Alcuronium kinetics in patients undergoing cardiopulmonary bypass surgery.

1 The disposition of alcuronium was investigated in 10 patients undergoing surgery involving cardiopulmonary bypass (CPB) and compared with results from a group of non-cardiac patients studied previously. 2 After intravenous administration of a combined bolus and infusion dosage regimen, plasma concentrations fell in a bi-exponential fashion to a mean value of 0.55 micrograms/ml immediately before the start of extracorporeal circulation. 3 During CPB an apparent steady-state of alcuronium was reached immediately after commencement of CPB, however plasma concentrations were some 50% higher than those noted prior to commencement of CPB and those predicted using previous pharmacokinetic data from normal surgical patients. 4 Once CPB was completed and the alcuronium infusion terminated, post-infusion alcuronium plasma concentrations again appeared to decline bi-exponentially with time. 5 Of the pharmacokinetic parameters which were calculated model-independently, the apparent volume of distribution (Vss) was unchanged (329 vs 313 ml/kg) and the elimination half-life (t1/2,z) (532 vs 199 min) was prolonged and the plasma clearance (CL) (0.8 vs 1.34 ml min-1kg-1) markedly reduced in these patients compared to non-cardiac surgical patients. 6 As a result of these changes in alcuronium concentration during CPB and the diminished elimination of alcuronium following CPB, a closer monitoring of neuromuscular function may be necessary in cardiac patients undergoing CPB.     

Papaverine disposition in cardiac surgery patients and the effect of cardiopulmonary bypass

Summary Cardiac surgery involving cardiopulmonary bypass (CPB) causes substantial physiologic changes which may potentially alter the pharmacokinetic properties of drugs used during and after the procedure. Studies with fentanyl have implied a relationship between prolonged elimination half-lives following CPB and decreased liver perfusion during and after the procedure. To further test this hypothesis, the effects of CPB on the pharmacokinetics of papaverine, a coronary vasodilator currently being added to the cardioplegic solution to prevent vasospasm, were studied. The drug was given to two groups of patients, one (n=6) undergoing surgery with and one (n=5) without CPB, the latter serving as controls. Plasma papaverine concentrations declined biexponentially in the control patients with a mean elimination half-life of 1.30±0.25 h, total plasma clearance of 13.8±3.75 ml/min/kg, volume of distribution of 1.52±0.45 l/kg and volume of distribution, steady-state, of 0.992±0.530 l/kg. For the CPB group, only half-life was estimated, and averaged 2.77±0.28 h, significantly greater (p<0.01) than that in the controls. These results further confirm the increased half-lives seen with other hepatically cleared drugs following CPB and have implications in the clinical management of patients given drugs eliminated in this manner.     

Haemodialysis does not affect the pharmacokinetics of nifedipine.

To establish dosage recommendations in patients with end-stage renal disease undergoing chronic haemodialysis, nifedipine kinetics were studied between and during haemodialysis sessions. In eight patients, during the interdialytic period, peak plasma concentrations of nifedipine (29-332 ng/ml) were reached 0.5-1.0 h after administration of a single 10 mg oral dose. Elimination half-life and oral plasma clearance were respectively 2.6 +/- 0.5 h and 1 176 +/- 412 ml/min. Nifedipine plasma protein binding was decreased in uraemic patients (88.8 +/- 0.3% vs 94.4 +/- 0.1%) but not affected by haemodialysis. Removal by haemodialysis was low: the dialyser extraction ratio and the dialysis clearance were respectively 2.3 +/- 0.8% and 2.8 +/- 0.9 ml/min.     

Alteration of vancomycin pharmacokinetics during cardiopulmonary bypass in patients undergoing cardiac surgery.

