Effects of olprinone, a new phosphodiesterase inhibitor, on gastric intramucosal acidosis and systemic inflammatory responses following hypothermic cardiopulmonary bypass

BACKGROUND: Phosphodiesterase (PDE) III inhibitors have both an inotropic and a peripheral vasodilatory effect, and also inhibit the activation of macrophages. Thus a newly developed PDE III inhibitor, olprinone, could modify gastric intramucosal pH (pHi), systemic oxygen consumption, and systemic inflammatory responses in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). METHODS: We studied 23 patients. In 15 patients, olprinone (0.1 or 0.2 microg x kg(-1) x min(-1)) was administered from the commencement of CPB until their admission to the ICU. The other 8 patients received placebo. The pHi and regional CO2 tension (PrCO2) were assessed by a capnometric air tonometry. Systemic inflammatory responses were evaluated by serum interleukin-6 (IL-6), IL-10, and leucocyte counts. RESULTS: The pHi and PCO2-gap, the difference between PrCO2 and arterial CO2 tension (PaCO2), showed a transient decrease and an increase after CPB, respectively. Although olprinone did not affect pHi, olprinone at 0.2 microg x kg(-1) x min(-1) significantly lessened post-CPB increase in PCO2-gap. Olprinone at 0.2 microg x kg(-1) x min(-1) significantly increased IL-10 and reduced the extent of leucocytosis, while it did not affect IL-6 levels. At the same dosage, olprinone also lessened the surge in systemic oxygen uptake index (VO2) and augmented the increase in mixed oxygen saturation (SvO2) both of which occurred after CPB. At 0.1 microg x kg(-1) x min(-1), however, olprinone did not show any significant effect. CONCLUSION: Our results suggest that olprinone at 0.2 microg x kg(-1) x min(-1) suppresses gastric intramucosal acidosis and systemic inflammation following CPB.     

Malignant hyperthermia following systemic rewarming after hypothermic cardiopulmonary bypass

Malignant hyperthermia (MH) is a rare hypermetabolic disorder of skeletal muscle that can be fatal if not recognized and treated aggressively. We describe a patient with a suspected family history of MH who developed hyperpyrexia, acidosis, and hypermetabolism after cardiac surgery despite a nontriggering anesthetic. No drugs were identified as being causative and we theorize that systemic rewarming was the inciting cause of MH in this MH-susceptible individual via a mechanism similar to heat stroke.     

Gastric intramucosal pH and hepatic venous oximetry after cardiopulmonary bypass in valve replacement patients

To determine splanchnic perfusion after cardiopulmonary bypass, gastric intramucosal pH (pH_i) and hepatic venous oxygen saturation (S_HVO₂) were measured in 14 patients with cardiac valve replacement. Blood samples were analysed at 6, 12 and 24 h after admission to an intensive care unit. Gastric pH_i increased significantly (P <0.01) from 7.21 at 6h to 7.31 at 12 h and increased to 7.37 at 24 h while S_HVO₂ increased significantly (P <0.05) from 48% at 6 h to 57% at 12 h and 24 h. Cardiac index was >41/min per m² and mixed venous oxygen saturation >70%. Despite sufficient cardiac output, splanchnic perfusion decreased after cardiopulmonary bypass and recovered within 24 h after admission to the intensive care unit. It is concluded that gastric pH_i and S_HVO₂ are useful parameters for monitoring postoperative splanchnic perfusion in patients with open-heart surgery.     

