Prostaglandin el attenuates impairment of cellular immunity after cardiopulmonary bypass

Objective It is well documented that cardiopulmonary bypass (CPB) severely impairs cellular immunity. The objective of this study was to investigate the effect of prostaglandin El (PGE1) on cellular immunity after CPB.Methods: Patients who underwent elective cardiac surgery were randomly divided into the PGE1 group (n=12) and the control group (n=12). In the PGE1 group, PGE1 was administered at 20 ng/kg/min from just after the induction of anesthesia to the end of surgery. Peripheral blood mononuclear cells (PBMCs) were taken before anesthesia and on postoperative days 1,3 and 7 (POD 1, POD 3 and POD 7). Proliferation responses of T cells to phytohemagglutinin (PHA) and pure protein derivative (PPD) antigen were measured as indicators of cellular immunity.Results: PGE1 significantly attenuated the impairment of both PHA and PPD response after cardiac surgery on POD 1 (PHA response, 30 ± 21% vs. 53±32%, control vs. PGE, p=0.048; PPD response, 18±21% vs. 39±27%, control vs. PGE, p=0.046). The reduced glutathione content of PBMCs in the control group was significantly decreased on POD 1.Conclusion: PGE1 attenuated the impairment of cellular immunity after cardiac surgery with CPB by reducing oxidative stress on PBMCs. (Jpn J Thorac Cardiovasc Surg 2006; 54:149-154)     

Cardiopulmonary bypass, steroid administration, and surgical injury synergistically impair memory T cell function and antigen presentation

Previous reports showed that cardiac surgery with cardiopulmonary bypass (CPB) impair cell-mediated immunity by using antigen-non-specific responses. This study elucidated the effects of cardiac surgery with CPB on antigen-specific immunity. Twenty patients who underwent elective cardiac surgery using CPB were randomly divided into two groups: group A (n=10) and group B (n=10) with and without steroid administration, respectively. Group C patients underwent off-pump CABG (n=8). Peripheral blood mononuclear cells (PBMCs) were taken before and after surgery. Proliferation responses to pure protein derivative antigen were measured. The effects of CPB and steroid on T cell response and antigen-presentation were assessed by cross-stimulation between the preoperative and the postoperative PBMCs. Antigen-specific T cell responses decreased to about 5% of the preoperative values immediately after surgery with CPB, regardless of steroid administration. The T cell response in group B on POD 7 was significantly higher than that in group A. CPB impaired mainly T cell responses, and steroid administration enhanced impairment of T cell response and antigen-presentation. Open-heart surgery with CPB severely impaired antigen-specific immunity. Steroid administration enhanced the impairment of antigen-presentation as well as T cell function, and retarded the recovery of antigen-specific immunity.     

Heparin influences human platelet behavior in cardiac surgery with or without cardiopulmonary bypass

The objective was to investigate whether the platelet dysfunction in cardiac surgery is caused by hemodilution or by shear stress due to cardiopulmonary bypass (CPB). Platelet count and function were prospectively analyzed in two groups of patients undergoing cardiac surgery either with or without CPB (n = 40). In the first study (n = 20; 10 patients with and 10 without CPB), platelet counts were assessed at seven time points. In the second study (n = 20; 10 patients with and 10 without CPB), platelet function was studied with platelet aggregometry at different points during surgery: (a) after induction of anesthesia; (b) after sternotomy; and (c) 1 h after heparin. In the first study, the CPB group showed a significant decrease in platelet count starting after sternotomy (230 +/- 34 vs. 182 +/- 25, P < 0.05) and a maximum decrease at day 1 postoperative (96 +/- 34, P < 0.05). A similar observation was made in the non-CBP group. In the second study, a significant decrease of ADP (54 +/- 13% vs. 38 +/- 9%, P < 0.05), AA (76 +/- 16% vs. 22 +/- 14%, P < 0.05), and Collagen (66 +/- 13% vs. 37 +/- 11%, P < 0.05) induced platelet aggregation was observed at MOMENT d compared to the beginning of surgery in the CPB group. In the non-CBP group a significant decrease was observed in AA-induced platelet aggregation at MOMENT d (83% +/- 4 vs. 44% +/- 14, P < 0.05). The reduction in platelet count is similar with or without cardiopulmonary bypass and is due to pure hemodilution. Platelet function reduces significantly after heparin administration. Hemodilution and predominantly heparin are the causes of platelet dysfunction after cardiac surgery.     