The alteration of vancomycin pharmacokinetics during cardiopulmonary bypass (CPB) in patients undergoing cardiac surgery was studied. Eighteen patients were enrolled in the study. Vancomycin (1 g) was intravenously infused one to two hours before surgery. Blood samples were taken before, during, and after CPB. Serum drug concentrations were determined by an automated fluorescence polarization immunoassay and adjusted, with a bayesian analysis, to a bi-compartmental model implemented in a pharmacokinetic system program. Serum creatinine, hematocrit, and plasma proteins were also measured before, during, and after CPB. During CPB, serum creatinine, hematocrit, and plasma protein values all decreased significantly (p < 0.05). Serum vancomycin concentration also diminished abruptly with CPB (7.04 micrograms/mL; 95% confidence interval, 5.70-8.38 micrograms/mL) but increased moderately during the next 30 minutes, probably attributable to redistribution into plasma from tissue stores. Vancomycin's apparent volume of distribution showed an important increase during CPB (58.8%) (p < 0.0005), and its systemic clearance also increased significantly after CPB (19.7%) (p < 0.0005). The decrease in serum vancomycin concentration seems mediated by the hemodilution associated with the pump prime volume. Vancomycin's mean +/- S.D. nadir serum concentration before the next dose was 7.13 +/- 2.1 micrograms/mL. In patients undergoing cardiac surgery and treated prophylactically with a 1-g preoperative i.v. dose of vancomycin, the onset of CPB was associated with a drop in serum vancomycin concentration.     

Pharmacokinetics and a simulation model of colforsin daropate, new forskolin derivative inotropic vasodilator, in patients undergoing coronary artery bypass grafting.

Colforsin daropate, a water-soluble forskolin derivative, is an adenyl cyclase activator with positive inotropic and vasodilatory effects that are useful in the treatment of ventricular dysfunction. We investigated the pharmacokinetics of colforsin daropate in cardiac surgery patients and performed simulations to determine the dosage necessary to maintain an effective plasma concentration following cardiopulmonary bypass.In six patients undergoing coronary artery bypass graft, colforsin daropate (0.01mgkg(-1)) was administered immediately after separation from cardiopulmonary bypass. Arterial blood was sampled over the next 16h and plasma concentrations of colforsin daropate and its initial active metabolite were determined by gas-chromatography. Extended nonlinear least-squares regression was used to fit a three-compartment model to each patient's data.Distribution half-life (t(1/2alpha)) was 3.9+/-1.1min, metabolic half-life (t(1/2beta)) was 1.9+/-0.7h, and elimination half-life (t(1/2gamma)) was 95.3+/-15.2h. Central-compartment volume was 591.0+/-42.8mlkg(-1), volume distribution was 2689.2+/-450.6mlkg(-1), and elimination clearance was 27.7+/-14.7mlkg(-1)min(-1). In the pharmacokinetic simulation model, 0.5, 0.75, and 1.0microgkg(-1)min(-1) continuous infusion of colforsin daropate produce effective concentration (5-10ngml(-1)) within 30, 20, and 10min, respectively following administration. An initial active metabolite of decreased rapidly to less than 1.0ngml(-1) within the first 10min.A colforsin daropate infusion of 0.7-1.0microgkg(-1)min(-1) for 10-20min followed by 0.5microgkg(-1)min(-1) continuous infusion is recommended to produce an effective concentration (5-10ngml(-1)) within 10-20min and to maintain a therapeutic concentration throughout the administration period after cardiopulmonary bypass.     

Pharmacokinetics of ciprofloxacin in elderly patients

For perioperative prophylaxis 200 mg ciprofloxacin were administered as a short intravenous infusion to 17 patients aged 57-84 years before transurethral resection (TUR-P) or transvesicular enucleation (TVP) of the prostate. 13 patients were injected simultaneously with 2.5 g ioxitalamic acid i.v. to determine the kidney function. In 11 patients the plasma concentrations were assayed and the pharmacokinetic parameters calculated. At the end of infusion the concentrations of ciprofloxacin in plasma reached 4.2 +/- 0.8 microgram/ml and decreased after a fast distribution period (plasma half-life 0.20 +/- 0.09 h) with a terminal half-life of 4.2 +/- 1.3 h to 0.2 +/- 0.09 microgram/ml after 10 h. The apparent volume of distribution in steady state was 183 +/- 45% of body weight, the plasma clearance 457 +/- 146 ml/min/70 kg. The average concentrations in prostatic adenoma tissue were at all sampling times higher (2fold) than in plasma. The mean concentrations in prostatic secretion were about half of the respective plasma concentrations. High concentrations of the concomitantly administered ioxitalamic acid in prostatic secretion are considered as an indicator of urinary contamination. In those patients high ciprofloxacin concentrations in prostatic secretion are not reliable.     

