Date Published: July 25, 2017
Publisher: Public Library of Science
Author(s): Xiuyun Liu, Joseph Donnelly, Marek Czosnyka, Marcel J. H. Aries, Ken Brady, Danilo Cardim, Chiara Robba, Manuel Cabeleira, Dong-Joo Kim, Christina Haubrich, Peter J. Hutchinson, Peter Smielewski, Martin Schreiber
Abstract: BackgroundAfter traumatic brain injury (TBI), the ability of cerebral vessels to appropriately react to changes in arterial blood pressure (pressure reactivity) is impaired, leaving patients vulnerable to cerebral hypo- or hyperperfusion. Although, the traditional pressure reactivity index (PRx) has demonstrated that impaired pressure reactivity is associated with poor patient outcome, PRx is sometimes erratic and may not be reliable in various clinical circumstances. Here, we introduce a more robust transform-based wavelet pressure reactivity index (wPRx) and compare its performance with the widely used traditional PRx across 3 areas: its stability and reliability in time, its ability to give an optimal cerebral perfusion pressure (CPPopt) recommendation, and its relationship with patient outcome.Methods and findingsFive hundred and fifteen patients with TBI admitted in Addenbrooke’s Hospital, United Kingdom (March 23rd, 2003 through December 9th, 2014), with continuous monitoring of arterial blood pressure (ABP) and intracranial pressure (ICP), were retrospectively analyzed to calculate the traditional PRx and a novel wavelet transform-based wPRx. wPRx was calculated by taking the cosine of the wavelet transform phase-shift between ABP and ICP. A time trend of CPPopt was calculated using an automated curve-fitting method that determined the cerebral perfusion pressure (CPP) at which the pressure reactivity (PRx or wPRx) was most efficient (CPPopt_PRx and CPPopt_wPRx, respectively).There was a significantly positive relationship between PRx and wPRx (r = 0.73), and wavelet wPRx was more reliable in time (ratio of between-hour variance to total variance, wPRx 0.957 ± 0.0032 versus PRx and 0.949 ± 0.047 for PRx, p = 0.002). The 2-hour interval standard deviation of wPRx (0.19 ± 0.07) was smaller than that of PRx (0.30 ± 0.13, p < 0.001). wPRx performed better in distinguishing between mortality and survival (the area under the receiver operating characteristic [ROC] curve [AUROC] for wPRx was 0.73 versus 0.66 for PRx, p = 0.003). The mean difference between the patients’ CPP and their CPPopt was related to outcome for both calculation methods. There was a good relationship between the 2 CPPopts (r = 0.814, p < 0.001). CPPopt_wPRx was more stable than CPPopt_PRx (within patient standard deviation 7.05 ± 3.78 versus 8.45 ± 2.90; p < 0.001).Key limitations include that this study is a retrospective analysis and only compared wPRx with PRx in the cohort of patients with TBI. Prior prospective validation is required to better assess clinical utility of this approach.ConclusionswPRx offers several advantages to the traditional PRx: it is more stable in time, it yields a more consistent CPPopt recommendation, and, importantly, it has a stronger relationship with patient outcome. The clinical utility of wPRx should be explored in prospective studies of critically injured neurological patients.
Partial Text: Traumatic brain injury (TBI) is an important global public health problem as a major cause of traumatic death and disability, especially in young people [1,2]. Management of these critically ill patients hinges on the early identification of secondary injuries to the brain and typically involves monitoring of intracranial pressure (ICP) and cerebral perfusion pressure (CPP). With increased sophistication of neuro-monitoring techniques, there is now the opportunity to interrogate cerebral homeostatic mechanisms that may represent hitherto underrecognized pathophysiological pathways . One such cerebral homeostatic mechanism is the ability of the brain to maintain constant cerebral blood flow despite variations in CPP—a mechanism known as cerebral autoregulation (CA) . Failure of this defensive mechanism, even for a short period, may lead to serious consequences, particularly in vulnerable patients following TBI. Therefore, monitoring of CA has been proffered as beneficial for the detection of secondary brain injuries and potentially has a therapeutic role in management of severe TBI .
The group of patients included 130 females and 385 males, with their characteristics described in Table 1. Their mean age was 38.4 ± 16 (mean ± SD) years old, median GCS score was 7 (interquartile range [IQR]: 3–9). The GCS and GOS score were missing in 34 and 73 patients, respectively. The average ABP and ICP of this cohort was 94.8 ± 15.3 mmHg and 16.2 ± 12.2 mmHg, respectively. Average CPP was 78.6 ± 15.8 mmHg. For the outcome analysis, patients with a missing GOS score were excluded. The outcome was distributed as follows: good recovery, n = 75 (17.0%), moderate disability, n = 117 (26.5%), severe disability, n = 142 (32.1%); persistent vegetative state, n = 11 (2.5%); and death, n = 97 (21.9%). The mean recording time per patient after artifact removal was 118.6 hours (range from 1 hour to 536 hours). Time trends of ABP, CPP, PRx, and wPRx are shown in Fig 1.
The wavelet transform is a time—frequency method that facilitates more accurate analysis of biological signals containing components that are nonstationary . In this study, we have introduced and developed a wavelet-based methodology of continuous assessment of CA for 515 patients with TBI, termed wPRx, and compared it with a widely used parameter, PRx. The ability of the new parameter to distinguish different patient outcomes was also examined. There were 5 principal findings in this study: (1) a close relationship existed between PRx and wPRx, (2) wPRx showed more stable trends, (3) wPRx demonstrated better performance than PRx in terms of distinguishing different patient outcomes, (4) wPRx makes CPPopt estimation more continuous, and (5) pressure reactivity deteriorated while the age is increased.
This study introduces a new, wavelet-based method for cerebral pressure reactivity assessment in patients with TBI. Based on these findings, wPRx is stable in time, yields consistent CPPopt recommendation, and, importantly, has a strong relationship with patient outcome.