Pharmacokinetics of cefuroxime and ceftazidime in patients with acute renal failure treated by continuous arteriovenous haemodialysis.

To determine appropriate doses of cefuroxime and ceftazidime for septic patients with acute renal failure (ARF) treated by continuous arteriovenous haemodialysis (CAVHD), we performed pharmacokinetic studies in patients receiving these antibiotics. All patients were treated by CAVHD using Hospal AN69S 0.43 m2 filters and Fresenius 1.5% peritoneal dialysis fluid at dialysate flow rates (Qd) of 1 and 2 l/h. Patients received cefuroxime 500 mg (n = 11) or 750 mg (n = 1), or ceftazidime 500 mg (n = 9) i.v. 12-hourly and all studies were done at steady-state. For cefuroxime, volume of distribution (Vdarea) was 22.8 +/- 3.5 l, terminal elimination half-life (t1/2) 12.6 +/- 2.2 h and total body clearance (TBC) 22.3 +/- 3.0 ml/min (mean +/- SEM). Mean sieving coefficient (SC) was 0.90 +/- 0.12 and filter clearances at Qd 1 and 2 l/h were 14.0 +/- 2.3 and 16.2 +/- 3.4 ml/min respectively. For ceftazidime, Vdarea was 31.1 +/- 6.5 l, t1/2 14.7 +/- 3.3 h, and TBC 24.8 +/- 0.8 ml/min. Mean SC was 0.86 +/- 0.03, and filter clearances at Qd 1 and 2 l/h 13.1 +/- 1.2 and 15.2 +/- 1.5 ml/min. Satisfactory plasma concentrations of both antibiotics were maintained in all patients during treatment. These data suggest that cefuroxime 500-750 mg and ceftazidime 500 mg 12-hourly are suitable doses for patients with ARF treated by CAVHD.     

Aluminum removal with hemodialysis, hemofiltration and charcoal hemoperfusion in uremic patients after desferrioxamine infusion. A comparison of efficiency

In order to compare the effectiveness of aluminum removal in uremic patients during extracorporeal treatment, 17 patients with endstage renal failure were given a desferrioxamine infusion of 40 mg/kg body weight after an ordinary dialysis treatment. Forty-eight hours later 7 patients were treated with hemodialysis, 6 with hemofiltration and 4 with a combination of hemodialysis and hemoperfusion. The clearance of aluminum was measured at different intervals. It was found that the aluminum clearance was 75 +/- 18 ml/min in hemofiltration compared to 30 +/- 10 ml/min in hemodialysis (p less than 0.001). A combination of hemodialysis and hemoperfusion with a charcoal column containing 100 g activated charcoal in series gave a total aluminum clearance of 56 +/- 11 ml/min. The total amount of aluminum in the ultrafiltrate after hemofiltration was found to be approximately 3 times as high (1,728 +/- 156 micrograms) as the total amount of aluminum in the hemodialysis water that had passed a single pass system during a 4-hour dialysis (576 +/- 104 micrograms). Our results indicate that hemofiltration or a combination of hemodialysis and hemoperfusion should be used to remove aluminum in patients with signs of severe aluminum accumulation such as encephalopathy or painful bone disease, because these methods are 2-3 times as effective as ordinary hemodialysis. In patients where aluminum has been accumulated but no severe symptoms occur hemodialysis gives a significant clearance of the aluminum desferrioxamine complex.     

Single-dose kinetics of imipenem/cilastatin during continuous arteriovenous haemofiltration in intensive care patients