The effect of preoperative antiplatelet therapy in coronary artery surgery: blood transfusion requirements for patients on cardiopulmonary bypass

INTRODUCTION: Bleeding after heart operations remains a common complication and contributes to morbidity and death. Recent studies have suggested that antiplatelet therapy (APT) may not increase homologous blood requirements in coronary bypass surgery. The purpose of this study was to examine the influence of APT therapy on haemorrhage and transfusion requirements in patients undergoing coronary artery bypass (CABG) on cardiopulmonary bypass (CPB). MATERIALS AND METHODS: Records from 290 consecutive patients who underwent CABG with CPB were retrospectively reviewed, including 145 patients who received APT within 5 days prior to surgery and 145 control patients (CON). Blood loss was measured up to 24 h. Demographic and clinical patient data were collected until hospital discharge. RESULTS: Both groups were well matched with respect to demographic and intra-operative data. There was significantly (p < 0.0005) more mediastinal tube drainage at 24 h in the APT group (1123 mL +/- 537 mL) compared to CON patients (874 mL +/- 351 mL). In addition, the APT group received significantly more units of blood (APT: 2.6 +/- 2.5 vs CON: 1.6 +/- 1.8; p < 0.0005), platelet units (APT: 1.2 +/- 1.8 vs CON: 0.2 +/- 0.8; p < 0.0005), and fresh frozen plasma units (APT: 2.0 +/- 2.2 vs CON: 1.3 +/- 2.0; p = 0.01). CONCLUSION: This study suggests consideration should be given to delaying elective CABG for patients who have received APT treatment until APT is discontinued for at least 5 days.     

Cefamandole pharmacokinetics during standard and pulsatile cardiopulmonary bypass

The pharmacokinetics of cefamandole during standard or pulsatile cardiopulmonary bypass were studied in 13 adult cardiac surgery patients. All patients received 20 mg/kg of cefamandole intravenously at midnight before surgery, 6 AM on the morning of surgery and just prior to the initiation of cardiopulmonary bypass (CPB) surgery. Serum, skeletal muscle, and fat samples were taken at the beginning of CPB and at 30-minute intervals thereafter and assayed for cefamandole concentration. The average elimination rate constant and elimination half-life for cefamandole in patients undergoing standard CPB were 0.73 +/- 0.09 hour-1 and 0.94 +/- 0.11 hour, respectively. In contrast patients undergoing pulsatile CPB had significantly slower elimination rate constants (0.50 +/- 0.1 hour-1 and 1.4 +/- 0.28 hours, respectively; P less than or equal to .05). Area under the curve (AUC) values for cefamandole in fat and muscle tissue were higher in patients undergoing pulsatile CPB, but the differences were not statistically significant. Prolonged elimination from the serum, skeletal muscle, and adipose tissue, as compared with normal subjects, is seen with both pulsatile and standard CPB but is greater for the pulsatile method. Intraoperative dosing of cefamandole is required to maintain adequate serum and tissue levels for operations lasting longer than 4 or 6 hours in which standard or pulsatile CPB, respectively, are used.     

New data on the pharmacokinetics of adriamycin and its major metabolite, adriamycinol

Twenty-two days after administration by intravenous bolus, of 50 mg of adriamycin to several patients we found concentrations of adriamycin and adriamycinol of the order of 100 pcg/ml. In theory, however, with a terminal half-life of 30 h, the plasma levels of adriamycin and adriamycinol should be close to 0.1 pcg/ml. Further pharmacokinetic investigation was therefore necessary. We have retained for this study nine male patients, aged between 53 and 69 years who received 25 to 50 mg of adriamycin by slow intravenous injection. The HPLC method permitted the detection of 50 pcg/ml of adriamycin and adriamycinol, with the possibility of monitoring their elimination during 120 h (and in one case during 160 h). The terminal half-lives of elimination estimated in 8 patients were respectively 110 +/- 52 h for adriamycin and 92 h 50 min +/- 43 h for adriamycinol. Surface ratios under adriamycinol curves against calculated adriamycin was 1.10 +/- 0.26. Plasma levels found during the To in certain patients correspond to the end of the drug elimination of the previous treatment. It is difficult with a half-life to 110 h to predict the effects of residual concentrations of adriamycin and adriamycinol.     

Pharmacokinetics of tinidazole in chronic renal failure and in patients on haemodialysis.

