Effect of pre-operative metoprolol on cardiovascular and catecholamine response and bleeding during hysterectomy.

The effect of a pre-operative dose of metoprolol on the catecholamine and cardiovascular responses to tracheal intubation and surgery, cardiac complications and intra-operative blood loss, were studied in patients undergoing elective hysterectomy during general anaesthesia. The study was double-blind and placebo controlled. The patients received metoprolol 100 mg or placebo orally 1-25 h before anaesthesia. In patients given metoprolol, heart rate and mean arterial pressure were lower during the first 45 min of anaesthesia. Plasma adrenaline and noradrenaline concentrations increased in both groups in response to tracheal intubation and surgery, but were higher after metoprolol. The incidence of arrhythmias was less after metoprolol. The mean operative blood loss was greater in the placebo group (486 +/- 170 ml (SEM) compared to 231 +/- 43 ml (SEM) after metoprolol). We conclude that oral premedication with metoprolol attenuates the hypertensive response to tracheal intubation and reduces both arrhythmias and operative blood loss.     

Usefulness of OPCAB from the viewpoint of fluctuations in the level of blood natriuretic peptides

Fluctuations in the level of blood natriuretic peptides (ANP and BNP) were compared between 41 patients who underwent conventional coronary artery bypass (CCAB) and 19 patients who underwent off-pump coronary artery bypass (OPCAB). A blood sample was collected before surgery, and 6, 12 and 24 hours; 2, 3, 5 and 7 days; and 1 month after the end of extracorporeal circulation. There were no significant differences in left ventricular ejection fraction (LVEF) before and after surgery in either group or between the two groups. On average, 3.3 +/- 1.0 bypass grafts were used for the CCAB group, and 2.2 +/- 0.8 grafts for the OPCAB group. Furthermore, the maximum postoperative creatine phosphokinase-MB (CK-MB) level for the CCAB group was 49.1 +/- 17.5 IU/l, whereas that for the OPCAB group was significantly lower at 23.2 +/- 24.8 IU/l. The preoperative level of blood ANP for the CCAB group was 24.6 +/- 19.9 pg/ml while that for the OPCAB group was 39.3 +/- 29.5 pg/ml, but there was no significant difference between the two groups. In both groups, the level of blood ANP reached a peak three days after the end of extracorporeal circulation and then decreased after that point. Although the level of blood ANP for the OPCAB group decreased to 51.4 +/- 26.4 pg/ml one month after the end of extracorporeal circulation, that for the CCAB group one month after the end of extracorporeal circulation remained significantly high at 61.3 +/- 30.6 pg/ml, when compared to that before surgery. Furthermore, the preoperative level of blood BNP for the CCAB group was 40.0 +/- 35.2 pg/ml and that for the OPCAB group was 75.5 +/- 59.7 pg/ml, but there was no significant difference between the two groups. Then, in both groups, the level of blood BNP reached a peak 2-5 days after the end of extracorporeal circulation and then decreased after that. Whereas the level of blood BNP for the OPCAB group decreased to 96.4 +/- 56.0 pg/ml one month after the end of extracorporeal circulation, that for the CCAB group one month after the end of extracorporeal circulation remained significantly high at 160.3 +/- 106.2 pg/ml when compared to that before surgery. The levels of ANP and BNP increased postoperatively for both OPCAB and CCAB groups since the following events caused a great degree of stress on the heart: general anesthesia, cardiac herniation, stabilizer compression, regional blood flow blockage and reperfusion injury. Although the level of natriuretic peptides for the CCAB group remained high one month after the end of surgical stress, that for the OPCAB group returned to near the preoperative level one month later, thus supporting the notion that OPCAB is less invasive.     

Study on CAZ levels in serum, urine and myocardial tissue during and after open-heart surgery with cardiopulmonary bypass