The single i.v. dose kinetics of a fixed combination of imipenem/cilastatin were investigated in ten critically ill patients treated by continuous arteriovenous haemofiltration (CAVH). Eight patients suffered from acute renal failure and two had normal renal function. Both drugs were measured in plasma and ultrafiltrate by high-performance liquid chromatography. While the pharmacokinetics of both drugs are almost identical in patients with normal renal function, we found the following dissociation of pharmacokinetic parameters in our patients with renal failure: for imipenem the total clearance and elimination half-life was 104 +/- 12 ml/min and 2.2 +/- 0.1 h, respectively, and for cilastatin 29 +/- 10 ml/min and 13.8 +/- 4.5 h. The pharmacokinetics of imipenem and cilastatin differ from each other in renal failure because imipenem, unlike cilastatin, undergoes marked elimination by non-renal pathways. Our results did not differ from previously reported data in healthy volunteers and patients with impaired renal function. Elimination of imipenem by CAVH was low (7% of the dose). As a consequence of the unsatisfactory non-renal clearance of cilastatin, however, the fraction of the dose removed by CAVH was significantly greater (approximately 30%) than that of imipenem. This did not, however, correct the dissociation of the pharmacokinetic profiles of the two drugs. In conclusion, the dose of imipenem/cilastatin in critically ill patients with renal failure treated by CAVH should be modified according to renal function but elimination by CAVH does not need to be considered.     

The effect of peritonitis on the transperitoneal transport of cefuroxime in patients on CAPD treatment

The pharmacokinetics and transperitoneal transport of cefuroxime were investigated in CAPD patients without peritonitis (n = 6), receiving 500 mg of the drug intravenously (i.v.) and intraperitoneally (i.p.) on separate occasions. CAPD patients with peritonitis were also investigated after i.p. administration of an initial dose of 500 mg cefuroxime followed by repeated doses of 250 mg. Routine hospital CAPD procedures and dwell-time schedules were followed during the study, and frequent blood and dialysate samples were collected. Cefuroxime was analysed by HPLC methods, and pharmacokinetic parameters were calculated. In the patients without peritonitis, the following pharmacokinetic parameters after i.v. and i.p. administration did not differ significantly (mean +/- SD): elimination half-life, 15.1 +/- 1.9 h; apparent volume of distribution 27.9 +/- 2.91; and total clearance, 21.5 +/- 1.2 ml/min. In contrast, the transperitoneal transport of cefuroxime differed significantly in the three studies. After i.v. administration the apparent transperitoneal clearance was low and time dependent, ranging from 4.2 +/- 1.2 to 1.4 +/- 0.4 ml/min. After i.p. administration the apparent transperitoneal clearance increased to 10.9 +/- 2.4 ml/min, whereas in the peritonitis patients a further increase to 21.5 +/- 3.5 ml/min was observed. In all patients we found cefuroxime concentrations in serum and dialysate, greatly exceeding MIC values of most pathogens involved in CAPD peritonitis and other systemic bacterial infections.     

Continuous arteriovenous hemofiltration in the treatment of 100 critically ill patients with acute renal failure: report on clinical outcome and nutritional aspects

The clinical outcome for 100 consecutive patients with multiorgan failure including acute renal failure (ARF) was studied. Fifty-eight of the patients had acute renal failure due to complications during and after major surgery. Seventy-three of the patients had a urine output of less than 400 ml/24 hours. The majority of the patients also had complications such as septicemia or respiratory insufficiency and required vasopressor infusions. All patients were treated with continuous arteriovenous hemofiltration (CAVH). The duration of the CAVH treatment varied between a few hours and 90 days, with a mean of 8 days. The mean ultrafiltration volume per 24 hours was, on the average, 12 liters. CAVH resulted in adequate uremic control in 89 cases, but additional treatment with intermittent hemofiltration was necessary in 11 patients. The total survival rate was 45% including survival rates as high as 54% in patients with ARF complicating abdominal aortic surgery. Only three patients were referred for chronic dialysis therapy. In a subgroup of 17 patients with ARF complicating abdominal aortic surgery the nutritional aspects during CAVH were studied. It is concluded that during CAVH therapy it is possible to give adequate nutritional support even to hypercatabolic and anuric patients.     