The pharmacokinetics of tinidazole after infusion (800 mg in 15 min) were studied in 12 patients with chronic renal failure (RI) and in five patients undergoing regular dialysis treatment (RD). Tinidazole elimination plasma half-life was 15.09 +/- 0.68 h (mean +/- s.e. mean) (RI) and 12.9 +/- 1.0 h after dialysis (RD), but there was a significant decrease in half-life during dialysis (4.25 +/- 0.43 h) P less than 0.001). The apparent volume of distribution (0.64 +/- 0.03 l/kg) was equal to extra and intracellular water volume and tinidazole was little bound to plasma protein (8%). There was a slight sex difference in apparent volume of distribution between male patients (0.70 +/- 0.09 l/kg) and female patients (0.59 +/- 0.10 l/kg) (P = 0.07), but as body clearance decreases in the same order, there was no modification of plasma half-life. In renal failure, pharmacokinetics of tinidazole were not disturbed because no correlation between half-life, body clearance and creatinine clearance occurred; urine elimination was about 7% of administered dose. Plasma clearance during dialysis was 49.9 +/- 3.2 ml/min and about 43% of the available drug was eliminated during the 6 h dialysis procedure. These results suggest that an additional half-dose infusion should be given after the end of dialysis in patients undergoing regular dialysis treatment.     

Pharmacokinetics of mitoxantrone in patients after 2 h and 24 h intra-arterial administration

The pharmacokinetic parameters of mitoxantrone in patients with liver metastasis after intra-arterial 2 h and 24 h infusion (dosage 12 mg/m2) were investigated. Peak plasma concentrations were 305 +/- 60 ng/ml at 2 h infusion and 244 +/- 89 ng/ml at 24 h infusion. These peak plasma concentrations occurred at 0.9 +/- 0.8 h during 2 h infusion and 5.5 +/- 3.4 h during 24 h infusion. No significant difference between both intra-arterial administrations in elimination half-life (50-223 h at 2 h infusion, 58-246 h at 24 h infusion) and area under the plasma concentration-time curve (AUC0-72 = 11.6 micrograms/ml.h for 2 h infusion, AUC0-72 = 11.2 micrograms/ml.h for 24 h infusion) could be found. The results indicate that no change of availability in the central compartment at infusion of mitoxantrone over a period of 24 h could be achieved. The 2 h infusion lead to sufficient plasma levels with pharmacokinetic parameters of mitoxantrone similar to 24 h infusion and showed a good clinical picture with mild toxicity.     

Pharmacokinetics of teicoplanin during cardiopulmonary bypass surgery

Teicoplanin is a recently introduced long-acting glycopeptide antibiotic effective against Gram-positive aerobic and anaerobic bacteria. The effects of hypothermic extracorporeal circulation on teicoplanin serum pharmacokinetics have been studied in 18 patients undergoing open-heart surgery for coronary artery bypass graft or prosthetic cardiac valve insertion. The patients received a single 600 mg dose of teicoplanin by intravenous (i.v.) bolus (five cases) or by i.v. infusion over 20 min (13 cases) approximately 1 h before the anticipated skin incision and 2 h before the anticipated extracorporeal circulation. Serum drug concentrations were measured by a microbiological method using Bacillus subtilis ATCC 6633 as the test organism. Following i.v. bolus injection and i.v. infusion, teicoplanin levels in serum (mean +/- s.d.) were respectively 13.9 +/- 6.8 and 11.4 +/- 2.4 mg/l at the beginning of extracorporeal circulation, 8.8 +/- 3.5 and 10.2 +/- 2.3 mg/l at the end of this procedure and 2.8 +/- 0.6 and 2.9 +/- 1.0 mg/l at 24 h after surgery. Mean AUCs were 378.1 +/- 52.5 and 328.9 +/- 88.0/l.h and mean elimination half-life values were 27.9 +/- 12.7 and 30.3 +/- 11.0 h, respectively under the same conditions. These differences in plasma pharmacokinetic parameters were not significant. Teicoplanin pharmacokinetics in patients undergoing cardiopulmonary bypass surgery were similar to those observed in non-surgical patients with normal renal and hepatic function, confirming experimental evidence for lack of effects of extracorporeal circulation.     