Temperature and ventilation after hypothermic cardiopulmonary bypass

Rewarming in the postoperative period after hypothermic cardiopulmonary bypass is often associated with hemodynamic and ventilatory instability. Temperature changes, PaCO2 values, and delivered mechanical ventilation were observed for the first 12 hr in the intensive care unit in 73 patients who had undergone cardiac surgery with hypothermic cardiopulmonary bypass. Mean rectal temperature increased from 34.7 to 38.3 degrees C over the first 8 hr after admission to the intensive care unit (P less than 0.001). The temperature curve was sigmoid rather than linear, and the most rapid rate of temperature increase occurred 2-4 hr after admission. During rewarming, the most common abnormality of PaCO2 on mechanical ventilation was acute respiratory acidosis (PaCO2 greater than 45 mm Hg, pH less than 7.35), which occurred in 42% of patients. This suggests that ventilatory management in the early postoperative period after hypothermic cardiopulmonary bypass should be carefully adjusted to the increased metabolic rate during rapid rewarming.     

Convective warming after hypothermic cardiopulmonary bypass

In a randomized, controlled study, we found that convectivewarming after hypothermic cardiopulmonary bypass did not acceleratethe rate of warming of the body core or the time to trachealextubation. The relationship between body core and shell temperature,however, was affected. In all patients inadequate time spentrewarming on cardiopulmonary bypass prolonged body core warmingtime and time to tracheal extubation. Rate of warming of bodycore was inversely related to body mass index. Convective warmingwas delivered using BairHugger (Augustine Medical Inc., MN,USA) and WarmTouch (Mallinckrodt Medical UK Ltd, Northampton,UK) blankets. There was no difference between the performanceof each blanket when powered by the BairHugger 500 power unitset at its medium setting of 38 °C, and when chest drainand radial artery cannulation sites were left exposed for observation.     

Enoximone and warming after hypothermic cardiopulmonary bypass

In a randomized, controlled study of 24 patients undergoing myocardial revascularization, we found that enoximone 0.5 mg kg-1 i.v., followed by 5 micrograms kg-1 min-1, when rewarming after hypothermic cardiopulmonary bypass, prevented subsequent cooling of the periphery after transfer to the intensive care unit. Skin surface temperatures on the foot increased by mean 0.33 (SD 0.5) degree C h-1 in the enoximone group, but decreased by 0.43 (0.4) degree C h-1 in the control group until core temperature had increased to 37 degrees C (P < 0.001); only then did peripheral temperatures begin to increase in the control group. Enoximone did not merely redistribute heat from the core to the periphery. The capacity to transfer heat by the circulation rather than the ability to generate heat in the core appeared to limit body warming in the ICU after hypothermic cardiopulmonary bypass.      

The effect of milrinone on metabolism after cardiopulmonary bypass

AIM: The aim of this study was to examine the effects of milrinone on tissue metabolism perioperatively in cardiac surgery patients using extracorporeal circulation, in comparison to adrenaline and placebo. These effects were measured indirectly by measuring serum lactate, base excess and glucose levels at standard intervals. METHODS: Seventy-seven consecutive patients, who underwent elective cardiac surgery, were allocated in 3 groups. Inotropic support was initiated coming off CPB (cardiopulmonary bypass) if there was evidence of hypotension (mean arterial pressure [MAP] <60 mmHg), after adequate preload (pulmonary capillary wedge pressure [PCWP] >10 mmHg). Milrinone was used in patients with pulmonary hypertension (MPAP >20 mmHg). Group 1 (N.=26) received no inotropes, placebo. Group 2 (N.=32) received adrenaline. Group 3 (N.=19) received adrenaline + milrinone at 0.5 microg/kg/min infusion. Adrenaline was infused at a variable dose (0.01-0.02 microg/kg/min) to achieve a MAP >60 mmHg. The serum lactate, base excess and glucose levels were measured at standard intervals in all 3 groups. Diabetic, hepatic or renal failure patients (serum creatinine >2 mg/dL), were excluded from the study. Patient demographic and clinical characteristics were similar in all 3 groups. RESULTS: Repeated measure analysis of variance between groups showed significantly lower serum lactate levels and higher base excess in the milrinone group (P<0.05), after 2 to 4 hours of treatment. Serum glucose levels were higher in the adrenaline group (P=0.01). There were no immediate complications, morbidity or mortality in the study groups. CONCLUSION: These findings suggest that milrinone has a beneficiary effect on aerobic tissue metabolism after extracorporeal circulation, reflected on serum lactate, base excess and glucose levels, possibly due to a combination of positive inotropic and peripheral vasodilatory effect of the drug.     

