Variability of plasma aprotinin concentrations in pediatric patients undergoing cardiac surgery

OBJECTIVES: Infants and children undergoing cardiopulmonary bypass for repair of congenital heart defects are at substantial risk for excessive bleeding, contributing greatly to morbidity and mortality. Aprotinin significantly reduces bleeding and transfusion requirements in adults but is of indeterminate value for pediatric patients. The aim of this study was to determine plasma aprotinin concentrations in these patients with a functional aprotinin assay. METHODS: Thirty patients less than 16 years of age scheduled for cardiac surgery with aprotinin were enrolled. Aprotinin was administered as a 25,000 KIU/kg bolus, 35,000 KIU/kg cardiopulmonary bypass prime, and 12,500 KIU.kg(-1).h(-1) continuous infusion. Blood samples for aprotinin concentrations (kallikrein-inhibiting units/milliliter) were obtained before aprotinin; 5 minutes post-bolus; 5 minutes after cardiopulmonary bypass initiation; 30 and 60 minutes on cardiopulmonary bypass; on discontinuation of aprotinin; 1 hour after aprotinin discontinuation; and 4 hours after permanent separation from cardiopulmonary bypass. For analysis, patients were grouped according to weight (<10 kg, 10-20 kg, >20 kg). Differences between weight groups were assessed using an exact test for categoric variables and 1-way analysis of variance for continuous variables. RESULTS: Aprotinin concentrations differed significantly across weight groups. Five minutes after aprotinin bolus and initiation of cardiopulmonary bypass, there was significant correlation between weight and aprotinin concentration (r =.57, P =.003; r =.69, P =.001, respectively). CONCLUSION: A functional assay reveals significant variability in aprotinin concentration for pediatric patients using current weight-based aprotinin dosing. Additional investigation is necessary to determine target aprotinin concentration dosing regimens to provide better efficacy.     

Comparison of continuous cardiac output measurements in patients after cardiac surgery

OBJECTIVE: To investigate in a direct comparison accuracy and precision of continuous cardiac output measurements assessed by continuous pulmonary artery thermodilution technique (TDCCO), continuous pulse contour analysis (PCCO), and noninvasive partial CO(2)-rebreathing technique (NICO) in patients after coronary artery bypass grafting (CABG) during the postoperative period. DESIGN: Prospective, controlled clinical study. SETTING: University hospital. PARTICIPANTS: Twenty-two patients undergoing elective CABG surgery. INTERVENTIONS: Hemodynamic measurements were performed after admission to the ICU and in sequence every 2 hours during the subsequent 6-hour period. Simultaneously, cardiac output (CO) was measured using a TDCCO, PCCO, and NICO. After the continuous cardiac output measurements were read, bolus thermodilution-derived cardiac output was obtained from thermodilution curves detected in the pulmonary artery (TDBCO(pa)). Four intermittent consecutive boli consisting of 10 mL of ice-cold saline were randomly injected over the ventilatory cycle. MEASUREMENTS AND MAIN RESULTS: The comparison between the continuous cardiac output measurement methods TDCCO versus PCCO showed a bias of -0.12 L/min, between TDCCO versus NICO -0.17 L/min, and between PCCO versus NICO -0.44 L/min. The comparison to the reference technique between TDBCO(pa) versus TDCCO revealed a bias of -0.28 L/min, between TDBCO(pa) versus PCCO -0.40 L/min, and between TDBCO(pa) versus NICO -0.64 L/min. CONCLUSIONS: The results of this clinical investigation show agreement between TDCCO and PCCO to satisfy clinical requirements in a setting of postoperative patients after cardiac surgery. In contrast, the NICO monitor is of very limited use in these patients.     

Effects of sevoflurane anesthesia on plasma inorganic fluoride concentrations during and after cardiac surgery