The level of neopterin in the plasma of patients with acute kidney failure during treatment with continuous arteriovenous hemofiltration

Neopterin is a biochemical marker of cellular mediated immune reactions and may be used in elucidating the cause of acute renal failure. 9 patients (6 males, 3 females) aged 23 to 56 years suffering from a severe form of the disease were examined. A continuous arteriovenous hemofiltration was used as a treatment with exchanging 29.2 +/- 2.0 (14-65) kg of fluid during 24 hours. The patients' diet included protein and amino acids of 1.2-1.5 g/kg of body weight, 35-45 Kcal/kg of body weight per 24 hours with meal and parenteral infusions. 4 patients died. Contents of neopterin in the plasma of the healthy equaled to 6.8 +/- 03 (3.4-11.3) nmol/l (radioimmunoassay; Henning; Berlin, GmbH). In patients with acute renal failure plasma neopterin contents were increased, i.e. 130.0 +/- +/- 9.6 (48.2-200.2) nmol/l and in two thirds of the cases and correlated with creatinine levels (r = + 0.60 +/- 0.17; p less than 0.05; n = 23), thus showing a simultaneous influence of anuria and continuous arteriovenous hemofiltration on a neopterin pool amount at the same time, in patients with tropical malaria and hemotransfusion shocks (2 cases), the neopterin contents were extremely high and did not correlate with the creatinine level. During continuous hemofiltration at a rate of 21.6 +/- 1.3 (15.9-36.9) ml/min neopterine clearance was 17.2 +/- 2.1 (6.7-36.2) ml/min. Neopterin hyperproduction after blood transfusion suggests an immune conflict as a possible cause of acute renal failure.     

Pharmacokinetics of fosfomycin in hemodialyzed patients

The pharmacokinetics of fosfomycin, an original antimicrobial agent, were investigated in 11 voluntary hemodialyzed patients. Fosfomycin, 2 g, was administered intravenously, 15 minutes before hemodialysis began in group 1 (6 patients), and just after hemodialysis in group 2 (6 patients). Blood samples were collected during 8 hours (group 1) and during 44 hours (group 2). Antibiotic concentrations were determined microbiologically. In group 1, half-life was 4.2 +/- 0.27 hours, total clearance 65.1 +/- 7.1 ml/mn and clearance by hemodialyzer 103 +/- 10 ml/mn. In group 2 plasma levels were 60 mg/l at the 44th hour and half-life was 48.8 +/- 17.5 hours. These results suggest that fosfomycin is actively eliminated by the hemodialyzer in group 1, and largely retained between two dialysis sessions in group 2. As for therapy, intravenous administration of 2 g after dialysis and further administration after each succeeding session are proposed.     

Plasma concentrations of lidocaine and its principal metabolites during intermittent epidural anesthesia

Plasma concentration-time courses of lidocaine and its principal metabolites (monoethylglycinexylidide, MEGX, and glycinexylidide, GX) were studied during intermittent epidural injections of lidocaine HCl in eight female patients (ASA status 1). The initial dose (320-400 mg without epinephrine) followed by top-up injections of about 60% of the mean initial dose every 35-55 min resulted in a plasma accumulation of lidocaine: the peak concentration increased from 2.30 +/- 0.46 (mean +/- SD) microgram/ml following the first injection and 3.34 +/- 0.76 microgram/ml after the second, to 4.11 +/- 0.72 microgram/ml following the third. The maximum concentrations of MEGX and GX were 0.66 +/- 0.22 and 0.28 +/- 0.08 microgram/ml, respectively. A pharmacokinetic model could successfully fit the entire plasma concentration-time profile of lidocaine during repeated epidural injections (r2 = 0.886 to 0.983). Such pharmacokinetic variables as elimination half-life (t1/2, 2.33 +/- 0.43 h), apparent volume of distribution divided by bioavailability (Vd/F, 2.51 +/- 0.61 l/kg), and clearance divided by bioavailability (Cl/F, 11.65 +/- 1.21 ml X kg-1 X min-1) obtained from the female patients were in reasonable agreement with those reported from healthy females receiving the intravenous lidocaine HCl. A computer-aided simulation generated from using the mean kinetic data in a 50-kg woman predicted that plasma lidocaine concentration would reach the postulated toxic range (approximately equal to 6 microgram/ml) after the fourth supplementary dose under a similar dosing scheme as performed in this study. In conclusion, an accumulation of lidocaine in plasma occurs during a usual intermittent epidural dosing.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence de l''hémofiltration artérioveineuse sur l''élimination de la teicoplanine

Objective

To assess the pharmacokinetics of a single dose of teicoplanin in critically ill patients treated with continuous arteriovenous haemofiltration (CAVH).

Study design

Prospective open clinical study.