米力农对体外循环期间胃肠灌注的影响

目的研究米力农对体外循环期间胃粘膜pH值(pHi)、内毒素血症及全身炎症反应的影响.方法选择20例风心病心内直视瓣膜置换术病人,诱导后插入胃管,吸尽胃内容物,注入无菌生理盐水30ml后夹闭胃管.将病人随机分为米力农组(M组)和对照组(C组),M组给予米力农30μg@kg-1.负荷量静注,而后用微泵0.5μg@kg-1min-1维持.负荷量后30min(To),转流后30min(T1),停机后30min(T2),术后6h(T3)取胃液在血气分析仪上测胃液PCO2,同时测动脉血HCO3,根据Henderson-Hasselbalch方程式算出pHi,取静脉血测血清内毒素浓度和TNF-α浓度.结果(1)pHi两组T1、T2与To比差异有显著性(P＜0.01),T3与To比差异无显著性(P＞0.05),M组与C组比,T0差异无显著性,T1、T2、T3差异均有显著性.(2)TNF-α,两组T1、T2、T3分别与T0比差异均有显著性,M组与C组比,To差异无显著性,T1、T2、T3差异均有显著性.(3)内毒素浓度两组T2、T3与T0比差异有显著性,T1与To比差异无显著性,M组与C组比,T0差异无显著性,T1、T2、T3差异均有显著性.结论米力农通过改善体外循环期间胃肠灌注,减轻内毒素血症及全身炎症反应.     

硝普钠控制性降压对椎板减压术病人术中胃粘膜pH值的影响

目的观察硝普钠控制性降压对胃粘膜pH值(pHi)、胃粘膜内二氧化碳分压(PgCO2)、PgCO2-PaCO2和动脉血气的影响。方法 15例椎板减压术病人,手术中应用硝普钠控制性降压,观察降压前(T1)、降压后30min(T2)、60min(T3)和停降压后30min(T4)的pHi、PgC02、PgcO2-PaCO3和动脉血气的变化。结果 在T2和T3平均动脉压分别下降35％和33％,比T1显著降低(P<0.01)。T2与T1比较,pHi显著降低(P<0.01),PgCO2和PgCO2-PaCO2显著升高(P<0.01),T3这三项指标与T1比较差异无显著性(P>0.05);动脉血气变化:pH在T2、T3和T4、剩余碱(BE)在T3和T4低于降压前(P<0.01),PaCO2和呼气末二氧化碳(PETCO2)在T4高于T2(P<0.05)。结论 硝普钠控制性降压早期胃肠道微循环有一过性障碍。     

Inhibitory effect of milrinone on cytokine production after cardiopulmonary bypass

BACKGROUND: It has been suggested that cyclic adenosine monophosphate-elevating agents suppress cytokine production. To evaluate the effects of milrinone, a phosphodiesterase III inhibitor, on cytokine production after cardiopulmonary bypass, we conducted a prospective randomized study. METHODS: Twenty-four patients undergoing coronary artery bypass grafting were randomized to receive either milrinone treatment (milrinone, n = 12) or no milrinone treatment (control, n = 12). Administration of milrinone (0.5 microg x kg(-1) x min(-1)) was started after induction of anesthesia and was continued for 24 hours. Blood samples for determination of plasma cyclic adenosine monophosphate, tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and interleukin-8 levels were collected perioperatively. RESULTS: No significant differences were observed in tumor necrosis factor-alpha and interleukin-8 levels between the groups. Interleukin-1beta and interleukin-6 levels after cardiopulmonary bypass were significantly (p < 0.05) lower in the milrinone group than in the control group. Plasma levels of cyclic adenosine monophosphate increased significantly (p < 0.05) after the administration of milrinone and the levels correlated inversely (r = -0.55, p < 0.01) with interleukin-6 levels. CONCLUSIONS: The results indicate that milrinone suppresses cytokine production by elevating cyclic adenosine monophosphate levels in patients undergoing cardiopulmonary bypass. With its positive inotropic and vasodilator activities, milrinone may have antiinflammatory effects.     

