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.     

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.     

Pharmacokinetics of diltiazem in patients undergoing coronary artery bypass grafting.

The pharmacokinetics of oral diltiazem (DZ) were studied in 10 patients on the day before cardiac surgery and on the next day during surgery and cardiopulmonary bypass (CPB). Six patients were taking DZ 60 mg q.i.d. and four patients were taking DZ 90 mg q.i.d. All had been receiving DZ treatment for at least 3 months. The plasma concentration profile of DZ on the day before surgery was assumed to reflect the steady-state condition. DZ showed dose-dependent kinetics. On the day of surgery, the levels of total DZ (TDZ) at 15 min and 1 h after the initiation of CPB were significantly reduced (approximately 50%) when compared with the pre-CPB level. The levels of unbound DZ (FDZ) and the two major metabolites, N-demethyl DZ (MA) and deacetyl-DZ (M1) were not changed significantly by CPB. The plasma unbound fraction value increased sharply from 0.43 +/- 0.12 before the onset of CPB to a peak value of 0.83 +/- 0.12 during CPB, and returned to baseline level 24 h after dosing. We conclude that CPB decreases the TDZ concentration but has little effect on FDZ, MA, and M1 levels. The lack of effect of CPB on FDZ was related to the reduction of plasma protein binding of DZ.     

万古霉素对老年患者肾毒性的观察及血药浓度监测的意义

目的 探讨老年患者使用万古霉素治疗过程中进行肾毒性观察及血药浓度监测的意义。方法 对69例明确有金黄色葡萄球菌感染的老年住院患者予万古霉素500mg或去甲万古霉素400mg静滴，每8小时1次，平均疗程11d，观察用药前后肾功能指标的变化。31例患者在药物治疗过程中监测万古霉素血药浓度，根据检查结果调整治疗方案。结果 65例老年患者在应用万古霉素前后血清肌酐、血尿素氮、内生肌酐清除率的变化差异无统计学意义（P〉0．05）。结论 老年患者应用万古霉素大多数是安全的，根据内生肌酐清除率调整用药剂量及（或）进行血药浓度监测，进行个体化给药，可以提高该药应用的安全性和有效性。     

Concentrations of cefotaxime in serum and myocardial tissue

Serum and myocardial concentrations of cefotaxime (CTX) were measured in 20 adult patients undergoing cardiac surgery. To all of these patients 1.0 g of CTX was given intravenously (in the range of 13.7--29.0 mg/kg) at the beginning of operation. The serum concentrations of CTX were determined at 5, 10, 30, 60 minutes and 120 minutes after administration. Myocardial concentrations of CTX were also determined at about 30 minutes (group I), 60 minutes (group II) and 120 minutes (group III). The following results were obtained. Average serum CTX concentrations were 132.8 +/- 34.1 micrograms/ml at 5 minutes, 92.0 +/- 23.1 micrograms/ml at 10 minutes, 44.6 +/- 12.3 micrograms/ml at 30 minutes, 24.5 +/- 7.7 micrograms/ml at 60 minutes and 12.3 +/- 4.9 micrograms/ml at 120 minutes after administration. Average myocardial CTX concentrations were 10.0 +/- 3.7 micrograms/g in group I, 3.6 +/- 2.1 micrograms/g in group II and 2.3 +/- 1.8 micrograms/g in group III. The myocardial/serum concentration ratio was 0.22 +/- 0.14 in group I, 0.15 +/- 0.08 in group II and 0.18 +/- 0.12 in group III, respectively. These results suggested that the serum and myocardial concentrations of CTX were high enough to be prophylactic and therapeutic against not only aerobic but also anaerobic and opportunistic infections during and after cardiac surgery.     

Tissue concentrations of cefepime in acute cholecystitis patients.

