The utility of the brain trauma evidence to inform paramedic rapid sequence intubation in out-of-hospital stroke

Strokes account for 10% of deaths worldwide [1]. Rapid Sequence intubation (RSI) is used in the emergency setting to improve survival in strokes, with perhaps 6 to 79% of strokes receiving intubation, depending on the stroke type [2]. Rapid sequence intubation is used to secure the airway using sedative and paralytic drugs to facilitate endotracheal intubation [2]. Strokes form 37% of RSI for non-traumatic brain pathologies undertaken by paramedics in Victoria, Australia [3]. Despite the not-infrequent use of RSI in unconscious out-of-hospital acquired brain injuries, no high quality evidence exists to support the use of RSI for strokes [2‐4]. A randomized controlled trial of RSI in traumatic brain injury (TBI) exist [5], but the evidence from this trial cannot necessarily be applied to stroke RSI due to differences between the stroke and TBI patient [2‐4].

Lower RSI survival for strokes compared to TBI suggests that the evidence from TBI might not be applicable to RSI in stroke [4]. It is important to investigate if brain trauma RSI evidence is transferable to strokes. That is, it would be vital to understand the RSI components that cause the survival difference of TBI compared to strokes. This study aims to find the constituents of RSI that could cause different survival between TBI and strokes. If any component of RSI impacts survival differently for TBI compared to strokes, it would follow that RSI itself has a different effect on these two pathologies. If RSI causes dissimilar survival for these two illnesses, then this would mean that the RSI TBI evidence-base cannot be transferred to strokes. Any such differences would imply that a stroke RSI trial is needed.

This cohort included 107,128 (Fig. 1) of which 1993 (1.9%) received RSI. A total of 80,324 (75%) had complete data of which 11,133 (13.9%) were diagnosed with haemorrhagic stroke and 26,754 (33.3%) with ischemic stroke and 42,437 (52.8%) with TBI. Baseline characteristics of the full-data cohort are compared in Table 1. The overall intubation success was 97.8% and first pass success was 89.6%, with no significant change in success over time for overall (p = 0.40) or first-pass (p = 0.12).

This analysis shows that RSI interact with strokes and traumatic brain injuries in terms of survival, indicating that the TBI evidence might not be useful to guide stroke RSI. As anticipated, this implies that the stroke patient differs from the TBI patient enough that RSI components impacts survival differently for these two pathologies. Significant interactions in the RSI-only group included number of intubation attempts, atropine, fentanyl, pulse rate and perhaps scene time, time to RSI as well as the age of the patient. Another suggestion that TBI evidence might not transferable is the difference in survival between the strokes and TBI for RSI. Haemorrhagic strokes have 14% lesser RSI survival, compared to ischemic stroke of 4% and TBI a lesser than 1% survival difference between RSI and no-RSI.

Large differences in the changes in systolic blood pressure with RSI use are evident when comparing strokes and TBI. The largest decreases in RSI-related blood pressure were found in haemorrhagic strokes, and the least in TBI. Survival follows this pattern too, with haemorrhagic stroke the poorest survival compared to TBI the best. However, it is not clear that these decreases in blood pressure are the causes of poorer survival. Our analysis show that decreases in blood pressure with RSI was not associated with a significant decrease in survival. This finding of no decrease in survival after a decrease in blood pressure with RSI is mirrored in the results of the GOLIATH trial, which compared conscious sedation to general anaesthesia in ischemic stroke [15]. In the GOLIATH trial general anaesthesia caused a greater mean blood pressure drop compared to the conscious sedation group, similar to the drop in systolic blood pressure found with RSI in our analysis. Despite the decreased blood pressure caused by general anaesthesia in the GOLIATH trial, no decreased survival with such a blood pressure drop was found. Interestingly, survival seems to increase for haemorrhagic stroke after decreased blood pressure, but this effect was not statistically significant. This suggestion of increased survival with decreasing blood pressure after clinical interventions in haemorrhagic strokes have been found in other studies [16].

Age could be the most important driver of the differences in RSI survival between strokes and TBI, not blood pressure. Age decreases survival for both strokes and TBI, but the survival decrease is much more rapid for haemorrhagic strokes. These differences in the steepness of decline of the age slopes are important when one considers that almost three quarters of all stroke RSI in our analysis were haemorrhagic strokes, and the average age of these haemorrhagic stokes were 65 years, compared to TBI of 43 years. Given this large difference in age between TBI and haemorrhagic stroke for those that received RSI, and keeping in mind the much steeper decline with age in survival when comparing haemorrhagic stokes to TBI, the large difference between the survival for haemorrhagic stroke compared to TBI is unsurprising. Large decreases in survival with advanced age for patients with haemorrhagic strokes are consistent with another Australian study [17].

Other important interactions in the RSI-only group were evident. An increased number of intubation attempts were associated with increased survival for haemorrhagic strokes. This surprising and possibly confounded effect could result from less obtunded patients needing more intubation attempts. Another significant interaction was atropine, with lower survival for TBI when atropine was used. The mechanisms of this finding are unexplained. Furthermore, the interaction of fentanyl on the pathologies showed TBI have better survival when fentanyl is used and ischemic strokes worse survival with fentanyl use. Fentanyl is used to blunt the hemodynamic effects of intubation [18], but causes a decrease in mean arterial pressure [19]. it is possible that the blood pressure effects of fentanyl could be the cause of this medications impact on survival in this analysis. Furthermore, our analysis also found an interaction between pulse rate and pathology, with both strokes and TBI associated with decreased survival with increased pulse rate. We believe that the effect of pulse rate is mainly through the impact of blood pressure changes, and not pulse rate itself. Also, RSI use is associated with an apparent reversal of the deleterious effect of staying on scene longer. This could be due to potential benefits of RSI or perhaps a selection effect: patient that lived long enough to receive RSI at later scene times would cause an association of better survival with longer times on scene.

It is a strength of our study that our measures of prognostic risk due to illness severity and comorbidities together predicted survival well with an area under curve of 0.83, which is higher than the 0.75 that would provide evidence of adequate risk adjustment [20]. Even so, it is possible that these results are still somewhat biased due to unmeasured confounding. Another strong point of our study is that it had a very large sample size, and consequently good statistical precision. This study has limitations. Firstly, the utility of observational methods to reveal treatment effects are limited, especially if the anticipated effect is small [21]. Secondly, we could not compare good neurological survival, which would have been a more suitable. Thirdly, we calculated the change in vital signs by subtracting the first values upon scene arrival from the last values before handover at the emergency department. Additionally, we believe that comparing the first vital signs measured upon arrival at the patient’s side to the last vital signs (measured after all prehospital treatments were given) would show the impact of the effects of RSI on these vital signs after adjustment for confounders. Our data did not allow for a comparison of vial sign changes during RSI. We did not consider non-linear interaction terms due to restrictions in the sample sizes of the RSI group, although we anticipated non-linear effects for many variables.

Rapid sequence intubation and related factors interact with stroke and TBI, which implies that RSI effects stroke survival differently from TBI. If RSI impact survival differently for strokes compared to TBI, then perhaps the TBI evidence cannot be used for stroke RSI. A trial comparing RSI to no-RSI in the out-of-hospital setting is urgently needed.