Effect of low-dose aprotinin on renal function after coronary after bypass grafting under cardiopulmonary bypass

Indian Journal of Thoracic and Cardiovascular Surgery -     

硝普钠降压对胃粘膜pH的影响

目的 观察硝普钠控制性降压对胃粘膜pH(i-pH)的影响。方法 选择ASAⅠ～Ⅲ级择期行神经外科手术的病人16例,术中用硝普钠控制性降低平均动脉压(MAP)至50 mmHg 90min,采用胃管法,分别于降压前、降压30、90 min和复压后120 min抽取胃液检测胃粘膜PCO_2(i-PCO_2)。同时抽动脉血监测pH、PaCO_2、PaO_2、HCO_3和BE。用Henderson-Hasselbalch公式计算i-pH。结果 i-pH于降压90 min比降压前显著降低(P<0.05),复压后120 min又恢复至降压前水平。结论 硝普钠控制性降压可降低i-pH,引起胃粘膜短暂的低灌注损害。     

Whole body oxygen consumption after hypothermic cardiopulmonary bypass

Whole body oxygen consumption and the substrate for energy production during the post-bypass period have not been clarified. We hypothesized that the substrate composition for energy production during post-bypass period might be different from that during pre-bypass period because of surgical diabetic state induced by hypothermic cardiopulmonary bypass (CPB). We measured whole body oxygen consumption, carbon dioxide production and respiratory quotient by the gas exchange method using the Datex Deltatrac before and after hypothermic cardiopulmonary bypass. We also measured oxygen consumption by Ficks principle. Whole body oxygen consumption (P 0.001) and carbon dioxide production (P 0.05) increased significantly above pre-CPB values after the termination of CPB. Respiratory quotient (P 0.01) decreased significantly below pre-CPB values after the termination of CPB. We conclude that oxygen consumption increased significantly above pre-bypass values after the termination of hypothermic cardiopulmonary bypass at least under the fentanyl, diazepam, chlorpromazine anesthesia with continuous infusion of nitroglycerin and nicardipine. The changes in respiratory quotient suggest a relatively higher ratio of lipid metabolism for energy production during post-bypass period.(Maruyama K, Hashimoto H, Nakamura K, et al.: Whole body oxygen consumption after hypothermic cardiopulmonary bypass. J Anesth 7: 1–7, 1993)     

Propofol and hypothermic cardiopulmonary bypass

The effects of propofol during low flow (1.6 l.min-1.m-2) hypothermic (27-29 degrees C) cardiopulmonary bypass on systemic haemodynamic and metabolic variables were studied in 20 patients in a parallel group comparison. Patients in the control group underwent two consecutive control periods, whereas those in the propofol group underwent a control period followed by a 'propofol' period during which they received an intravenous bolus of propofol 5 mg.kg-1 followed by an infusion at a rate of 20 mg.kg-1.h-1. Haemodynamic and metabolic variables were measured at the end of each period. The propofol group showed a significant reduction in both systemic vascular resistance (p less than 0.001) and systemic oxygen uptake (p less than 0.05). There was a small but significant fall in lactate in the control group (p less than 0.02); however, there was no significant change in the propofol group. These findings could indicate impaired tissue perfusion, although they more likely indicate systemic metabolic depression with washout of lactate from previously hypoperfused tissues.     