Adaptive immunity is severely impaired by open-heart surgery

OBJECTIVE: The influence of open-heart surgery on antigen-specific immunity, also called adaptive immunity, remains to be clarified. We explored the effects of open-heart surgery on adaptive immunity. METHODS: In 8 consecutive adult patients undergoing elective cardiac surgery with cardiopulmonary bypass, we measured the T cell-response to purified protein derivative (PPD) antigen perioperatively. We separately measured the proliferation of T cells and the antigen presentation of antigen-presenting cells (APCs) using a cross-reaction system. RESULTS: T cell response to PPD antigen was severely impaired by open-heart surgery. Compared to preoperative values, T cell response to PPD antigen fell to 5.7 +/- 4.4% immediately after surgery, 4.5 +/- 3.2% on postoperative day (POD) 1, to 22.4 +/- 24.6% on POD 3 and to 50.1 +/- 34.3% on POD 7. T cell proliferation on POD1 decreased to 29 +/- 26%. APC antigen-presentation on POD 1 also decreased to 31 +/- 36%. CONCLUSIONS: Open-heart surgery impaired both T cell proliferation and the antigen-presentation. Such synergistic impairment severely impaired adaptive immunity. This impairment was both severer and longer than we anticipated based on previous studies using the response of T cells to lectin as a marker of cell-mediated immunity.     

Neutrophilia and granulocyte colony-stimulating factor levels after cardiopulmonary bypass

PURPOSE: The precise mechanism of neutrophilia after cardiac surgery is unknown. Granulocyte colony stimulating factor (G-CSF) can increase the number of leukocytes. The purpose of this study was to evaluate the relationship between serum G-CSF levels and peripheral blood leukocyte counts after cardiac surgery. METHODS: We prospectively studied 10 patients undergoing cardiac surgery (coronary artery bypass grafting) using cardiopulmonary bypass (CPB). Plasma G-CSF levels and neutrophil count were measured before induction of anaesthesia, at the end of surgery, and on the first postoperative day. These changes were compared with those in patients undergoing non-cardiac major surgery (control group). RESULTS: At the end of surgery, G-CSF levels increased (P < 0.01) in both groups, but were higher in the control than in the cardiac group (3,250 +/- 690 vs 194 +/- 29.5 pg ml(-1), respectively, mean +/- SEM, P < 0.01). On the first postoperative day, G-CSF levels were still high in both groups, and were still higher in the control (710 +/- 179 vs 122 +/- 19.9, respectively, P < 0.01). However, neutrophilia was greater in the cardiac group than in the control. G-CSF response correlated positively with neutrophilia in the control group (r = 0.656, P < 0.05) but not in the cardiac group. CONCLUSIONS: Our results indicate that changes in leukocyte count following cardiac surgery are unique to patients undergoing CPB. G-CSF plays an important role as the mediator of neutrophilia after non-cardiac surgery, but not after cardiac surgery with CPB.     

The role of prostaglandin E2 in immune suppression following injury.

It has been thought for some time that prostaglandin E2 (PGE2) released from activated monocytes/macrophages may contribute to the suppression of immunity seen after burns and major injury because PGE2 inhibits the activation of T lymphocytes. To clarify this issue, we studied 15 patients with total body surface area burns of 20% to 90% (mean, 48%). Peripheral blood mononuclear cells (PBMC) were obtained from these patients one to two times each week for 1 month after burn and were stimulated with the T-cell mitogen phytohemagglutinin (PHA). On 14 occasions the PBMCs from eight patients were significantly suppressed (30% or more) in their response to PHA (suppressed [sup] burn) as compared with PBMCs from normal controls. In 38 instances PBMCs from 12 patients were not significantly suppressed in PHA (nonsuppressed [nonsup] burn). Sup burn PBMCs and control PBMCs were cultured with or without the addition of the cyclooxygenase (CO) inhibitor indomethacin (Indo, 1 microgram/mL) and studied for PHA response and the production of the stimulatory cytokine interleukin-2 (IL-2). Indo partially restored the PHA response of sup burn PBMCs to normal. Sup burn PBMCs also were deficient in production of IL-2. Indo increased IL-2 production by sup burn PBMCs significantly more (160% +/- 20%, p less than 0.005) than control (57% +/- 5%) and nonsup PBMCs (67% +/- 8%). Next inhibition of the PHA response of PBMCs from 12 burn patients and 17 controls was studied by exogenous PGE2. At all time periods after burn injury, patients' PBMCs were significantly more sensitive to inhibition by PGE2 (50% inhibition at 10(-8) mol/L [molar] PGE2) than PBMCs from normal controls (50% inhibition at 10(-6) mol/L PGE2) with maximum sensitivity occurring 8 to 14 days after injury. Peripheral blood mononuclear cells from patients with more than 40% burns were significantly (p less than 0.05) more sensitive to PGE2 than those from patients with lesser burns. Interleukin-2 was added to cultures of sup burn PBMC, nonsup burn PBMC, and controls containing 10(-7) mol/L PGE2. Interleukin-2 totally reversed PGE2 inhibition of the PHA response in PBMC from both controls and burn patients. Because endotoxin leak from the gut has been implicated as a trigger for a number of the metabolic and immunologic abnormalities following injury, the authors looked for the effect of a bolus infusion of Escherichia coli endotoxin (Endo, 4 ng/kg) in seven normal healthy volunteers on the response of PBMC to PHA and on the production of PGE2 and IL-2.(ABSTRACT TRUNCATED AT 400 WORDS)     

