Michael Sorkin

The Influence of Peritoneal Catheter Exit-Site Infections on Peritonitis, Tunnel Infections, and Catheter Loss in Patients on Continuous Ambulatory Peritoneal Dialysis

The importance of exit-site infections (ESIs) as a source of peritonitis and catheter loss in continuous ambulatory peritoneal dialysis (CAPD) patients is unknown. We collected data on 137 CAPD patients over a 5-year period (2,052 cumulative patient months). Patients with a history of ESIs were more likely to have peritonitis and tunnel infections than patients without a history of ESIs. A larger percentage of patients with a history of ESIs lost catheters and transferred to hemodialysis than those without such a history, independent of the effect of peritonitis. These data confirm the importance of reducing the incidence of ESIs. More information is needed to determine the nature of the relationship between ESIs and peritonitis.

Peritoneal access and related complications in continuous ambulatory peritoneal dialysis.

Over a four-year period, 50 patients underwent continuous ambulatory peritoneal dialysis. After 24 months, 48 percent of the patients continued to receive continuous ambulatory peritoneal dialysis treatment (including those who underwent continuous ambulatory peritoneal dialysis with bottled solutions from 1977 to 1978). Using solutions in plastic bags, 63 percent of patients continued to undergo continuous ambulatory peritoneal dialysis after 24 months. The mortality rate at 24 months was 23 percent overall and 15 percent for those using plastic bags. There was an overall average of 2.4 episodes of peritonitis a year per patient and 1.3 episodes a year per patient from 1979 through 1980, when only the technique with plastic bags was used. The number of days a patient was hospitalized averaged 48 per year, and 37 days per year in 1979 and 1980. Fifty-five percent of catheters remained functional at 24 months. Other complications included 15 hernias, 15 skin and tunnel infections, 12 leaks, and five cuff extrusions. Improved catheters and further reductions in the incidence of peritonitis will most likely result in a decreased number of patients who withdraw from continuous ambulatory peritoneal dialysis therapy.

A Five-Year Study of the Microbiologic Results of Exit Site Infections and Peritonitis in Continuous Ambulatory Peritoneal Dialysis

We studied the culture results from 321 continuous ambulatory peritoneal dialysis (CAPD) related infections (exit site, tunnel infections, and peritonitis) in 137 patients over a 5-year period to determine the contribution of exit site and tunnel infections to peritonitis and catheter loss. Seventeen percent of peritonitis episodes were associated temporally and by microbiologic results with exit site or tunnel infections. Twenty-one percent of exit site and tunnel infections and 20% of peritonitis episodes resulted in catheter loss. Peritonitis due to Staphylococcus aureus was more likely to be associated with an exit site or tunnel infection and was more likely to result in loss of the catheter than peritonitis due to Staphylococcus epidermidis. Peritonitis and exit site infections due to Pseudomonas sp also frequently resulted in catheter removal. We found that exit site infections cause significant morbidity in CAPD patients. Further studies in this area are needed.

Catheter Infections as a Factor in the Transfer of Continuous Ambulatory Peritoneal Dialysis Patients to Hemodialysis

The effect of peritoneal catheter infections on the transfer of continuous ambulatory peritoneal dialysis (CAPD) patients to hemodialysis over a 9-year period were examined. Twenty-seven percent (68/247) of all patients were transferred permanently to hemodialysis after a mean of 15 +/- 14 months of CAPD. An additional 29% transferred temporarily one or more times during the study period (mean time of peritoneal dialysis, 35 +/- 23 months). The reasons for permanent transfer to hemodialysis were catheter infections (15/68, 22%), peritonitis (13/68, 19%), catheter infections associated with peritonitis (10/68, 15%), patient preference (9/68, 13%), mechanical problems (4/68, 6%), noncompliance (7/68, 10%), inadequate clearance or ultrafiltration (6/68, 9%), with other reasons for the remainder (4/68, 6%). Temporary transfers to hemodialysis were also mainly due to catheter infections (32%), peritonitis (23%), and simultaneous catheter infections and peritonitis (24%). Catheter infection rates were much higher in the groups that permanently and temporarily were transferred to hemodialysis in comparison with those patients who remained on peritoneal dialysis. We conclude that catheter infections are a leading cause of both temporary and permanent transfer of CAPD patients to hemodialysis.

