Single mean arterial blood pressure drops during stroke thrombectomy under general anaesthesia are associated with poor outcome

Mechanical thrombectomy (MT) has become the recommended treatment for acute ischemic stroke caused by anterior circulation large vessel occlusion (LVO) [1]. While there is no debate regarding a higher chance for improved outcome with successful recanalization, it is not yet clear if MT should be performed under general anaesthesia (GA), conscious sedation (CS) or local anaesthesia alone. Recent single-centre randomized controlled trials found no difference in outcome between these approaches [2‐4], while larger observational studies suggested a predominantly worse outcome for thrombectomy patients under GA [5, 6].

One reason for this could be the greater challenge of blood pressure management during the induction of GA where post-induction hypotension is common due to cardio-depressive and vasodilatory side effects of most anaesthetic agents [7]. There is, however, conflicting evidence whether hypotension during MT is independently related to worse outcome [8‐12]. Previous studies on the relation of blood pressure (BP) during MT and outcome also vary in their suggestions of BP target levels and whether absolute BP levels or relative changes in BP from pre-intervention levels are more critical [8, 10]. The 2018 AHA/ASA stroke guidelines note that BP should be kept ≤ 180/105 mmHg during MT and recommend correction of hypotension and hypovolemia but do not indicate what minimal BP should be maintained [13]. Anaesthesiologic guidelines recommend preservation of a systolic BP > 140 mmHg during MT, but this is not based on hard data [14]. It is also unclear whether systolic, diastolic or mean arterial blood pressure (SAP/DAP/MAP) has the greatest impact on outcome in the context of MT. Additionally, the influence of single critical BP drops during MT has not been investigated in depth and no specific cut-off values have been discovered yet. A commonly recommended minimal threshold for adequate cerebral blood flow autoregulation in the absence of increased intracranial pressure is a mean arterial pressure (MAP) ≥ 60 mmHg [15]. Moreover, BP drops are likely particularly deleterious in patients with poor collaterals, but this has not been specifically investigated in MT patients thus far [16].

In view of these uncertainties, we explored the impact of different BP values (absolute and relative BP changes, SAP, DAP, and MAP) and their course during MT on outcome. Specifically, we hypothesized that critical BP drops of MAP ≤ 60 mmHg during MT were related to worse 3-month functional outcome. For this purpose, we analysed consecutive anterior LVO stroke patients who underwent GA for MT and had continuous invasive BP monitoring.

In this retrospective cohort study, we found that MAP drops below 60 mmHg during GA for MT were independently associated with worse functional outcome at 3 months post-stroke. As ideal BP targets or thresholds for patients undergoing MT have not yet been agreed upon, our work adds several aspects to this debate.

The first important point is that our results suggest that absolute BP values have a stronger impact on neurological outcome than relative changes, both during induction of anaesthesia and throughout the whole thrombectomy procedure. Cerebral autoregulation helps to provide adequate blood flow to the brain across a range of BP values, but might be impaired in pathological conditions such as stroke [18, 19]. Our results show the strongest association between unfavourable outcome and an MAP that dropped below 60 mmHg at any point in time during MT. This could indicate the lower end of the autoregulatory capacity of the brain where cerebral blood flow becomes directly dependent on BP. It needs to be considered however, that the individual autoregulatory curve of patients might well be unpredictably shifted to the right, in particular in patients with long standing arterial hypertension and also differ between different cerebral pathologies [19].

