Changes in drug plasma concentrations of an extensively bound and highly extracted drug, propofol, in response to altered plasma binding

OBJECTIVE: Cardiopulmonary bypass is known to result in a reduction in the plasma binding of drugs. The resulting effect on the hepatic clearance of drugs with low extraction is well understood. However, the situation with those that are highly extracted is less clear. Studies were, therefore, undertaken with one such drug, propofol, for which plasma binding was changed during cardiac surgery with cardiopulmonary bypass. METHODS: After induction of anesthesia with midazolam in 19 patients, propofol was infused continuously at a rate of 4 mg. kg(-1). h(-1) during surgery. Propofol's concentration was measured by HPLC in blood samples collected from the radial artery and hepatic vein during surgery at predetermined intervals. The drug's unbound fraction in arterial plasma was estimated via equilibrium dialysis. RESULTS: The total concentration of propofol in blood was unchanged during surgery except shortly after the initiation of cardiopulmonary bypass. By contrast, the fraction of unbound propofol in blood increased by 2-fold during cardiopulmonary bypass and then decreased after the completion of cardiopulmonary bypass. The hepatic extraction ratio of propofol was greater than 0.8 and remained constant throughout surgery. The ratio of propofol concentration in erythrocytes to that in blood increased by 1.6-fold during cardiopulmonary bypass. CONCLUSIONS: During cardiopulmonary bypass, a significant increase in the concentration of unbound propofol occurred without alteration in the total propofol concentration in blood. The effect of the changes of propofol's protein binding on its kinetics was consistent with the predictions based on the well-stirred model of hepatic elimination for an intravenously infused high-clearance drug. Our finding on propofol pharmacokinetics may be the first example demonstrating the theoretic prediction of the well-stirred model.     

Myocardial metabolism and adaptation during extreme hemodilution in humans after coronary revascularization.

OBJECTIVE: This study was designed to evaluate the oxygen transport adjustments and myocardial metabolic adaptation that occurs with different levels of hemodilution during normothermia after cardiopulmonary bypass. DESIGN: Prospective, nonrandomized study. SETTING: Operating room in a university hospital. PATIENTS: Eight patients with ejection fractions (> 40%) undergoing elective coronary artery bypass grafting. METHODS: Before the institution of cardiopulmonary bypass, blood was withdrawn from patients to a target hematocrit of 15%. After coronary artery bypass grafting, a catheter was inserted directly into the coronary sinus. After the patients were rewarmed to 37 degrees C, they were weaned from cardiopulmonary bypass. Hemodynamic indices were measured, as well as measurements of myocardial oxygen consumption (VO2) and myocardial metabolism (lactate extraction and coronary sinus hypoxanthine). Measurements were made at three different hematocrit values: 15%, 20%, and 25%. Hematocrit was increased by autologous blood transfusion. MEASUREMENTS AND MAIN RESULTS: The three levels of hemodilution (hematocrit: 17.4 +/- 3.4%; 23.0 +/- 3.7%; 27.8 +/- 4.8%) were significantly different from baseline (hematocrit 37 +/- 2.6%; p < .05). Oxygen delivery, which increased with autologous transfusion, exceeded 350 mL/min/m2 at each level of dilution. The myocardial VO2 increased significantly after autologous transfusion compared with the most dilute condition (7.0 +/- 3.7 mL/min at hematocrit 17.4% vs. 11.2 +/- 4.8 mL/min at hematocrit 23.0% and 12.4 +/- 4.0 mL/min at hematocrit 27.8%). This transfusion-induced increase was also true of myocardial oxygen extraction. Lactate extraction and hypoxanthine release were normal and unchanged at each level of hemodilution. Systemic oxygen extraction ratio increased with hemodilution and decreased with autologous transfusion. CONCLUSIONS: Hemodilution to a hematocrit of approximately 15% is tolerated in anesthetized humans after coronary artery bypass surgery. There was no evidence of myocardial ischemia, as demonstrated by absence of S-T depression on the electrocardiogram, lactate extraction, or hypoxanthine release. In selected patients, postoperative transfusion may be based on systemic physiologic end-points, such as oxygen extraction ratio, rather than set hematocrit values.     

