Chest
Volume 141, Issue 1, January 2012, Pages 36-42
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Original Research
Pulmonary Vascular Disease
The Effect of Diluent pH on Bloodstream Infection Rates in Patients Receiving IV Treprostinil for Pulmonary Arterial Hypertension

https://doi.org/10.1378/chest.11-0245Get rights and content

Background

Recent studies have reported an increase in catheter-related bloodstream infections (BSIs) and gram-negative BSIs among patients with pulmonary arterial hypertension treated with IV treprostinil. One possible explanation is the neutral pH of the treprostinil diluent compared with the basic pH of epoprostenol. We hypothesized that administering IV treprostinil with epoprostenol diluent will lower the rate of gram-negative BSI.

Methods

We prospectively enrolled patients treated with IV treprostinil and changed the diluent from native diluent to epoprostenol diluent. We compared the incidence of BSI and gram-negative BSI between those receiving IV treprostinil with epoprostenol diluent (n = 25) and those actively receiving IV epoprostenol (n = 61), as well as with a cohort of patients who received IV treprostinil in native diluent (n = 34). Incidence rates of BSI were expressed as a fraction of 1,000 medicine treatment days.

Results

There were similar rates of BSI in those treated with treprostinil with epoprostenol diluent and those treated with epoprostenol (0.32 of 1,000 vs 0.40 of 1,000; P = .79). Also, there were similar rates of gram-negative BSI in these two cohorts (0.08 of 1,000 vs 0.20 of 1,000; P = .46). BSI rates were not statistically different between those treated with treprostinil with epoprostenol diluent and those treated with treprostinil (0.32 of 1,000 vs 0.90 of 1,000; P = .06). However, gram-negative BSIs were significantly lower in patients treated with treprostinil with epoprostenol diluent than in those treated with treprostinil (0.08 of 1,000 vs 0.71 of 1,000, respectively; P = .01).

Conclusions

Patients treated with treprostinil with epoprostenol diluent have a lower incidence of gram-negative BSI than do those treated with treprostinil and a similar rate to those treated with epoprostenol. Changing the diluent of treprostinil to epoprostenol diluent, in combination with the use of water-tight seals throughout the delivery system, appears to be an effective safety measure.

Section snippets

Materials and Methods

This study was performed at the University of Chicago Medical Center (UCMC) and was approved by the institutional review board (IRB No. 13351A). All patients enrolled in this study provided informed consent for entry into our Pulmonary Hypertension Connection registry. The details of this registry have been reported previously.16

Results

Overall, the three cohorts in the study consisted of 25 patients treated with IV treprostinil in epoprostenol diluent, 61 patients treated with IV epoprostenol, and 34 patients treated with IV treprostinil in native diluent from the historical cohort. There were a total of 56,563 treatment days among the three cohorts (12,599 days of IV treprostinil in epoprostenol diluent, 29,889 days of IV epoprostenol, and 14,075 days of IV treprostinil in native diluent).

Baseline characteristics in these

Discussion

In this prospective study of patients with PAH receiving IV prostanoid therapy, the administration of IV treprostinil with the pH-basic epoprostenol diluent resulted in a lower incidence of gram-negative BSI. We found no statistically significant difference in BSI and gram-negative BSI in those treated with IV treprostinil in epoprostenol diluent compared with those treated with IV epoprostenol. These findings highlight the significance of the diluent in infection risk and should ultimately

Limitations

One limitation and potential confounding factor that may have affected our findings is the possible differences among the patient cohorts in terms of catheter care. The historical control cohort of IV treprostinil predated the newest catheter care guidelines and was thus unlikely to have used the closed-hub system or waterproofed connections. Also, all patients in the treprostinil in epoprostenol diluent cohort were reminded to adhere to the catheter care guidelines at the time that their

Conclusions

BSI rates, especially gram-negative infections, in patients with PAH treated with IV treprostinil in epoprostenol diluent are lower than those seen in patients treated with IV treprostinil in its native diluent and similar to those seen in patients treated with epoprostenol. Thus, when treating patients with IV treprostinil in the future, we encourage practitioners to use the alkaline epoprostenol diluent in combination with the use of water-tight seals throughout the delivery system in

Acknowledgments

Author contributions: Dr Rich takes responsibility for the integrity of the work.

Dr Rich: contributed to the design of the study, data analyses, and drafting of the manuscript.

Ms Glassner: contributed to data collection and analyses and manuscript revisions.

Dr Wade: contributed to manuscript revisions.

Ms Coslet: contributed to data collection and manuscript revisions.

Dr Arneson: contributed to data analyses and manuscript revisions.

Ms Doran: contributed to manuscript revisions.

Dr

References (24)

  • D Pittet et al.

    Nosocomial bloodstream infection in critically ill patients. Excess length of stay, extra costs, and attributable mortality

    JAMA

    (1994)
  • M Gomberg-Maitland et al.

    Transition from intravenous epoprostenol to intravenous treprostinil in pulmonary hypertension

    Am J Respir Crit Care Med

    (2005)
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    Funding/Support: This study was supported by an investigator-initiated grant from United Therapeutics.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

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