Focus on blood pressure targets and vasopressors in critically ill patients

Abstract

For patients in shock, decisions on blood pressure targets are an ongoing task for the clinicians at the bedside in critical care settings. In general, there are only limited amount of data from studies with lower risk of bias to support the clinicians in these decisions. However, in recent years, large cohort studies and randomised clinical trials (RCTs) have given us somewhat better data to support better care.What blood pressure target is chosen will likely have important clinical implications, not only because different blood pressure targets may affect organ perfusion differently, but also because they require different dosing and choices of vasopressor agents. A delicate balance likely exists between the consequences of hypotension-induced hypoperfusion, on one side, and on the other side, the consequences of the interventions given, mainly vasopressors and their dosages and the duration of administration.In a large registry study from 110 ICUs in the US, hypotension-as time-weighted averages-in patients with sepsis was associated with increased risk of myocardial injury, acute kidney injury and death [1]. For the two latter outcomes, the odds for worse outcome increased with decreasing mean arterial pressures (MAP) from 85 mmHg. This does not mean that we should apply 85 mmHg as the target for vasopressor therapy, because observational data cannot prove causality and any timedependent interactions with interventions and any other physiological markers are very difficult to control for in such analyses [2][3][4]. In addition, registry data often contain few or no data on important clinical markers, in this case the simple markers of peripheral perfusion, which likely interacts with any effects of hypotension on mortality [5,6]. Importantly, a recent individual patient data meta-analysis (IPDMA) of two RCTs [7, 8] of lower vs. higher blood pressure targets in ICU patients with shock suggested that no sub-groups were harmed from lower MAP targets [9]. If anything, two sub-groups of patients were harmed from a higher MAP target being patients with more than 6 h of vasopressor exposure before randomization and those aged 65 years or above. Taken together, clinical equipoise exists [10], and more RCTs on blood pressure targets in shock patients are underway, including the large 65-trial on permissive hypotension in patients aged above 65-year who have shock (ISRCTN10580502). The results of the 65-trial should be presented soon as enrolment has ended. Uncertainty may remain regarding the need to individualize blood pressure targets based on habitual blood pressure levels or the trajectory of critical illness, e.g., the phases of resuscitation, stabilization and recovery.The choice of vasopressor to obtain the blood pressure target is also likely to matter. A recent multicenter, blinded RCT of the longer-acting vasopressin-analogue terlipressin, which has higher affinity for the V 1a receptor, showed no effect on the primary outcome 28-day mortality as compared with noradrenalin in patients with septic shock (Tabl...