Postoperative hypotension in patients discharged to the intensive care unit after non-cardiac surgery is associated with adverse clinical outcomes

The postoperative period can be extremely dangerous for patients, and postoperative hypotension (POH), specifically, is associated with significant harm [1]. Mortality is 1000 times more common postoperatively than intraoperatively [2], and if mortality within 30 days of surgery was classified as a separate indication, it would be the third leading cause of death in the USA [3]. Myocardial infarction is the leading cause of attributable postoperative death [4], and other common pathologies include acute ischemic stroke (AIS) and acute kidney disease [3]. Furthermore, escalation of the complexity of postoperative critical care is not only costly, but is also associated with a decreased quality of life in the years following hospitalization [5].

Despite its association with significant patient harm and cost, only a limited number of studies have investigated POH, particularly none previously in cohorts without preceding intraoperative hypotension (IOH) [1, 6]. A mixed cohort of critically ill patients (including patients from the coronary care unit, general, medical, cardiac and surgical intensive care units (ICU)) revealed an increased risk of myocardial injury, mortality and kidney injury at MAP thresholds of 85 mmHg with a progressive increase at lower pressures [7]. A specific investigation in a postoperative population demonstrated that patients in the surgical ICU following non-cardiac surgery are especially sensitive to even mild amounts of hypotension [8]. However, taking a closer look at the data, post hoc analyses revealed that the relationship between ICU hypotension and the risk of adverse outcomes was dependent on the amount of IOH [8]. Moreover, there is a paucity of literature which examines various absolute blood pressure thresholds in postoperative ICU patients.

Understanding the impact of POH at different hemodynamic thresholds without the contribution from IOH on adverse clinical outcomes among post-surgical critical care patients can provide better insight into the importance of POH management and potentially inform strategies to assist in early intervention. For example, in a recent randomized clinical trial (HYPE), the use of a machine learning-derived early warning system resulted in less IOH and potentially fewer adverse outcomes (although not statistically significant) than the standard of care [9]. Furthermore, continuous hemodynamic monitoring and individualized blood pressure management might assist early intervention and thus result in overall better clinical outcomes, including risk reduction for postoperative organ dysfunction such as risk of AKI [10, 11].

This multi-center retrospective cohort study sought to evaluate the association of POH across multiple hemodynamic thresholds (≤ 75, ≤ 65 and ≤ 55 mmHg), in the absence of IOH (≤ 65 mmHg), among patients in the ICU after non-cardiac surgery. The primary outcome was major adverse cardiac or cerebrovascular events (MACCE) in the first 30 days. Additional clinical adverse outcomes investigated included: all-cause 30- and 90-day mortality, 30-day AMI, 30-day AIS, 7-day AKI stage II/III, 30-day readmissions and the need for continuous renal replacement therapy (CRRT)/dialysis in the first 7 days.

This is the first study to examine the association between multiple postoperative hemodynamic thresholds in the absence of prior IOH (≤ 65 mmHg) with adverse clinical outcomes in the ICU setting. We demonstrate that POH at various hemodynamic thresholds (≤ 75, ≤ 65 and ≤ 55 mmHg) in the absence of IOH is associated with a larger absolute number of adverse clinical events as compared to patients with no POH exposure. Our findings underscore the importance of the immediate postoperative period (48 h) on patient outcomes among patients without intraoperative hypotension. Overall, the risk of MACCE and 30- and 90-day mortality progressively increased with decreasing MAP thresholds. For example, we saw an 11.1% increase in MACCE and 13.6% and 15.1% increase in 30- and 90-day mortality, respectively, in patients who had exposure to POH in the ICU, despite being stable in the intraoperative period.

The risk of experiencing 30-day MACCE, 30-day or 90-day mortality was significantly increased at blood pressure thresholds of ≤ 65 mmHg and ≤ 55 mmHg. The high incidence of 30-day MACCE (17.1%) in the overall population is likely driven by 30-day mortality (16.3%), as 30-day AMI (1.2%) and AIS (2.6%) had a relatively low incidence in our population. This would also explain the lack of significant demonstrable associations of POH in the ICU with AMI or AIS. Our mortality rate in this critically ill population is supported by other recent studies in surgical and non-surgical ICU populations, which report rates of mortality between 16 and 20% [1, 30‐34]. In particular, our mortality rate is consistent with a large cohort analysis of ~ 50,000 patients across 65 ICUs in Sweden which reported a 30-day mortality rate of 17% [32]. Indeed, our study population had 36% of overall patients (across all blood pressure thresholds) classified with CCI ≥ 4, suggesting that these patients were suffering from a number of comorbid conditions prior to their non-cardiac surgery, which could have contributed to adverse events with an associated increased risk of mortality.

