Theophylline in asthma

The pharmacology of cefamandole in seven patients with stable renal insufficiency and in eight patients undergoing hemodialysis was determined. All patients had creatinine clearances less than 5 ml/min. The half-life of cefamandole in those patients with stable chronic renal failure was 7.7 +/- 2.2 h. The mean venous level 1 h after intravenous injection of a 1-g dose was 85.3 +/- 32.0 mug/ml. The mean venous half-life of cefamandole during hemodialysis was 6.1 h. The venous serum level after 5.5 of hemodialysis was 50.4 +/- 20.8 mug/ml. The mean coefficient of extraction was 0.155, and the mean clearance was 34.7 ml/min. The time interval between doses of cefamandole administered intravenously should be lengthened to 24 h in the presence of stable renal failure. No major change in dosage schedule is necessary for patients undergoing dialysis.     

Pharmacokinetics of gadodiamide injection in patients with severe renal insufficiency and patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis

RATIONALE AND OBJECTIVES: The authors performed this study to evaluate the pharmacokinetics, dialysability, and safety of gadodiamide injection in patients with severely reduced renal function not treated with renal replacement therapy and patients undergoing hemodialysis or continuous ambulatory peritoneal dialysis. MATERIALS AND METHODS: Twenty-seven patients--nine with severely reduced renal function (glomerular filtration rate, 2-10 mL/min), nine undergoing hemodialysis, and nine undergoing continuous ambulatory peritoneal dialysis--were followed up for 5, 8, and 22 days, respectively, after receiving gadodiamide injection (0.1 mmol per kilogram body weight). RESULTS: Gadodiamide injection caused no changes in renal function. In patients with severely reduced renal function, the elimination half-life of gadodiamide injection was prolonged (34.3 hours +/- 22.9) compared with data in healthy volunteers (1.3 hours +/- 0.25). An average of 65% of the gadodiamide injected was eliminated during a hemodialysis session. After 22 days of continuous ambulatory peritoneal dialysis, 69% of the total amount of gadodiamide was excreted; this reflects the low peritoneal clearance. In all patients, no metabolism or transmetallation of gadodiamide was found. There were no contrast material-related adverse events. CONCLUSION: Gadodiamide is dialysable and can safely be used in patients with severely impaired renal function or those undergoing hemodialysis or continuous ambulatory peritoneal dialysis. No precautions to increase the elimination are necessary.     

Ambulatory blood pressure monitoring in dialysis patients and estimation of mean interdialytic blood pressure

To define blood pressure (BP) patterns and control in dialysis patients, 48-hour ambulatory BP monitoring was performed in 36 hemodialysis and 18 peritoneal dialysis patients. Monitoring began during a dialysis session for hemodialysis patients. Data revealed significantly lower diastolic BP (DBP) and lower diastolic load (percentage of diastolic values > 90 mm Hg) in hemodialysis patients compared with peritoneal dialysis patients (80.6 mm Hg v 88.8 mm Hg, respectively, [P < 0.03] and 26% v 45%, respectively [P < 0.03]) for the 48-hour period. When the 2 days were analyzed separately, the difference in diastolic pressures and loads was significant only for the first (dialysis) day. Similarly, trends toward lower systolic BP (SBP) and systolic load in hemodialysis patients existed throughout monitoring and were greater in magnitude during the first day. BP data were fit to a random-coefficient growth curve model to detect periodicity. This sensitive model did not detect diurnal variation of BP in either group. The incidence of hypotension did not differ between the two groups (2.0% v 1.0% of total observations, hemodialysis v peritoneal dialysis). In the hemodialysis group, the proportion of hypotensive observations was significantly greater during the 4 hours postdialysis compared with other periods (5.6% v 1.6%; P < 0.02), a finding that likely reflects the practice of holding antihypertensives until after hemodialysis. However, patient diaries did not reflect hypotensive symptoms during this time. In the hemodialysis group, mean BP and predialysis BP did not correlate with interdialytic sodium load or weight gain. Predialysis and postdialysis BP (recorded by dialysis nurses) correlated significantly with mean BP. Predialysis SBP overestimated mean SBP by an average of 10 mm Hg, while postdialysis SBP underestimated mean SBP by an average of 7 mm Hg. To create formulas to estimate mean SBP and DBP in hemodialysis patients, multiple linear regression was used to model these variables against age, sex, race, and average prehemodialysis/posthemodialysis BP. The model achieved a high degree of fit (r2 = 0.72 for SBP; r2 = 0.65 for DBP), demonstrating that prehemodialysis and posthemodialysis BP can be used to predict mean BP in hemodialysis patients. In summary, our data show the absence of a diurnal variation of BP in dialysis patients and lower BP in hemodialysis patients compared with peritoneal dialysis patients. Among hemodialysis patients, more hypotension occurred after dialysis compared with other periods, and predialysis and postdialysis BP can be used to model mean BP levels.     