Patients

Eleven patients with acute renal insufficiency and suspected of a Gram negative infection.

Method

After injection of teicoplanin, 6 mg·kg⁻¹ over 30 minu- tes, the plasma and haemofiltrate concentrations were measured over 24 hours with high power liquid chomatography (HPLC).

Results

In plasma, the mean half-life of the first phase was 0.6 ± 0.2 hour and terminal half-life was 16.4 ± 5.8 hours, total clearance 30.4 ± 7.1 mL·h⁻¹·kg⁻¹, volume of distribution was 0.7 ±0.3 L·kg⁻¹ and the mean resident time 19.2 ± 7.4 hours. In the hemofiltrate, the amount of teicoplanin eliminated after 24 hours was less than 1 % in seven patients, between 1.8 and 3.7% in three and reached 7% in one patient.

Conclusion

During CAVH, the elimination of a single dose of teicoplanin in the haemofiltrate is low.     

Pharmacokinetics of ciprofloxacin and vancomycin in patients with acute renal failure treated by continuous haemodialysis.

To determine appropriate doses of ciprofloxacin and vancomycin for septic patients with acute renal failure (ARF) treated by continuous arteriovenous and venovenous haemodialysis, (CAVHD/CVVHD), we performed pharmacokinetic studies in patients receiving these antibiotics. All patients were treated by CAVHD/CVVHD using Hospal AN69S 0.43 m2 filters and Fresenius 1.5% peritoneal dialysis fluid at dialysate flow rates (Qd) of 1 and 2 l/h. Patients received ciprofloxacin 200 mg i.v. 12-hourly (n = 6) or 8-hourly (n = 5); vancomycin 1 g i.v. was administered to 10 patients approximately every 48 h to maintain therapeutic plasma levels. For ciprofloxacin, volume of distribution (Vdarea) was 136.5 +/- 9.81, terminal elimination half-life (t1/2) 6.4 +/- 0.8 h, and total body clearance (TBC) 264.3 +/- 22.9 ml/min (mean +/- SEM). Mean sieving coefficient (S/C) was 0.76 +/- 0.05 and filter clearances at Qd 1 and 2 l/h were 16.2 +/- 1.9 and 19.9 +/- 1.1 ml/min respectively. For vancomycin, Vdarea was 60.7 +/- 5.11, t1/2 24.7 +/- 2.6 h and TBC 31.0 +/- 4.6 ml/min. Mean S/C was 0.66 +/- 0.08 and filter clearances at Qd 1 and 2 l/h 12.1 +/- 2.0 and 16.6 +/- 2.0 ml/min. These data suggest that patients with ARF treated by CAVHD/CVVHD should be given ciprofloxacin 200 mg i.v. 8-12-hourly and vancomycin every 48 h.     

Trimethoprim-sulfamethoxazole pharmacokinetics during continuous ambulatory peritoneal dialysis

Eight adult patients without peritonitis maintained on chronic ambulatory peritoneal dialysis (CAPD) were administered a single oral dose of 320 mg trimethoprim (TMP) and 1600 mg sulfamethoxazole (SMX) to characterize the pharmacokinetics of TMP and SMX. Ten blood samples were drawn following the dose. TMP and SMX-active (SMXA) concentrations were quantified in serum and dialysate. The half-life of TMP and SMXA determined by model independent methods were 33.7 +/- 10.5 h (mean +/- SD) and 13.8 +/- 2.2 h respectively. Total body clearance of TMP was 32.8 +/- 10.1 ml/min and SMXA was 21.9 +/- 6.4 ml/min. CAPD clearance of TMP was 2.27 +/- 0.81 ml/min and SMXA was 1.72 +/- 0.93 ml/min. The average peritoneal dialysate concentrations over the 72-hour collection period of TMP and SMXA were 0.9 +/- 0.1 mg/l and 5.3 +/- 0.8 mg/l respectively. A dose of 320 mg TMP and 1600 mg SMX every 48 hours is recommended for CAPD patients with mild to moderate systemic infections.     