Ceftazidime (CAZ) was administered to 10 patients who underwent open heart surgery using an artificial heart and lung (AHL), and the concentrations of the drug in the blood, urine, filtrate and cardiac muscle were measured. Following anesthesia induction, patients were injected intravenously with 2 g CAZ, and then 2 g CAZ was injected initially into the filling solution of the AHL followed by 1 g every 1 hr. After the surgery, patients received 1 g CAZ intravenously followed by the same dose every 12 hr till Day 5 of the surgery. Results obtained were as follows: 1) The concentration of CAZ in the cardiac muscle averaged 41.2 +/- 12.3 micrograms/g, and the ratio to the concentration in the plasma averaged 0.61 +/- 0.12, being considered to be reasonable. 2) The change in the mean plasma concentration of CAZ during extracorporeal circulation was maintained within the range of 109.7 to 337.0 micrograms/ml, and the concentration increased slightly with the repeated injection. In 2 cases, the plasma concentration was transiently more than 400 micrograms/ml, however, no side effect was observed. 3) The mean plasma concentration of CAZ after surgery attained 214.4 +/- 38.9 micrograms/ml, and half-time averaged 2.8 hr. 4) The excretion rates of CAZ in urine and filtrate by the termination of the extracorporeal circulation were 30.6 and 5.2%, respectively, thus the excretion of the drug in filtrate was lower than that in urine. The total excretion rate in both urine and filtrate for 6 hr after surgery was 55.3%. 5) Neither postoperative infection nor side effect were observed in all cases. CAZ is considered to be a useful antibiotics in the cardiac surgery management.     

The influence of extracorporeal circulation on erythrocytes and flow properties of blood

The influence of extracorporeal circulation on red blood cells and flow properties of blood was studied in 10 patients undergoing aorta-coronary bypass grafting. Blood samples were drawn on admission, under general anesthesia before the operation, during extracorporeal circulation, immediately after extracorporeal circulation, and 24 hours after extracorporeal circulation. Echinocytes were found during and shortly after extracorporeal circulation, but disappeared within 24 hours. Washing the cells in buffer restored the normal discocytic shape, which indicated that a plasma factor was responsible. Red cell membrane lipids were not affected. Analysis of the membrane proteins revealed a decrease of ankyrin after extracorporeal circulation, which was prevented by protease inhibitors during preparation. This suggests an increased proteolytic activity of the plasma after extracorporeal circulation. Red cell deformability was not altered. Plasma viscosity and hematocrit were markedly reduced by hemodilution with the priming solution. Their low levels resulted in a low blood viscosity during extracorporeal circulation, which was even lower at 26 degrees C than before or after the operation at 37 degrees C. We conclude that the red cell is affected by extracorporeal circulation. The flow properties of blood, however, are not impaired, but are improved by hemodilution.     

Contribution of autologous blood transfusion in cardiac surgery in the adult

The use of autologous blood transfusion in cardiac surgery is still controversial. This study was prospectively designed to evaluate the haemodynamic and haematological benefits of this method, with special attention to its impact on reducing bank blood requirements. Between November 1983 and October 1984, 160 patients underwent cardiac surgery with extracorporeal circulation and were randomly assigned to two groups: group I (81 patients) was the control group and group II (79 patients) received autologous transfusion following extracorporeal circulation. Blood was withdrawn immediately after the induction of anaesthesia via a jugular catheter and stored in CPD solution at room temperature. The volume of blood removed was replaced with gelatin solutions; after bypass, blood was returned to the patient. There was no difference in systolic, diastolic or mean blood pressures between the two groups. Right atrial pressure and heart rate were not statistically different in both groups. Myocardial perfusion and myocardial oxygen consumption remained unchanged in group II compared with group I. Complete haematological evaluation was carried out before and during bypass, and thereafter daily for the first twelve days of the postoperative period. There was no significative difference between the two groups in platelet counts, fibrinogen levels, prothrombin and partial thromboplastin times. During extracorporeal circulation, mean haematocrit was 22.9 +/- 0.4% in group II and 25.3 +/- 0.5% in group I (p less than 10(-3)). The mean haematocrit time course was similar in both groups during the postoperative period and returned to preoperative value at discharge.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of metoprolol on perioperative outcome in coronary patients undergoing nonvascular abdominal surgery