Reduction of neutrophil activation by prostaglandin E1 in open heart surgery]

This study was designed to demonstrate the effect of prostaglandin E1 (PGE1) on neutrophil activation in open heart surgery. Twenty adult patients undergoing cardiopulmonary bypass (CPB) for various cardiac operations were divided into 2 groups. PGE1 group consisted of 10 patients (7 males and 3 females) and the control group consisted of 10 patients (6 males and 4 females). In PGE1 group patients, 20-50 ng/kg/min of PGE1 was administered intravenously from the induction of anesthesia to the completion of CPB. Blood samples were taken before, during, after CPB, and in the morning of the first postoperative day. Differential counts of white blood cells, plasma neutrophil elastase (PNEL) activity, serum complements activity (C3a, CH50) and superoxide production of neutrophils were measured. Superoxide production by isolated neutrophils was evaluated utilizing luminol dependent chemiluminescence. After the initiation of CPB complements were activated markedly, and PNEL activity increased significantly in both groups. Although after CPB PNEL activity turned to decrease, it was still significantly higher on the first postoperative day than the preoperative value. There were no significant differences between two groups as for complements activation and PNEL activity. The total number of white blood cells unchanged during CPB and neutrophilia appeared after CPB, but no significant difference between two groups. Superoxide production of neutrophils relatively decreased during CPB and significantly increased after CPB in the control group. However, in PGE1 group superoxide production was reduced after CPB, especially on the first postoperative day. These results showed that PGE1 reduced neutrophil-mediated superoxide production in open heart surgery. In conclusions, PGE1 is useful agent to reduce the hazardous effects of neutrophils after CPB.     

前列腺素E1不同给药时机治疗围术期先天性心脏病肺动脉高压的观察

目的　观察先天性心脏病合并重度肺动脉高压（ＰＨ）患者围术期血液动力学的变化。方法　２０ 例先天性心脏病合并重度肺动脉高压患者以前列腺素Ｅ１ 应用不同时机分对照组和试验组,每组１０例。试验组在体外循环开始后从中心静脉持续泵注前列腺素Ｅ１２０ｎｇ·ｋｇ－ １ ·ｍ ｉｎ－ １;对照组在体外循环中,开放升主动脉后开始用前列腺素Ｅ１ 。观察围术期平均动脉压（ＭＡＰ）、平均肺动脉压（ＰＡＰ）、动脉压与肺动脉压之比（ＰＰ／ＰＳ）、心脏指数（ＣＩ）、肺阻力指数（ＰＶＲＩ）、体循环阻力指数（ＳＶＲＩ）的动态变化。结果　体外循环后各时点的肺动脉压力与主动脉压力之比较术前显著降低,（Ｐ＜ ０．０１）。肺阻力指数和体循环阻力指数在体外循环后逐渐升高,试验组肺阻力指数在升主动脉开放后６ 小时显著低于对照组,（Ｐ＜ ０．０１）。试验组心指数在开放循环后２～４ 小时高于对照组,（Ｐ＜０．０５）。结论　重度肺动脉高压心内畸形矫正手术中,体外循环开始即应用前列泉素Ｅ１ 的效果优于传统的开放升主动脉后给药的效果。     

Cerebral oxygenation is better during mild hypothermic than normothermic cardiopulmonary bypass

