Even Small Decreases in Blood Pressure during Conscious Sedation Affect Clinical Outcome after Stroke Thrombectomy: An Analysis of Hemodynamic Thresholds

Discussion

The optimal hemodynamic management of patients undergoing endovascular therapy for acute ischemic stroke remains a topic of debate among clinicians. The 2014 Society for Neuroscience in Anesthesiology and Critical Care Expert Consensus Statement recommends the use of continuous hemodynamic monitoring with maintenance of systolic blood pressure at 140–180 mm Hg,⁸ but these recommendations are not based on data from patients having undergone thrombectomy. Instead, they originate from large epidemiologic studies that examined the associations between poor outcome and baseline hemodynamics or variation during the acute phase of acute ischemic stroke.^9⇓–11 Davis et al³ have investigated the association between favorable neurologic outcome and the lowest systolic blood pressure of >140 mm Hg based on the same extrapolation. In a subsequent study, our group selected a threshold of MAP of >70 mm Hg after dividing our range of observed MAP into quartiles.⁴ Most recently, Löwhagen Hendén et al¹² showed that a >40% fall in MAP during endovascular reperfusion with the patient under general anesthesia is an independent predictor of poor neurologic outcome. We saw a need to more closely examine how various blood pressure changes influence outcome for patients undergoing thrombectomy.

We sought to perform our analysis in a large but relatively homogeneous study population to best observe the relationship between intraprocedural hypotension and outcome. We chose to restrict our analysis to those patients who achieved successful reperfusion (modified TICI 2b/3) because even the best blood pressure control would be unlikely to improve outcome if the vessel remained occluded. Because hypotension has been shown to be collinear with general anesthesia,³ we restricted our analysis to those patients whose procedures were performed under MAC to eliminate confounding by anesthesia type.

Despite the perceived hemodynamic stability of thrombectomy with the patient under sedation, we observed substantial drops in blood pressure during the procedures. Our baseline and lowest pressures are similar to the MAC/sedation cohorts reported from the Cleveland Clinic (n = 99)¹³ and Mayo Clinic (n = 38).¹⁴ Rates of vasopressor use were also quite similar across the 3 studies. The results from these 3 institutions suggest that it is difficult to replicate the tight hemodynamic control in the Calgary cohort reported by Davis et al.³ One potential reason might be differences in the depth of sedation or drugs used. Although the former is impossible to determine, we can make crude comparisons of the latter. The Calgary patients received only fentanyl and midazolam for sedation, whereas our institution uses dexmedetomidine infusions with supplemental fentanyl and midazolam if needed. The practice at the Cleveland Clinic mirrors ours except they also use propofol infusions.¹³ In contrast, most patients at the Mayo Clinic received only fentanyl and midazolam for sedation but still experienced significant drops in blood pressure.¹⁴ It therefore appears that no particular sedative regimen can ensure tight hemodynamic control.

Not only are blood pressure drops common during MAC, but even modest drops in blood pressure can have a dramatic impact on neurologic outcome. This is perhaps best illustrated by our finding that a decrease in MAP from baseline of >10% carries an OR for poor outcome of 4.38. Such tight hemodynamic control may not always be possible, but it should be a goal even with the patient under minimal sedation. From the receiver operating characteristic curves and multivariate models, we found no single MAP threshold. Instead, the lowest MAP showed a dose effect in which each 10-mm Hg drop below 100 mm Hg increased the odds of poor outcome. Although we consistently observed the benefit of keeping the MAP close to baseline, the critical MAP threshold may vary by the severity of the underlying stroke. Patients with an NIHSS score of <15 had high rates of good outcome across a wide range of MAPs, whereas the lowest MAP below 80 mm Hg had a large outcome effect for those with NIHSS scores of >20. For those patients in the middle (NIHSS score, 15–20), the threshold appeared to be 70 mm Hg. Presumably, in a homogeneous cohort of large-vessel occlusion strokes, patients with higher NIHSS severity have poorer collaterals and, thus, are more dependent on blood pressure compared with patients with milder stroke severity.

Low blood pressure has been reported to be an independent risk factor for poor outcome in 2 mixed populations of MAC and patients under general anesthesia ^3,4 and 1 pure general anesthesia group.¹² We found that this relationship holds true even in populations with no general anesthesia. What remains unknown, however, is whether intervention to correct hypotension can actually improve outcomes. One group recently reported their experience instituting hemodynamic parameters for their patients undergoing thrombectomy.¹⁵ They noted similar blood pressures in the groups with poor and favorable outcomes but that the cumulative dose of norepinephrine was independently associated with poor outcome.¹⁵ These data raise the possibility that vasopressors may improve peripheral blood pressures without improving blood flow to the ischemic penumbra. Future work might approach this question through a prospective, randomized trial evaluating strict blood pressure control by using vasopressors in comparison with usual anesthesia care. Until the results of such a trial are available, it seems reasonable to minimize hypotension during endovascular thrombectomies for acute ischemic stroke.

The present study has several limitations. Although larger than the previous studies, it remains retrospective in nature. As with all such studies, missing data may bias the results in unpredictable ways. For example, we did not collect prestroke mRS scores. The lowest blood pressures before reperfusion were captured from the anesthesia records as the lowest MAP rather than lowest systolic pressure. However, our rationale was that most blood pressure data were acquired by using noninvasive oscillometric cuff sphygmomanometers, which measure the MAP and derive systolic and diastolic pressures from an algorithm.⁷ Additionally, our choice of a study population with minimal confounders may limit the generalizability of our results to other patients undergoing thrombectomy, such as those with posterior circulation stroke or patients receiving general anesthesia. Nevertheless, the hemodynamic variables we identified may provide a useful way to control for the effect of hypotension in future studies on the effect of anesthesia on outcome.