Dialysis in the treatment of renal failure in patients with liver disease

The value and effects of treating renal failure by dialysis are analyzed in a series of 84 patients with various types of liver disease. Although none of the 25 patients with cirrhosis survived, six of 50 with fulminant hepatic failure recovered completely as did seven of nine patients with renal failure secondary to extrahepatic biliary tract obstruction or with liver and renal damage following episodes of severe hypotension. Dialysis was required for seven weeks before diuresis occurred in one patient in the latter group. Both peritoneal and hemodialysis satisfactorily controlled plasma urea and creatinine levels, except in patients with fulminant hepatic failure in whom this was only achieved by hemodialysis. Complications of dialysis were most common in patients with cirrhosis and fulminant hepatic failure and included hypotension, gastrointestinal bleeding, and intraperitoneal sepsis. Overall, the results show that dialysis is only worth attempting in those patients in whom recovery of the underlying liver lesion is possible, and even then treatment for prolonged periods may be necessary.     

Intermittent intraperitoneal ceftazidime dosing in end-stage renal disease

Infections are a common problem in dialysis patients. As hospital stay shortens, many require outpatient antibiotic therapy. Parenteral administration may pose considerable logistic and financial burdens, whereas daily intraperitoneal dosing increases the risk of contamination. Ceftazidime, with its long half-life, may provide adequate dosing when administered intraperitoneally thrice weekly. The authors therefore studied the kinetics of a 2 g loading dose followed by a 1.5 g dose every 48 hr in seven stable chronic peritoneal dialysis patients. In vitro stability at 4 degrees C (measured by high performance liquid chromatography) was 91% at 120 hr. Peak serum concentration (60 +/- 22 microg/ml) was reached at 4.9 +/- 2.2 hr. Serum values were 25 +/- 9 and 8 +/- 3 microg/ml at 24 and 48 hr, respectively. However, median trough levels at 48 hr in dialysate were significantly lower than in serum (2.8 vs 8.5 microg/ml, respectively; p = 0.0425). Pharmacokinetic parameters were as follows: bioavailability (F), 88% +/- 8%; volume of distribution at steady state (VDss), 20 +/- 8 L; absorption half-life (T1/2(abs)), 1.8 +/- 1.3 hr; elimination half-life (T1/2(el)), 11.4 +/- 4.5 hr; and clearance (CL), 22 +/- 10 ml/min. Intraperitoneal ceftazidime every 48 hr is a practical alternative to parenteral therapy of nonperitoneal infections. In peritonitis, whether increased permeability results in improved dialysate levels remains to be defined.     

Bacteremia complicating peritonitis in peritoneal dialysis patients

Bacteremia is a rare complication of peritonitis in end-stage renal failure (ESRF) patients treated by peritoneal dialysis. Three of our ESRF patients on peritoneal dialysis developed bacteremia during a peritonitis episode (1/19 peritonitis episodes). In 2 cases, the responsible organism was Escherichia coli and peritonitis was most likely associated with infection of the biliary tract. The 3rd patient had a perforation of the colon and Klebsiella spp. was the infective organism. Only the last patient survived but had to be transferred to hemodialysis. Bacteremia during peritonitis is infrequent in peritoneal dialysis patients and it appears to be related to other intra-abdominal events.     

Estrogen-stimulated neurophysin in chronic renal failure

Estrogen-stimulated neurophysin (ESN) was determined by radioimmunoassay in three groups of patients with chronic renal failure: predialysis patients, patients on hemodialysis and patients on continuous ambulatory peritoneal dialysis. ESN levels were significantly elevated in all patients. ESN of these patients is undistinguishable from highly purified pituitary ESN. Immunological and physicochemical analyses of ESN in patients with renal failure suggest that the elevated plasma level is due to a failure of renal clearance. In addition, heterogeneity of urinary ESN, revealed by multiple immunoreactive peaks after gel filtration, indicates altered renal metabolism.     

