Leanne Calviello

Pressure Autoregulation Measurement Techniques in Adult Traumatic Brain Injury, Part I: A Scoping Review of Intermittent/Semi-Intermittent Methods.

This work was made possible through salary support through the Cambridge Commonwealth Trust Scholarship, the Royal College of Surgeons of Canada – Harry S. Morton Travelling Fellowship in Surgery, the University of Manitoba Clinician Investigator Program, R. Samuel McLaughlin Research and Education Award, the Manitoba Medical Service Foundation, and the University of Manitoba Faculty of Medicine Dean’s Fellowship Fund. JD is supported by a Woolf Fisher Scholarship (NZ). These studies were also supported by National Institute for Healthcare Research (NIHR, UK) through the Acute Brain Injury and Repair theme of the Cambridge NIHR Biomedical Research Centre, an NIHR Senior Investigator Award to DKM. Authors were also supported by a European Union Framework Program 7 grant (CENTER-TBI; Grant Agreement No. 602150)

Validation of Pressure Reactivity and Pulse Amplitude Indices against the Lower Limit of Autoregulation: Part I: Experimental Intracranial Hypertension.

The purpose of this study was to provide validation of intracranial pressure (ICP) derived continuous indices of cerebrovascular reactivity against the lower limit of autoregulation (LLA). Utilizing an intracranial hypertension model within white New Zealand rabbits, ICP, transcranial Doppler (TCD), laser Doppler flowmetry (LDF), and arterial blood pressure were recorded. Data were retrospectively analyzed in a cohort of 12 rabbits with adequate signals for interrogating the LLA. We derived continuous indices of cerebrovascular reactivity: PRx (correlation between ICP and mean arterial pressure [MAP]), PAx (correlation between pulse amplitude of ICP [AMP] and MAP), and Lx (correlation between LDF-based cerebral blood flow [CBF] and cerebral perfusion pressure [CPP]). LLA was derived via piecewise linear regression of CPP versus LDF or CPP versus systolic flow velocity (FVs) plots. We then produced error bar plots for PRx, PAx, and Lx against 2.5 mm Hg bins of CPP, to display the relationship between these indices and the LLA. We compared the CPP values at clinically relevant thresholds of PRx and PAx, to the CPP defined at the LLA. Receiver operating curve (ROC) analysis was performed for each index across the LLA using 2.5 mm Hg bins for CPP. The mean LLA was 51.5 ± 8.2 mm Hg. PRx and PAx error bar plots demonstrate that each index correlates with the LLA, becoming progressively more positive below the LLA. Similarly, CPP values at clinically relevant thresholds of PRx and PAx were not statistically different from the CPP derived at the LLA. Finally, ROC analysis indicated that PRx and PAx predicted the LAA, with areas under the curve (AUCs) of 0.795 (95% confidence interval [CI]: 0.731-0.857, p < 0.0001) and 0.703 (95% CI: 0.631-0.775, p < 0.0001), respectively. Both PRx and PAx generally agree with LLA within this experimental model of intracranial hypertension. Further analysis of clinically used indices of autoregulation across the LLA within pure arterial hypotension models is required.

Intra- and Extra-Cranial Injury Burden as Drivers of Impaired Cerebrovascular Reactivity in Traumatic Brain Injury

Impaired cerebrovascular reactivity has been associated with outcome following traumatic brain injury (TBI), but it is unknown how it is affected by trauma severity. Thus, we aimed to explore the relationship between intracranial (IC) and extracranial (EC) injury burden and cerebrovascular reactivity in TBI patients. We retrospectively included critically ill TBI patients. IC injury burden included detailed lesion and computerized tomography (CT) scoring (i.e., Marshall, Rotterdam, Helsinki, and Stockholm Scores) on admission. EC injury burden was characterized using the injury severity score (ISS) and the Acute Physiology and Chronic Health Evaluation II (APACHE II) score. Pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC were used to assess autoregulation/cerebrovascular reactivity. We used univariate and multi-variate logistic regression techniques to explore relationships between IC and EC injury burden and autoregulation indices. A total of 358 patients were assessed. ISS and all IC CT scoring systems were poor predictors of impaired cerebrovascular reactivity. Only subdural hematomas and thickness of subarachnoid hemorrhage (SAH; p < 0.05, respectively) were consistently associated with dysfunctional cerebrovascular reactivity. High age (p < 0.01 for all) and admission APACHE II scores (p < 0.05 for all) were the two variables most strongly associated with abnormal cerebrovascular reactivity. In summary, diffuse IC injury markers (thickness of SAH and the presence of a subdural hematoma) and APACHE II were most associated with dysfunction in cerebrovascular reactivity after TBI. Standard CT scoring systems and evidence of macroscopic parenchymal damage are poor predictors, implicating potentially both microscopic injury patterns and host response as drivers of dysfunctional cerebrovascular reactivity. Age remains a major variable associated with cerebrovascular reactivity.