Purpose. Sevoflurane metabolism results in the production of inorganic fluoride, which is known to be nephrotoxic. Since marked changes in body temperature and hemodynamics in cardiac surgery affect sevoflurane metabolism, plasma inorganic fluoride concentrations may differ in this situation compared with other types of surgery. We therefore measured plasma inorganic fluoride concentrations during and after sevoflurane anesthesia in patients undergoing cardiac surgery. Methods. Sixteen patients undergoing coronary artery bypass grafting or valve replacement were premedicated with 5–10 mg midazolam and 0.5 mg scopolamine injected intramuscularly. Anesthesia was induced with 5–10 mg midazolam, 0.5–1 mg fentanyl, and 0.12–0.15 mg·kg⁻¹ vecuronium. Following tracheal intubation, anesthesia was maintained with oxygen, sevoflurane, and fentanyl. At the onset of cardiopulmonary bypass (CPB), sevoflurane was discontinued, and additional fentanyl, midazolam, and pancuronium were administered. Plasma inorganic fluoride concentrations were measured before anesthesia, immediately before and after CPB, and at 0, 2, 6, 12, 24, and 48 h after anesthesia. Results. The individual maximum plasma inorganic fluoride concentration was 19.2 ± 7.2 μmol·l⁻¹ (mean ± SD; range, 9.2–36.7). The mean plasma inorganic fluoride concentrations increased during anesthesia, but the rate of increase decreased after the initiation of CPB. Concentrations peaked at 2 h after anesthesia and decreased thereafter. The concentrations in three cases continued to increase 2 h after anesthesia. Conclusion. The plasma inorganic fluoride concentrations observed in patients undergoing cardiac surgery were below nephrotoxic levels. However, the decrease in mean fluoride concentration after anesthesia was slower than that in the previous study in general surgical patients. Received for publication on December 4, 1998; accepted on April 25, 1999     

Diuretic effects of aminophylline in patients after cardiac surgery

Diuretic effects of aminophylline in patients after cardiac surgery were studied by using the local renal thermodilution catheter (Goodman Co. Ltd.). The subjects were 11 patients who underwent cardiac surgery in our hospital. All patients had shown almost normal renal and endocrine function. On the day of operation, we indwelld renal thermodilution catheter into the left renal vein under fluoroscopy. After operation, when the urinary volume decreased below 1 ml.kg-1.hr-1, we administered aminophylline at a rate of 2 ml.kg-1.hr-1. We measured HR, BP, CO, PAP, CVP, renal blood flow, urinary volume, urinary electrolytes, plasma renin activity, angiotensin II, aldosteron, ADH and alpha hANP just before and after infusion of aminophylline. The urine volume, renal blood flow and renal blood flow distribution rate showed significant increases of about 70%, 40% and 35% respectively. But hemodynamic parameters including HR, mean BP and CO increased for 5%, 10% and 8% respectively after administration of aminophylline. In the endocrine system, only angiotensin II increased significantly but aminophylline did not cause any change in endocrine system. The results suggest that diuretic effect of aminophylline is mainly achieved by increasing renal blood flow.     

Comparison of the hemodynamic effects of milrinone with dobutamine in patients after cardiac surgery.

OBJECTIVE: To compare the hemodynamic effects, efficacy, and safety of intravenous milrinone (M), 50 microg/kg during 10 minutes followed by 0.5 microg/kg/min, with intravenous dobutamine (D), 10 to 20 microg/kg/min, in patients with low cardiac output after cardiac surgery. DESIGN: Randomized, open-label, multicenter study. SETTING: Cardiothoracic surgery departments, operating rooms, and intensive care units in 6 university hospitals. PARTICIPANTS: Patients (n = 120; 60 per group) after elective cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Analysis compared the hemodynamics at baseline and the percentage change from baseline during 4 hours of the drug infusion. The incidence of adverse events was recorded. Both groups had low mean (+/- SEM) cardiac indices (M, 1.6 ([0.03] L/min/m(2); D, 1.7 [0.03] L/min/m(2)) in association with adequate mean pulmonary capillary wedge pressures (M, 13.7 [1.3] mmHg; D, 12.7 [1.9] mmHg) at baseline. Group M had significantly higher systemic arterial pressures and systemic vascular resistances compared with group D; otherwise, the hemodynamics in both groups were comparable. During the study, hemodynamic responses included the following: group D had greater increases in cardiac index (at 1 hour, D = 55%, M = 36%; p < 0.01), heart rate (at 1 hour, D = 35%, M = 10%; p < 0.001), arterial pressures (mean arterial pressure at 1 hour, D = 31%, M = 7%; p < 0.001), and left ventricular stroke work index (at 1 hour, D = 75%, M = 45%; p < 0.05). Group M had greater decreases in mean pulmonary capillary wedge pressure (at 1 hour, D = -3%, M = -14%; p < 0.05). Comparisons of adverse events showed that dobutamine was associated with a higher incidence of hypertension (D = 40%, M = 13%; p < 0.02) and change of rhythm from sinus to atrial fibrillation (D = 18%, M = 5%; p < 0.04). Milrinone was associated with a higher incidence of sinus bradycardia (D = 2%, M = 13%; p < 0.03). CONCLUSIONS: Milrinone and dobutamine are appropriate and comparable for the pharmacologic treatment of the low- output syndrome after cardiopulmonary bypass.     

