Temperature Variations around Medication Cassette and Carry Bag in Routine Use of Epoprostenol Administration in Healthy Volunteers

<div><h3>Background</h3><p>According to several treatment guidelines, epoprostenol is an important treatment option for pulmonary arterial hypertension. However, the pharmacokinetic characteristics and poor stability of epoprostenol at room temperature make its administration challenging. We therefore studied temperature fluctuations between the drug administration cassette and atmosphere to promote the safe use of epoprostenol.</p> <h3>Methods and Findings</h3><p>Five healthy volunteers carried a portable intravenous infusion pump attached to a medication cassette containing saline in a bag during their ordinary activities over 16 days during which the mean atmospheric temperature was 29.6±1.5°C. The temperature around the medication cassette was not less than 25°C on any occasion, and the mean period over 24 h during which the temperature around the cassette exceeded 35°C and 40°C was 96.9±156.4 min and 24.4±77.3 min, respectively. Significant correlations were observed between the temperatures outside the bag and around the cassette, as well as between temperatures around the cassette and of the saline solution in the cassette (r = 0.9258 and 0.8276, respectively). There were no differences in the temperatures outside the bag or around the cassette with respect to the bag material.</p> <h3>Conclusions</h3><p>Temperatures around a medication cassette and outside the bag containing the medication increase with sunlight exposure. The temperature around cassettes used for administering epoprostenol must therefore be kept low for as long as possible during hot summer conditions to maintain the drug stability.</p> </div

Temperature changes around the medication cassette.

<p>Temperature changes around the medication cassette.</p

Atmospheric temperature and time durations when the temperature around the cassette exceeded 25°C, 35°C, and 40°C.

<p>Atmospheric temperature and time durations when the temperature around the cassette exceeded 25°C, 35°C, and 40°C.</p

Difference in temperature correlation by material of the bag.

<p>Correlations between temperature outside the bag and temperature around the cassette in (A) cloth bags and (B) leather/synthetic leather bags in daytime (×) and nighttime (○). The relativity of temperatures within groups was analyzed using the CORR procedure. Regression curves from plotted graphs were calculated using the GLM procedure.</p

Typical protocols for rapid and slow initiation of therapy.

<p>The blue and red lines indicate the standard dosing schedules for the slow- and rapid-initiation IVI epoprostenol therapy, respectively.</p

Patient inclusion.

<p>Flow chart describing patient inclusion protocol. Within the study period (2001–1013) 58 patients with PAH received IVI epoprostenol in Keio University hospital. Among the group, 16 patients were excluded from this study because they were lost to follow up, had missing protocols, died, or underwent a lung transplantation soon after the initiation of IVI epoprostenol.</p

Improvements in hemodynamic data following IVI epoprostenol therapy.

<p>At follow up, the rapid-initiation group achieved significant improvements in mPAP, PVR and CI compared with the slow-initiation group, while there were no significant differences at baseline. mPAP: mean pulmonary artery pressure, PVR: pulmonary vascular resistance, CI: cardiac index, NS: not significant</p

Baseline clinical characteristics.

<p>Plus–minus values are means ± SE.</p><p>* <i>P</i> values indicate the statistical difference between slow and rapid initiation of therapy.</p><p>PAH, pulmonary arterial hypertension; IPAH, idiopathic pulmonary arterial hypertension; HPAH, heritable pulmonary arterial hypertension; CTD-PAH, PAH associated with connective tissue disease, ES, Eissenmenger’s syndrome; NYHA, New York Heart Association; PDE5i, phosphodiesterase type 5 inhibitor; ERA, endothelin receptor antagonist.</p><p>Baseline clinical characteristics.</p

Cumulative epoprostenol dose for each patient.

<p>Bars show the cumulative dose of epoprostenol per body weight within the initial 180 days. The blue and red bars describe each patient’s cumulative dose in the slow- and rapid-initiation groups, respectively.</p

Receiver operating characteristic (ROC) curves for pentraxin 3 (PTX3).

<p>The area under the ROC curve was 0.866 (95% confidence interval 0.805–0.928). The star indicates the threshold concentration of 2.84 ng/mL PTX3 that maximized true-positive and false-negative results (sensitivity 74.0%, specificity 84.0%).</p