PURPOSE: Normothermic cardiopulmonary bypass (CPB) has been recently used in cardiac surgery. However, there is a controversy whether there is a difference in incidence of neurological disorder after coronary artery bypass graft (CABG) surgery between normothermic CPB and mild hypothermic CPB. In this study, we assessed the effects of normothermia and mild hypothermia (32 degrees C) during CPB on jugular oxygen saturation (SjvO2). METHODS: Twenty patients scheduled for elective CABG surgery were divided into two groups. Group 1 (n = 10) underwent normothermic (>35 degrees C) CPB, and Group 2 (n = 10) underwent mild hypothermic (32 degrees C) CPB. Alpha-stat blood gas regulation was applied. After inducing anesthesia, a 4.0 French fibre optic oximetry oxygen saturation catheter was inserted into the right jugular bulb to monitor SjvO2 continuously throughout anesthesia and surgery. RESULTS: The SjvO2 in the normothermic group was decreased at 20 (41.5+/-2.4%) and 40 min (43.8+/-2.8%) after the onset of CPB compared with control (53.9+/-5.4%, P<0.05). However, there was no change in SjvO2 in the mild hypothermic group during the study. No changes in jugular venous-arterial differences of lactate or creatine phosphokinase isoenzyme BB were observed in two groups during the study. CONCLUSIONS: Cerebral oxygenation, as assessed by SjvO2 was increased during mild hypothermic CPB than during normothermic CPB.     

IL-8, IL-6 and ICAM-1 in serum of paediatric patients undergoing cardiopulmonary bypass with and without cardiocirculatory arrest

BACKGROUND: The aim of the present study was to evaluate the systemic inflammatory response to CPB in paediatric patients undergoing surgical correction of congenital heart diseases. METHODS: Experimental design: comparative investigation. Setting: paediatric cardiology hospital Intervention: ICAM-1, IL-8, and IL-6 production were analysed before and during CPB, and after surgery in 9 paediatric patients, submitted to cardiocirculatory arrest (Group A); and in 11 without cardiocirculatory arrest (Group B). Measures: ICAM-1, IL-8, and IL-6 production were analysed from arterial samples before and during CPB, and after surgery. RESULTS: In group A vs group B a significant increase of IL-8 was detected during (297+/-250 vs 11+/-19 pg x ml(-1), p<0.001) and after (100+/-230 vs n.d. pg x ml(-1)) surgery and was correlated with the duration of operation (r=0.759; p=0.0001) and clamping time (r=0.738; p<0.05). After surgery in group A, IL-6 levels (35+/-43 pg x ml) were higher than those in group B (2+/-5 pg x ml), and a good correlation was observed between IL-6 and duration of aortic clamping (r=0.714; p=0.048), cardiac arrest, (r=0.714; p=0.048), and length of surgery (r=0.867; p=0.04). CONCLUSIONS: In children who underwent CPB with cardiocirculatory arrest cytokine production seems related to duration of operation and amplified by ischemia-reperfusion phenomena.     

Large-dose propofol during cardiopulmonary bypass decreases biochemical markers of myocardial injury in coronary surgery patients: a comparison with isoflurane

We investigated if increasing propofol's dosage to augment its antioxidant capacity during cardiopulmonary bypass (CPB) could confer cardiac protection. Fifty-four coronary artery bypass graft surgery patients were randomly assigned to small-dose propofol (Group P; n = 18), large-dose propofol (Group HiP; n = 18), or isoflurane Group (Group I; n = 18). After the induction, anesthesia was maintained with an inspired concentration of isoflurane 1%-3.5% (Group I) or a continuous infusion of propofol 60 microg x kg(-1) x min(-1) (Group P) throughout the surgery. In Group HiP, this dose of propofol was increased to 120 microg x kg(-1) x min(-1) for 10 min before the onset of CPB until 15 min after aortic unclamping and then decreased to 60 microg x kg(-1) x min(-1) until the end of surgery. The duration of aortic cross-clamping was 83 +/- 24, 88 +/- 22, and 81 +/- 20 min in Group P, Group HiP, and Group I, respectively (P > 0.1). Plasma malondialdehyde, a marker of oxidative stress, was significantly lower at 8 h after CPB, and Troponin I was lower at 24 h after CPB in Group HiP compared with Group P and Group I (P < 0.05). There was a significant reduction in inotropic requirements for separation from CPB in Group HiP compared with Group I. Postoperative systemic vascular resistance was significantly reduced in Group HiP as compared with Group I. Mean cardiac index was significantly higher at 24 h after CPB in Group HiP compared with Group P and Group I (P < 0.05) (Group I, 2.2 +/- 0.1; Group P, 2.3 +/- 0.2; and Group HiP, 2.8 +/- 0.3 L x min(-1) x m(-2), respectively). The duration of intensive care unit stay was significantly shorter in Group Hi-P compared with Group I. We conclude that administration of a large dose of propofol during CPB attenuates postoperative myocardial cellular damage as compared with isoflurane or small-dose propofol anesthesia.     