Perioperative changes in plasma brain natriuretic peptide concentrations in patients undergoing cardiac surgery

P < 0.0001 versus baseline). They had returned to the baseline values when measured 3 weeks postoperatively. The preoperative plasma BNP concentration correlated significantly with the left ventricular ejection fraction (r = −0.895). The peak plasma BNP concentration 24 h after bypass correlated with the cardiac index (r = −0.64), stroke volume index (r = −0.62), injection rate of dopamine hydrochloride (r = 0.65), and aortic crossclamp time (r = 0.57). There was also a significant correlation between the preoperative BNP concentration and the plasma BNP concentration 24 h post-CPB. These findings led us to conclude that the plasma concentrations of BNP become markedly and acutely elevated after cardiac surgery with CPB, and reflect the state of left ventricular function. Moreover, the severity of acute heart failure after cardiac surgery can be predicted by the preoperative plasma BNP concentration. (Received for publication on Sept. 19, 1996; accepted on Mar. 4, 1997)     

衰弱与老年心脏手术关系的研究进展

衰弱是老年人多个生理系统储备功能减退,致机体易损性增加及维持自体稳态能力降低的一种老年综合征。近年来,众多研究已证实将衰弱作为老年心脏手术患者的术前评估可预测其术后再入院、不良心血管事件及死亡等不良预后。该文就衰弱的概念、衰弱与心脏手术的关系、老年心脏手术患者合并衰弱的评估及干预策略等进行系统综述,旨在为老年心脏手术患者的危险分层及围术期管理提供决策依据。     

加速康复外科在老年心脏瓣膜手术患者的应用

目的:探讨加速康复外科(enhanced recovery after surgery,ERAS)方案应用于CPB下老年心脏瓣膜手术患者的安全性和有效性。方法:前瞻性入组因心脏瓣膜病择期行CPB下瓣膜成形或置换手术的老年住院患者,按随机数字表法分为ERAS组(22例)和对照组(28例),ERAS组患者接受ERAS方案进行围手术期管理,对照组患者接受常规围手术期处理。对比两组患者住院时间、ICU停留时间、术后气管导管带管时间、舒芬太尼用量、苏醒时间、术后红细胞悬液用量、术后Hb、术后首次通便时间、术后血管活性药物使用时间以及术后引流管拔除时间、术后VAS评分、住院费用和术后不良事件发生情况。结果:与对照组比较,ERAS组患者住院时间、ICU停留时间、术后气管导管带管时间、苏醒时间、术后首次通便时间、术后血管活性药物使用时间和术后引流管拔除时间均较短,其中ICU停留时间、术后气管导管带管时间、苏醒时间、术后首次通便时间和术后引流管拔除时间差异有统计学意义(P<0.05)。ERAS组患者舒芬太尼用量少于对照组,差异有统计学意义(P<0.05)。ERAS组患者术后不良事件发生情况较对照组低(P<0.05)。两组患者术后红细胞悬液用量、术后Hb、术后VAS评分、住院费用差异无统计学意义(P>0.05)结论:ERAS方案可以安全、有效地应用于实施CPB手术的老年心脏瓣膜手术患者。     

Studies on morphine disposition: plasma concentrations of morphine and its metabolites in anesthetized middle-aged and elderly surgical patients

The effects of aging on the disposition of morphine and its metabolites have been investigated in 10 middle-aged patients (36 to 55 years of age) undergoing lower abdominal or body surface surgery, and compared with 10 elderly patients (65 to 83 years of age) undergoing similar surgery. All patients received 10 mg morphine sulphate pentahydrate IV over 30 seconds as part of a balanced anesthetic technique. Peripheral venous blood samples were collected to 180 min, and plasma concentrations of morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) were assayed by differential radioimmunoassay. There were no differences between the two groups for morphine elimination half-life (middle-aged patients, 129 min; elderly patients, 162 min), mean residence time (154 and 207 min), and apparent volume of distribution at steady state (116 and 107 l). However, clearance was significantly greater in the younger patients (853 vs. 559 ml/min; p less than 0.02). The area under the curve (AUC0-180) for M3G and M6G were similar in the two patient groups, as were the peak metabolite concentrations and times to peak concentrations. M6G has been shown in both animals and humans to exert analgesic properties. Despite the reduced clearance of the parent drug, there was an unaltered AUC for M6G, presumed due to the greater decrease in glomerular filtration rate seen during anesthesia in the elderly patient. This phenomenon may result in enhanced analgesic efficacy from a given dose of morphine in the elderly patient.     