STUDY OBJECTIVE: To analyze the clinical effectiveness of the beta-1-adrenergic blocker, metoprolol. DESIGN: Prospective, observational, clinical study. SETTING: Operating room and intensive care unit of a tertiary-care teaching hospital. PATIENTS: 111 ASA physical status II, III, and IV consecutive patients who were scheduled for open abdominal nonvascular surgery. INTERVENTIONS: Patients were divided into two stratification groups: 83 (74.8%) of 111 received metoprolol, and 28 (25.2%) of 111 were controls. Within 24 to 96 hours, the drug was used parenterally in a dose of 5, 10, and 15 mg per 24 hours. Metoprolol cardioprotection was applied during the whole perioperative period, in the form of tablets in a dose of 25, 50, and 100 mg per 24 hours until the 30th postoperative day. MEASUREMENTS: During surgery, and in the first 72 postoperative hours, patients were monitored by continuous ST-T segment monitoring. A 12-lead electrocardiogram was attached immediately after surgery; on postoperative days 1, 2, and 7; and one day before discharge from the hospital. Serum troponin-T level was controlled 6, 24, and 96 hours after surgery. MAIN RESULTS: Postoperative mortality of cardiac etiology after 30 days of surgery was 1.2% (1/83) in the metoprolol group versus 7.1% (2/28) in the nonmetoprolol group (P<0.05). The causes of death in these three patients were acute myocardial infarction, congestive heart failure, and malignant arrhythmias. CONCLUSIONS: Perioperative cardioprotection significantly reduced mortality until postoperative day 30 in patients having open abdominal nonvascular surgery with general anesthesia.     

Low dose clonidine premedication accentuates the hyperglycemic response to surgery

PURPOSE: To investigate the influence of low dose clonidine premedication on perioperative glucose homeostasis. METHODS: Sixteen patients undergoing abdominal hysterectomy for benign uterine myoma were randomly assigned to receive either iv clonidine (1 microg x kg(-1)) 30 min before induction of general anesthesia (clonidine, n=8) or saline (control, n=8). Plasma concentrations of glucose, insulin, cortisol, epinephrine and norepinephrine were measured before, during and two hours after surgery. At the same time heart rate, mean arterial pressure and cardiac output were recorded. RESULTS: In both groups, glucose concentrations significantly increased during and after surgery. Intraoperative glucose plasma concentration in the clonidine group was higher than in the control group (clonidine: 6.8 +/- 0.6 mmol x L(-1) vs control: 5.7 +/- 0.8 mmol x L(-1), P < 0.05). This was accompanied by a lower insulin plasma concentration (clonidine: 3.9 +/- 1.9 microU x mL(-1) vs control: 6.5 +/- 2.8 microU x mL(-1), P <0.05). Heart rate, mean arterial pressure and cardiac output remained unchanged throughout the study period without any differences between the groups. While norepinephrine plasma concentrations increased in the control group only (P <0.05), the plasma concentrations of epinephrine and cortisol increased in both groups (P <0.05). Clonidine significantly attenuated the cortisol response as reflected by lower intra- and postoperative cortisol plasma concentrations than in the control group (P <0.05). CONCLUSION: Premedication with clonidine 1 microg x kg(-1) accentuates the hyperglycemic response to lower abdominal surgery caused by the decrease in insulin plasma concentrations.     

Efficacy of a single dose of urapidil for preventing arterial hypertension during the pre-bypass period in coronary surgery

OBJECTIVES: To assess the effect of a single prophylactic dose of urapidil for arterial hypertension during the period before start of extracorporeal circulation. PATIENTS AND METHODS: Forty-four patients with good ventricular function (ejection fraction < 40%) scheduled for coronary surgery were enrolled for prospective study. The patients were randomly assigned to receive 0.5 mg/kg of urapidil (group U, n = 22) or nothing (group N, n = 22) 3 min before skin incision. If hypertension developed sodium nitroprusside was administered, starting with a dose of 0.5 microgram/kg/min. Monitoring of arterial pressure, heart rate and ST segment (DII and V5) was continuous. The study ended with cannulation of the aorta. RESULTS: The demographic features, cardiovascular history, medication and duration of surgery were comparable in the two groups. Six patients in group U (27%) and 19 in group N (86%) developed arterial hypertension (p < 0.001), the duration of which was 2.23 +/- 4.49 min in group U and 9.64 +/- 9.7 min in group N (p < 0.05). Arterial hypotension was observed in 13 group U patients and 7 group N patients (NS). No significant differences in duration of tachycardia, bradycardia or myocardial ischemia were found. CONCLUSIONS: The administration of a single dose of urapidil prevents arterial hypertension during the phase before extracorporeal circulation for coronary surgery and reduces the need for nitroprusside. No clinically relevant side effects are evident.     

