Alpha-2 adrenoceptor agonists and sepsis: improved survival?

mended for segregating the eff ect of dexmedetomidine, an alpha-2 adrenoceptor agonist, in sepsis [1]. However, three questions arise from their study: what are the Pvalues for the data reported in Table 1? Why was there such a discrepancy between the fentanyl dose given to patients on dexmedetomidine and those on lorazepam (1,114 versus 117 μg/day, P = 0.01) considering the 50 to 80% reduction in the use of opiates commonly observed in the literature when alpha-2 adrenoceptor agonists are administered? And how many days did the patients spend on spontaneous (for example, pressure support) versus controlled/assisted ventilation? In their study, survival was better (a 70% reduction in risk of dying at 28 days) in patients on dexmedetomidine (n = 31) than in those on lorazepam (n = 32). Improved survival was observed earlier in tetanus patients [2] (rate of death of 50% versus 11% in control (n = 10) versus clonidine-treated (n = 17) patients; P = 0.04; this 1998 reference is not cited in the bibliography). In the study of Dr Pandharipande and colleagues, baseline charac teristics were slightly diff erent (Table 1 in [1]): tempera ture, heart/ respiratory rate, incidence of vaso pressors (dexmedetomidine, 32%; lorazepam, 56%) and drotre co gin alpha (activated; P = 0.20) were higher and systolic pressure lower in the lorazepam group despite ‘similar severity of illness’. Could bias explain partially improved survival? As concluded by the authors [1], a larger trial should demonstrate improved survival (for example, upon septic shock [3]). Secondly, the dexmedetomidine patients received ten times more fentanyl and had more ventilator-free days. Usually, alpha-2 adrenoceptor agonists reduce the need for opiates by 50 to 80% and preserve spontaneous ventilation. So why this discrepancy? Th irdly, vasopressor requirements were reduced in the dexmedetomidine group (Table 3 in [1]). A 2003 reference [4] showed previously a reduced vasopressor require ment and was not cited in the bibliography. Could more ventilator-free days lead to less infections [5,6], improved survival, lowered intra thoracic pressure and reduced vasopressor requirements?