Hemofiltration in acute kidney failure. Experiences of a surgical intensive care station

Until recently acute renal failure (ARF) in critically ill patients has been known to have a very poor prognosis, particularly when associated with multiple organ failure (MOF). Mortality rates for ARF in combination with at least two other failing organ systems have ranged over 90%. Despite the use of intermittent hemodialysis no better outcome was possible until continuous arteriovenous hemofiltration (CAVH) was introduced by Kramer in 1977. From several extracorporeal clearance methods we chose to evaluate the pump-driven intermittent venovenous hemofiltration (HF) system in the ICU and its effect on mortality in MOF. PATIENTS and METHODS. Over a period of 39 months we evaluated 63 patients, 58 of them with MOF undergoing altogether 532 sessions of HF. The reason for the development of ARF was prerenal in 47% (circulatory shock, hypovolemia), renal in 43% (septic) and other problems in 10% (ARDS, cardiac failure). After special optimizing therapy for patients with ARF (10), HF was required for treatment as defined by a serum creatinine greater than 3 mg/dl (BUN greater than 150 mg/dl), oliguria of less than 30 ml/h or a creatinine clearance of less than 20 ml/min. Vascular access was obtained by a double lumen venous cannula inserted into the subclavian vein. HF was performed by a machine equipped with 3 roller pumps and an electronic fluid equilibration system using a hollow fiber filter running for 6-8 h. The average flow of ultrafiltrate was 74 ml/min. RESULTS. The average decrease per hemofiltration of creatinine levels was 1.97 +/- 0.77 mg/dl, of BUN 73.5 +/- 28.3 mg/dl. Moreover, we noticed decreasing platelet counts, fibrinogen and osmolarity levels, as well as a slight increase in pH values. Mortality was 37%. DISCUSSION. When comparing HF with other clearance methods such as hemodialysis there are some remarkable advantages: easier handling of the fluid and electrolyte balance; the possibility of total i.v. alimentation in septic, hypercatabolic patients, safe and precise administration of antibiotics, glycosides and sedatives because of their highly predictable and steady elimination rates throughout HF; last but not least, the removal of renal and vasoactive toxins. There was practically no impairment of the cardiovascular system during HF. Our experiences in the ICU show that HF has been successfully used with decreasing mortality. This kind of treatment improved the fate of the critically ill patient with ARF alone or combined with MOF to the extent that the patient's prognosis was excellent if the main surgical problems could be solved.     

Gentamicin removal during intermittent peritoneal dialysis

Gentamicin removal during intermittent peritoneal dialysis was studied in 13 uremic patients. The peak serum level after 80 mg of gentamicin intravenous drip was 6.00 +/- 1.3 micrograms/ml with a serum half-life of 13.6 +/- 4.07 h. The gentamicin dialysate level did not correlate with the corresponding serum concentration. The peritoneal gentamicin clearance (10.0 +/- 3.65 ml/min) correlated with the rate of protein loss, but not with the peritoneal clearances of urea and creatinine. When 4% glucose dialysate was used, the clearance of the drug increased considerably along with the ultrafiltration rate. Adding gentamicin (5 micrograms/ml) to the dialysate resulted in a sustained serum drug level. The mechanism of gentamicin transport through the peritoneal membrane is discussed. The study demonstrated significant removal of gentamicin during intermittent peritoneal dialysis.     

Pharmacokinetics of intravenous and intraperitoneal fosfomycin in continuous ambulatory peritoneal dialysis

Kinetics of fosfomycin were investigated in six patients undergoing continuous ambulatory peritoneal dialysis. Each subject received both an i.v. and an i.p. 1 g dose of fosfomycin with a one week washout between doses. Fosfomycin was assayed by a microbiological diffusion technique. After intravenous injection the fosfomycin serum kinetic parameters were as followed: elimination half-life (t1/2 beta) 38.4 +/- 8.7 h; volume of distribution 0.32 +/- 0.02 l/kg; total plasma clearance 7.0 +/- 1.4 ml/min and peritoneal clearance 3.2 +/- 0.2 ml/min. Dialyzate fosfomycin concentrations reached a maximum mean value of 32.2 +/- 2.8 micrograms/ml at 4 h post-injection and fosfomycin was detectable in dialyzate samples for up to 72 hours post-dosing. After intraperitoneal instillation, fosfomycin appeared in the serum rapidly and the mean peak plasma concentration was 36.2 +/- 2.8 micrograms/ml at the 4th h. The absorption rate (ka) was 0.580 +/- 0.039 h-1 and the absorption of fosfomycin from peritoneal space was 68.4 +/- 6.0%. These data suggest a bidirectional exchange through the peritoneal membrane. Intraperitoneal administration of 1 g either 48 h apart for anephric patients or 36 h apart for patients with residual renal function may achieve therapeutic serum concentrations.     