The influence of renal function on clinical pharmacokinetics of moxonidine

Investigations were carried out on 24 hypertensive or borderline hypertensive patients with different degrees of renal function. Eight had normal renal function [glomerular filtration rate (GFR) greater than 90 ml/min], 8 moderate (GFR 30 to 60 ml/min) and 8 severe renal impairment (GFR less than 30 ml/min). All patients were given moxonidine 0.3mg once daily for 7 days and both pharmacokinetic and pharmacodynamic data were determined. During moxonidine treatment plasma elimination half-life, area under the plasma concentration-time curve (AUC) and apparent total clearance (CLT) showed statistically significant differences among patients in the 3 groups. Elimination half-life was 2.6 +/- 0.9 hours in patients with a GFR greater than 90 ml/min and increased to 6.9 +/- 3.7 hours in those with a GFR less than 30 ml/min (mean +/- SD; p = 0.012). Correspondingly, AUC0-24 h rose from 5.4 +/- 2.7 to 17.2 +/- 7.9 micrograms/L . h (p = 0.001), and CLT decreased from 1150 +/- 602.l ml/min to 369 +/- 227.6 ml/min (p = 0.001). These data suggest that once-daily administration of 0.3mg moxonidine may be appropriate in patients with impaired renal function. Independent of renal function, moxonidine was well tolerated in 22 of 24 patients. No deterioration in renal function as a consequence of the use of moxonidine was found. Thus, in patients with renal failure, dosage of moxonidine should be individually titrated according to the desired clinical response, as is recommended for hypertensive patients without renal impairment.     

Pharmacokinetics and hemodynamic effects of long-term nifedipine treatment in hypertensive patients

In six patients with essential hypertension, pharmacokinetics and pharmacodynamics of nifedipine were investigated during 6 weeks of treatment. On day 1 nifedipine was infused intravenously (6.0 mg within 60 min), and on day 2 oral nifedipine treatment (20-mg tablets, twice daily) was started. Patients came to the hospital once weekly, when blood samples were taken and blood pressure and heart rate were assessed prior to tablet intake and 3 h later. After 6 weeks of oral treatment the intravenous infusion experiment was repeated. At the first intravenous nifedipine infusion a total systemic plasma clearance of 671 +/- 240 ml/min (mean +/- SD), an elimination half-life of 95 +/- 36 min, and a volume of distribution of 60.2 +/- 11.9 L were found. Protein unbound fraction of nifedipine amounted to 4.6 +/- 0.3%. After 6 weeks of oral treatment half-life was almost doubled (p less than 0.05), whereas in most patients the volume of distribution had slightly increased and systemic plasma clearance was decreased. Using a sigmoidal model, hemodynamic effects were fitted to nifedipine plasma concentrations. After 6 weeks the maximal effect of intravenous nifedipine on both systolic and diastolic blood pressures had significantly decreased. In four patients the potency had decreased considerably. During oral nifedipine treatment the mean plasma half-life was 5.8 +/- 1.0 h; trough concentration was 11.3 +/- 4.1 ng/ml and peak concentrations were 36.8 +/- 14.3 ng/ml. During chronic treatment heart rate was not significantly changed, whereas systolic and diastolic blood pressures were significantly reduced (p less than 0.02 and less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical pharmacokinetics of dothiepin. Single-dose kinetics in patients and prediction of steady-state concentrations

The pharmacokinetics of dothiepin were evaluated in 9 depressed patients following a single oral dose of 75 mg. Blood and plasma concentrations of dothiepin and 2 major metabolites, northiaden and dothiepin S-oxide, were measured by gas chromatography/mass fragmentography. The mean (+/-SD) peak plasma concentrations of dothiepin were 49 +/- 27 micrograms/L at 3 +/- 1.2h. Mean (+/-SD) estimates of other parameters were as follows: absorption half-life 1.1 +/- 1.1h; distribution half-life 2.2 +/- 0.8 h; elimination half-life 25 +/- 7h; apparent volume of distribution 70 +/- 62 L/kg; and oral clearance 2.1 +/- 1.6 L/kg/h. The mean (+/-SD) peak plasma concentration of dothiepin S-oxide was 125 +/- 43 micrograms/L at 3.5 +/- 1.3h with an elimination half-life of 22 +/- 12 h. The mean peak plasma concentration of northiaden was 6 +/- 3 micrograms/L at 4.5 +/- 1.1h, with an elimination half-life of 31 +/- 12 h. No significant differences were found in pharmacokinetic parameters compared with a previous study in 7 healthy volunteers. When data for the patients and healthy volunteers were combined (n = 16), pharmacokinetic parameters were not found to be affected by age. However, a significant difference was found between males and females for the elimination half-lives of dothiepin and northiaden, and for the apparent volume of distribution of dothiepin. The 24-hour blood/plasma concentrations of dothiepin and dothiepin S-oxide accurately predicted the steady-state concentrations obtained following 4 weeks' treatment with dothiepin 150 mg nocte.     