Pressure Autoregulation Measurement Techniques in Adult TBI, Part II: A Scoping Review of Continuous Methods

This work was made possible through salary support through the Cambridge Commonwealth Trust Scholarship, the Royal College of Surgeons of Canada – Harry S. Morton Travelling Fellowship in Surgery, the University of Manitoba Clinician Investigator Program, R. Samuel McLaughlin Research and Education Award, the Manitoba Medical Service Foundation, and the University of Manitoba Faculty of Medicine Dean’s Fellowship Fund. JD is supported by a Woolf Fisher Scholarship (Woolf Fisher Trust, NZ). These studies were also supported by National Institute for Healthcare Research (NIHR, UK) through the Acute Brain Injury and Repair theme of the Cambridge NIHR Biomedical Research Centre, an NIHR Senior Investigator Award to DKM. Authors were also supported by a European Union Framework Program 7 grant (CENTER-TBI; Grant Agreement No. 602150)

Do ICP-Derived Parameters Differ in Vegetative State from Other Outcome Groups After Traumatic Brain Injury?

OBJECTIVE In nearly 1,000 traumatic brain injury (TBI) patients monitored in the years 1992-2014, we identified 18 vegetative state (VS) cases. Our database provided access to continuous computer-recorded signals, which we used to compare primary signals, intracranial pressure (ICP)-derived indices and demographic data between VS patients, patients who survived but who were not VS (S), and patients who died (D). METHOD Mean values of ICP, arterial blood pressure (ABP) and cerebral perfusion pressure (CPP) from the whole monitoring periods were compared between the different outcome groups. Secondary indices included pressure reactivity index (PRx), the magnitude of slow ICP vasogenic waves, the pulse amplitude of the first harmonic component of the ICP waveform and heart rate (HR). RESULTS Mean blood pressure was lowest in the VS group-significantly in comparison to those who died (p = 0.02) and almost significantly (p = 0.1) in comparison to the patients who survived. Mean ICP in VS patients was lower than those who died (VS, 13 ± 5 mmHg; D, 22 ± 14 mmHg; p < 0.001), but not significantly different from those who survived (p > 0.05). The magnitude of slow vasogenic ICP waves was the same in VS patients and those who died, but significantly lower than in those who survived (S, 1.04 ± 0.57 mmHg; VS, 0.74 ± 0.45; p = 0.01). CONCLUSION Patients who progress to a VS differ from non-VS survivors in displaying decreased power of slow vasogenic waves and from those who die by not experiencing as high a burden of intracranial hypertension.

Critical Closing Pressure During Controlled Increase in Intracranial Pressure—Comparison of Three Methods

Goal: Critical closing pressure (CrCP) is the arterial blood pressure (ABP) threshold, below which small arterial vessels collapse and cerebral blood flow ceases. Here, we aim to compare three methods for CrCP estimation in scenario of a controlled increase in intracranial pressure (ICP), induced by infusion tests performed in patients with suspected normal pressure hydrocephalus (NPH). Methods: Computer recordings of directly-measured ICP, ABP, and transcranial Doppler cerebral blood flow velocity (CBFV), from 37 NPH patients undergoing infusion tests, were retrospectively analyzed. The CrCP was calculated with three methods: one with the first harmonics ratio of the pulse waveforms of ABP and CBFV (CrCPA) and two methods based on a model of cerebrovascular impedance, as functions of both cerebral perfusion pressure (CrCPinv), and of ABP (CrCPninv). Conclusion: All methods give similar results in response to ICP changes. In the case of individual CrCP measurements for each patient, CrCPA may provide negative, nonphysiological values. Invasive critical closing pressure is most sensitive to variations in ICP and CPP and can be used as an indicator of the cerebrospinal and the cerebrovascular system status during infusion tests.