Traumatic brain injury (TBI) is a major global health problem and the leading cause of death and disability in people under 40 in many countries. Approximately 24% of patients with severe isolated TBI experience cardiovascular dysfunction prior to physician-led emergency helicopter assessment. These patients have lower GCS, higher heart rate and lactate, and worse coagulopathy compared to those without cardiovascular dysfunction. They also require more blood transfusions, have higher mortality, and are less likely to be discharged home. Further research is needed to better understand the pathophysiology of cardiovascular dysfunction following severe TBI in order to improve recognition and treatment in the critical hyperacute phase after injury.

1. TBI and CV dysfunction
Dr Flora Bird
LAA

3. Traumatic brain injury – Why?

4. Background – Why care?
• Traumatic brain injury (TBI)
- Worldwide global health problem; International call for further research (Rosenfeld 2012)
- Most common cause of death or disability in < 40 years-old in the UK (NICE 2014)
- Europe – 37% (95% CI 36-38) of all injury-related deaths (Majden 2016)
- USA – 50% trauma deaths assoc with Head AIS ≥ 4 (Bardes 2018)
- 2:1 (M:F) (Majden 2016)
• LAA data (2019-2020):
>5 per week severe TBI (GCS ≤ 8) (clinical interpretation)
>1 per week severe isolated TBI conveyed to MTC
• Lack of improvement in outcome in last 30 years (Patel, 2005; Stein, 2010; Cole, 2019)

5. Golden Hour
Golden seconds to minutes
‘Hyperacute phase’

7. • Early pathophysiology
• Cardiovascular sequalae
• CV dysfunction/ shock
• Clinical challenges

8. Pathophysiology of severe TBI
• Multi system effects – not limited to the brain alone
• Sequalae associated with axonal stretch
• Apnoea and dysventilation
• Systemic inflammatory response (pro-inflammatory, coagulopathy)
• Cardiovascular

9. ‘Shock does not result from isolated brain injuries’
ATLS

10. CASE
81 F, Pedestrian vs. motorbike
Immediately unconscious, breathing with dysventilation
GCS 4, Unequal pupils
IMP:
1. Significant TBI - suspected SAH, SDH, IPH.
2. Left rib fractures
3. Right scapula fracture ? Rib fractures.
4. At risk of intra abdominal injury and pelvic fracture.
5. Open left tib fib.

13. Treatment?

14. Treatment?
• Blood transfusion
• RSI
• Thoracostomies
• HTS
• Arterial line
• POCUS
• Escort to MTC – Code Red/ Code Black

15. Outcome
• Bilateral rib fractures and surgical emphysema. No flail. left and right tibial
fractures. Unstable pelvic fracture with haematomas. Grade 2 splenic lac.
• Subarachnoid blood and cerebral contusions. Right skull fracture and facial
fractures. C6/7 ?ligament injury.
• Admitted to ICU with bolt.
• 3 RBC and 2FFP given in resus.

16. Outcome
• Bilateral rib fractures and surgical emphysema. No flail. left and right tibial
fractures. Unstable pelvic fracture with haematomas. Grade 2 splenic lac.
• Subarachnoid blood and cerebral contusions. Right skull fracture and facial
fractures. C6/7 ?ligament injury.
• Admitted to ICU with bolt.
• 3 RBC and 2FFP given in resus.
• Sadly RIP

18. Data
• Observational cohort database study of severe iTBI patients (Head AIS 3+) at a Level 1 trauma
centre (2008-2019) and from a physician-led air ambulance service (2019-20)
• CV Dysfunction = HR >100 with SBP <100mmHg
• Aims: (1) determine the prevalence and phenotype of CVD after iTBI in the hyper-acute phase
(2) compare treatment and clinical outcomes in those with CVD vs non-CVD.

19. Results
• N 168
• Median 46 years (IQR 30-61)
• 77% were male
• Median ISS was 25 (IQR 17-29) (51% having Head AIS 5)
• Incident to HEMS on scene: 31 min (IQR 20-42); 1 in 4 <20 min
• 20% had physiological shock on initial assessment
• 24% of LAA cohort had CVD prior to PHEA

20. Table 1
Variable Non-CVD (n 135) CVD (n 33)
Age 46 (30 - 60) 40 (30 - 63)
Sex n (%) MALE 106 (79%) 24 (73%)
ISS 25 (17 - 29) 25 (12 - 30)
Head AIS 5 (4 - 5) 5 (3-5)
Time: Injury to pre-hospital
assessment (min)
31 (20-41) 31 (21 - 44)
Time: Injury to hospital (min) 83 (69 - 99) 88 (76 - 100)
GCS on scene 5 (3 - 7) 3 (3 - 5) **
First observation on scene:
HR
SBP
82 (68-97)
142 (137-147)
103 (50-120)
73 (0-110) **
ED arrival observations:
HR
BP
Lactate
86 (72-99)
139 (117-159)
2.4 (1.4 - 3.3)
104 (94-113) **
107 (94-119) **
6.1 (1.7 - 10.9) **
Clotting on arrival to hospital n (%)
INR >1.2 OR PT >17.4 19 (15%) 13 (43%) **