Applicability of tools to assess pain in elderly patients after cardiac surgery

Background: Post-operatively, elderly patients with impaired vision and cognitive dysfunction may experience difficulties understanding standard pain assessment tools such as the 10-cm Visual Analogue Scale (VAS) and the Verbal Rating Scale (VRS). Thus, there is a need to identify more feasible post-operative pain assessments for elderly patients. With this goal in mind, we compared the VAS and VRS with two more expressive tools: the 50-cm Red Wedge Scale (RWS) and the Facial Pain Scale (FPS).
Methods: Cardiac surgery patients (73 ± 5 years, mean ± SD) were allocated to an RWS ( n =80) or an FPS ( n =80) group. Pain was assessed at rest and after movement during the first 4 days after tracheal extubation. The RWS or FPS assessments were repeated after 10 min. All patients completed the VRS and VAS.
Results: The rates of successful pain measurement on study day 1 were: VRS 86%, VAS 62%, RWS 78%, and FPS 60%. Pain measurements with the RWS correlated with the VAS ( r =0.758, P <0.001) and weaker with the VRS ( r =0.666, P <0.001) measurements. Pain measurements with the FPS correlated well with the VAS ( r =0.873, P <0.001) and weaker with the VRS ( r =0.583, P <0.001) measurements. With all scales, success rates improved during the study period.
Conclusion: In elderly patients, immediately after cardiac surgery, the VRS is the most feasible pain scale, followed by the RWS. The traditional 10-cm VAS is unsuitable for pain measurement in this population.     

Newly developed T-wave inversion with cardiac wall-motion abnormality predominantly occurs in middle-aged or elderly women after noncardiac surgery

Purpose. The study was done to determine the characteristics and prevalence of myocardial ischemia with inverted T waves after noncardiac surgery. Methods. A list of patients who developed electrocardiogram (ECG) T-wave inversion associated with wall-motion abnormalities observed by transthoracic echocardiography (TTE) following noncardiac surgery was generated from the intensive care unit (ICU) medical records database between January 1, 1995, and December 31, 2000. The hospital records of these patients were analyzed retrospectively. Results. Among 4219 patients (2187 men and 2032 women) who were admitted to the ICU after noncardiac surgery, 13 developed myocardial ischemia with inverted T waves postoperatively. All of the patients were middle-aged or elderly women with no history of coronary artery disease; nine of them had undergone intraabdominal surgery. Characteristic ECG findings included inverted T waves in the left precordial leads, which subsequently became prominent with QT prolongation. In all of these patients, wall-motion abnormalities were observed on the anterior wall, but these resolved within 60 days of the episode. Myocardial ischemia was asymptomatic, with neither hemodynamic changes nor adverse cardiac events. Conclusion. Newly developed giant negative T waves with QT prolongation in the ECG may indicate myocardial stunning, but do not in themselves imply a poor prognosis. The marked preponderance of middle-aged and elderly women with this type of myocardial ischemia remains to be explained. Received: June 7, 2002 / Accepted: December 20, 2002 Address correspondence to: Y. Esaki     

Comparison of surgical outcomes of gastric cancer in elderly and middle-aged patients

BACKGROUND: We compared clinicopathological features and results of surgery for gastric carcinoma in elderly and middle-aged patients to develop appropriate treatment for elderly patients with gastric carcinoma. METHODS: Surgical results were assessed for 135 elderly patients (over 75 years old) and 665 middle-aged patients (between 45 and 65 years old) with gastric cancer. RESULTS: Distinct characteristics of elderly patients were male predominance; macroscopically well, or ill-defined, histologically differentiated tumors; and advanced stage disease. There was a significant difference in overall survival between the groups for early stage carcinomas but no difference in cause-specific survival. Postoperative morbidities did not differ between the curatively resected patients in the 2 groups. Moreover, deaths from other cancers or comorbid disease were frequent among the elderly. CONCLUSION: Meticulous treatment and follow-up not only for gastric carcinoma but also for other diseases would improve survival in elderly patients, particularly those with early-stage tumors.     