Middle-molecule oligopeptide kinetics during intermittent hemofiltration in patients with acute kidney failure

Acute renal failure was treated by intermittent hemofiltration in 19 patients (8 males and 11 females), 13 of which survived and 6 died. All of them underwent examinations for kinetics and clearance of middle-mass oligopeptides (MMOP) performed by gel filtration (sephadex G-15) and densitometry in UV light (280 nm) using C phi-24 device. Plasma levels of oligopeptides in acute renal failure were found increased 20-fold. They consisted mainly of MMOP (1000-3000 D) entering the 13th eluate fraction. There appeared a correlation between oligopeptides and creatinine plasma levels. Under hemofiltration lasting for 6.45 hours and replacing approximately total body fluid, nearly all the baseline extracellular oligopeptide pool was removed. The average rate of the filtration reached 127 ml/min, clearance of oligopeptides being 57.9 ml/min or more than 22 1 of fluid per one procedure. Intermittent hemofiltration went in enhanced (8-fold) MMOP generation responsible for residual high levels of them in plasma after the procedure.     

The pharmacokinetics of sufentanil in surgical patients

The pharmacokinetics of sufentanil, a new thienyl analogue of fentanyl, were studied in 10 surgical patients. Sufentanil, 5 micrograms/kg, was given intravenously as a bolus injection and plasma concentrations measured at intervals up to 8 h. Plasma sufentanil concentrations decreased rapidly after injection--98% of the administered dose having left the plasma within 30 min. In 9 of the 10 patients, a tri-exponential equation optimally described the sufentanil concentration decay curve, with average (+/-SEM) half-lives for the rapid (pi) and slow (alpha) distribution phases of 1.4 +/- 0.3 min and 17.7 +/- 2.6 min, respectively. The average terminal elimination (beta) half-life was 164 +/- 22 min. The average value for Vd beta was 2.9 +/- 0.2 1/kg, Vdss 1.7 +/- 0.2 1/kg and total plasma clearance 12.7 +/- 0.8 ml X kg-1 X min-1 (935 +/- 50 ml/min). In one patient, a bi-exponential equation was sufficient to describe the concentration-time data, yielding a distribution half-life of 4.7 min and an elimination half-life of 117 min.     

Pharmacokinetics of unchanged morphine in normal and cirrhotic subjects

Published reports of morphine pharmacokinetics differ, perhaps because of analytical discrepancies and different study protocols. A highly specific radioimmunoassay (N-carboxymethylnormorphine RIA) was used to measure unchanged morphine in plasma in six normal subjects and in eight cirrhotic patients with hypoalbuminemia, hyperbilirubinemia, and prolonged prothrombin time. All subjects received a single intravenous bolus of morphine hydrochloride (0.1 mg/kg). Peripheral blood samples were collected at frequent intervals from 2 min to 36 hr after injection. In cirrhotic patients as compared with normal subjects, terminal half-life of unchanged morphine was longer (201 +/- 39 vs 111 +/- 32 min (mean +/- SD), P less than 0.01) and total body clearance was slower (21 +/- 7.5 vs 33.5 +/- 8 ml X min-1 X kg-1, P less than 0.05). The apparent volume of distribution and the steady-state volume of distribution did not differ in the two groups. In conclusion, cirrhotic patients have a prolonged terminal half-life of unchanged morphine that is attributable to a decrease in total body clearance.     