Pharmacokinetics of valproic acid in patients with bipolar disorder

The pharmacokinetics of valproic acid (VPA) were studied in nine patients with bipolar disorder who were receiving VPA as prophylactic therapy, following the full daily dose (400-1500 mg), on which the patients had been maintained for at least the past 3 months. The data from our study showed that the pharmacokinetics of valproate followed a two compartment open model. A time lag of 1-2 h was observed in each patient, followed by rapid absorption, with the peak concentrations being recorded approximately 4 h after drug administration. The average 12 h trough concentration was found to be 54.73+/-11.96 microg/ml. The plasma level decline was biphasic with a terminal half-life of 14.2+/-6.39 h. Total plasma clearance was 0.095+/-0.035 ml/min/kg. The steady-state apparent volume of distribution was found to be 0.11+/-0.05 l/kg. A positive correlation (r = 0.69) was found between the dose (mg/kg) and steady-state serum concentration (Css) of VPA and all patients, except one, had their Css above 50 microg/ml. Most of the pharmacokinetic parameters in this study involving euthymic bipolar patients on long-term VPA monotherapy were found to be in agreement with those reported in literature on seizure disorder patients on similar regime; however, the plasma elimination half-life appears to be prolonged in bipolar patients.     

Pharmacokinetics of cefoperazone and sulbactam in liver transplant patients

The authors evaluated the pharmacokinetics of cefoperazone and sulbactam in 9 liver transplant patients. Cefoperazone and sulbactam were administered as an intravenous infusion over 30 minutes every 12 hours for six doses, and multiple blood samples were collected immediately after the first dose (administered during the surgery) and after the last dose. The concentrations of cefoperazone and sulbactam in serum and, when possible, in urine and bile collected over one dosing interval were measured by high-pressure liquid chromatography. The concentration of cefaperazone ranged from 436 to 4118 microg/ml, and sulbactam ranged from 3.3 to 8.7 microg/ml in the bile samples. The intraoperative clearance of cefoperazone (0.53+/-0.18 ml/min/kg) was significantly higher than the postoperative clearance (0.21+/-0.23 ml/min/kg). The half-life of cefaperazone, although not statistically significantly different, was prolonged in all patients during the postoperative period. The clearance of sulbactam (1.51+/-0.51 ml/min/kg) was lower than what is reported in patients with normal renal function but was comparable to what has been reported in patients with renal impairment and in critically ill patients. There were no significant differences in any of the pharmacokinetic parameters of sulbactam during and after surgery. The pharmacokinetic parameters of cefoperazone and sulbactam were significantly altered in liver transplant patients compared to what has been reported in normal subjects but were similar to what has been reported in patients with liver and renal impairment. There was a significant impairment in the biliary excretion of cefoperazone during the postoperative period in liver transplant patients. Although the percentage of the dose of cefoperazone excreted in the bile was drastically reduced, the biliary concentrations were generally high and above the MIC for most organisms. Given that both renal and hepatic elimination of cefoperazone is decreased, leading to a lower clearance and longer half-life in liver transplant patients, lower doses (1-2 g per day) of cefoperazone may be sufficient in liver transplant patients during the immediate postoperative period.     

