and a decrease in MAP. Group B maximum [K+] was 5.2 mmol/L (27.5% increase). Group C was also 5.2 mmol/L (26.0% increase). Group C showed the largest pressure decrease, the minimum mean pressure was 45 mmHg (21.3% decrease). The Group B minimum mean pressure was 45 mmHg (8.7% decrease). Our results show that patients undergoing CPB operations who are deemed to be at increased risk of suffering adverse effects from hypotensive episodes may benefit from bicaval cannulation and caval snaring, in preference to right atrial cannulation. Crystalloid cardioplegia may be preferable to blood cardioplegia in these cases to maintain the MAP.     

体外循环对血浆原降钙素及细胞因子水平的影响

目的 评价心脏瓣膜置换术围术期血浆原降钙素（PCT）、TNF-α、IL-6、IL-8、IL-10水平的动态变化。方法　16例风湿性心脏病体外循环下行瓣膜置换术患者（体外循环组）和7例心包剥离术患者（对照组）被随机纳入本研究对象,于麻醉诱导前、气管插管后、体外循环心肺转流前、体外循环心肺转流后即刻、手术后第1天、第3天和第5天采集静脉血,采用三明治免疫发光法定量测定血浆中PCT水平,采用酶联免疫法（ELISA）定量测定血浆中TNF-α、IL-6、IL-8和IL-10水平。结果体外循环组心肺转流后即刻血浆TNF-α、IL-6、IL-8和IL-10水平明显增加（P<0.05）,术后第3天恢复;血浆PCT水平于术后第1天升高并达峰值（10.62±3.51）ng/ml,术后第5天恢复。对照组呈现同样变化趋势。但两组间参数的升高幅度有显著性差异（P<0.05）。结论 体外循环不仅促发了TNF-α、IL-6、IL-8、IL-10等促炎症和抗炎症介质的释放,而且促发了PCT的大量产生。PCT在体外循环诱发的全身炎症反应中可能发挥重要作用。     

心肺转流中吡那地尔超极化停搏液对实验犬冠脉流量的影响

目的　观察心肺转流 (CPB)中吡那地尔超极化停搏液与传统高钾停搏液对犬冠脉流量的影响。方法　 12条雄性杂种狼犬 ,随机分为两组 ,对照组 (Ⅰ组 ) :心肌保护液灌注 4℃St.Thomas停搏液 (K+ 2 0mmol/L) ,每 30分钟一次 ;实验组 (Ⅱ组 ) :心肌保护液灌注 4℃含吡那地尔 5 0 μmol/L的St.Thomas停搏液 (K+ 5mmol/L) ,每 5 0分钟一次。两组犬主动脉均阻断 15 0min并分别于CPB前、再灌注后 10、30、6 0min时测定冠脉流量 ,同时监测围术期血液动力学。结果　与CPB前比较 ,Ⅱ组在再灌注后 10min冠脉血流量明显增加 ,再灌注后 30min进一步增加 ,且在再灌注后 6 0min继续维持在高流量水平 ,而Ⅰ组只有在再灌注 6 0min时 ,冠脉流量有所增加 (P <0 0 5 ) ;在再灌注后的各个时点 ,Ⅱ组的冠脉流量远远高于Ⅰ组 (P <0 0 5 ) ,两组之间血液动力学指标无显著性差异 (P >0 0 5 )。结论　吡那地尔可明显增加实验犬的冠脉流量 ,而冠脉流量的增加可能与其心功能的恢复无关     

Serum levels of prophylactic cefazolin during cardiopulmonary bypass surgery

BACKGROUND: Controversy exists regarding the appropriate prophylactic dose of cefazolin for coronary artery bypass grafting (CABG) surgery requiring cardiopulmonary bypass (CPB) because the effect of CPB on serum drug levels is poorly understood. Current standards of prophylaxis are based primarily on empiric studies. Few studies have attempted to quantify serum cefazolin levels in either cardiac or noncardiac surgeries. This study was conducted to measure and assess the adequacy of the intraoperative serum levels of prophylactic cefazolin in CPB surgery. METHODS: This prospective study serially measured six intraoperative serum cefazolin levels in 10 subjects undergoing elective and urgent CABG surgery. We compared the serum levels with the minimum inhibitory concentrations (MIC90) for the most common organisms causing postoperative infection. RESULTS: Serum-free cefazolin levels fluctuated considerably during the operation but remained above the MIC90, for Staphylococcus aureus and S. epidermidis. The serum levels fell below the MIC90 for Enterobacter, Serratia, Escherichia coli, and Proteus mirabilis. CONCLUSIONS: Serum cefazolin levels during CPB remained consistently above the MIC for two of the three main organisms causing postoperative infection but were suboptimal for the remainder. Additional studies are needed to assess the intraoperative serum levels of single-dose cefazolin prophylaxis and to explore alternate dosing methods that minimize intraoperative fluctuations in serum cefazolin levels.     