Cefepime is a new broad-spectrum cephalosporin with activity against Staphylococcus, Streptococcus, Pseudomonas, and the Enterobacteriaceae. The purpose of this study was to measure cefepime concentrations in plasma, peritoneal fluid, bile fluid and appendix tissue in patients undergoing elective cholecystectomy. Patients were randomly assigned to receive either cefepime, 2 g intravenously in phosphate buffer (IVPB) q 12 h or gentamicin 1.5 mg/kg IVPB q 8 h plus mezlocillin 4 g IVPB q 6 h. During surgery, gall bladder tissue, plasma, peritoneal fluid, and bile fluid samples were obtained at approximately the same time. Thirty-three patients had data acceptable for analysis. Values are given as mean +/- standard deviation. The mean delta time (defined as the time between the administration of cefepime and the time the samples were obtained) was 8.58 +/- 3.53 h. The values for plasma, peritoneal fluid, bile fluid, and gall bladder tissue concentrations were 7.63 +/- 14.17 micrograms/ml, 5.66 +/- 6.80 micrograms/ml, 15.51 +/- 16.94 micrograms/ml, and 5.36 +/- 6.57 micrograms/gm, respectively. The peritoneal fluid/plasma ratio was 2.10 +/- 2.33, the bile fluid/plasma ratio was 14.44 +/- 31.99, and the gall bladder tissue/plasma ratio was 1.44 +/- 1.82. There was a significant correlation between peritoneal fluid and plasma concentration (r = 0.91, p less than 0.0005), and gall bladder tissue and plasma concentration (r = 0.90, p less than 0.0005). There was no correlation between bile fluid and plasma cefepime concentrations. The minimum inhibitory concentration (MIC) data from previous in vitro studies indicate that cefepime concentrations achieved in this patient population would be adequate against typical biliary tract pathogens.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Buprenorphine pharmacokinetic parameters during coronary artery bypass graft surgery

The pharmacokinetic parameters of buprenorphine (BN) after a single bolus dose of 10 microg/kg i.v. was investigated in 6 male patients whose age averaged 59+/-9.8 years and body weight of 65.8+/-5.7 kg undergoing coronary artery bypass graft surgery (CABG). The unbound BN plasma concentrations were detected using ultrafiltration and high performance liquid chromatography/electro-chemical detection (HPLC/ECD) method. During cardiopulmonary bypass (CPB) there was a fall in BN plasma concentrations, observations similar to reports on fentanyl, sufentanil and alfentanil. This is probably due to haemodilution, hypothermia and hydrophobic sequestration of drug on to the CPB tubing. After CPB the concentrations rose to values higher than during CPB, though it did not attain pre CPB concentrations. These variations were not statistically significant indicating that plasma levels were adequately stable during CPB. The plasma concentration time curves were biexponential and the pharmacokinetic parameters obtained were : distribution half-life 37.24+/-6.57 min, elimination half-life 482.69+/-79 min, clearance 1221.97+/-209.42 ml/min, and volume of distribution 736.46+/-71.25 L. BN in the dose used follows the pharmacokinetic pattern of other commonly used narcotics during CABG. The mean +/- SEM plasma BN concentration during CPB was 0.51+/-0.03 ng/ml which was adequate for the maintenance of analgesia and anaesthesia, as none of our patients expressed the signs and symptoms of awareness during surgery. Further, unlike the other narcotics muscle rigidity was absent. Thus BN is a safe and good alternative to other narcotics for patients undergoing CABG.     

Acetazolamide blood concentrations are excessive in the elderly: propensity for acidosis and relationship to renal function

