PHP is a chemically modified hemoglobin which scavenges nitric oxide (NO). This study examined the effect of PHP on catecholamine use, morbidity and mortality in patients with distributive shock.
Phase II multicenter randomized (1:1) placebo controlled trial of standard care plus PHP vs placebo (Plasma-Lyte A“) in patients with 2 of 4 SIRS criteria and persistent catecholamine dependence despite adequate fluid resuscitation (PCWP >12 mm Hg). Patients with significant cardiac disease, burns or trauma within 48h, those deemed moribund or with underlying conditions likely to be rapidly fatal were excluded. After informed consent was obtained, PHP [0.25 ml (20 mg)/kg/h] or an equal volume of placebo was administered for up to 100h and pressors and ventilatory support were weaned by protocol. Data are presented as mean (±SD).
Sixty-two patients were randomized to PHP (n=33) or placebo (n=29). Age, gender, etiology of shock (sepsis in 94%) and APACHE II scores (33.1±8.3 vs 30.0±7.0) were similar in PHP and placebo patients, respectively. Plasma nitrite plus nitrate levels were markedly elevated in both groups. PHP infusion increased systemic BP (p<0.01) within minutes. Overall 28 day mortality was similar (58%PHP vs 59% placebo) but PHP survivors tended to be weaned from pressors faster (p=0.07, TablePHP survivors (n=14)Placebo survivors (n=12)Catecholamine withdrawal, h13.7 (±8.2)26.3 9±21.4)Vent free, days17.4 (±9.9)10.4 (±10.2)ICU stay, days13.6 (8.6)17.9 (±8.2)Hosp D/C by day 28, n108) and spent less time on mechanical ventilation.(p=0.21). Adjusting for age, sex, APACHE II score and etiology of sepsis favored PHP treatment (odds ratio 0.79, 95% CI 0.39-1.59). No excess morbidity was noted with PHP use. PHP survivors tended to leave the ICU earlier and more were discharged by day 28.
PHP is a hemodynamically active NO scavenger. Even though no significant effect on mortality was observed, PHP therapy was safe and associated with favorable trends in catecholamine use, duration of mechanical ventilation, ICU and hospital stay.
The role of PHP therapy in patients with distributive shock remains to be determined in a Phase III clinical trial.
G.T. Kinasewitz, None.