Plasma fibronectin depletion after cardiac surgery in children with or without cardiopulmonary bypass

Plasma fibronectin depletion decreases resistance to sepsis. After cardiac surgery, septic complications occur more frequently when the surgical procedure is managed with a cardio-pulmonary bypass than when it is not. To determine whether cardio-pulmonary bypass produces a greater decrease in plasma fibronectin than surgery without cardio-pulmonary bypass, we studied plasma fibronectin concentrations in two groups of children operated for congenital heart diseases. Group I: 10 children undergoing surgery with cardio-pulmonary bypass. Group II: 11 children undergoing surgery without cardio-pulmonary bypass. Plasma fibronectin was monitored pre-operatively (t 1) and post-operatively at the 6th hour (t 2), 1st (t 3) and 7th (t 4) days. In both groups, plasma fibronectin concentration dropped at (t 2) and (t 3) and rose again at (t 4). There was no significant difference in plasma fibronectin levels between the two groups at any time. We conclude that the plasma fibronectin decline alone cannot explain why septic complications after surgery are more frequent with cardio-pulmonary bypass than without.     

Blood use in patients undergoing repeat coronary artery bypass graft procedures: multivariate analysis

BACKGROUND : The prevailing clinical opinion is that patients undergoing repeat coronary artery bypass graft (CABG) operation require more blood transfusions than do patients undergoing primary CABG operation. To determine the extent of this increased demand and the variables responsible for it, the cases of 196 patients who had undergone primary procedures and 65 patients who had had repeat procedures at the same institution were reviewed. STUDY DESIGN AND METHODS : To analyze the differences in transfusion requirements for these two groups, the following data were obtained: number of transfusions given between the time of surgery and the time of hospital discharge; preoperative hemoglobin (Hb), hematocrit (Hct), prothrombin time, and platelet count; Hb and Hct at hospital discharge; time the patient was on cardiopulmonary bypass; number and type of grafts; estimates of intraoperative blood loss; and chest-tube blood shed during the first 48 hours after surgery. RESULTS : The groups were comparable with respect to age, body weight, preoperative Hb and Hct, number of grafts, and aspirin exposure. Patients in the repeat group had 35-percent greater blood loss and required 75-percent more blood components than did the patients undergoing primary procedures. The mean number of blood components transfused per patient was as follows: red cells, 3.8 +/? 0.5 units in repeat patients and 2.2 +/? 0.2 units in primary patients (p = 0.002); platelets, 2.9 +/? 0.9 vs. 1.1 +/? 0.2 (p = 0.043); fresh-frozen plasma, 1.6 +/? 0.4 vs. 0.8 +/? 0.1 (p = 0.044). Analysis of variables by regression method for repeat patients showed a predictive effect of blood loss (p < 0.0001), prolonged time on cardiopulmonary bypass (p < 0.0001), preoperative Hb (p = 0.0003), and aspirin exposure (p = 0.0094) on red cell transfusion rate in repeat patients (R-square = 0.7778, Prob > f = 0.0001). CONCLUSION : Repeat CABG patients have higher transfusion rates. These findings may be attributed to the increased microvascular bleeding, prolonged time on cardiopulmonary bypass, lower preoperative Hb, and the use of preoperative antiplatelet medications.     

Limitations of the hematocrit level to assess the need for red blood cell transfusion in hypovolemic anemic patients

BACKGROUND: The transfusion trigger that physicians use to determine whether a patient requires a red blood cell (RBC) transfusion is the peripheral venous hematocrit (Hct) value. Although this measurement is an indicator of the concentration of RBCs in the blood, it does not reveal the RBC volume, plasma volume, or total blood volume, nor does it give any indication of whether the patient is hypovolemic, normovolemic, or hypervolemic. STUDY DESIGN AND METHODS: Two patient populations were studied: 41 consecutive patients subjected to elective vascular surgery and 20 consecutive patients subjected to cardiopulmonary bypass surgery. The RBC volume was measured with (51)Cr- or (99m)Tc-labeled autologous fresh RBCs, and the plasma volume and total blood volume were estimated from the measured RBC volume and the total body Hct level. Measurements made 1 to 2 and 24 hours after surgery were compared to the preoperative values for these two groups of patients. RESULTS: During the 24-hour postoperative period, the RBC, plasma, and total blood volumes were reduced compared to the preoperative volumes. These patients were hypovolemic and anemic, and their Hct values during the 24-hour postoperative period were increased by a mean of 4 to 5 volume-percent compared to values that would be expected if they were normvolemic and anemic. CONCLUSIONS: The Hct values in hypovolemic anemic patients are elevated because the plasma volume does not increase to achieve the normovolemic anemic state.     