Prophylactic use of pentoxifylline on inflammation in elderly cardiac surgery patients

BACKGROUND: Inflammation plays a pivotal role in the pathogenesis of organ injury after cardiopulmonary bypass (CPB). Elderly patients appear to be especially prone to develop general inflammation. Use of pentoxifylline (PTX) before surgery may be a promising approach to minimize the negative effects of CPB in these patients. METHODS: In a prospective, randomized study, patients more than 80 years old undergoing aortocoronary artery bypass grafting received either PTX (n = 15) after induction of anesthesia (initial bolus of 300 mg followed by a continuous infusion of 1.5 mg.kg(-1).h(-1) during the next 2 days) or saline as placebo (control group; n = 15). Polymorphonuclear neutrophil (PMN) elastase, C-reactive protein (CRP), and interleukins (IL-6, IL-8, IL-10) were measured from arterial blood samples before surgery (T0), at the end of surgery (T1), 5 hours after surgery (T2), and at the morning of the first (T3) and second (T4) postoperative day. RESULTS: Postoperatively, PTX-treated patients less often needed catecholamines and were extubated earlier than the control patients (p < 0.05). On the intensive care unit, cardiac index inceased more in the PTX-treated (from 1.95 +/- 0.3 to 3.26 +/- 0.4 L.min(-1).m(-2)) than in the control patients (from 1.89 +/- 0.2 to 2.78 +/- 0.3 L.min(-1).m(-2)). Increase in CRP and PMN-elastase was significantly higher in the untreated control than in the PTX patients. After CPB, IL-6, IL-8, and IL-10 increased in both groups showing a significantly higher increase in the untreated control patients (IL-8 control: from 11.3 +/- 2.6 to 154.4 +/- 57 pg/mL [T1]); IL-8 PTX: from 10.9 +/- 2.7 to 71.8 +/- 23 pg/mL [T1]). CONCLUSIONS: In elderly cardiac surgery patients, use of PTX before surgery and continued after CPB resulted in less inflammatory response than in an untreated control group. The value of attenuating the inflammatory process by PTX on outcome in this patient population needs to be evaluated in further controlled studies.     

A randomized, double-blind, placebo-controlled study assessing the anti-inflammatory effects of ketamine in cardiac surgical patients

OBJECTIVE: To determine whether ketamine administration affects markers of inflammation in cardiac surgery with cardiopulmonary bypass (CPB) and to investigate differences between 2 low-dose ketamine regimens. DESIGN: Prospective, randomized, placebo-controlled trial. SETTING: Single-center university hospital. PARTICIPANTS: Patients undergoing cardiac surgery with CPB. INTERVENTION: Patients (n = 50) were randomized to 1 of 3 groups: ketamine, 0.25 mg/kg (n = 15); ketamine, 0.5 mg/kg (n = 18);or placebo (n = 17) in a double-blind manner at the time of induction of general anesthesia. MEASUREMENTS AND MAIN RESULTS: Serum C-reactive protein (CRP) and interleukin (IL)-6, IL-8, and IL-10 were measured at baseline, on intensive care unit (ICU) arrival, and on the first postoperative day (POD 1). Both ketamine doses decreased the serum IL-6 response at ICU arrival and POD 1 compared with placebo (p < 0.05). CRP was lower in the 0.5-mg/kg group than placebo on POD 1 (p = 0.003). IL-10 was lower in the ketamine groups (p = 0.01) at POD 1 compared with placebo; IL-8 levels were not affected by ketamine. Mean arterial pressure and systemic vascular resistance were higher at the end of surgery, arrival in the ICU, and POD 1 in the ketamine groups (p < 0.05). CONCLUSION: Low-dose ketamine (0.5 mg/kg) attenuates increases in CRP, IL-6, and IL-10 while decreasing vasodilatation after CPB.     