Elderly glaucoma patients are often treated with acetazolamide, a carbonic anhydrase inhibitor with clearance dependent on renal function. A high incidence of metabolic acidosis and other adverse effects have been noted among these patients but the reasons for this have not been explained. We hypothesized that commonly used doses of acetazolamide among the elderly result in excessive blood concentrations and that these concentrations are related to acid-base disturbances. We measured steady-state acetazolamide levels in plasma, plasma ultrafiltrate (unbound), and erythrocytes among 12 elderly subjects (79.2 +/- 7.6 years old). Mean plasma (18.9 +/- 10.9 micrograms/mL) and ultrafiltrate concentrations (1.0 +/- 0.7 microgram/mL) exceeded the therapeutic range (plasma 5-10 micrograms/mL; ultrafiltrate 0.25-0.50 microgram/mL) for glaucoma control by two fold and were elevated in 75% of subjects. Plasma and ultrafiltrate acetazolamide levels significantly correlated with the dose adjusted for creatinine clearance (r = 0.91, P less than 0.001; r = 0.89, P less than 0.001, respectively). Acidotic subjects (serum total carbon dioxide less than or equal to 22 mEq/L) tended to have higher plasma, ultrafiltrate, and erythrocyte acetazolamide levels compared with nonacidotic subjects. Serum total carbon dioxide levels were significantly correlated with erythrocyte acetazolamide concentrations (r = -0.75, P = 0.03). The ratio of erythrocyte acetazolamide concentration to creatinine clearance separated acidotic from nonacidotic subjects (P less than 0.01). These findings suggest that some of the adverse effects of acetazolamide can be avoided by reducing the dose to compensate for age-related reductions in renal drug clearance.     

体外循环对血小板的影响及其与术后急性肺损伤的关系

目的探讨体外循环(CPB)对血小板的影响及其与术后急性肺损伤的关系。方法对20例体外循环下行心脏手术的患者,在肝素化前、转流30 min、体外循环停机时和术后24 h分别测定体外循环前后血小板计数(PLT)、血栓烷B2(TXB2)值变化;分别于术后用乌司他丁注射液20万U加入100 mL生理盐水中静脉滴注,参麦注射液30 mL加入5%葡萄糖注射液250 mL中静脉滴注,每日1次,连用14 d。并于手术后即刻、2 h和6 h行动脉血气分析、肺动态顺应性和氧合指数测定。观察术后不同时间点肺功能改变。结果与体外循环术前相比,血小板计数在术中和术后降低,血栓烷B2在术中明显增高,术后很快下降但仍高于术前(P<0.05或P<0.01)。肺动态顺应性和氧合指数在术后降低(P<0.05或P<0.01)。结论体外循环可导致血小板数量的改变和功能障碍,并在术后肺损伤中发挥重要作用。     

The pharmacokinetics and transfer into atrial muscle of ceftizoxime in open heart surgery

A study of serum and atrial muscle concentration of ceftizoxime (CZX) was performed in 28 adult patients having cardiac surgery. Patients were administrated a single dose of CZX 2 g intravenously. Serum and atrial muscle samples were obtained at suitable intervals before extracorporeal circulation, and assayed CZX concentration. Serum concentrations were 54.5 micrograms/ml at 60 minutes, and 21.8 micrograms/ml at 180 minutes. Atrial tissue levels were 29.9 micrograms/g at 60 minutes, and 14.8 micrograms/g at 180 minutes. Tissue/serum concentration ratio was high value; 0.549 at 60 minutes, 0.679 at 180 minutes. Judging from its favorable transfer into atrial muscle and MIC80 against the suspected pathogen, CZX seemed to be clinically useful in the treatment of infection after cardiac surgery.     

Effect of cardiopulmonary bypass on plasma concentrations of diltiazem and its two active metabolites

Abstract— Diltiazem is often used to prevent myocardial ischaemia during the perioperative period of coronary artery bypass surgery. The purpose of this study was to investigate the effect of cardiopulmonary bypass (CPB) on plasma concentrations of diltiazem and of its two main and active metabolites (N-monodemethyldiltiazem (N-desmethyldiltiazem) and desacetyldiltiazem). The patients were administered their usual treatment during the preoperative days. The last dose was administered immediately before anaesthesia. At the onset of CPB, a significant decrease in the plasma concentrations of diltiazem and its metabolites was observed, whereas the variation was slight and not significant when the plasma concentrations were corrected for haemodilution. These results confirm that the decrease observed at the initiation of the bypass procedure can be ascribed to the haemodilution induced by the CPB. During CPB, the concentrations of diltiazem and its metabolites remained constant suggesting that the rate of metabolism and excretion of the drug was altered during the bypass procedure. At the end of CPB, there was no increase of drug plasma concentrations suggesting that no redistribution of diltiazem from tissues to plasma occurred. Furthermore, this study shows that only 33% of subjects have therapeutic levels of diltiazem before anaesthesia, and that all subjects have subtherapeutic levels during and after the CPB. These results suggest that a higher chronic oral dose of the drug should be given in patients undergoing cardiac surgery with CPB.     