Bloodless cardiac surgery and the pediatric patient: a case study

Peri-operative transfusion of blood or blood products is associated with increased morbidity and mortality after cardiac surgery. However, excessive hemodilution as a result of avoiding the use of homologous blood products can also lead to decreased oxygen delivery to vital end organs and dilutional coagulopathy. This is particularly challenging in pediatric cardiac surgery where there is a large discrepancy between the patient circulating blood volume and the priming volume of the cardiopulmonary bypass (CPB) circuit. Strategies to avoid the use of homologous blood products during pediatric cardiac surgery must also incorporate miniaturization of the CPB circuit and other bypass techniques in order to avoid problems with excessive hemodilution. We report a 5.9 kg male infant who underwent successful surgical correction of a ventricular septal defect without the use of homologous blood transfusion. Our strategies included the pre-operative administration of erythropoietin and iron to increase red blood cell mass, acute normovolemic hemodilution (ANH) before the institution of CPB, retrograde autologous priming (RAP), cell salvage, continuous ultrafiltration, vacuum-assisted venous drainage to minimize the circuit size and priming volume, and the use of near infrared spectroscopy (NIRS) to monitor the patient during the entire procedure. The utilization of these strategies is now standard for our entire pediatric cardiac surgical population.     

Cardiovascular adjustments and gas exchange during extreme hemodilution in humans

OBJECTIVE: To examine the cardiovascular adjustments and pattern of gas exchange that occur during hemodilution. DESIGN: Nonrandomized prospective study. SETTING: Operating room in a university hospital. PATIENTS: Seven patients undergoing elective aortocoronary artery bypass surgery. INTERVENTIONS: Before initiating cardiopulmonary bypass, the patients' hematocrit levels were decreased to approximately 15%. This hemodilution was done by removing a sufficient amount of autologous blood from the aortic cannula and replacing it with a sufficient amount of crystalloid solution. After the discontinuation of cardiopulmonary bypass, measurements were made at a hematocrit of approximately 15%. Then, after autologous blood infusion, measurements were made at a hematocrit of 20%, followed by more blood infusion to approximately 25% with repeat measurements. MEASUREMENTS AND MAIN RESULTS: The following measurements were made before hemodilution and then at all three levels of hemodilution: heart rate, mean arterial pressure (MAP), right atrial pressure, mean pulmonary artery pressure, pulmonary artery occlusion pressure, and cardiac output. From these measurements, the following derived variables were calculated: cardiac index, systemic vascular resistance, and pulmonary vascular resistance. From measurements of arterial oxygen content, mixed venous oxygen content, and cardiac output, intrapulmonary shunt (Qsp/Qt), oxygen uptake (VO2), oxygen extraction ratio, and oxygen delivery (DO2) were derived. The MAP was lowest (57 +/- 3 [SD] vs. 92 +/- 3 mm Hg) at the lowest hematocrit. The cardiac index was highest (4.0 +/- 0.3 vs. 2.3 +/- 0.6 L/min.m2) at the lowest hematocrit. DO2 was lowest at the lowest hematocrit but VO2 remained constant at all levels of hematocrit. The oxygen extraction ratio increased as hematocrit decreased. With progressive increases in hematocrit, DO2 increased and Qsp/Qt decreased. CONCLUSIONS: The data suggest that, during hemodilution, tissue autoregulation of VO2 and utilization are not impaired, but gas exchange function (Qsp/Qt) is impaired.     

