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. 2021 Nov 24;12:676154. doi: 10.3389/fphar.2021.676154

TABLE 3.

Main representative studies evaluating link between PRx and cerebral compensatory reserve with age/biological sex.

References Monitoring technique Number of patients Patient characteristics Relevant results Relevant conclusions
Cerebrovascular Reactivity
Czosnyka et al. (2008) - ICP: intraparenchymal probe (Camino ICP transducer in 12 patients and Codman ICP Microsensors in 566 patients) or via a ventricular drain and an external pressure transducer (34 patients) 612 total patients, 469 with PRx data - Severe TBI - Sex: 371 males; 98 females - There was significantly worse cerebrovascular pressure reactivity in females compared to males below 50 years; PRx in males was 0.044±0.031 and females was 0.11±0.047, p < 0.05
- ABP: indwelling arterial catheter in the radial artery - Median admission GCS was 6 in both males and females - Mean age: females 34 SD 16.5 years - This was not reflected in patients over 50 years
Males 34 SD 17 years - Younger patients who showed abnormal PRx of >0.3 had intracranial hypertension (mean ICP >25 mmHg), seen in 60% females and 20% males (p < 0.05)
Adams et al. (2017) - ICP: Intraparenchymal microsensor (Codman) 601 total patients, 556 with PRx data - Severe TBI - Sex: based on total cohort of patients (601): 464 males, 137 females - Mean PRx and SD in Functional Survivors group was 0.05±0.15 a.u. and in the Fatal Outcome group was 0.16±0.21 a.u., p < 0.001
- ABP: radial or femoral artery - Based on total cohort of patients (601): best preintubation GCS 3–8 in 435 patients and 9–15 in 166 patients Based on 556 patients with PRx data: Functional Survivors group: 360 males, 108 females - Males were predominant in both groups
- Two groups of patients were monitored Fatal Outcome group: 68 males, 20 females - The Fatal Outcome group had older patients with higher mean PRx
- Based on 556 patients with PRx data: best preintubation GCS in Functional Survivors group was 3–8 in 329 patients and 9–15 in 139 patients - Mean age: based on total cohort of patients (601): 39 SD 17 years
In Fatal Outcome group was 3–8 in 71 patients and 9–15 in 17 patients Based on 556 patients with PRx data: Functional Survivors group: 38±16 years
Fatal Outcome group: 45±18 years
Sorrentino et al. (2012) - ICP: intraparenchymal transducer (Codman) 459 - Mild to severe TBI - Sex: 359 males; 100 females - PRx threshold for survival was higher in males than females and for favorable outcome was higher in females than males
- ABP: radial or dorsalis pedis artery - Median admission GCS was 7 range 3–15, IQR 5 - Median age: 34, IQR 27 years
338 patients had GCS ≤8 and 121 patients had a GCS ≥9 - PRx survival threshold was 0.25, p < 0.001 while favorable outcome threshold was 0.05, p < 0.001
- No PRx threshold was found for survival or favorable outcome in patients >55 years old
- PRx threshold for survival in patients ≤55 years was 0.3, p < 0.001 and 0, p < 0.001 for favorable outcome
- PRx threshold for survival in females was 0.25, 0.3, p < 0.001 and for favourable outcome was 0.25, 0.3, p = 0.026
- PRx threshold for survival in males was 0.3, p = 0.002 and 0, p < 0.001 for favorable outcome
Zeiler et al. (2018) - ICP: Intraparenchymal strain gauge probe (Codman) 358 - Moderate to severe TBI - Mean/median age with SD/IQR: RAC < −0.05 group was 39.2 (16.7) years and in ≥0.05 group was 50.6 (17.5) years, p value <0.0001 for both groups - A notable difference was seen between age and APACHE scores of those patients below and above index thresholds; increased age and APACHE scores was seen in those above the thresholds