Renal protection by radical scavenging in cardiac surgery patients

OBJECTIVE: Renal function impairment is a common complication in cardiac surgery patients. Because cardiopulmonary bypass and cardioplegic arrest are associated with formation of free radicals, which have been shown to impair various organs including the kidneys, radical scavenging may protect renal function. Therefore, the purpose of our study was to evaluate the impact of the radical scavenger N-acetylcysteine (NAC) versus placebo on peri-operative renal function in cardiac surgery patients. RESEARCH DESIGN AND METHODS: We reanalyzed the data of our previous study in which 40 coronary artery surgery patients (66 +/- 9 [SD] years, 9 women and 31 men) with normal pre-operative renal function had been randomized in a double-blind fashion to receive either NAC (100 mg/kg into the cardiopulmonary bypass prime followed by infusion at 20 mg/kg/h; n = 20) or placebo (n = 20). We determined serum creatinine levels as an indicator for renal function pre- and at 1 day post-surgery as well as peri-operative urinary output and diuretic medication. Creatinine clearance was calculated according to Cockcroft and Gault. RESULTS: Biometric and intra-operative patient data were similar between both groups. In the placebo group, serum creatinine increased from 93.1 +/- 35.4 micromol/L pre-operatively to 115.9 +/- 47.2 micromol/L on post-op day 1 (p < 0.001). In contrast, serum creatinine in the NAC group remained unchanged (92.3 +/- 31.3 micromol/L pre-op; 99.3 +/- 25.4 micromol/L on post-op day 1; p = 0.084). Accordingly, creatinine clearance decreased by 16.9 +/- 14.3 mL/min in the placebo group as compared to 7.5 +/- 17.7 mL/min in the NAC group (p = 0.039). Urinary output and diuretic medication were similar between NAC and placebo. CONCLUSIONS: Our data suggest that free radical-scavenging using NAC protects renal function in patients subjected to cardiac surgery on cardiopulmonary bypass.     

Overestimation of vancomycin concentrations utilizing fluorescence polarization immunoassay in patients on peritoneal dialysis

During a study of vancomycin pharmacokinetics in patients undergoing continuous ambulatory peritoneal dialysis (CAPD), a discrepancy was noted when serum concentrations were determined by high performance liquid chromatography (HPLC) in comparison to a fluorescence polarization immunoassay (FPI) technique. Following three weekly intraperitoneal doses (30 mg/kg/2 L), peak serum concentrations (at the end of the 6-h dwell) by FPI were 42.1 +/- 9.1, 43.1 +/- 8.7, and 45.6 +/- 7.4 micrograms/ml. In comparison, the same samples when analyzed by HPLC yielded 36.3 +/- 9.4, 32.2 +/- 8.9, and 31.6 +/- 9.1 micrograms/ml, respectively. A subsequent in vitro study of vancomycin (40 micrograms/ml) in serum indicated a degradation half-life of 693 (FPI) compared with 210 (HPLC) h. These data suggest that vancomycin degradation products accumulate in CAPD patients and lead to an overestimation of vancomycin serum concentrations when measured by FPI.     