体外循环手术患者血浆C3和C4的检测及临床意义

目的 了解体外循环手术(CPB)对患者血浆中补体C3、C4的影响.方法 用透射比浊法测定行心脏瓣膜置换术前后患者血浆中C3、C4的浓度,并进行比较.结果 术前与术后血浆中C3、C4差异有统计学意义,血浆中C3、C4降低的谷值在CPB末.结论 CPB导致术后早期大量补体激活,易引起全身性炎症反应综合征(SIRS),减少补体激活程度可降低炎症反应强度.     

Reduction of hemodilution in small adults undergoing open heart surgery: a prospective, randomized trial

BACKGROUND: Given that there is an association between the degree of hemodilution during cardiopulmonary bypass (CPB) and postoperative complications, patients-outcome might be improved if the nadir hematocrit concentration is kept within an optimal range. Smaller patients are more likely to have a low hematocrit during CPB: this phenomenon may be related, at least partially, to the extreme hemodilution induced by a large fixed CPB priming volume. METHODS: Forty patients with a body surface area (BSA) < 1.7 m2 undergoing open heart operations were randomized to either standard CPB with full prime volume (control group) or reduced prime extracorporeal circuit and vacuum-assisted venous drainage (VAVD) (study group). RESULTS: There were no significant differences between the groups with respect to baseline characteristics, body surface area, hematologic profile and operative data. Clinical outcomes were similar. Nadir hematocrit and hemoglobin on bypass were significantly lower in the control group (22 +/- 2.3 vs. 24 +/- 2.5%, p < 0.02 and 7.4 +/- 0.7 vs. 8 +/- 0.9 g/dl, p < 0.04, respectively). Postoperative chest tube drainage was significantly higher in the control group (272 +/- 253 vs. 139 +/- 84 ml, p < 0.04). There was no difference in blood transfusion in the two groups (0.5 +/- 1.14 vs. 1.0 +/- 1.77 units of packed red blood cells (PRBC), p = 0.29). CONCLUSIONS: Lowering CPB priming volume by means of using a small oxygenator and vacuum-assisted venous drainage (VAVD) resulted in a significant decrease of intraoperative hemodilution. This technique should be strongly considered for patients with a small BSA (<1.7 m2) undergoing open heart surgery.     

Effect of corticosteroids on arginine vasopressin after pediatric cardiac surgery

Introduction

Arginine vasopressin’s (AVP) efficacy in the treatment of refractory hypotension is, in part, dependent upon preinfusion endogenous AVP concentration. Corticosteroids, also commonly used to treat refractory hypotension, have been shown to suppress endogenous AVP release. We aimed to determine if corticosteroids affect endogenous AVP concentrations in children recovering from cardiac surgery.

Materials and methods

We reviewed the records of children who underwent cardiac surgery between January 2008 and January 2009 and had AVP concentrations available as part of a prior prospective study. Doses of hydrocortisone, methylprednisolone, and dexamethasone administered within the first 48 hours after cardiopulmonary bypass were quantitated. Multivariable linear regression was performed to determine if corticosteroids had a significant effect on 48-hour plasma AVP concentration.

Results

Sixty-nine children with plasma AVP concentrations available were reviewed, 34 (49%) of which received corticosteroids within 48 hours after cardiopulmonary bypass. On multivariable regression, greater number of corticosteroid doses but not cumulative corticosteroid dosage was significantly associated with low 48-hour AVP concentration (β = − 4.0; 95% confidence intervals, − 6.5 to − 1.4).

Conclusions

Children who receive multiple doses of corticosteroids after cardiac surgery, regardless of potency, are likely to have low endogenous AVP concentrations. Children who remain unstable despite corticosteroids may respond favorably to exogenous AVP therapy.     

Rifampin blood and tissue levels in patients undergoing cardiac valve surgery.