Analysis of continuous ambulatory peritoneal dialysis-related pseudomonas aeruginosa infections

The outcomes of all continuous ambulatory peritoneal dialysis-related infections due to Pseudomonas aeruginosa (n = 33) were analyzed and compared with the outcomes of infections due to all other microorganisms (n = 663) over a seven-year period. There were 16 catheter infections (exit site or tunnel infection or both), seven episodes of peritonitis, and 10 episodes of catheter infections associated with peritonitis due to P. aeruginosa. Catheters were removed in 58 percent (19 of 33) of the infections due to P. aeruginosa, but in only 16 percent (104 of 663) of the infections due to other organisms (p less than 0.01). All P. aeruginosa catheter infections associated with P. aeruginosa peritonitis resulted in catheter loss. P. aeruginosa catheter infections not associated with peritonitis also often did not resolve with antibiotic therapy (nine of 16 or 56 percent of catheters removed compared with 42 of 317 or 13 percent of catheters removed for other organisms, p less than 0.01). However, P. aeruginosa peritonitis episodes that were not associated with a catheter infection were no more likely to result in catheter loss than were peritonitis episodes due to other organisms (one of seven compared with 37 of 256, 14 percent for both). It is concluded that catheter infections due to P. aeruginosa with or without associated peritonitis usually require catheter removal. Conversely, P. aeruginosa peritonitis without a catheter infection often does not require catheter removal.

The Effect of the Y-Set on Catheter Infection Rates in Continuous Ambulatory Peritoneal Dialysis Patients

We hypothesized that catheter infections in continuous ambulatory peritoneal dialysis (CAPD) patients may be reduced with a disconnect system. We examined this theory in 116 CAPD patients over a 2-year period. In CAPD patients who switched to the Y-set (n = 22), the catheter infection rate decreased from one per 13 patient-months to one per 26 patient-months (P = 0.05), whereas the catheter infection rate in matched controls (n = 22) remained unchanged. Patients who began CAPD using the Y-set (n = 36) had catheter infection rates of one per 14 patient-months versus one per 8 patient-months in matched controls (n = 36, P = 0.05). Staphylococcus aureus was the most common cause of catheter infections in both groups of patients. However, Pseudomonas aeruginosa replaced Staphylococcus epidermidis as the second most common cause of catheter infections in the patients using the Y-set. The number of catheters that had to be removed due to catheter infections, mainly those due to S aureus or P aeruginosa, was the same in the Y-set and control groups. We conclude that the Y-set system is associated with reduced numbers of catheter infections, but that catheter loss from catheter infections remains a serious problem.

Triazolam protein binding and correlation with alpha‐1 acid glycoprotein concentration

On two occasions separated by a minimum of 1 wk, plasma was obtained from 12 patients (aged 18 to 73 yr) on dialysis after an overnight fast. Samples were assayed for albumin and α1‐acid glycoprotein (AGP) concentrations. 14C‐Triazolam was added to each sample to a final concentration of 5 ng/ml. Protein binding was determined by equilibrium dialysis. Unbound triazolam ranged from 6.4% to 15.4% (X̄ = 10.0%). AGP concentrations ranged from 71.8 to 205.1 mg% (X̄ = 123.4 mg%). Triazolam binding ratio (bound/unbound concentration) correlated with AGP concentration (r2 = 0.69) but not with albumin concentration, age, or sex. This correlation was verified by adding AGP in varying amounts to control plasma.