艾司洛尔对常温不停跳心内直视手术期间心肌损伤标志物的影响

目的 探讨艾司洛尔对常温不停跳心内直视手术期间心肌损伤标志物的影响。方法选择48例择期二尖瓣置换术病人随机分为对照组(C组)和艾司洛尔组(E组),每组各24例,常规建立心肺转流(CPB),平行循环后不降温及不主动复温,阻断腔静脉,不阻断主动脉,平均动脉压(MAP)维持在50～70mmHg,在心脏跳动下进行手术。E组在心内直视手术开始前予艾司洛尔1～2mg/kg静脉注射后,以0.3％的浓度静滴维持心率在30～50次/分。分别于手术前、术后即刻、术后6小时、12小时、24小时、48小时取动脉血测定血清C—反应蛋白(CRP)、肌酸激酶同工酶(CK—MB)、肌钙蛋白T(cTnT)和肌钙蛋白I(cTnI)浓度变化。结果 两组病人性别、年龄、心功能、心胸比值(C/T)差异无显著意义;术前两组间CRP、CK—MB、cTnT、cTnI差异无显著意义(P>0.05),两组患者血清CRP、CK—MB、cTnT、cTnI浓度在CPB后即刻显著升高(P<0.01),E组于术后6小时达峰值,术后24小时降至正常水平,C组于术后12小时达峰值,术后48小时降至正常值,同一时点比较,E组明显低于C组(P<0.05 or 0.01)。结论 艾司洛尔用于常温不停跳心内直视手术中可显著降低心肌损伤标志物升高程度,使酶峰提前,促进术后心功能恢复,具有良好的心肌保护作用。     

Inappropriate use of metronidazole in gastrointestinal surgery

Pharmacokinetic data suggest that current treatment regimens of metronidazole in abdominal surgery are not always appropriate. We have examined antibiotic concentrations during emergency and elective surgery using a specific and sensitive high pressure liquid chromatography assay. Serum and tissue concentrations were measured after intravenous infusion during intra-abdominal surgery and after suppositories given before appendicectomy. After intravenous dosage, bactericidal concentrations were reached in serum (13.6 +/- 7.8 micrograms/ml), bowel (9.0 +/- 6.6 micrograms/g), tumour (9.9 +/- 7.1 micrograms/g) and subcutaneous fat (4.9 +/- 3.2 micrograms/g). After suppositories the concentrations were: serum 4.6 +/- 2.7 micrograms/ml, appendix 1.1 +/- 0.6 micrograms/g, fat 1.5 +/- 0.9 micrograms/g and peritoneal fluid 4.7 +/- 4.3 micrograms/g. These values were obtained at a mean interval of 86.9 +/- 27.5 min following administration of the drug. Serum concentrations were measured during post-surgical infusion of 500 mg i.v. 8 or 12 hourly. Mean concentrations after 8 hourly doses were 16.3 +/- 4.85 micrograms/ml pre-dose and 28.7 +/- 6.76 micrograms/ml post-dose, with evidence of drug accumulation by detection of metabolites. Twelve hourly infusions gave pre-dose levels of 7.4 +/- 3.86 micrograms/ml and post-dose levels of 17.1 +/- 3.69 micrograms/ml. Metronidazole (500 mg) intravenously at induction of anaesthetic gives effective prophylactic concentrations in all tissues including tumour, but a metronidazole 1 g suppository before appendicectomy does not provide reliable tissue concentrations. Metronidazole (500 mg) i.v. 12 hourly gives effective bactericidal concentrations of the drug and is more economical.     

Altered gentamicin pharmacokinetics during the perioperative period

The effect of surgery on the pharmacokinetics of gentamicin sulfate in hospitalized patients was studied. Patients with cancer undergoing surgery of the head and neck were given gentamicin sulfate in doses calculated to achieve peak serum concentrations of 6-8 micrograms/mL and trough concentrations of 1-2 micrograms/mL. Each patient received a loading dose at the time of surgical incision, followed by five maintenance doses at eight-hour intervals. Steady-state peak and trough serum gentamicin concentrations were predicted using a one-compartment open pharmacokinetic model and literature values for volume of distribution (V) and first-order elimination rate constant (k). Serum gentamicin concentrations were measured 0.25 hours before and at 0.5, 3.5, and 6.5 hours after completion of infusion of the second maintenance dose. Peak and trough serum concentrations were obtained by extrapolation from these measured concentrations using weighted, nonlinear least squares regression. Predicted versus measured serum gentamicin concentrations and estimated versus observed values for V and k were compared. Eight men and seven women had evaluable serum gentamicin concentrations. Patients received a mean calculated maintenance dose of 4.4 +/- 0.7 mg/kg/day. Mean extrapolated peak and trough serum gentamicin concentrations were significantly lower than predicted, and observed values of V and k were significantly greater than estimated values. Gentamicin dosages calculated using standard pharmacokinetic variable values may not produce therapeutic concentrations in patients undergoing surgery. Monitoring of serum concentrations with dosage adjustment when indicated is necessary for optimal therapy in these patients.     