Pharmacokinetics of vancomycin in patients undergoing hemodialysis with polyacrylonitrile

The pharmacokinetics of vancomycin in patients undergoing dialysis with cuprophane membranes are well known, however little has been reported of the use of polyacrylonitrile membranes in dialysis. We studied, in a crossover design, eight dialysis patients (7 men, 1 woman) aged 30 to 66 years who prospectively received 1 gram of vancomycin i.v. before first dialysis and were subsequently hemodialyzed with cuprophane every second day for a total of three times. A month later trial was repeated using polyacrylonitrile. A mono-compartment model was used to calculated pharmacokinetic parameters. Mean +/- standard deviation of vancomycin clearance varied from 5.2 +/- 2.1 ml/min in the interdialysis period to 9.7 +/- 2.7 ml/min during dialysis with cuprophane and to 58.4 +/- 15.6 ml/min during dialysis with polyacrylonitrile (p less than 0.001). Vancomycin half-life varied from 71.5 +/- 23.0 to 35.9 +/- 9.8 and to 6.1 +/- 1.4 hours, respectively (p less than 0.001). Fractional removal of vancomycin increased from 4% using the cuprophane dialyzer to 34% using the polyacrylonitrile dialyzer (p less than 0.001). Serum vancomycin levels at 100 and 168 hours were higher with cuprophane than with polyacrylonitrile (7.0 +/- 2.2 vs 3.9 +/- 1.2 micrograms/ml) (p less than 0.001). Moreover, the mean levels at 100 hours were suboptimal on polyacrylonitrile. Approximately 208 +/- 53 mg of vancomycin were removed during one polyacrylonitrile dialysis. Thus, those patients who undergo dialysis with polyacrylonitrile and are treated with vancomycin may need supplementary doses post dialysis or to lessen dosage intervals than those traditionally used for dialysis patients since clearance of the drug is significantly higher than with cuprophane dialyzers. Continuous monitoring of vancomycin levels is also recommended.     

The pharmacokinetics of droperidol in anesthetized patients

A pharmacokinetic study of droperidol was performed in ten anesthetized patients receiving an intravenous bolus dose of 150 micrograms/kg of droperidol. Plasma concentrations were measured using a specific radioimmunoassay method. The pharmacokinetics of droperidol can be described according to a three-compartment open model. The mean (+/- SD) half-life for the rapid (t 1/2 pi) and slow distribution t 1/2 alpha) phases was 1.4 +/- 0.5 min and 14.3 +/- 6.5 min, respectively. The mean elimination half-life, t 1/2 beta was 103.8 +/- 20.2 min. The mean (+/- SD) total body clearance was 14.1 +/- 4.4 ml X min-1 X kg-1, and the total apparent volume of distribution (Vd beta) was 2.04 +/- 0.50 l/kg. The short terminal half-life of droperidol does not correlate with the well-known, relatively prolonged duration of its pharmacologic action.     

Deferoxamine and coated charcoal hemoperfusion to remove aluminum in dialysis patients

We studied the in vitro and in vivo characteristics of aluminum (Al) removal by coated charcoal hemoperfusion (HP) in combination with intravenous deferoxamine (DFO). DFO enhanced the clearance of Al by HP in vitro after 180 minutes of perfusion with a solution containing 403.3 +/- 14.0 ng/ml of Al at 150 ml/min. The Al clearance was 139 +/- 1.0 ml/min with DFO and 49 +/- 10.0 ml/min (P less than 0.001) without DFO. Addition of DFO enhanced in vitro Al removal from 5.5 +/- 0.9 mg to 10.0 +/- 1.2 mg (P less than 0.05). During our in vivo studies, an HP device was in series in the dialysis circuit after a Cuprophan hemodialyzer. Eight patients with Al toxicity were studied on twelve occasions. Patients received DFO (40 mg/kg) 40 hours before the study. The total Al clearance with the combined hemodialysis (HD) and HP devices was higher than that obtained by the dialyzer alone at 30 minutes (62 +/- 4.9 ml/min vs. 25 +/- 2.5 ml/min, P less than 0.02) and after 180 to 210 minutes (32 +/- 3.0 ml/min vs. 19 +/- 2.9 ml/min, P less than 0.02). After 120 minutes the Al clearance by the HP device alone was significantly lower than the initial Al clearance by HP. Combined HD plus HP removed 2.9 +/- 0.4 mg of Al, whereas the total removal of Al by HD alone was 1.5 +/- 0.3 mg (P less than 0.01).