Khanna and colleagues reported that increasing amounts of hypotension at pressures previously regarded as normal were associated with myocardial injury, mortality and renal injury among surgical ICU patients; however, there was an interaction between IOH and critical care outcomes related to POH, making it difficult to evaluate the selective contribution of POH among ICU patients in the absence of IOH [8]. Therefore, our study builds upon Khanna and colleagues as it effectively evaluated the association of POH with adverse clinical events in postoperative critical care patients that did not experience intraoperative hypotension. Our observations that POH in the ICU with MAP ≤ 65 mmHg is associated with increased risk of MACCE as well as 30- and 90-day mortality suggest that POH in the critically ill is hazardous and blood pressure should be carefully, and preferably, continuously monitored using invasive and non-invasive methods as clinically indicated. Furthermore, this study evaluated several hemodynamic thresholds and demonstrated that POH, even at a MAP of 75 mmHg, though not statistically significant, results in an increased rate of adverse clinical events (MACCE, mortality measures and AKI/CRRT) compared to maintaining MAP above 75 mmHg. This finding is novel and opens room to question conventional wisdom of MAP goal 65 mmHg in ICU patients, as illustrated by a recent editorial [35]. Other randomized trials of blood pressure in the ICU have not found a difference in outcomes comparing different blood pressure targets, though these were septic patients and different from our novel postoperative ICU population that had a stable intraoperative course prior to ICU admission [36, 37]. Overall, our data suggest the importance of aggressive monitoring and early intervention to correct blood pressure in the ICU which may decrease mortality and adverse clinical events.

Our study has several limitations which must be considered, the first being that as this study was observational in nature, the data were subject to reporting bias/data entry errors. While we calculated E-values to measure uncontrolled confounding, we cannot exclude that it may not exist. Overall, we controlled for numerous confounders available in our dataset, however, if hypotension was simply an indicator of the degree of severity of the underlying illness, our estimated risks could be overestimations [1]. Second, since this was a retrospective study, we had no control over the treatments chosen for the hypotension events and the specific protocols within and across various hospitals. Third, while we made every attempt to minimize gaps between blood pressure readings (limiting gaps to one 2-h gap in-between readings), this presents a limitation (therefore time below thresholds as time-weighted averages was not modeled). One reason for this is that only nurse or provider validated blood pressure readings were entered into electronic records; therefore, we sacrificed blood pressure data granularity at the cost of possibly greater accuracy. Additionally, since MAP recordings were intermittent in nature, there was the potential for unstable MAP readings especially at higher MAP values which might have resulted in higher average times below the MAP thresholds. Fourth, our study population was focused on ICU patients; therefore, our results cannot be generalized to surgical patients discharged to the ward after the operative procedure. Fifth, AKI stage II/III was chosen as an outcome for this study because at the time a large volume of literature suggested that hospital mortality was associated with stage II/III renal dysfunction [24]. Although, we realize now that AKI stage I has similar long-term renal dysfunction when compared with stage II/III [38]. Sixth, our study design allows for a patient to have multiple non-cardiac procedures in our cohort as procedures > 30 days prior to the index visit could also be included in this study. Therefore, any hypotension experienced during or after that procedure could have resulted in unknown long-term effects. Finally, because we utilized an algorithm with a positive predictive value of 0.97 to help assign patients without a known care location to the ICU, 3% of patients could be misidentified.

In conclusion, our analyses revealed a strong association between POH at several different hemodynamic thresholds in critical care patients with no hypotensive episodes during surgery (MAP > 65 mmHg), and adverse clinical outcomes in a multi-center retrospective cohort post-non-cardiac surgery. This study advances the field on POH among the critically ill as no study to date has evaluated the association among various POH thresholds in the absence of any prior hypotension with adverse clinical outcomes. The data here are hypothesis generating and should serve as a pilot for a larger interventional trial investigating the optimal blood pressure thresholds and need for improved hemodynamic monitoring for postoperative ICU patients, in order to improve short- and long-term outcomes of this vulnerable patient population.