Single 600-mg capsules of rifampin were given orally to 26 patients as prophylaxis during cardiac valve replacement. Antibiotic concentrations were measured in blood (serum or plasma) and tissue (excised cardiac valve). The serum or plasma levels of rifampin in 18 patients who ingested this drug 2 h before they received preoperative opiates and anticholinergics intramuscularly were not significantly different from the levels in four normal volunteers who received the drug. These levels were 15.9 +/- 6.5 micrograms/ml (mean +/- standard deviation) 2 h after drug administration, 7.1 +/- 4.3 micrograms/ml 8 h after drug administration and 2 h after a mean of 1.4 h on cardiopulmonary bypass, and 1.6 +/- 1.6 micrograms/ml 24 h after drug ingestion. The valve tissue level was 3.8 +/- 2.7 micrograms/g (mean +/- standard deviation; n = 10). This value was 65% of the simultaneous serum and plasma levels and 31% of the peak serum and plasma levels. Eight patients who were given rifampin at the same time that they received other preoperative medications had significantly lower blood levels than the 18 patients who received rifampin 2 h earlier (P less than 0.001). No rifampin was detected in valves from seven of these patients. Decreased rifampin absorption due to simultaneous administration with opiates and anticholinergics was the probable reason for the low plasma and serum levels observed. These data suggest that, if properly dosed, rifampin administered orally gives high blood and valve tissue levels, which are affected minimally by cardiopulmonary bypass in patients undergoing cardiac valve surgery.     

Myocardial inflammatory activation in children with congenital heart disease

OBJECTIVE: In several cardiac-related diseases, there is a strong association between systemic endotoxemia, myocardial cytokine production, and cardiac failure. Because pre- and postoperative endotoxemia recently was reported in children with congenital heart disease, we sought direct evidence of myocardial inflammatory activation in a cohort of children undergoing congenital heart surgery on cardiopulmonary bypass. Inflammatory activation was prospectively defined as the presence of nuclear factor-kappaB nuclear translocation in myocardial tissue samples. DESIGN: Prospective observational study. SETTING: Tertiary care pediatric intensive care unit. PATIENTS: Fifteen children with congenital heart disease undergoing operative repair on cardiopulmonary bypass. INTERVENTIONS: All patients underwent operative repair of congenital heart disease on cardiopulmonary bypass and had plasma samples obtained for endotoxin and tumor necrosis factor-alpha, both pre- and postoperatively. Myocardial tissue samples were obtained intraoperatively, both before and during cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: Elevated plasma endotoxin concentrations were documented in all 15 patients during the study period. In 12 patients, plasma endotoxin was elevated before cardiopulmonary bypass. The median preoperative tumor necrosis factor-alpha concentration was 16.4 pg/mL, which is higher than concentrations reported in adults with New York Heart Association class III congestive heart failure. Examination of myocardial tissue samples revealed nuclear factor-kappaB nuclear translocation (predominantly p50/p65 heterodimers) in nine of 15 patients (60%). Four of these nine patients had nuclear factor-kappaB nuclear translocation before initiation of cardiopulmonary bypass, with p50/p50 homodimers present in two of the four. CONCLUSIONS: These data provide the first evidence of nuclear factor-kappaB activation in children with congenital heart disease and the first evidence of myocardial nuclear factor-kappaB translocation in human hearts before explant for transplantation. Furthermore, these data suggest that, similar to adults with advanced congestive heart failure, the myocardial inflammatory cascade may contribute to the pathophysiology of congenital heart disease in infants and children.     

低剂量鱼精蛋白拮抗肝素围体外循环期血浆肝素浓度变化与凝血功能损害

目的：探讨低剂量鱼精蛋白拮抗肝素围体外循环(CPB)期血浆肝素浓度变化的规律及其与术后凝血功能损害的关系。方法：采用发光底物法测定25例风湿性心脏瓣膜病瓣膜置换手术病人低剂量鱼精蛋白拮抗肝素下围CPB期血浆肝素浓度，并同时检测凝血功能指标：激活凝血时间(ACT)、血浆凝血酶原时间(PT)和活化部分凝血活酶时间(APTT)。结果：CPB结束时血浆肝素平均水平(11．06U／mL)显著地降低到肝素化初期浓度(13．16U／mL)的0．84左右(P<0．05)，低剂量鱼精蛋白拮抗肝素后5h内血浆肝素水平基本上稳定在CPB前水平(P>0．05)；当鱼精蛋白中和肝素后，ACT值迅速接近至术前水平(P>0．05)，并稳定于术前水平，而PT、APTT则仍显著异常高于正常水平(P<0．05)，但有明显恢复至正常的趋势。结论：CPB结束时采用低剂量鱼精蛋白拮抗肝素(0．8mg鱼精蛋白：100U肝素)能充分有效地中和血中肝素：CPB后凝血功能并不立即恢复正常，主要原因不是肝素中和不足，而是CPB本身使凝血功能受到损害。     