Antithrombin III substitution for optimization of the heparin effect during extracorporeal circulation in heart surgery

In a prospective randomised study 20 patients undergoing coronary bypass surgery were assigned to two groups. Patients in group I (n = 10) received initially 250 IU heparin X kg-1 before the start of extracorporeal circulation. Patients in group II (n = 10) were given the same amount of heparin and in addition 1 000 units of purified human antithrombin III (AT III) concentrate. A highly significant lower heparin coefficient [2.69 +/- 0.57 IU X kg-1 X min-1, which is a parameter of heparin consumption (units of heparin X kg-1 given per minute during the time of heparinisation)], was found in group II compared to group I (3.73 +/- 0.56 IU X kg-1 min-1). Heparin sensitivity, measured as an increase in the ratio of activated coagulation time (ACT) X IU heparin-1 X kg-1 as a response to initial heparin dose, was found to be significantly higher (1.22 +/- 0.30 sec X IU heparin-1 X kg-1) in patients receiving AT III as measured in the control group (0.95 +/- 0.23 s X IU heparin-1 X kg-1). Mean values of ACT during the period of heparinisation were comparable (group I: 533 +/- 81 s, group II: 512 +/- 62 s) in the two groups. The substitution of AT III led to an increase of plasma AT III activity of 1.4% per substituted unit AT III X kg-1. AT III plasma activity, corrected to initial haematocrit levels to avoid dilution dependency, decreased as a consequence of extracorporeal circulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Red blood cell aggregation during cardiopulmonary bypass: a pathogenic cofactor in endothelial cell activation?

OBJECTIVE: The bio-incompatibility of the cardiopulmonary bypass (CPB) circuit and the use of artificial colloids trigger massive defense reaction that involves endothelial cells and several blood cells: platelets, neutrophils, monocytes, red blood cells (RBC) and lymphocytes. Investigating the effects on RBC aggregation and endothelial cells activation, the present study addresses two different prime solutions commonly used in the clinical practice. METHODS: RBC aggregation was measured by means of Laser-assisted Optical Rotation Cell Analyzer, in an in vitro study designed to mimic the human blood-material interactions during extracorporeal circulation. A clinical study investigating endothelial activation was conducted in 20 patients undergoing elective coronary bypass surgery, randomly assigned for CPB using two different priming solutions: HAES-steril 6% (HES 200/0.5) and Voluven 6% (HES 130/0.4). RESULTS: Circulation trough a Chandler loop of HES-blood mixes altered significantly RBC aggregability. The use of HES 130/0.4 resulted in marked decrease in RBC aggregation (aggregation index (AI) before and after circulation was 23.5+/-3.8 and 18+/-2.9, respectively), no significant differences being found when compared with Ringer's lactate group. The use of HES 200/0.5 resulted in better maintained RBC aggregation (AI 39.7+/-5.9 and 29.7+/-4.7 before and after circulation, respectively). The AI measured for the whole blood (control) sample was 61.9+/-4.9 before circulation, and 58.1+/-4 after. Markers of endothelial activation (von Willebrand factor (vWF), thrombomodulin (TM), tissue plasminogen activator (tPA) and E-selectin) significantly increased during CPB. Differences between HES treatment groups were evident post-bypass. While the markers of endothelial activation returned to baseline in HES 200/0.5 group, HES 130/0.4 was associated on the first post-operative day with further increase of vWF and tPA. CONCLUSION: RBC aggregation significantly drooped as consequence of blood dilution and blood-material interaction. We reason that low RBC aggregation added to plasma viscosity reduction and non-physiologic flow conditions during extracorporeal circulation are important factors contributing to loss of shear stress at the venous endothelial wall. The loss of shear stress triggers complex signaling leading to endothelial activation. Additional fundamental research is needed in order to verify the hypothesis introduced by the present study. Characterizing the impact of rheologic parameters on endothelial function could prove to be valuable in patients undergoing CPB.     

High dose aprotinin to reduce blood loss in patients undergoing redo open heart surgery.