- ABP: radial or femoral arterial lines attached to pressure transducers - Two groups of patients were monitored For RAC < −0.10 group was 38.9 (16.7) years and in ≥ −0.10 group was 49.7 (17.0) years, p value <0.0001 for both groups - Of statistical significance was patient’s age with impaired cerebrovascular reactivity which showed high AUCs and low p values
Mean and median GCS with SD/IQR for RAC < −0.05 group was 7 (4–10) and in ≥ - 0.05 group was 5 (3–8.25) - The univariate logistic regression analysis showed generally increasing values for AUC and p values for age and sex in relation to PRx >0, 0.25 and 0.35
For RAC < −0.10 group was 7 (4–10) and in ≥ −0.10 group was 6 (3–8.25) - Advancing age was linked to impaired autoregulation
Czosnyka et al. (2005) - ICP: intraparenchymal probe (Camino ICP transducer in 12 patients and Codman ICP Microsensors in 346 patients) 358 - Mild to severe TBI - Sex: 288 males; 60 females - Study showed that elderly people suffered worse outcomes post TBI
- ABP: obtained invasively - Initial GCS scores ranged from 3–15, 20% patients had a GCS score above 8 - Age range: 16–87 years - PRx showed deterioration of cerebrovascular autoregulation and worsening of outcomes with age r = 0.24, p = 0.003
Cerebral Compensatory Reserve
Zeiler et al. (2018) - ICP: intraparenchymal strain gauge probe 358 - Moderate to severe TBI - Sex: 272 males; 86 females - No difference was noted in mean RAP variables among males and females, p > 0.05
- ABP: radial or femoral arterial lines attached to pressure transducers - Median admission GCS was 7 IQR 3–9 - Mean age: 40.6 SD 17.2 years - There was no relationship between RAP variables and patient age, p > 0.05
Zeiler et al. (2019) - ICP: Intraparenchymal strain gauge probe (Codman), parenchymal fiber optic pressure sensor or external ventricular drain 196 - Moderate to severe TBI - Sex: 150 males; 46 females - Mean/median RAP (+/- SD/IQR) was 0.614 (0.206) a.u. and wICP was 5.8 (7.9) mmHg
- ABP: radial or femoral arterial lines attached to pressure transducers - Mean/median and SD or IQR for admission GCS was 8±5–13 - Mean/median age: 46.6 SD 19.7 years - High mean age and compensatory-reserve-weighted intracranial pressure (wICP) was associated with worse outcomes and this considerable difference was noted between both Alive/Dead and Favorable/Unfavorable outcome groups
- p < 0.0001 for high mean age in Alive/Dead group and p = 0.001 for Favourable/Unfavourable outcome group
- p < 0.0001 for wICP in Alive/Dead group and p = 0.002 for Favourable/Unfavourable outcome group
Czosnyka et al. (1996b) - ICP: Camino transducer or subdural catheter 56 - Severe TBI - Sex: 40 males - There was no overall correlation made about this parameter with age and sex, but three specific examples were given where patients died from uncontrollable intracranial hypertension
- ABP: radial or dorsalis pedis artery - Mean GCS was 6 range 3–13 16 females - In these cases, RAP either dropped from around +1 to 0 or negative values
- Mean age: 36 range 6–75 years - Patients: 18 year old, GCS 3 on admission and RAP decreased toward 0 and time average RAP became negative; 35 year old male, GCS 3 on admission, RAP decreased to 0 and 15 year old male, GCS 3, RAP 0

ABP, arterial blood pressure; APACHE, acute physiology and chronic health evaluation; AUC, area under the ROC, curve; ICP, intracranial pressure; GCS, glasgow coma scale; GOS, glasgow outcome scale; IQR, interquartile range, p = p-value, PRx, pressure reactivity index, % = percentage, ROC, receiver operating characteristic curve, r = correlation coefficient, RAP = (R – correlation, A – pulse amplitude of ICP, P – intracranial pressure), SD, standard deviation; TBI, traumatic brain injury; wICP, compensatory–reserve-weighted intracranial pressure.