21. Table 1
Variable Non-CVD (n 135) CVD (n 33)
Age 46 (30 - 60) 40 (30 - 63)
Sex n (%) MALE 106 (79%) 24 (73%)
ISS 25 (17 - 29) 25 (12 - 30)
Head AIS 5 (4 - 5) 5 (3-5)
Time: Injury to pre-hospital
assessment (min)
31 (20-41) 31 (21 - 44)
Time: Injury to hospital (min) 83 (69 - 99) 88 (76 - 100)
GCS on scene 5 (3 - 7) 3 (3 - 5) **
First observation on scene:
HR
SBP
82 (68-97)
142 (137-147)
103 (50-120)
73 (0-110) **
ED arrival observations:
HR
BP
Lactate
86 (72-99)
139 (117-159)
2.4 (1.4 - 3.3)
104 (94-113) **
107 (94-119) **
6.1 (1.7 - 10.9) **
Clotting on arrival to hospital n (%)
INR >1.2 OR PT >17.4 19 (15%) 13 (43%) **

22. Table 2
Variable Non-CVD (n 135) CVD (n 33)
Prehospital treatment
Drug assisted intubation (%)
Hypertonic saline (NaCl 5%) n (%)
Blood products (PRBC)
Blood products (FFP)
47 (94%)
40 (30%)
0 (0)
0 (0)
17 (90%)
13 (39%)
0 (0 - 2) **
0 (0 - 1) **
24 hour blood transfusion (units) 0 (0) 3 (0 - 8) **
Neurosurgical Intervention 48 (43%) 13 (43%)
ICU LOS (days) 11 (3 - 19) 12 (2 - 25)
Vasopressor days 2 (0 - 5) 2 (0 - 4)
Total LOS (days) 28 (13 - 47) 32 (10 - 61)
Time to death (days) 2.5 (2 - 6) 2.5 (1 - 6)
28-day mortality 42 (31%) 20 (61%) **

23. Table 2
Variable Non-CVD (n 135) CVD (n 33)
Prehospital treatment
Drug assisted intubation (%)
Hypertonic saline (NaCl 5%) n (%)
Blood products (PRBC)
Blood products (FFP)
47 (94%)
40 (30%)
0 (0)
0 (0)
17 (90%)
13 (39%)
0 (0 - 2) **
0 (0 - 1) **
24 hour blood transfusion (units) 0 (0) 3 (0 - 8) **
Neurosurgical Intervention 48 (43%) 13 (43%)
ICU LOS (days) 11 (3 - 19) 12 (2 - 25)
Vasopressor days 2 (0 - 5) 2 (0 - 4)
Total LOS (days) 28 (13 - 47) 32 (10 - 61)
Time to death (days) 2.5 (2 - 6) 2.5 (1 - 6)
28-day mortality 42 (31%) 20 (61%) **

24. 0
10
20
30
40
50
60
AIS 3 AIS 4 AIS 5 AIS 6
Incidence
(%)
AIS non-CVD CVD
*
**
0
10
20
30
40
50
60
70
80
90
EDH SDH SAH/IP/IV DAI HIE
Incidence
(%)
TBI pathology non-CVD CVD
**
0
5
10
15
20
25
30
35
40
45
50
Fall >2m Fall <2m RTC Assault Other
Incidence
(%)
Mechanism of Injury non-CVD CVD
0
5
10
15
20
25
30
1
0
-
1
9
2
0
-
2
9
3
0
-
3
9
4
0
-
4
9
5
0
-
5
9
6
0
-
6
9
7
0
-
7
9
8
0
-
8
9
9
0
-
9
9
Proportion
(%)
Age (years) non-CVD CVD

25. 0
5
10
15
20
25
30
AIS 3 AIS 4 AIS 5 AIS 6
Mortality
(%)
AIS non-CVD CVD
**
*
0
10
20
30
40
50
60
70
Died Nursinghome/Hospital Home
Proportion
(%)
Destination non-CVD CVD
**

26. Pathophysiology
Cardiovascular – systemic CAs
• Animal models
- 1894 - stress response to TBI (Polis, 1894)
- 1980s - CA surge (Rosner, 1984)
• Humans
- Plasma CAs correlate with ISS, GCS (Woolf, 92)
- Elevated plasma CAs assoc with
functional outcome & mortality (Rizoli, 2017)
Rosner et al. J. Neurosurgery. 1984, 61 (1)

27. Pathophysiology
Cardiovascular – local CAs
Local myocardial effects:
• CA release from efferent cardiac sympathetic neurons
• Opens b1-A Ca channels, Ca influx, myofibril contraction,
ATP depletion, mitochondrial damage, myocyte death
• Contraction band necrosis on autopsy (normal coronary
arteries)
• ‘Neurogenic stunned myocardium’
(Karch et al. 1986)
(Mann et al. 1991)

28. A hypothesis for CV dysfunction in iTBI:
Apnoea ➜ hypoxia, hypercarbia, acidosis
+
Systemic CA surge ➜ increased SVR, afterload, myocardial demand
+
Local CA effects ➜ myocyte hypercontraction & death
+
Systemic inflammatory mediated response
• See ‘shocked state’, fluctuating BPs, changes on ECHO
• Results inadequate cerebral perfusion and oxygen delivery

29. • How to recognise?
• How to best treat?
• How to best optimise CO
and cerebral perfusion/
cerebral oxygenation?
The challenge

30. Responding to the challenge
• Importance of impact in the hyperacute phase
• Role of dispatch
• “Exquisite attention to detail from the earliest point of contact”
• Use of POCUS

31. Conclusion
• TBI a major concern and proportion of pre-hospital trauma work; Lack of
improvement in outcome over last 30 yrs
• Likely no quick fix; Improvement may come from precise pre-hospital
management in the hyperacute phase; Importance of dispatch and bystanders
• CV dysfunction in severe TBI present in 24% patients pre-PHEA
• Requires better understanding of early pathophysiology

32. Thank you