Effect of cardiopulmonary bypass on the plasma concentrations of fentanyl and alcuronium

This study was conducted to examine the effect of cardiopulmonary bypass surgery on the total and unbound plasma concentrations of fentanyl and the total plasma concentrations of alcuronium. Total fentanyl concentrations were measured by gas chromatography, the plasma protein binding of fentanyl by ultrafiltration, and alcuronium concentrations by high‐performance liquid chromatography. Sixteen patients were studied.
On initiation of cardiopulmonary bypass (CPB), there were mean decreases of 58·8±7·1% and 47±3·2% for total concentrations of fentanyl in plasma and haemoglobin in blood, respectively. The magnitude of these reductions in individual patients was significantly related (Spearman |gr =0·65, P<0·05). The unbound fraction of fentanyl rose from 0·23 to 0·34 after the start of CPB. The total fentanyl concentration remained relatively stable during bypass until near the end of CPB when the mean total concentration increased, coinciding with rewarming. The size of the increase was related to the body mass index (BMI) of the patient (Spearman |gr =0·85, P<0·01). The estimated elimination half‐life of fentanyl using the grouped data was 4·7 h.
The total alcuronium concentration in plasma fell by 29% on initiation of CPB and there was no increase on rewarming. The estimated elimination half‐life of alcuronium using the grouped data was 234 min.
Despite marked declines in the plasma concentrations of both drugs on initiation of CPB, suitable levels of anaesthesia were maintained throughout the procedure.     

Venous drainage--gravity or assisted?

Since the early start of cardiopulmonary bypass, vascular access has been recognized as a main variable for obtaining optimal blood flow during cardiopulmonary bypass. In particular, venous drainage can limit the maximum flow as the wide, low-resistance, collapsible veins are connected with smaller stiff cannulas and tubing. Due to the introduction of long venous cannulas for minimally invasive cardiac surgery and the desire to limit hemodilution during cardiopulmonary bypass, more and more centers have started using assisted venous drainage techniques. This article gives an overview of these techniques, with their respective advantages and disadvantages.     

Ways to decrease blood loss during total hip joint endoprosthesis

Total replacement (endoprosthesis) of the hip joint was carried out in 93 patients aged 18-60 years. Sixteen operations were performed under prolonged epidural blockade, 66 under neuroleptanalgesia, and 16 under ataralgesia. A deficiency of circulating blood volume was detected in all patients before surgery. The lowest mean arterial pressure was recorded in the prolonged epidural block group, while in the neuroleptanalgesia and ataralgesia groups the mean arterial pressure was virtually the same. Isovolemic hemodilution in patients with preoperative deficit of circulating blood volume decreased blood loss during long traumatic operations. Prolonged epidural blockade in combination with isovolemic hemodilution and spontaneous respiration led to a notable (70%) decrease of the true blood loss in comparison with the traditional neuroleptanalgesia.     

Effect of delayed blood processing on the yield of factor VIII in cryoprecipitate and factor VIII concentrate

Current standards for the preparation of factor VIII (FVIII) concentrates from human plasma recommend separation of plasma from red cells (RBCs) within 6 hours of blood donation, thereby reducing the volume of plasma from donated whole blood available for processing to FVIII concentrate. The decay of FVIII clotting activity (FVIII:C) in whole blood and plasma stored at 22 and 4 degrees C and the recovery of FVIII:C in cryoprecipitate and FVIII concentrate prepared from plasma separated from whole blood stored overnight at 4 degrees C were investigated. In whole blood stored at 22 degrees C and plasma stored at either 4 or 22 degrees C, 90 percent of the original FVIII:C was present at 6 hours, 80 percent at 12 hours, and 65 to 70 percent at 18 hours. At these times lower levels of FVIII:C were recovered from whole blood stored at 4 degrees C, that is, 84, 68, and 56 percent, respectively. In cryoprecipitates prepared from plasma separated from RBCs after 18 hours' storage at 4 degrees C (18-hour plasma), 43 percent of FVIII:C activity was recovered, as compared with 61 percent recovered from standard plasma separated within 6 hours of donation (6-hour plasma), p less than 0.05. With large-scale preparation of FVIII concentrates, however, the yield of FVIII:C was similar whether 18- or 6-hour plasma was used. Thus FVIII concentrates--but not cryoprecipitates--can be prepared from plasma separated from whole blood stored at 4 degrees C for up to 18 hours without undue loss of potency.     