Recently, aprotinin has been demonstrated to be effective in reducing post-operative bleeding after open heart surgery. The aim of this study was to evaluate the effectiveness of high dose aprotinin in patients undergoing redo open heart surgery in whom perioperative bleeding is generally increased. Fifty-eight patients, mean age 55 years, underwent a second open heart surgery for single valve replacement in 37 patients (mitral or aortic), for double valve replacement in 16 patients and for coronary artery by-pass grafting in 4 patients. In 30 of the 58 patients (Group A) aprotinin was infused with the following scheme: 2 million KIU in 30 minutes during induction of anesthesia, 2 million KIU in the priming volume of extracorporeal circulation and 500,000 KIU every hour until the end of the surgical procedure. The remaining 28 patients served as control group (Group B). No adverse reactions to aprotinin were observed. There was no significant difference in cardiopulmonary by-pass time and minimum temperature achieved between the two groups of patients. During the operative day blood loss was significantly lower in group A than in group B (492 +/- 336 ml vs. 628 +/- 273 ml) (p < 0.01). This difference was not significant during the following days. However 3 days after the operation a still significant difference was reported in total blood loss between group A and group B (816 +/- 507 ml vs. 1018 +/- 373 ml) (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Blood lactate levels during fast-track cardiac anesthesia

BACKGROUND: Lactate is a very sensitive marker of outcomes in critically ill patients. The aim of this study was to investigate the significance of blood lactate measurement during fast-track cardiac anesthesia. METHODS: We examined arterial blood lactate levels of 12 patients following coronary artery bypass graft surgery under intermittent aortic cross clamping with fast-track cardiac anesthesia. Anesthesia was induced with propofol and fentanyl, and maintained with propofol, fentanyl (total 400-1000 micrograms) and isoflurane. Blood samples were collected from a radical artery catheter. RESULTS: At the termination of the extracorporeal circulation, the blood lactate was 10.3 +/- 2.0 (7.4-12.5) mmol.l-1. This value decreased slowly to 1.5 +/- 0.4 mmol.l-1 on the second postoperative day. All patients were extubated within 4 hours after surgery. Vital signs were stable, and no cardiac events occurred perioperatively. CONCLUSIONS: A continuous decline in blood lactate levels was related to a favorable postoperative course. Further research might be required to prevent transient hyperlactecemia at the end of cardiopulmonary bypass.     

Influence of hypothermic cardiopulmonary bypass on atrial natriuretic factor levels

Atrial natriuretic factor (ANF) is a peptide released from the heart in response to atrial distension. This peptide causes diuresis, vasodilatation, decreased blood pressure, and antagonizes the renin-aldosterone and antidiuretic hormone neuraxes. The influence of cardiopulmonary bypass and cardiac surgery on the circulation and release of ANF is unknown. Plasma ANF concentrations were therefore determined in patients undergoing coronary artery revascularization (CABG) and mitral valve replacement (MVR). Peptide levels were unchanged following anaesthetic induction. Plasma ANF concentrations decreased significantly during hypothermic (less than or equal to 28 degrees C) cardiopulmonary bypass in both patient groups. After 60 minutes of cardiac bypass, ANF declined from (mean +/- SEM) 512 +/- 132 to 20 +/- 6 pg.ml-1 (P less than 0.05) during MVR, and from 178 +/- 41 to 110 +/- 48 pg.ml-1 during CABG (P less than 0.05). Rewarming during bypass was associated with an increase in ANF concentration in both groups. Heparin anticoagulation and protamine reversal had no effect on immunoreactive ANF levels. In patients undergoing CABG, there was a linear relationship between plasma ANF concentration (pg.ml-1) and right atrial pressure (mmHg) prior to cardiopulmonary bypass (r = 0.86, P less than 0.005). However, one and three hours after cardiopulmonary bypass there was no significant relationship between right atrial pressure and ANF plasma levels. These results suggest that reduction in plasma ANF concentration occurs during hypothermic cardiopulmonary bypass. Furthermore, the proportional relationship between atrial distension and circulating ANF concentration was altered following cardiac surgery.     

Neuron-specific enolase increases in plasma during and immediately after extracorporeal circulation

BACKGROUND: Minor cerebral complications are common after cardiac surgery. Several biochemical markers for brain injury are under research; one of these is neuron-specific enolase (NSE). The purpose of this study was to investigate the release of this enzyme into the blood during and immediately after extracorporeal circulation and to evaluate the effect of hemolysis on this release. METHODS: Sixteen patients scheduled for elective heart surgery were included in the study. Blood samples for analysis of NSE and free hemoglobin in plasma were drawn before, during, and up to 48 hours after the end of extracorporeal circulation. The release of NSE from erythrocytes and its correlation to the release of free hemoglobin was studied by serial dilution and hemolysis in vitro. RESULTS: The peri- and postoperative course was uneventful in all patients. Extracorporeal circulation initiated a release of NSE that reached a maximum 6 hours after the end of perfusion. Thereafter, the levels declined with an estimated t1/2 of 30 hours. The concentration of free hemoglobin increased during the perfusion, with maximum levels at the end of perfusion, after which they fell rapidly to normal values. The in vitro study showed a strong linearity between the release of NSE and free hemoglobin after induced hemolysis. CONCLUSIONS: The increased levels of enolase at the end of cardiopulmonary bypass can, to a major part, be explained by the release from hemolysed erythrocytes. The value of NSE as a marker for brain injury in these situations is therefore doubtful.     