Thyroid dysfunction in uremia: evidence for thyroid and hypophyseal abnormalities

Disturbances in thyroid function and a high prevalence of goiter develop in patients on chronic hemodialysis. This study shows that in patients on dialysis, mean serum thyroxine and triiodothyronine levels are lower than normal. Patients with chronic renal failure not on dialysis, have mean serum thyroxine levels similar to normal subjects and low mean serum triiodothyronine levels. However, both serum thyroxine and triiodothyronine concentrations decrease as the renal failure worsens. In addition, both groups of patients with renal failure have a decreased serum thyroxine response to oxogenous thyrotrophin and a diminished serum thyrotrophin response to thyrotrophin-releasing hormone. These data suggest the presence of an intrathyroidal and an hypophyseal defect in uremic patients. Although serum iodide concentrations are elevated, there is no correlation between the level of serum iodide and the degree of renal failure. Therefore, we have no direct evidence that iodide excess is responsible for the abnormalities observed.     

Acetohexamide hypoglycemia: treatment by peritoneal dialysis

Acetohexamide hypoglycemia in a patient with renal failure has been successfully treated by peritoneal dialysis. Peritoneal dialysis was done in such a patient, and specimens of serum were collected to measure levels of acetohexamide and its main active metabolite, hydroxyhexamide. During dialysis, hypoglycemia was corrected. After 17 1/2 hours of dialysis, serum acetohexamide level was essentially unchanged. Serum hydroxyhexamide level had decreased at a slower rate than the rate of decrease previously measured in a uremic patient not on dialysis. Although peritoneal dialysis may correct the hypoglycemia, the data suggest that acetohexamide and hydroxyhexamide are not dialyzable. Due to these problems this drug should not be used in patients with chronic renal failure. The drug of choice to control hyperglycemia in patients with renal insufficiency is insulin. If for any reason insulin cannot be used, tolbutamide is the oral hypoglycemic agent of choice.     

Peritoneal dialysis. Current status

Peritoneal dialysis has a definite role in the treatment of acute or chronic renal failure and certain fluid and electrolyte disturbances. Its major advantages are simplicity and availability. On the other hand, it is less effective and causes more patient discomfort than hemodialysis. Many factors enter into the decision to use one method of dialysis or the other, and the two should be considered complementary. The numerous complications that may occur during peritoneal dialysis can be avoided by careful attention to technical details. With the recent development of indwelling catheters and automatic cycling devices, long-term peritoneal dialysis is being used increasingly and successfully in the home, particularly in patients for whom home hemodialysis is difficult or inappropriate.     

Serotonin inhibits nitric oxide synthesis in rat vascular smooth muscle cells stimulated with interleukin-1

The elimination half-life of fluoride is significantly increased in patients with chronic renal failure. This led us to conduct a study of variations of its plasma levels in 35 patients receiving dialysis treatment. In this population, there is a gaussian distribution of the values before and after the hemodialysis session, with a significant decrease in the averages. Furthermore, there is a highly significant correlation between fluoride levels before and after the dialysis session (P < 0.00001), and also between the amount of time in hemodialysis (in months) and the average fluoride level before dialysis (r = 0.624; P = 0.008). The presence of a group of patients consuming fluoride waters such as Vichy St-Yorre Water was easily identified by their excessive fluoride levels (above 100 micrograms/l), which could have a tendency to increase the risks of this group.     

Neurotoxicity associated with acyclovir in end stage renal failure

AIMS: To alert practitioners to the danger of acyclovir neurotoxicity occurring in the presence of renal failure. METHODS: Two case reports of acyclovir neurotoxicity in the patients on continuous ambulatory peritoneal dialysis. RESULTS: In one case neurotoxicity resulted from the use of a dosage regimen that would be appropriate in patients with normal renal function. In the other case, neurotoxicity occurred even though a reduced dose of acyclovir was given. Supportive management resulted in a complete recovery. CONCLUSIONS: In patients with end stage renal failure with varicella zoster infections, when acyclovir is prescribed the loading dose should be 400 mg and the maintenance dose should be 200 mg twice daily.     

Bradycardia-induced syncope

Vascular surgeons well versed in peritoneal dialysis applications understand the importance of this modality among the limited options afforded to patients in renal failure. Peritoneal and hemodialysis strategies are interdependent and should be considered in concert. Careful assessment often shows that patients with diminishing vascular access have been overlooked as viable peritoneal dialysis candidates. This chapter summarizes peritoneal dialysis in terms of its history, physiological principles, indications, contraindications, catheter placement, types of administration, and the identification and management of complications.     