Effects of end-stage renal disease and aluminum hydroxide on temazepam kinetics

The kinetics of temazepam, 30 mg, were evaluated in 11 patients with end‐stage renal disease. Age ranged from 18 to 65 years. On two occasions separated by 1 week, single oral 30 mg doses of temazepam were given once with water (TM) and once with 3600 mg aluminum hydroxide gel (TM + AHG). There were no significant differences in the maximum plasma concentration, the time to reach maximum concentration, or elimination rates between TM and TM + AHG dosing. In approximately half the subjects there were secondary temazepam peak concentrations. In the remaining subjects, temazepam elimination was biphasic, with the terminal t½ ranging from 11 to 77 hours. There was a lag time before absorption in all subjects. The percent free temazepam in plasma from dialysis subjects ranged from 4.4% to 8.8% (X̄ = 5.9%). Compared with literature reports of subjects with normal renal function, the maximum plasma concentration was lower and the percent free temazepam was higher in dialysis subjects. When sedation score was plotted against plasma temazepam concentration, there was clockwise hysteresis consistent with tolerance or adaptation to effects of the drug. Thus aluminum hydroxide gel does not affect temazepam absorption. The clinical significance of the low plasma concentrations and high free temazepam fraction in dialysis subjects is uncertain.

Effects of dipyridamole on peritoneal clearances

To see if oral dipyridamole increases peritoneal clearances in humans undergoing peritoneal dialysis, two types of double-blind clinical studies were undertaken. In a single-dose study, 7 patients were randomized to take dipyridamole or placebo early in a peritoneal dialysis with 2 L, hourly cycles; later in the same dialysis a crossover administration was studied. In a multidose study, 17 patients were randomized to take dipyridamole or placebo three times daily and clearance studies were performed on days 1, 4, and 8 during 2 L, hourly peritoneal dialysis cycles. Neither the single dose of dipyridamole or placebo significantly altered drainage volumes, clearances, or dialysate protein from control periods. In the multidose study, mean values on dipyridamole or placebo were not significantly changed from respective baseline predrug values. Mean values with dipyridamole and placebo usually were not significantly different. Dipyridamole did not appear to improve peritoneal clearances even with repeated ingestion.

Aminoglycosides, Ototoxicity, and Peritoneal Dialysis

The ease of administering aminoglycosides intraperitoneally has made it a common practice in patients treated with peritoneal dialysis who require this therapy. Their nephrotoxic and ototoxic potential is well known. Although renal failure is not usually a concern for those receiving these drugs intraperitoneally, audiovestibular damage, often irreversible and disabling, may occur and can be a major problem. Most nephrologists prescribing intraperitoneal (or any parenteral) aminoglycosides can recall patients who have developed functionally significant ototoxicity during a “routine” course of treatment. Based on the type of ototoxicity produced, the aminoglycosides can be divided into two groups. Streptomycin, gentamicin, and tobramycin attack the vestibular apparatus while kanamycin, neomycin, netilmicin, and amikacin produce auditory impairment. The distinction is not perfect, however, and either or both functions may be affected by either group. Gentamicin and tobramycin are the aminoglycosides most commonly used intraperitoneally, but all the aminoglycosides behave similarly. A concentrationdependent transfer across the normal peritoneum results in the absorption of about 50% of the “loading” dose during a 4-6 hour dwell (I) . Inflammatory changes which occur in peritonitis significantly increase the absorption (2). A constant and predictable plasma concentration can be easily achieved by placing appropriate doses of drug in the dialysis solution. Unfortunately, continuous therapeutic concentrations of the aminoglycosides in plasma may not be an advantage. Continuous therapeutic plasma concentrations are more toxic than high peak concentrations followed by very low trough concentrations (3). Duration of treatment, total dose, and preexisting damage to the audiovestibular apparatus also play a role in ototoxicity, although the relative importance of these factors is not known. Other risk factors for ototoxicity are not well established. Exposure to other ototoxic agents or even noise may produce damage that might increase the risk for aminoglycoside ototoxicity. Renal failure itself may have inherent ototoxicity (4). Unfortu-