强化胰岛素治疗对心肺转流术患者心血管功能的影响

目的 探讨强化胰岛素治疗对心肺转流术(CPB)患者血浆一氧化氮(NO)和内皮缩血管肽1(ET-1)表达的影响.方法 36例心脏瓣膜置换术患者随机分为常规治疗组(RT,n=18)和强化胰岛素治疗组(IT,n=18).RT组术中血糖变化不作处理,术后控制在13.9 mmol/L以内;IT组血糖术中控制在3.9～10.0 mmol/L,术后在3.9～6.1 mmol/L.分别于术前、CPB开始时及CPB结束后不同时间点测量两组患者的血浆NO和ET-1水平.结果 RT组血浆NO含量在CPB开始时即略有下降,CPB结束时达到最低(P＜0.05);此后回升,CPB结束后48 h时接近术前水平.RT组血浆ET-1含量在CPB开始时即开始升高,CPB结束时达高峰(P＜0.01);此后下降,至CPB结束后24 h时降至术前水平.IT组各时间点的血浆NO和ET-1含量与术前比较均无差异.结论 强化胰岛素治疗可减小CPB心脏手术中所致NO和ET-1的变化幅度,对心血管功能具有保护作用.     

The effect of leucodepletion on leucocyte activation, pulmonary inflammation and respiratory index in surgery for coronary revascularisation: a prospective randomised study.

OBJECTIVE: Leucocyte activation is central to end-organ damage that occurs during cardiac surgery under cardiopulmonary bypass (CPB). Exhaled nitric oxide (NO) increases in inflammatory lung conditions and has been proposed as a marker of pulmonary inflammation during CPB. This study examined the effect of leucodepletion on leucocyte activation, pulmonary inflammation and oxygenation in patients undergoing coronary revascularisation. METHODS: Fifty low-risk patients undergoing first time coronary artery bypass graft (CABG) were randomised to two groups. Twenty-five patients had an arterial line leucocyte-depleting filter and 25 controls had a standard filter. Arterial blood samples were taken before CPB, 5 and 30 min on CPB, 5 min after aortic clamp removal and 6 h post-operatively. Activated leucocytes were identified with Nitroblue Tetrazolium staining. NO was sampled via an endotracheal teflon tube 15 min after median sternotomy before CPB and 30 min after discontinuation of CPB using a real-time chemiluminescense analyser. Respiratory index (alveolar-arterial oxygenation index, AaOI) was calculated before CPB, 1, 2, 4, 8 and 18 h post-operatively. Clinical outcome end-points were also recorded. RESULTS: Total and activated leucocyte counts were significantly lower following leucodepletion during CPB (P < 0.0001). Exhaled NO rose significantly after CPB in the control group (3.8+/-1 ppb/s before CPB vs 5.6+/-2 ppb/s after CPB (P = 0.003) but not in the leucodepleted group (3.7+/-1 ppb/s before CPB vs 3.9+/-1 ppb/s after CPB (P = 0.051). AaOIs were consistently lower after leucodepletion (anova, P = 0.001). The duration of mechanical ventilation, the intensive care and hospital stay and the frequency of cardiac and respiratory complications were similar in the two groups. CONCLUSIONS: Leucodepletion reduces the numbers of circulating activated leucocytes and the pulmonary inflammation during CPB. This appears to limit lung injury and improve oxygenation in low-risk patients undergoing CABG surgery. Larger numbers of patients are required to evaluate the effect of continuous arterial line leucodepletion on the clinical outcome.     

Hyperosmolar volume replacement in heart surgery]

The ideal solution for use in volume therapy is still a matter of debate. Hypertonic sodium (HS) solutions have been advocated for resuscitation from hemorrhagic shock (small volume resuscitation). As hypertonic fluids may also be of interest in cardiac surgery, the effects of a new HS solution were studied. METHODS. In 90 patients undergoing aorto-coronary bypass grafting studies were performed at three different periods: I (n = 30) after induction of anesthesia (before onset of the operation); II (n = 30) during cardiopulmonary bypass (CPB); III (n = 30) after termination of bypass. During these periods the patients were randomly allocated to one of three groups with 10 patients in each group: group 1 received a new hypertonic solution prepared in hydroxyethyl starch (HES) solution (72 g/l NaCl, 60 g/l HES, 2400 mosmol/l; HS-HES patients), group 2 received a 6% HES solution (200/0.5; HES patients), and group 3 received no volume infusion and served as controls. RESULTS. After the induction of anesthesia, significantly less HS-HES solution (4.5 +/- 0.5 ml/kg) than 6% HES solution (10.1 +/- 1.4 ml/kg) was necessary to double the baseline PCWP. The fluid balance during CPB was negative in the patients who had received HS-HES preoperatively (-0.03 +/- 0.01 ml/kg.min CPB), whereas 6% HES (+0.06 +/- 0.02 ml/kg.min CPB) and control patients (+0.13 +/- 0.03 ml/kg.min CPB) had a positive fluid balance. Both after the induction of anesthesia and after termination of bypass, CI increased more in the HS-HES group than in the HES patients, and it even decreased in the control group. SVR decreased in the HS-HES patients, whereas it increased in the control group. Rapid infusion of HS-HES during CPB was followed by a significant, but short-lasting decrease in MAP (-40 mmHg) and an increase in the oxygenator volume. Pulmonary gas exchange (= paO2) was least compromised in the HS-HES patients; the sodium concentration increased only in the HS-HES patients, but never exceeded 150 mmol/l. DISCUSSION. Cardiac surgery procedures offer a special situation for volume therapy as there is a possibility of deterioration in the macro- and microcirculation before, after, and during the period of CPB. Hemodynamic effects of the new HS-HES solution included an increase in CI and a decrease in SVR, which were not merely transient as has been reported which hypertonic saline solution used alone. It was also observed that HS-HES patients required significantly smaller volumes of fluids, both during CPB and during the early postoperative period. This effect seems to be due to a redistribution of interstitial fluid to the intravascular space, possibly decreasing tissue edema. CONCLUSION. The hypertonic saline HES solution adds a new dimension to volume therapy for cardiac surgery patients. The improvement in hemodynamics was effective and not only transient. Fluid requirements were significantly reduced during as well as after CPB, and pulmonary gas exchange was least compromised in these patients.     