Whole blood aggregometry and platelet adenine nucleotides during cardiac surgery

The influence of extracorporeal circulation (ECC) on human platelet adenine nucleotides has been studied in 28 coronary bypass patients before, during and after operation. An oscillating pattern of transient increases and decreases in total platelet ATP was observed following the sternotomy until the end of the operation. A highly significant increase in platelet ATP (20% +/- 14 of the pre-anaesthesia values) occurred during the first 24 h after surgery. Total platelet ADP however, did not show this oscillation nor was there any significant release of ADP from the platelets during ECC. Following collagen activation, increased amounts of 'releaseable ATP' were found after protaminization (124% +/- 38 of pre-anaesthesia values) (p less than 0.05), although whole blood aggregability was slightly reduced (89% +/- 18 of pre-anaesthesia values). This study indicates that 1) the metabolic ATP pool of circulating platelets underwent rapid changes during open heart surgery; 2) the majority of platelets did not release inert ADP during ECC; 3) there may be a compensatory enhancement of platelet function by other blood cells, which could explain the discrepancy between our aggregatory results in whole blood and those reported in platelet rich plasma (PRP) aggregometry.     

Pharmacokinetics of oral tramadol drops for postoperative pain relief in children aged 4 to 7 years--a pilot study

Tramadol hydrochloride is an analgesic with mu receptor activity suitable for administration to children as oral drops. As the serum concentration profile and pharmacokinetic parameters in young children are not known via this route, we studied 24 healthy ASA 1 children to determine those parameters. The children's mean age was 5.3 +/- 1.1 years and their mean weight was 17.8 +/- 3.1 kg. They underwent general anesthesia with sevoflurane for dental surgery. The mean duration of anesthesia was 27.9 +/- 10.1 minutes. Tramadol 1.5 mg/kg (this dose was chosen because we have previously shown it to be effective in providing analgesia following pediatric dental surgery) was administered as oral drops 30 minutes before anesthesia. Venous blood samples were taken following the tramadol at 30-minute intervals for 4 hours, every 2 hours for 6 hours, and every 4 hours for 12 hours. The samples were centrifuged and the serum stored at -20 degrees C, and nonstereoselective gas chromatography was used to determine the concentration of (+) and (-) tramadol enantiomers plus their o-demethyltramadol (M1) metabolite concentrations. The tramadol absorption was rapid, the maximum measured serum concentration present occurring before the first sample at 30 minutes. That first sample had a concentration of 352 +/- 83.4 ng/mL. The concentration remained above the 100 ng/mL analgesic level until 6.8 +/- 0.9 hours. The elimination half-life was 3.6 +/- 1.1 hours, the serum clearance 5.6 +/- 2.7 mL/kg/min, and the volume of distribution 4.1 +/- 1.2 L/kg. The (+) enantiomer concentration was 14.2 +/- 4.9% greater than that of the (-) enantiomer. The M1 metabolites had a (-) enantiomer concentration 92.3 +/- 75.1% greater than the (+) enantiomer. From the peak concentration at 4.5 +/- 1.5 hours, the concentration of the metabolite was approximately one third that of the parent drug. The M1 elimination half-life was 5.8 +/- 1.7 hours. Apart from the rapid rise in the serum concentration, these kinetic parameters are similar to those seen in healthy young adults. The concentration profile supports an effective clinical duration in the region of 7 hours.     