丙泊酚对低温体外循环期间胃粘膜酸中毒的影响

目的　探讨丙泊酚对心内直视手术病人低温心肺转流 (CPB)期间胃粘膜酸中毒的影响。方法　 2 0例心内直视手术病人随机分为对照组 (A组 ,n =10 )和丙泊酚组 (B组 ,n =10 )。用芬太尼、咪唑安定、潘库溴铵维持麻醉 ,间断吸入异氟醚。B组于CPB开始至停机前持续静脉注入丙泊酚 5～ 8mg·kg-1·h-1。分别于CPB前 (T1)、停机前 (T2 )和停机后 4 0分钟 (T3)测定PaCO2 和胃粘膜PCO2 (PiCO2 ) ,计算PiCO2 与PaCO2 之差 [P(i a) CO2 ]和胃粘膜pH( pHi)。 结果　A、B两组T2 P(i a)CO2 较组内各时点均明显增高 ,pHi明显降低 (P <0 0 1) ;与A组比较 ,B组T2 、T3P(i a) CO2 显著降低 ,pHi显著增高 (P <0 0 5 ) ;与T1比较 :A组T3P(i a) CO2 仍显著增高 ,pHi显著降低 (P <0 0 5 ) ,B组T3P(i a) CO2 和 pHi基本恢复至T1水平。结论　低温CPB期间持续静脉注入一定剂量的丙泊酚可减轻胃粘膜低灌流和酸中毒。     

Direct expiratory gas analysis after hypothermic cardiopulmonary bypass.

We hypothesized that patients who have undergone hypothermic cardiopulmonary bypass may have abnormal oxygen metabolism after cardiac surgery because of oxygen debts that occurred during cardiopulmonary bypass. A prospective study was designed to determine oxygen consumption and carbon dioxide production using an indirect calorimeter in 45 adult patients who underwent hypothermic cardiopulmonary bypass. Inspiratory and expiratory gases were analyzed and the respiratory exchange ratio (carbon dioxide production/ oxygen consumption) was obtained every 6 hours up to 24 hours after surgery. The respiratory exchange ratio immediately following cardiopulmonary bypass was abnormally high then gradually decreased. The respiratory exchange ratio at 18 or 24 hours after surgery was significantly lower than the one on admission to the intensive care unit. Duration of cardiopulmonary bypass was the most significant parameter which correlated to the respiratory exchange ratio on admission to the intensive care unit (r = 0.82, p < 0.001). We conclude that the respiratory exchange ratio can be used to monitor systemic metabolism, especially during the recovery phase from metabolic abnormality following hypothermic cardiopulmonary bypass.     

孕羊低温体外循环对胎羊血流动力学以及碳水化合物代谢的影响

目的 探讨孕羊低温体外循环(CPB)对胎羊血流动力学以及碳水化合物代谢的影响.方法 孕羊20头,随机分成对照组,开胸不建立体外循环;常温CPB组(35～36℃)、浅低温组CPB(32～34℃)和中低温CPB组(28～31℃),建立常规体外循环,转流降温、复温30 min.分别监测孕羊和胎羊的心率、平均动脉压、胎羊脐动脉和颈内动脉的搏动指数(pulse index,PI),孕羊与胎羊血糖、乳酸含量和HCO-3值的变化.结果 母羊和胎羊平均动脉压差异无统计学意义(P＞0.05).浅低温组和中低温组颈内动脉PI值较对照组和常温组显著增高(P＜0.05),脐动脉PI值组间差异无统计学意义,但随体外循环时间的延长而增高.血糖水平胎羊各组间差异无统计学意义(P＞0.05),但中低温CPB组中胎羊显著低于孕羊(P＜0.05).中低温CPB组胎羊血乳酸随时间延长有上升趋势(P＜0.05),而且显著高于孕羊(P＜0.05),但各CPB组间血乳酸差异无统计学意义.结论 孕羊低温体外循环降温时,胎羊心率明显下降,复温后胎羊心率能回复正常,体外循环对胎羊平均动脉压无明显影响,但低温降低胎羊脑部和脐动脉的血流;低温体外循环导致胎羊血糖水平降低,而血乳酸浓度显著增高.