The effects of two rewarming strategies on heat balance and metabolism after coronary artery bypass surgery with moderate hypothermia

BACKGROUND: Postoperative hypothermia is common in cardiac surgery with hypothermic cardiopulmonary bypass (CPB). This trial was designed to evaluate whether rewarming over the normal bladder temperature (over 37 degrees C) at the end of hypothermic CPB combined with passive heating methods after CPB might result in a better heat balance, lower energy expenditure (EE) and decrease of disturbances in oxygen balance compared to only rewarming the patients to a bladder temperature of 35-37 degrees C. METHODS: A prospective, randomized controlled clinical study was performed in 38 patients scheduled for elective coronary artery bypass surgery. Twenty patients (group C) were rewarmed to a bladder temperature of 35-37 degrees C at the end of hypothermic (28 degrees C) CPB. Eighteen patients (group W) were rewarmed to a bladder temperature of 37-38.5 degrees C. RESULTS: At the end of CPB, the bladder temperature was 36.2+/-0.7 degrees C (mean+/-SD) in group C and 37.9+/-0.5 degrees C in group W. After half an hour's stay in the ICU, the mean body temperature (MBT) was 35.1+/-0.6 degrees C in group C and 36.6+/-0.7 degrees C in group W. During the following five hours, MBT increased to 37.4+/-0.8 degrees C in group C and to 38.0+/-0.6 degrees C in the other group. The peak value of EE in the ICU was 1.73+/-0.44 (group C) vs 1.35+/-0.29 (W/kg) (group W) (P=0.003). EE was significantly (P=0.044) higher in group C than in the other group between 1.5 and 5.5 h in the ICU. The increased energy expenditure due to heat production was associated with an increase in O2 consumption (VO2) 61.6+/-30.4% vs 25.2+/-24.1%, (peak values) compared to the basal values of the two groups measured before anesthesia (between groups P<0.001). Between 1.5 and 5.5 h in the ICU, group C had significantly higher VO2 (P=0.026), CO2 production (P=0.017), venous pCO2 (P<0.001) and minute ventilation (p=0.014) than group W. Venous pH was lower (P<0.001) in group C. The peak value of oxygen extraction was also higher (P=0.045) in group C. On the other hand, the lowest value of venous oxygen saturation was higher (P=0.04) in group W. CONCLUSION: With rewarming the patients at the end of CPB to a bladder temperature of over 37 degrees C combined with passive heating methods after CPB, it was possible to decrease EE and VO2 compared to the control group (rewarmed to bladder temperature of 35-37 degrees C) after coronary artery bypass surgery with moderate hypothermia.     