Change of platelet function after the beginning of repeated hemodialysis treatment in patients with uremia

The disturbances of platelet function in end-stage renal failure varies in dialysed and non-dialysed patients. We examined some platelet function in 11 uremic patients treated conservatively (TC) and, again in the same patients, 3-month after the beginning of repeated hemodialysis treatment (HD). The blood samples were taken before hemodialysis. In TC patients normal platelet count, prolonged bleeding time, normal platelet aggregation, unchanged PF4 activity and decreased PF3 availability were shown, compared with control group. In HD patients also normal platelet count and prolonged bleeding time were noted, but increased platelet aggregation, increased PF4 activity and PF3 availability were observed, compared with control group and with TC patients. We conclude that in TC patients rather decreased platelet function was observed; after the beginning of hemodialysis treatment some platelet function became significantly enhanced, which suggests platelet activation. Moreover, in HD patients the disturbances of platelet function before dialysis were shown, then it is possible that platelet activation persists in interdialytic period.     

Pharmacokinetic study of an oral cephalosporin, cefdinir, in hemodialysis patients

The pharmacokinetics of cefdinir were investigated in six hemodialysis patients. For the present study, two tests were carried out, one with 4 h of hemodialysis and the other without hemodialysis. Cefdinir was given orally to each patient in a dose of 100 mg, and blood was collected serially for 48 h after dosing in the test without dialysis and for 72 h in the test with dialysis. In the test without dialysis, the maximum plasma concentration (Cmax) was 2.36 +/- 0.53 micrograms/ml (mean +/- standard deviation) and the time to Cmax was 9.00 +/- 2.45 h. The terminal elimination half-life (t1/2) and area under the concentration-time curve (AUC) were 16.95 +/- 1.20 h and 69.05 +/- 14.84 micrograms.h/ml, respectively. In the test with dialysis, t1/2 during hemodialysis decreased approximately to one-sixth of that obtained in the test without dialysis, although t1/2 in the latter elimination phase did not differ from that in the nondialysis test. AUC was reduced to 43% of that in the test without dialysis. The fractional removal of cefdinir by hemodialysis was 61%. These findings indicate that clearance of cefdinir is prolonged in patients with renal failure, and cefdinir is well removed by introduction of hemodialysis, although t1/2 (during hemodialysis) and AUC were two and eight times higher than the data previously reported for healthy volunteers, respectively. The pharmacokinetic data suggest that 100 mg of oral cefdinir once a day would result in a sufficient concentration in plasma in hemodialysis patients, but this remains to be confirmed by multiple-dose studies.     

Single-dose pharmacokinetics of teicoplanin during hemodialysis therapy using high-flux polysulfone membranes

Teicoplanin is a new glycopeptide antibiotic with potent activity against Gram-positive bacteria. It has been considered to be non-dialyzable due to its high molecular weight (1875-1891 d) and high protein binding (89%). Therefore, a reduced dose was recommended for patients on hemodialysis therapy, with the loading dose being followed by a considerably lower maintenance dose and/or extension of the interval between doses. The present study was performed to evaluate the pharmacokinetics of teicoplanin during hemodialysis therapy using high flux membranes. The pharmacokinetic parameters of teicoplanin were studied in 15 patients with chronic renal failure on hemodialysis. A high flux polysulfone membrane (ultrafiltration coefficient of 40 ml/h/mmHg) was used. Teicoplanin was administered at a dosage of 10 mg.kg-1 body weight in 100 ml isotonic saline solution during the first 10 minutes of hemodialysis therapy. Pharmacokinetic analysis was performed using a three compartment analysis. After a single dose of teicoplanin plasma peak levels were 26.4 +/- 12.0 micrograms/mL (mean +/- SD) after 30 minutes. Teicoplanin concentrations rapidly declined to a nadir of 6.1 +/- 2.5 micrograms/mL at the end of the 3.5-hour session dialysis. Extracorporeal clearance was 39.7 +/- 24.5 mL/min. Removal of 19.3 +/- 7.7% of the drug was estimated if infused during hemodialysis. T 1/2 alpha were 0.37 +/- 0.25 hrs, t 1/2 beta 20.1 +/- 7.1 hrs, and t 1/2 gamma 549.7 +/- 210.5 hrs. We conclude that teicoplanin levels are reduced to a subtherapeutic range during one single high-flux dialysis session if the drug is administered during hemodialysis. Thus, in contrast to previous suggestions relevant amounts of teicoplanin are removed during hemodialysis and thus teicoplanin cannot be viewed as non-dialyzable drug. We recommend obligatory drug monitoring to achieve therapeutic plasma concentrations.     

