To our knowledge, our report is the first formal examination of the issue of procedural sedation and intubation within a controlled acute interventional ischemic stroke trial. Our data adds to considerable discussion in the literature regarding the potential beneficial and untoward effects of sedative medications on patient outcome and stroke recovery. In particular, the intensive care and anesthesia literatures have shown that continuous use of sedative medications prolongs intubation time and lengthens ICU stays.8,9
Continuous sedation has also been associated with an increased likelihood of developing pneumonia in intubated patients.10
Conversely, the potential neuroprotective benefits of some sedative medications have been investigated for years, though have never been proven to be of benefit in acute stroke.11,12,13
Our goal was to clarify the factors that were associated with the use of higher levels of sedation in patients undergoing angiography. Further, we wanted to discern the association, if any, between the use of sedation and clinical outcomes and the ability to obtain successful reperfusion. Our analysis shows that higher baseline NIHSS scores correlated with use of deeper sedation during or prior to angiography and/or intervention. Heavily sedated patients were also significantly less likely to obtain successful angiographic reperfusion as measured by post-treatment TIMI scores, a finding that is perhaps related to higher rates of ICA occlusions and associated with longer procedural durations. From a clinical standpoint, it is not surprising that we found that patients with the lowest levels of sedation fared better.
We are unable to conclude whether sedation is a cause of poor outcome due to causing increased complications or impairing recovery or whether patients with large strokes, as measured by higher baseline NIHSS, are more likely to be sedated. It is clear that patients with higher baseline NIHSS have poorer clinical outcome, higher morbidity and mortality and greater rates of symptomatic ICH. However, sedation category remained a predictor of poor outcome and death when baseline NIHSS score was accounted for in multivariable analysis. It remains possible, therefore, that the use of sedation itself is related to clinical outcome, given our findings. Alternatively, it is also possible that the use of heavier sedation is a non-specific marker for a group of unmeasured clinical factors that predict poor outcome.
From a procedural standpoint, there was a non-significantly lower rate of access site-related complications associated with heavier sedation. Whether this difference is found to be significant in additional studies remains to be seen. In this analysis, access site-related complications were limited to groin hematomas, a single arterial pseudoaneurysm, a moderate severity common iliac occlusion, and/or local bleeding. There were no significant retroperitoneal hemorrhages in this cohort. In practice, the vast majority of the above access site-related complications can be treated by manual compression or conservative measures. Based on our analysis, we suggest that reducing the rate of access site-related complications should not influence neurointerventional specialists to heavily sedate or pharmacologically paralyze their patients alone.
Conversely, heavy sedation or paralysis may be warranted if patient movement is felt to pose an increased risk of vessel perforation or dissection. In this analysis, the only vessel dissection occurred in a cervical carotid artery in a patient in the heavily sedated group. Whether patient agitation or movement may have contributed to dissection is unknown. Because these complications are rare, however, we are unable to conclude whether greater sedation or paralysis is useful in avoiding these complications.
We did find a significantly higher rate of infection in those patients receiving heavy sedation or pharmacological paralysis. Whether short-term or long-term use of sedative medications is in part responsible for higher infection rates in those patients is unclear based on this analysis. However, given these findings, we cannot overlook the fact that medication effects may play some role in immunosuppression, aspiration risk, or prolongation of intubation time.
This analysis is limited by its small sample size. While we were able to demonstrate a significant association between sedation and outcome, the magnitude of that association is unclear, as evidenced by the wide confidence intervals around the odds ratios. In a larger population, we might be able to conclude whether sedation alone appears to influence outcome. Our inability to precisely determine the types of medications, their duration of use, or the route of administration in each case also limits this analysis. While we did record all medications used as part of the study, the times of administration with respect to the angiographic procedure were not recorded, nor was their duration of use.