The second important finding is that MAP drops showed a stronger association with worse outcome than systolic BP drops. Notably, MAP thresholds are not included in current recommendations for anaesthesiologic management of endovascular treatment for acute ischemic stroke [14]. From a pathophysiological point of view, MAP is the most important and commonly used blood pressure target value regarding cerebral blood flow [20]. Our clinical results now support this important role of mean over systolic BP. For clinical management of patients with low MAP, it needs to be considered, that diastolic pressure has a higher impact than systolic pressure. Therefore, elevation of diastolic pressure is probably the therapeutic approach of choice and could be achieved via fluid administration in many cases. However, this might be challenging in the neurointervention suite before the induction of anaesthesia for MT, in particular in patients with cardiac or renal comorbidities as it can lead to fluid overload and cardiac decompensation. Especially in clinically hypovolemic patients, early initiation of fluid administration already in the emergency department could potentially mitigate these risks. Disproportionate elevation of SAP by vasoconstrictor agents to increase MAP on the other hand, might potentially impede microcirculatory cerebral blood flow [21].

The effect of a drop in MAP < 60 mmHg regarding unfavourable outcome was quite strong in our study cohort and—besides well-established prognostic factors—remained significant in multivariable analysis. Furthermore, there were no baseline differences between patients who dropped to an MAP < 60 mmHg versus those who always had an MAP above this critical threshold. The strict avoidance of an MAP < 60 mmHg should therefore be of paramount importance when GA is chosen for MT. This corresponds well with data from traumatic brain injury, showing that even a single episode of severe hypotension is associated with worse outcome [22]. While it could be assumed that longer duration of critical hypotensive periods leads to accumulated impact on patient outcome, we did not find such an effect. However, many hypotensive episodes in our study were short and the rather low number of longer hypotensive periods may have been too small to find statistically significant effects.

Notably, hypotensive episodes were not rare in our “real world” cohort; however, the severity and frequency of periinterventional hypotension was comparable to a previous retrospective study [8]. Post hoc analysis of the SIESTA trial in regards to BP values on the other hand revealed no association between periinterventional BP and functional outcome after 3 months [11]. However, this was a prospective trial investigating anaesthesia in MT and followed strict BP targets. Furthermore, single BP drops were not specifically explored. Therefore, the difference to our results may be explained by the different study designs and a more rigorous adherence to BP targets in the prospective study setting.

Our study may have unravelled a potential reason for the different performance of GA compared to CS for MT in small single-centre randomized controlled trials compared to observational and retrospective studies. Hypotension is more difficult to prevent in GA (especially during anaesthesia induction, after which most of the critical BP drops occurred in our study) and may occur more often (and more severe) in real-world patients compared to prospective studies which specifically investigated anaesthesia management of MT. This could be a possible—or at least partial—explanation why the prospective randomized controlled trials investigating anaesthesia for MT showed no difference in outcome between CS and GA [2‐4], while observational and retrospective studies indicated worse outcomes under GA [5, 6].

Previous studies on anaesthesia management for MT have not particularly studied the pre-interventional collateralization status. Our finding that patients with worse collaterals are even more prone to worse outcome due to BP drops is in line with pathophysiological considerations [23].

This study has several strengths. All patients had invasive BP monitoring, which allowed us to precisely record BP. BP values were recorded and saved in the electronic anaesthesia records automatically. Patients with missing or incomplete records were excluded, the accuracy and data quality of BP measurements, the core variable for this study, can therefore be assumed to be very good. Notably, patients who were excluded from the study did not differ from study patients regarding important clinical baseline characteristics, except from higher NIHSS values in excluded patients, caused by the very high NIHSS values of prehospitally intubated patients (which were excluded from the study). Furthermore, clinical parameters were recorded prospectively in our study and we were able to include important radiologic parameters such as collateral status and pre- and postinterventional ASPECTS in our analysis.

Even though the retrospective nature of this study comes with known limitations, it also limits any possible observer effect in particular in regards to BP management, resulting in our study representing real-world data outside of well-controlled prospective trials on BP management in stroke. We did not explore the impact of different anaesthetic drugs and doses on both blood pressure and patient outcome as well as BP management before and after MT, which should be explored in further studies.

The uniformity of our study cohort limits the generalizability of our findings to other settings and particularly to other methods of anaesthesia (such as CS) for MT. Larger studies involving multiple centres and different anaesthetic management during MT are required to confirm our results and give further insights in periinterventional management of stroke patients.