Abstract：

Objective To evaluate effects of maternal hypothermic cardiopulmonary bypass on fetal homodynamic and carbohydrate metabolism. Methods Twenty pregnant sheep were divided into four groups randomly: control group(n=5),normothermic group (35-36℃)(n=5), mild hypothermic group(32-34℃)(n=5) and moderate hypothermic group (28-31℃)(n=5).Thoracotomy was performed without CPB in the control group. Routine CPB was established with different temperature in other three groups. The temperature of normothermic group was kept normal; the left two groups were cooled down to the set point of temperature and then rewarmed back to normal level. Fetal and maternal temperatures, heart rate,mean blood pressure(BP), pulse index (PI) of fetal umbilical artery (UA) and internal carotid artery (CA) were evaluated at cooling and rewarming stages. Biochemical indicators including blood glucose and lactic acid were also measured at the same time. Results There are no differences in mesn BP of ewas and fetal lambs between the different groups (P＞0.05). CA PI value of mild hypothermic group and moderate hypothermic group were significantly higher than those of control group and normothermic group (P＜0.05). There was no difference of UA PI in the four groups, but PI increased following the prolonged duration of CPB. There was no difference change of blood glucose in the four group of fetus, which was significantly lower than the ewe groups. An upward trend of fetal blood lactic acid with time was observed in three CPB groups. The whole level of fetal blood lactic acid was much higher than that of maternal blood of lactic acid. Conclusion Cooling of maternal bypsss decreases fetal heart rate significantly,and fetal heart rate recovered to base line following rewarming phase. There was no signicant effect of CPB on fetal mean BP. However, CPB impacted on the blood flow of fetal brain and umbilical artey. Hypothermia CPB can increase fetal blood glucose and blood lactic acid dramatically.     

变温水毯在中低温体外循环术后的应用

目的 观察中低温体外循环(CPB)术后使用变温水毯对鼻咽温、凝血功能、发生寒战和气管内插管时间的影响。方法 根据CPB后是否使用变温水毯，将80例患者用随机抽签法分为变温水毯组和对照组，每组40例。分别记录术后两组患者鼻咽温度，全血激活凝血时间(ACT)值，24小时胸腔引流量，寒战发生率，气管内插管时间。结果 对照组住ICU后出现鼻咽温降低(P=0．034)，并低于同时点变温水毯组(P=0．008)。变温水毯组住ICU后ACT值低于对照组(P=0．026)，胸腔引流量、寒战发生率和气管内插管时间均少于或低于对照组(P=0．004，0．007，0．037)。结论 采用变温水毯能降低鼻咽温和减少寒战发生率，改善凝血功能，减少术后出血，缩短气管内插管时间。     

Neuromuscular blockade significantly decreases systemic oxygen consumption during hypothermic cardiopulmonary bypass.

The design limits of cardiopulmonary bypass (CPB) equipment and the performance characteristics of membrane oxygenators may place the patient with a very large body surface area at risk for incurring an oxygen debt during CPB. The influence of resting muscle tone on systemic oxygen consumption (VO2) during hypothermic (25 to 28 degrees C) nonpulsatile CPB was calculated using the Fick equation prior to, and following, neuromuscular blockade (pancuronium, 0.15 mg/kg, n = 10; or succinylcholine, 1.5 mg/kg, n = 7). During hypothermic CPB, initial VO2 was 70 +/- 30 mL/min/m2, which was significantly reduced (by 30%) to 49 +/- 13 mL/min/m2 after onset of neuromuscular blockade, with a concomitant increase in mixed venous O2 saturation from 73% +/- 18% to 83% +/- 14%. Choice of muscle relaxant did not influence the change in VO2. With succinylcholine there was a return of VO2 to control values with recovery of neuromuscular function. This study demonstrates that in the unconscious and unmoving patient during hypothermic CPB, administration of muscle relaxants to achieve complete neuromuscular blockade can significantly reduce systemic oxygen consumption.