A study on the mechanism of the postoperative fall in serum iron concentration

The purpose of this study was to investigate the mechanism of the postoperative fall in serum iron concentration. Simultaneous measurements of iron uptake from, and release to, the plasma were made using two iron radioisotopes. Eight rabbits were submitted to laparotomy and eight were used as controls. Six hours after laparotomy, when the plasma iron concentration was decreasing, the clearance half-time from the plasma was decreased from 82.0 +/- 3.0 min in controls to 25.0 +/- 4.0 min (P less than 0.001) but the amount of iron uptake was increased from 0.289 +/- 0.013 to 0.574 +/- 0.092 mumole/liter blood/day (P less than 0.001). Twenty-four hours after laparotomy, when the plasma iron concentration was increasing, the half-time remained shortened in the operative group but the amount of iron uptake was decreased from 0.39 +/- 0.28 to 0.25 +/- 0.1 mumole/liter blood/day although this difference is not significantly different. At both times studied there was no difference in the amount of iron released to the plasma. These results suggest that the fall in iron concentration after surgery is due to increased uptake from the plasma.     

Enhanced cardiac performance following cardiopulmonary bypass

Changes in cardiac performance during coronary revascularization surgery were followed in 22 selected patients with normal or mildly impaired left ventricles; vasoactive or inotropic drugs were generally avoided. Arterial pressure, filling pressures, and cardiac output were measured; stroke volume and work were calculated before induction of anesthesia, following sternotomy, soon after discontinuation of extracorporeal circulation, and one hour postoperatively. Induction and sternotomy were associated with a depressant effect on cardiac performance. After extracorporeal circulation, however, cardiac performance recovered, cardiac output increased to 7 +/- 0.5 l/min from a preoperative control of 4.9 +/- 0.3 L/min (p less than 0.002) without an elevation of atrial pressures. This increase in cardiac output after bypass resulted from decreased afterload and increased preload secondary to hemodilution. Cardiac performance approached control values early in the postoperative period.     

Estimation of total body fluid shifts between plasma and interstitium in man during extracorporeal circulation

Fluid transport between plasma and interstitium during extracorporeal circulation was studied in seven patients undergoing aortocoronary bypass grafting. The absolute shifts in plasma volume during hypothermia were determined as the difference between input and loss of fluid and the changes in blood volume. The change in haemoglobin concentration due to acute haemodilution when starting extracorporeal circulation was used to calculate the absolute blood and plasma volume. The Starling equation for exchange across the capillary wall was used to describe fluid shifts. The total fluid filtered during the 60- to 90-min period of extracorporeal circulation averaged 34.1 +/- 11.1 (s.d.) ml/min. The total body filtration coefficient from the Starling relationship averaged 0.046 +/- 0.012 ml/kg.mmHg.min (0.354 +/- 0.092 ml/kg.kPa.min). Haemodilution, reducing colloid osmotic pressure in plasma (COPP) by approximately 10 mmHg (1.3 kPa) will result in a loss of plasma fluid of around 2 1 per hour. When corrected for lower fluid viscosity due to hypothermia during extracorporeal circulation, CFC would be about 40% higher, and a filtered volume of nearly 3 1 in a normothermic 70-kg person would be expected. Crystalloid haemodilution for shorter periods of time does not produce excessive oedema and thus may be well tolerated.     

Penetration of penicillins into cardiac valves and auricles of patients undergoing open-heart surgery

Prophylactic use of antibiotics in open-heart surgery for insertion of prosthetic valves is common, because of the serious consequences of postoperative staphylococcal infections, most notably prosthetic valve endocarditis. To ensure effective antibiotic cover during surgery, the penetration of cloxacillin and benzylpenicillin into the heart muscle and valves was studied intraoperatively. Both antibiotics were given intravenously (respective initial doses 2 g and 6 g) at induction of anesthesia to ten patients undergoing replacement of aortic or mitral valve, and the same doses were repeated after 4 hours. Serial serum samples and tissue samples from the right atrial auricle and the excised heart valve were analyzed for antibiotic concentrations. The mean serum concentrations of cloxacillin were 204 +/- 93 mg/l 10 min after the initial dose and less than or equal to 26 mg/l 30 min before the second dose. The corresponding values for benzylpenicillin were 323 +/- 145 and 43 +/- 24 mg/l. The cloxacillin concentrations in the auricle just before the start of extracorporeal circulation ranged from 4.5 to 80 mg/kg and (later) in the excised heart valves they were 8.5 to 45 mg/kg. The benzylpenicillin range was 16 to 153 mg/kg in auricle and 13 to 87 mg/kg in valve tissue. The authors conclude that the employed doses of the penicillins are adequate cover against the staphylococci which may be implicated in postoperative infections.