In harmony with the latter observation http://www.selleckchem.com/products/Dasatinib.html [37], neither AVP nor TP negatively affected renal function in the present study.AVP has been reported to activate platelets via V1 receptors, leading to an increase in CD62 expression [39,40] and a decrease in platelet count in patients with normal platelets, but not in patients with low platelets [39]. In this context, it is another interesting finding of the present study that TP, as compared with AVP and NE, significantly decreased platelet count. However, in accordance with a previous study [40], neither AVP nor NE negatively affected the coagulation system.The present study has some limitations that we would like to acknowledge.
First, because there are no equivalent doses or data comparing different doses of AVP and TP, we decided to evaluate the efficacy of fixed doses of the study drugs in reaching the threshold MAP and to investigate their effects on open-label NE requirements. We therefore chose the AVP dose investigated in VASST (i.e. 0.03 U/min of AVP and 15 ��g/min of NE) [5] and a low TP dose previously reported to be safe and effective in a case series [13]. In this regard, it needs to be considered that AVP was administered at a fixed dose of 0.03?U/min. It might be argued that a weight-adjusted TP dose was compared with a fixed AVP dose and thus the chosen doses might not have been pharmacologically equivalent. Therefore, it is possible that the TP dose was relatively higher as compared with the AVP dose.Second, we performed a pilot study with the reduction of open-label NE requirements as the primary endpoint.
In this regard, it has to be underlined that there is no reliable evidence that a reduction in catecholamine requirements may lead to an improved outcome. Third, we investigated only a small number of septic shock patients treated over a relative brief period. In this regard, the risk of positive results in a study with numerous secondary variables and time points has to be taken into account. Thus, caution should be exercised in interpreting the results of the secondary outcome variables. Properly powered, randomized controlled trials are required to determine the effects of TP infusion on clinical outcome. All patients included in the present study received hydrocortisone, so we cannot judge if and how corticosteroids affected our results [41,42].
For safety reasons, we opted for a 48-hour intervention period, because it was impossible to measure the circulating levels of TP. Although there is no evidence of drug accumulation over time, we cannot rule out this possibility when TP is infused over a more prolonged period. Moreover, hepatosplanchnic Entinostat perfusion was assessed using PDR and CBI. Although PDR and CBI have been found to be a good predictor of survival in critically ill patients, at best it reflects the total splanchnic blood flow without separating hepatic arterial from portal venous flow.
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