Association between vasopressor dependence and early outcome in patients after cardiac surgery

Arterial hypotension with vasopressor dependence is a major problem after cardiac surgery. We evaluated the early postoperative course of 1558 consecutive patients scheduled for cardiac surgery, and compared the outcome of patients with and without vasopressor dependence (defined as the need for > 0.1 microg x kg(-1) x h(-1) noradrenaline for > 3 h in the face of normovolaemia). Vasopressor dependence was diagnosed in 424 patients (27%) and was associated with a higher incidence of postoperative renal failure (67 (15.7%) vs 7 (0.6%), respectively; p < 0.0001), a longer duration of ventilation (median IQR [range]) 14 (8-26 [6-39]) h vs 8 (5-11 [4-32]) h; p < 0.0001), a greater need for red cell transfusion (3 (1-5 [0-10]) units vs 1 (0-2 [0-4]) units; p < 0.001) and a longer length of stay in the ICU (4 (2-6 [2-9] days) vs 2 (1-3 [1-6] days; p < 0.001). Vasopressor dependence could be predicted from a combination of factors, including pre-operative ejection fraction < 37%, cardiopulmonary bypass lasting > 94 min, and postoperative interleukin-6 > 837 pg x ml(-1).     

Changes in plasma total and ionized magnesium concentrations and factors affecting magnesium concentrations during cardiac surgery

The purpose of this study was to measure blood total and ionized magnesium concentrations ([TMg] and [Mg²⁺], respectively) and to investigate factors that might be affecting their changes during cardiac surgery using hypothermic cardiopulmonary bypass. Eight patients were examined. All the patients received diuretics and predeposited autologous blood during surgery. No drugs containing Mg²⁺ were administered. Nine blood samples and eight urine samples were collected from the pre-induction period to the end of surgery. Hematocrit, [TMg], [Mg²⁺], plasma concentrations of calcium ([Ca²⁺]), creatinine, parathyroid hormone (PTH), urinary concentrations of TMg, and creatinine were measured, and the fractional excretion of Mg (FEMg) was calculated. Both [TMg] and [Mg²⁺] decreased significantly in the prebypass period and remained significantly depressed thereafter. The ionized fraction of magnesium ([Mg²⁺]/[TMg]) was decreased during the postbypass period. Hematocrit decreased significantly from the prebypass period, and FEMg increased significantly after aortic cross-clamping. In conclusion, hemodilution and renal loss were main causes of hypomagnesemia, and citrate in predeposited autologous blood may contribute to the decrease in [Mg²⁺]/[TMg] in the postbypass period. These results suggest that magnesium supplementation under close monitoring of [Mg²⁺] should be required during cardiac surgery.     

合并2型糖尿病老年患者心脏术后医院感染分析

目的分析心血管外科重症监护室合并2型糖尿病的老年患者心脏手术后医院感染及病原学特点,以探讨防治措施及抗菌药物合理应用。 方法回顾性分析2007年8月至2014年8月某院心血管外科65岁以上合并糖尿病患者心脏手术后发生医院感染的临床资料。 结果2007年8月至2014年8月收集65岁以上合并糖尿病行心脏手术患者共407例,其中发生医院感染46例（11.3%）,感染例次59例次（14.5%）。分离各种病原菌138株,以呼吸系统（55.9%）及血液系统（15.2%）感染为主。糖化血红蛋白> 7%的老年患者心脏术后医院感染比例显著高于糖化血红蛋白≤ 7%的患者（17.1% vs. 12.3%,χ² = 5.8、P = 0.01）。糖化血红蛋白> 7%患者及≤ 7%患者中,均以呼吸系统感染为主,差异无统计学意义（8.0% vs. 6.4%,χ²= 0.4、P = 0.58）。导尿管留置15 d以上患者泌尿系统感染的比例显著高于留置15 d以下者（6.5% vs. 1.3%,χ²= 6.8、P = 0.001）。革兰阴性菌中以鲍曼不动杆菌为主（21.7%）,革兰阳性菌中以表皮葡萄球菌为主（13.1%）。鲍曼不动杆菌、溶血性葡萄球菌及金黄色葡萄球菌均显示多耐药。 结论合并2型糖尿病的老年患者心脏术后医院感染发生率高,耐药性逐渐增强。围手术期密切监测控制血糖,术后合理应用抗菌药物,对降低合并2型糖尿病老年患者的医院感染及病死率十分必要。