Pharmacokinetics and bactericidal activity of a single daily dose of netilmicin in the treatment of CAPD-associated peritonitis

Single daily dosage of netilmicin is generally accepted in systemic infections, due to biphasic bactericidal activity and prolonged postantibiotic effect of aminoglycosides. Since little is known about the efficacy of single daily intraperitoneal application of netilmicin in the treatment of CAPD-associated peritonitis, we conducted this prospective study. Seven patients with CAPD-associated peritonitis were treated with a single daily dose of netilmicin (loading dose 1.5 mg/kg, followed by 40 mg/21 bag/day). Serum and intraperitoneal levels as well as bactericidal activity of netilmicin against Acinetobacter baumanii, E. coli and Pseudomonas aeruginosa were measured for 48 hours. Serum and peritoneal levels widely varied among the patients due to different interindividual plasma clearance of netilmicin. The intraperitoneal antibacterial action of netilmicin was decreased, more over, substantial differences in the bactericidal activity were found among the patients. However, with high initial netilmicin levels sufficient bactericidal activity was found for Acinetobacter and E. coli, but not for Pseudomonas aeruginosa. Hence, a single daily dosage of netilmicin can be a suitable treatment of CAPD-associated peritonitis, only if the dose is adapted according to the first serum and peritoneal levels. In infections with Pseudomonas aeruginosa higher peritoneal levels of netilmicin and the combination with other antibiotics will be needed for a sufficient peritoneal bactericidal activity.     

Type of hemodialysis and preference for behavioral involvement: Interactive effects on adherence in end-stage renal disease.

Examined the effects of hemodialysis type (staff controlled, in center vs patient controlled, home) and patient preference for behavioral involvement on adherence and emotional adjustment in 53 adult patients with end-stage renal disease. Measures included the Krantz Health Opinion Survey and the Beck Depression Inventory. Higher levels of preference for behavioral involvement were associated with better dietary adherence (i.e., lower serum potassium) for Ss receiving dialysis at home but worse dietary adherence for Ss receiving treatment in a dialysis center. A similar, though weaker, patient by treatment type matching pattern was observed for fluid-intake adherence (i.e., interdialytic weight gain). Self-reported depression did not seem to affect adherence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Control of clofibrate toxicity in uremic hypertriglyceridemia

A daily dose of 1.5 to 2.0 gm of clofibrate lowers serum triglyceride (TG) levels in patients with normal renal function but causes muscle toxicity and elevated creatine phosphokinase (CPK) levels in patients with long-term renal failure. Plasma clofibrate disappearance is prolonged as much as seven times normal in severely uremic patients. A marked reduction in the standard 14 gm/wk clofibrate dose to a total dose of 1.0 to 1.5 gm/wk effectively lowered serum TG levels (--28%, p less than 0.02) in hypertriglyceridemic hemodialysis patients without toxicity. The serum clofibrate level at this dose was comparable to that in hypertriglyceridemic nonuremic patients receiving 14 gm/wk of clofibrate. The dose of clofibrate administered to hemodialysis patients can be adjusted to avoid toxicity and provide the desired therapeutic effect by monitoring serum CPK and TG levels.     

Effects of paramagnetic cations on the nonexponential spin-lattice relaxation of rare spin nuclei in solids

Absolute and functional iron deficiency is the most common cause of epoetin (recombinant human erythropoietin) hyporesponsiveness in renal failure patients. Diagnostic procedures for determining iron deficiency include measurement of serum iron levels, serum ferritin levels, saturation of transferrin and percentage of hypochromic red blood cells. Patients with iron deficiency should receive supplemental iron, either orally or intravenously. Adequate intravenous iron supplementation allows reduction of epoetin dosage by approximately 40%. Intravenous iron supplementation is recommended for all patients undergoing haemodialysis and for pre-dialysis and peritoneal dialysis patients with severe iron deficiency. During the maintenance phase (period of epoetin therapy after correction of iron deficiency), the use of low-dose intravenous iron supplementation (10 to 20 mg per haemodialysis treatment or 100 mg every second week) avoids iron overtreatment and minimises potential adverse effects. Depending on the degree of pre-existing iron deficiency, markedly higher iron doses are necessary during the correction phase (period of epoetin therapy after correction of iron deficiency) [e.g. intravenous iron 40 to 100 mg per haemodialysis session up to a total dose of 1000 mg]. The iron status should be monitored monthly during the correction phase and every 3 months during the maintenance phase to avoid overtreatment with intravenous iron.