In this study, we hypothesized that exposure to hypotension within six hours after ROSC would be associated with lower survival to hospital discharge. Using standardized criteria to classify arterial hypotension, we found that the presence of two or more systolic blood pressures below 100 mmHg in the first six hours after ROSC was associated with a greater than three fold increased odds of in-hospital death. Our group employs the concept of “exposure” to hypotension to emphasize the significance of the event as an independent predictor of death. Previously two large observational studies showed that in the general, non-traumatic patient population, early exposure to arterial hypotension was a strong independent predictor of long-range outcome including in-hospital mortality.21, 22
We sought to determine the strength of the relationship between early exposure to hypotension and mortality in this specific post-ROSC patient population. Our findings indicate that post-ROSC hypotension, especially in the early hours, may be an important determinant of outcome.
Although it may be an expected finding that patients with overt shock have worse clinical outcomes, highlights that even patients with episodic hypotension had high mortality risk and therefore our findings are not entirely driven by subjects who manifest sustained hypotension and suggest that any hypotension may be deleterious.
We acknowledge that our data have important limitations. Although all of our subjects had blood pressures measured early and frequently, the retrospective design did not permit measurements to be accrued at fixed time intervals, and therefore it is possible that some subjects with less frequent measurements had exposure to hypotension that was not detected. Due to the potential heterogeneity in number of blood pressures measurements, we also could not perform a cumulative analysis (i.e. area under the curve for exposure) over time. Therefore we cannot comment on the impact of the depth and duration of post-ROSC hypotension (i.e. akin to a dose-response effect). In addition, we recognize that it is possible that some subjects who were moribund or deemed non-salvagable by clinicians may have received less aggressive care and thus were more likely exposed to hypotension. However, this concern is attenuated by the fact that the exposure group actually received more repeat CPR in the first 72 hours post-ROSC compared to non-exposures.
We chose arterial hypotension as the hemodynamic variable of interest because it is a hallmark of circulatory insufficiency and is a readily available parameter for all clinicians. After ROSC, hypotension leads to persistent tissue hypoperfusion which may produce secondary cellular injury after the initial ischemic insult. Furthermore, the associated cardiovascular instability may increase the propensity to suffer repeat cardiac arrest. Post-cardiac arrest studies in animals have defined impaired myocardial function after cardiac arrest and shown that cardiovascular derangements in the hours after ROSC lead to poor neurologic outcome.28, 29
In humans, Laurent et al showed that persistent low cardiac index at 24 hours post-ROSC was associated with death and multiorgan failure.8
In addition, Mullner and colleagues found that hypotension in the first two hours after ROSC was related to poor neurologic outcome at 6 months.30
We know of no prior study specifically examining the relationship between arterial hypotension after ROSC and survival.
In the last decade scientific advances showed that interventions after ROSC can save lives.2, 3
In 2005, the European Resuscitation Council added ‘Post Resuscitation Care’ as the final link in the Chain of Survival paradigm for treating cardiac arrest.31
This change in the classical view denotes a new focus on the post-resuscitation period as a window of opportunity to intervene and develop treatments to change the trajectory of post-cardiac arrest syndrome. Although we now know that body temperature may play a significant role in determining outcomes,2, 3
little is known as to what other physiologic parameters may be important in the post-ROSC period. Specifically, although consensus recommendations advocate for hemodynamic optimization in the post-ROSC period, there is little empiric evidence on the association between post-ROSC hemodynamic derangements and outcome.32, 33
Identifying new target parameters in the post-ROSC period will be the next steps in the development of novel treatment strategies to improve survival after cardiac arrest. Therapeutic hypothermia for neuroprotection represents the first step in this process. In this study, we showed that arterial blood pressure may be a major determinant of outcome in this disease and therefore it may represent a new therapeutic target during post-ROSC treatment. Our findings provide scientific rationale for further investigation to determine the value of arterial blood pressure optimization as a part of an early goal-directed treatment strategy for post-cardiac arrest syndrome.