Plasma levels of main granulocyte components during cardiopulmonary bypass

Plasma levels of granulocyte lactoferrin, myeloperoxidase, and elastase in alpha 1-proteinase inhibitor complex were compared with C3a and C5a levels in 10 patients undergoing cardiopulmonary bypass. At the end of the operation, plasma levels of lactoferrin increased from 97.0 +/- 22.8 to 1257 +/- 139.8 ng/ml, myeloperoxidase increased from 37.1 +/- 4.3 to 170.9 +/- 34.9 ng/ml, and elastase in alpha-proteinase inhibitor complex rose from 89.4 +/- 7.4 to 437.8 +/- 97.3 ng/ml. There was also a significant anaphylatoxin formation. To investigate the relationship between complement and granulocyte activation, patients undergoing cardiopulmonary bypass received the calcium channel blocker nifedipine (orally and intravenously) and the antiplatelet drug dipyridamole. The continuous infusion of nifedipine (5.91 +/- 0.53 micrograms/kg body weight per hour) caused significantly lower levels of elastase in alpha-proteinase inhibitor complex and lactoferrin but not anaphylatoxin. Dipyridamole was without effect on complement and granulocyte activation during cardiopulmonary bypass. Our data demonstrate inhibition of granulocyte activation during cardiopulmonary bypass by continuous infusion of nifedipine, even in the presence of complement activation.     

Plasma vasopressin levels during cardiopulmonary bypass with and without profound haemodilution

In cardiopulmonary bypass the effect on plasma vasopressin levels of the addition of whole blood to the pump priming solution was measured. Six patients (Group I) had blood added to the lactated Ringer's solution for the prime, and six patients (Group II) had only lactated Ringer's solution. Neither group had significant changes in plasma vasopressin levels until surgical stimulation occurred. Comparable significant elevations occurred during bypass in both groups. Greater decreases in haematocrit and urinary K+ and greater increases in urinary Na+ occurred in Group II. The degree of haemodilution does not appear to effect plasma vasopressin levels but may alter the degree of electrolyte shift.     

Adrenocortical hormone levels during cardiopulmonary bypass with and without pulsatile flow

To determine the effect of hypothermic pulsatile and nonpulsatile cardiopulmonary bypass (CPB) with hemodilution on adrenocortical function we measured plasma levels of adrenocorticotropic hormone (ACTH), cortisol, aldosterone, and renin in two groups of patients. Group I, comprising 11 patients had routine CPB (nonpulsatile), and Group II, comprising 12 patients, had pulsatile flow during CPB (pulsatile). Both groups demonstrated comparable increases in cortisol, ACTH, and aldosterone with operation. Levels for all three hormones appeared to decline during CPB and then rose again in the post-CPB period. There were no significant differences between groups. Plasma renin activity gradually declined in a comparable manner in both groups. In the post-CPB period, renin activity was slightly higher in the nonpulsatile group (1.7 +/- 0.5 versus 0.8 +/- 0.2 ng/ml/hr, p less than 0.05). Correction for the effect of hemodilution demonstrated no decrease in cortisol and a slight increase in ACTH in both groups during CPB. Significant increases occurred in both groups during CPB in urinary Na+ excretion rate and urinary Na+/K+ ratio, more so for the nonpulsatile group. There was no correlation between urinary Na+/K+ ratios and either plasma cortisol or aldosterone levels. Thus routine CPB demonstrates no evidence of adrenocortical hypofunction and the addition of pulsatile flow produces little improvement.     

Effects of pulsatile perfusion on plasma catecholamine levels and hemodynamics during and after cardiac operations with cardiopulmonary bypass

Thirty patients scheduled for elective coronary artery bypass grafting were studied in two groups. Group A had standard cardiopulmonary bypass with nonpulsatile perfusion and group B had pulsatile perfusion. Measurements of plasma epinephrine, norepinephrine, granulocyte elastase, and hemodynamic parameters including mean arterial pressure total peripheral resistance, cardiac index, and pulmonary capillary wedge pressure were made before and after anesthesia induction, after surgical incision, during cardiopulmonary bypass, and 2, 4, and 24 hours after the operation. The venous compliance of the total body venous bed was measured at the end of the operation. In all patients the total net fluid balance was determined during bypass and in the postoperative period. In both groups plasma catecholamine levels increased 5 minutes after institution of bypass (epinephrine 176 +/- 56 to 611 +/- 108 pg/ml and norepinephrine 231 +/- 48 to 518 +/- 100 pg/ml in group A; epinephrine 168 +/- 40 to 444 +/- 100 pg/ml and norepinephrine 162 +/- 44 to 267 +/- 52 pg/ml in group B). The maximum catecholamine level was measured between the end of bypass and 2 hours after the end of bypass (epinephrine 1489 +/- 169 pg/ml and norepinephrine 1542 +/- 108 pg/ml in group A; epinephrine 990 +/- 134 pg/ml and norepinephrine 934 +/- 197 pg/ml in group B). During the same period mean arterial pressure and total peripheral resistance were also significantly higher in group A than in group B mean arterial pressure, 61.4 +/- 3 versus 53.6 +/- 3, p less than 0.06; total peripheral resistance, 1055 +/- 60 versus 899 +/- 45, p less than 0.01). The venous compliance was significantly higher in group A than in group B (2.4 +/- 0.3 versus 1.2 +/- 0.3 ml/mm Hg/kg body weight). The intraoperative and perioperative net fluid balance were significantly higher in group A than in group B (p less than 0.005). The average postoperative tracheal intubation time was also significantly longer in group A than in group B (4.6 +/- 1.2 hours versus 2.7 +/- 0.8 hours, p less than 0.001). No significant difference was detected in either hemoglobin or plasma free hemoglobin content between the two groups postoperatively. The results suggest that pulsatile perfusion, when compared with nonpulsatile perfusion, can attenuate the catecholamine stress response to cardiopulmonary bypass, reduce the fluid overloading of patients, and improve the postoperative recovery period as evaluated by tracheal intubation time.