The importance of colloid osmotic pressure during open heart surgery in infants

Fifty-five infants with transposition of the great arteries and with total anomalous pulmonary venous return underwent intracardiac repair under combined surface/perfusion hypothermia and total circulatory arrest in 1975 to 1983. Although cardiopulmonary bypass (CPB) time is limited when hypothermic circulatory arrest is employed, fluid balance derangement is one of the major postoperative complications. Fluid balance at the end of CPB averaged +299.5 ml (+63.4 ml/kg) when hemodilution with lactated Ringer's was utilized (Group A). Since colloid osmotic pressure (COP) plays an important role in regulating fluid balance, colloid hemodilution prime (whole blood and plasma) was employed in the last 3 years (Group B). COP and total protein concentration during CPB with colloid prime were maintained at around 19 mmHg and 5 g/100 ml, respectively. In Group B, fluid balance at the end of CPB averaged +81.1 ml (+16.3 ml/kg) and was significantly less than in Group A (p less than 0.01). The ICU stay period for survivors in Group B (average 10.9 days) was reduced to half the period in Group A (average 20.6 days) (p less than 0.05). The mortality rate in Group A was 42%, whereas 23% in Group B. It was concluded that well-maintained COP levels during CPB with colloid hemodilution prime reduced fluid accumulation in the body and made patient care easier following open heart surgery in infants.     

Alterations in anion gap following cardiopulmonary bypass.

OBJECTIVES: To evaluate the changes in the anion gap and their relation to hyperlactatemia and alterations in plasma proteins after cardiopulmonary bypass. DESIGN: Prospective study. SETTING: Cardiothoracic intensive therapy unit. PATIENTS: One hundred eleven consecutive patients after cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: Data were collected before cardiopulmonary bypass and every 6 hrs for 24 hrs after cardiopulmonary bypass. Results were analyzed for the entire cohort and for hyperlactatemic subgroups. The major finding of this study was that the anion gap decreased significantly at all sampling periods relative to precardiopulmonary bypass values, despite the presence of clinically important hyperlactatemia. No correlation between the decrease in plasma protein concentrations and the decrease in anion gap could be demonstrated. CONCLUSIONS: The decrease in anion gap after cardiopulmonary bypass appears to represent a balance between the influences of increased serum chloride and lactate concentrations and reduced plasma protein concentrations. This analysis demonstrates the limitations of the anion gap in the evaluation of a metabolic acidosis after cardiopulmonary bypass.     

Immunoreactants in murine lupus nephritis: effects of azathioprine

We studied the effects of azathioprine on immunoreactants of plasma and kidney to determine factors that might be relevant to the arrest of nephritis in NZB/W mice. Before and after a course of azathioprine (or saline injections) for 12 weeks, we determined the plasma concentrations of IgG, complement (C3), antiDNA antibodies, and C1q-reactive materials; in the kidneys, we studied deposits of IgG, IgM, and C3 in glomeruli, and we determined the concentration of IgG and antiDNA activity of the eluted proteins. Azathioprine administered at the onset of nephritis preserved glomerular structure and function; the amount of tissue-bound immunoreactants was decreased overall, and immunoreactants were preferentially localized in mesangial areas. A decreased plasma concentration of IgG, but not the concentrations of antiDNA antibodies, C3 and C1q-reactive materials, was associated with the arrest of nephritis. The antiDNA activity in renal eluates was very low and was comparable in treated and untreated mice. Immune complex systems other than, or in addition to, DNA-antiDNA likely play a role in the pathogenesis of murine lupus nephritis.