心血管手术术中经食管超声监测的价值

目的 探讨心血管手术术中麻醉医生行经食管超声心动图(TEE)监测的临床价值.方法 326例患者行体外循环心血管手术,全麻诱导插管后由麻醉医师行围术期 TEE监测,与术前经胸壁超声心动图(TTE)比较,及时调整手术方式,术中实时监测判断手术效果,术后判断心脏功能,指导血管活性药物应用.结果 经TEE提示,15例(4.60%)更改了手术方式,8例(2.45%)及时再次手术处理,26例(7.98%)停体外循环保留经食管探头监测心脏功能及指导用药至拔除气管导管.结论 麻醉医师在体外循环术中行TEE监测有助于手术的成功实施.     

Serum cystatin C for the prediction of glomerular filtration rate with regard to the dose adjustment of amikacin, gentamicin, tobramycin, and vancomycin

Dosage regimes of aminoglycosides and vancomycin are modified according to the glomerular filtration rate (GFR). In 130 hospitalized patients who were administered amikacin, gentamicin, tobramycin, and vancomycin by intermittent intravenous infusion, we compared the predicted GFR values from the serum concentrations of creatinine (Cockcroft and Gault. Nephron. 1976;16:31-41) and cystatin C (Larsson et al. Scand J Clin Lab Invest. 2004;64:25-30) with respect to their relevance for proper dosage. In 83% and 67% of the cases, respectively, the serum levels of albumin and cholinesterase were below the corresponding lower limit of the reference range. The ratio of creatinine/cystatin C concentrations presented significant correlations with the predicted rate of creatinine production (r=0.762, P<0.001), serum albumin concentration (r=0.205, P<0.05), and catalytic serum concentrations of cholinesterase (r=0.207, P<0.05), gamma glutamyltransferase (r=-0.273, P<0.01), and alkaline phosphatase (r=-0.289, P<0.01). The GFR (mean+/-SD; median) predicted by the serum creatinine (84.0+/-35.1 mL/min/1.73 m; 82.6 mL/min/1.73 m) was significantly higher (P<0.001) than that predicted by the serum cystatin C (53.1+/-30.2 mL/min/1.73 m; 44.9 mL/min/1.73 m). The ratio between the GFR values predicted by creatinine and cystatin C had a highly significant negative correlation with the rate of creatinine production (r=-0.912, P<0.001). Furthermore, significant differences were found for the peak concentrations and clearances of amikacin and vancomycin estimated by means of the Abbottbase Pharmacokinetic Systems program, and using the GFR values predicted by the serum creatinine and cystatin C (P<0.005). In patients with hepatic dysfunction, the clearance of creatinine predicted by the Cockcroft-Gault formula leads to a significant overestimation of the GFR. Cystatin C seems to be a valid alternative as a GFR marker with regard to drug dose adjustment in these cases.     

FXII levels, FXIIa-like activities and kallikrein activities in normal subjects and patients undergoing cardiac surgery

A new chromogenic peptide substrate assay kit was used to measure factor XII (FXII) levels in plasma samples from 115 male patients with heart disease awaiting cardiac surgery, 40 age-matched normal healthy male blood donors and 20 patients before, during and after cardiopulmonary bypass surgery (CPB). Kallikrein-like and FXIIa-like activities were also determined in the CPB patient group. FXII levels were significantly lower (p = 0.0049) in the heart disease patients awaiting surgery when compared with values for the healthy donors and 13 patients (11.3%) had FXII levels below 50% compared with 1 normal donor (2.5%). During CPB significant decreases in FXII levels and significant increases in FXIIa-like and kallikrein-like activities were found indicating activation of the FXII-plasma kallikrein pathway during CPB.