Impact of tranexamic acid vs. aprotinin on blood loss and transfusion requirements after cardiopulmonary bypass: a prospective, randomised, double-blind trial

INTRODUCTION: Aprotinin (AP) reduces blood loss and transfusions after cardiopulmonary bypass (CPB), but may sensitise patients and is expensive. Tranexamic acid (TA) has less side-effects, but data regarding its efficacy are controversial. The aim of our prospective, randomised, double-blind study was to compare the impact of AP vs. TA on drainage blood loss and transfusion requirements in patients undergoing first time CABG on CPB. MATERIALS AND METHODS: One hundred and twenty adult patients were randomised to receive either high-dose AP according to Hammersmith or a total of 2 g TA. Perioperative blood products were transfused in a standardised fashion. Blood loss was measured up to 24 h. Demographic and clinical patient data were collected until hospital discharge. RESULTS: The data from 118 patients (TA: n = 58, AP: n = 60) who completed the study according to protocol were analysed. Blood loss at 24 h postoperation in TA patients was significantly higher (896 +/- 354 ml) as compared to AP patients (756 +/- 347 ml; p = 0.03). TA patients received 1.5 +/- 1.5 units of red blood cells (AP: 1.5 +/- 1.7, p = 1.0), 1.3 +/- 2.0 units of fresh frozen plasma (AP: 1.0 +/- 2.0, p = 0.38) and 0.5 +/- 1.4 units of platelets (AP: 0.2 +/- 0.7, p = 0.15). Clinical data, including perioperative myocardial infarction rate, acute renal failure, mechanical ventilation, hospital stay and mortality, were not significantly different between either group. CONCLUSION: Our data show a difference in blood loss between TA and high-dose AP. Although statistically significant, it has little clinical relevance, because perioperative transfusion requirements were similar for both groups. Thus, TA appears to be a cost-effective alternative to AP in primary CABG patients.     

Endothelin plasma levels in old and young patients during open heart surgery: correlations to cardiopulmonary and endocrinology parameters.

We compared endothelin (ET) plasma levels during and after aortocoronary bypass (CPB) grafting in old and young patients. Correlations to cardiopulmonary parameters and catecholamines were tested. The study included 22 patients (11 aged greater than 70 years and 11 aged less than 55 years). Measurements were performed after induction of anesthesia (baseline), before bypass, during bypass, after patients were weaned off bypass, at the end of operation, and after 4-h intensive care (IC) treatment. ET [radioimmunoassay (RIA) technique] and catecholamines [high pressure liquid chromatography (HPLC) technique] plasma levels were determined from arterial blood samples; hemodynamics (pulmonary artery catheter), oxygen data, and laser Doppler flow were also monitored. Baseline ET plasma levels were within normal range (young, 3.1 +/- 0.9 pg/ml, old, 4.5 +/- 1.4 pg/ml). Old patients had higher values during the entire investigation period. During CPB ET plasma levels increased to a maximum immediately after patients were weaned off bypass. A significant increase (twofold to baseline) was noted during IC therapy. ET plasma levels did not correlate to catecholamine plasma levels or to hemodynamic or laser Doppler flow parameters. A significant correlation existed between ET plasma levels and oxygen consumption. Monitoring ET plasma levels appears to be of minor value in predicting circulatory changes and assessing surgical stress. Further investigations must elucidate the increase in oxygen consumption and its correlation to ET plasma level.     

Pharmacokinetics and tissue concentrations of cefazolin in pediatric patients undergoing gastrointestinal surgery

Limited information is available on the pharmacokinetics and tissue penetration of cefazolin in pediatric patients. Nine children (age 0.8-10 years) undergoing gastrointestinal operations were studied. A single dose of cefazolin, 15-26 mg/kg was given i.v. over 2-3 min at the time of induction of anaesthesia. Multiple (5-8) blood samples were collected during the operative procedure and in the recovery room. Tissue samples from the rectus abdominis muscle were obtained at the time of incision, during surgery, and at closure. The concentration of cefazolin was measured by a high performance liquid chromatographic method. Peak serum concentrations of cefazolin ranged from 85.8-269.4 mcg/ml. Serum and tissue concentrations at incision were 50.5-169.9 mcg/ml and 1.8-29.7 mcg/g; at closure the serum and tissue concentrations ranged from 17.3-60.9 mcg/ml and 1.19-29.70 mcg/g, respectively. Total clearance, apparent distribution volume, and elimination half-life of cefazolin were 1.43 +/- 0.54 ml/min/kg, 0.08 +/- 0.03 l/kg, and 1.68 +/- 0.55 h respectively. Tissue concentrations of cefazolin were maintained above its minimum inhibitory concentrations against common susceptible pathogens. Hence, the current dosing regimen of cefazolin is adequate to protect against infection in pediatric patients undergoing gastrointestinal surgery.