Changes in respiratory mechanics during cardiac surgery

We investigated the role of cardiopulmonary bypass (CPB) in compromised lung function associated with cardiac surgery. Low-frequency respiratory impedance (Zrs) was measured in patients undergoing cardiac surgery with (n = 30; CPB group) or without (n = 29; off-pump coronary artery bypass [OPCAB] group) CPB. Another group of CPB patients received dopamine (DA) (n = 12; CPB-DA group). Extravascular lung water was determined in five CPB subjects. Zrs was measured before skin incision and after chest closure. Airway resistance and inertance and tissue damping and elastance were determined from Zrs data. Airway resistance increased in the CPB group (74.9% +/- 20.8%; P < 0.05), whereas it did not change in the OPCAB group (11.8% +/- 7.9%; not significant) and even decreased in the CPB-DA patients (-40.6% +/- 9.2%; P < 0.05). Tissue damping increased in the CPB and OPCAB groups, whereas it remained constant in the CPB-DA patients. Significant increases in elastance were observed in all groups. There was no difference in extravascular lung water before and after CPB, suggesting that edema did not develop. These results indicate a significant and heterogeneous airway narrowing during CPB, which was counteracted by the administration of DA. The mild deterioration in tissue mechanics, reflecting partial closure of the airways, may be a consequence of the anesthesia itself. IMPLICATIONS: We observed that cardiopulmonary bypass deteriorates lung function by inducing a heterogeneous airway constriction, whereas no such effects were observed in patients undergoing cardiac surgery without bypass. The impairment in parenchymal mechanics, which was obtained in both groups, may result from peripheral airway closure and/or be a consequence of mediator release.     

Prostaglandin E1 infusion fails to inhibit the increase of serum granulocyte elastase and myeloperoxidase and the decrease of plasma angiotensin converting enzyme in patients undergoing open-heart surgery]

We studied whether prostaglandin E1 (PGE1) could inhibit the increase of serum granulocyte elastase (GEL) and myeloperoxidase (MPO), and the decrease of plasma angiotensin converting enzyme (ACE) induced by oxygenator in 19 patients undergoing open-heart surgery. The patients were randomly allocated into 2 groups: one group (PGE1 group, n = 9) received a continuous infusion of PGE1 at a rate of 30 ng.kg-1.min-1 during cardiopulmonary bypass (CPB), and the other group (control group, n = 10) received saline infusion. GEL, MPO and ACE were measured serially at 8 points: before induction of anesthesia (as baseline), immediately before initiation of CPB, 10 min after initiation, 60 min after initiation, immediately after the end of CPB, 60 min after CPB, 120 min after CPB, and on the first postoperative day. Serum levels of GEL and MPO during 120 min after the end of CPB in both groups increased significantly compared with the baseline values. There was no significant difference between the two groups. Plasma levels of ACE in both groups decreased significantly immediately after the end of CPB compared with values taken 10 min after the initiation of CPB. There was no significant difference between the groups. We conclude that the infusion of PGE1 30 ng.kg-1.min-1 failed to inhibit the increase of GEL as well as MPO, and the decrease of ACE.     

High colloid oncotic pressure priming of cardiopulmonary bypass in neonates and infants: implications on haemofiltration, weight gain and renal function

Objective: To evaluate the influence of high colloid oncotic pressure (COP) priming of cardiopulmonary bypass (CPB) on fluid balances, haemofiltration, capillary leakage and renal function in neonates and infants. Methods: Twenty neonates or infants underwent heart surgery using CPB and were randomised in two groups. For group 1 (FFP-group) a blood priming with fresh frozen plasma (FFP, low oncotic pressure) was chosen, for group 2 (HA-group) a blood priming containing FFP and human albumin 20% (HA) to realise higher oncotic pressures was substituted. All patients were monitored before, during and 6h after CPB. We measured weights, fluid balances, transfusion volumes, colloid oncotic pressures, inflammatory parameters (c-reactive protein, interleukin-6, interleukin-8, thrombocytes, leucocytes) and renal function (creatinine clearances, renal protein losses). Results: Patient's demographics and operational procedures were comparable in both groups with no further differences in operation procedures regarding palliation or correction. Colloid oncotic pressures of the priming solutions were higher in the HA-group (28mmHg+/-4.9) than in the FFP-group (6mmHg+/-1.3, p<0.001). Relative weight gain as a marker of capillary leakage in the HA-group (2%+/-4.5) was significantly lower 6h post CPB than in the FFP-group (8%+/-8.0, p=0.015). Haemofiltration rates were higher in the HA-group (569ml+/-197 vs 282ml+/-157, p=0.002) on CPB. There were no differences of creatinine clearances 6h after the end of CPB. Renal protein losses were elevated in both groups without any inter-group differences during and 6h after CPB. Conclusion: Addition of concentrated human albumin to priming fluids in paediatric cardiac surgery leads to less weight gain even after CPB. Supplementing paediatric patients undergoing cardiac surgery with concentrated human albumin does not affect renal function more severely than in paediatric patients undergoing cardiac surgery on CPB with blood priming.