Chiara Robba

Non-invasive assessment of intracranial pressure

Monitoring of intracranial pressure (ICP) is invaluable in the management of neurosurgical and neurological critically ill patients. Invasive measurement of ventricular or parenchymal pressure is considered the gold standard for accurate measurement of ICP but is not always possible due to certain risks. Therefore, the availability of accurate methods to non‐invasively estimate ICP has the potential to improve the management of these vulnerable patients. This review provides a comparative description of different methods for non‐invasive ICP measurement. Current methods are based on changes associated with increased ICP, both morphological (assessed with magnetic resonance, computed tomography, ultrasound, and fundoscopy) and physiological (assessed with transcranial and ophthalmic Doppler, tympanometry, near‐infrared spectroscopy, electroencephalography, visual‐evoked potentials, and otoacoustic emissions assessment). At present, none of the non‐invasive techniques alone seem suitable as a substitute for invasive monitoring. However, following the present analysis and considerations upon each technique, we propose a possible flowchart based on the combination of non‐invasive techniques including those characterizing morphologic changes (e.g., repetitive US measurements of ONSD) and those characterizing physiological changes (e.g., continuous TCD). Such an integrated approach, which still needs to be validated in clinical practice, could aid in deciding whether to place an invasive monitor, or how to titrate therapy when invasive ICP measurement is contraindicated or unavailable.

Ultrasound non-invasive measurement of intracranial pressure in neurointensive care: A prospective observational study

Background The invasive nature of the current methods for monitoring of intracranial pressure (ICP) has prevented their use in many clinical situations. Several attempts have been made to develop methods to monitor ICP non-invasively. The aim of this study is to assess the relationship between ultrasound-based non-invasive ICP (nICP) and invasive ICP measurement in neurocritical care patients. Methods and findings This was a prospective, single-cohort observational study of patients admitted to a tertiary neurocritical care unit. Patients with brain injury requiring invasive ICP monitoring were considered for inclusion. nICP was assessed using optic nerve sheath diameter (ONSD), venous transcranial Doppler (vTCD) of straight sinus systolic flow velocity (FVsv), and methods derived from arterial transcranial Doppler (aTCD) on the middle cerebral artery (MCA): MCA pulsatility index (PIa) and an estimator based on diastolic flow velocity (FVd). A total of 445 ultrasound examinations from 64 patients performed from 1 January to 1 November 2016 were included. The median age of the patients was 53 years (range 37–64). Median Glasgow Coma Scale at admission was 7 (range 3–14), and median Glasgow Outcome Scale was 3 (range 1–5). The mortality rate was 20%. ONSD and FVsv demonstrated the strongest correlation with ICP (R = 0.76 for ONSD versus ICP; R = 0.72 for FVsv versus ICP), whereas PIa and the estimator based on FVd did not correlate with ICP significantly. Combining the 2 strongest nICP predictors (ONSD and FVsv) resulted in an even stronger correlation with ICP (R = 0.80). The ability to detect intracranial hypertension (ICP ≥ 20 mm Hg) was highest for ONSD (area under the curve [AUC] 0.91, 95% CI 0.88–0.95). The combination of ONSD and FVsv methods showed a statistically significant improvement of AUC values compared with the ONSD method alone (0.93, 95% CI 0.90–0.97, p = 0.01). Major limitations are the heterogeneity and small number of patients included in this study, the need for specialised training to perform and interpret the ultrasound tests, and the variability in performance among different ultrasound operators. Conclusions Of the studied ultrasound nICP methods, ONSD is the best estimator of ICP. The novel combination of ONSD ultrasonography and vTCD of the straight sinus is a promising and easily available technique for identifying critically ill patients with intracranial hypertension.

Extracorporeal membrane oxygenation for adult respiratory distress syndrome in trauma patients: A case series and systematic literature review.

BACKGROUND Venovenous extracorporeal membrane oxygenation (vv-ECMO) is an established salvage therapy for severe respiratory failure, and may provide an alternative form of treatment for trauma-induced adult respiratory distress syndrome (ARDS) when conventional treatments have failed. The need for systemic anticoagulation is a relative contraindication for patients with bleeding risks, especially in multitraumatic injury. METHODS We describe a case series of four trauma patients with ARDS who were managed with ECMO admitted to the neuro critical care unit at Addenbrooke’s Hospital, Cambridge (UK), from January 2000 to January 2016. We performed a systematic review of the available literature to investigate the safety and efficacy of vv-ECMO in posttraumatic ARDS, focusing on the use of different anticoagulation strategies and risk of bleeding on patients with multiple injuries. RESULTS Thirty-one patients were included. A heparin bolus was given in 16 cases. Eleven patients developed complications during treatment with ECMO with three cases of major bleeding. In all documented cases of bleeding a bolus and infusion of heparin was administered, aiming for an activated clotting time (ACT) target longer than 150 seconds. Two patients treated with heparin-free ECMO developed thromboembolic complications. Four patients died, and death was never directly or indirectly related to use of ECMO. CONCLUSION vv-ECMO can be lifesaving in respiratory failure. Our experience and our literature review suggest that vv-ECMO should be considered as a rescue treatment for the management of severe hypoxemic respiratory failure secondary to ARDS in trauma patients. For patients with a high risk of bleeding, the use of ECMO with no initial anticoagulation could be considered a valid option. For patients with a moderate risk of bleeding, use of a heparin infusion keeping an ACT target shorter than 150 seconds can be appropriate. LEVEL OF EVIDENCE Therapeutic study, level V.

Cerebral haemodynamics during experimental intracranial hypertension

Intracranial hypertension is a common final pathway in many acute neurological conditions. However, the cerebral haemodynamic response to acute intracranial hypertension is poorly understood. We assessed cerebral haemodynamics (arterial blood pressure, intracranial pressure, laser Doppler flowmetry, basilar artery Doppler flow velocity, and vascular wall tension) in 27 basilar artery-dependent rabbits during experimental (artificial CSF infusion) intracranial hypertension. From baseline (∼9 mmHg; SE 1.5) to moderate intracranial pressure (∼41 mmHg; SE 2.2), mean flow velocity remained unchanged (47 to 45 cm/s; p = 0.38), arterial blood pressure increased (88.8 to 94.2 mmHg; p < 0.01), whereas laser Doppler flowmetry and wall tension decreased (laser Doppler flowmetry 100 to 39.1% p < 0.001; wall tension 19.3 to 9.8 mmHg, p < 0.001). From moderate to high intracranial pressure (∼75 mmHg; SE 3.7), both mean flow velocity and laser Doppler flowmetry decreased (45 to 31.3 cm/s p < 0.001, laser Doppler flowmetry 39.1 to 13.3%, p < 0.001), arterial blood pressure increased still further (94.2 to 114.5 mmHg; p < 0.001), while wall tension was unchanged (9.7 to 9.6 mmHg; p = 0.35).This animal model of acute intracranial hypertension demonstrated two intracranial pressure-dependent cerebroprotective mechanisms: with moderate increases in intracranial pressure, wall tension decreased, and arterial blood pressure increased, while with severe increases in intracranial pressure, an arterial blood pressure increase predominated. Clinical monitoring of such phenomena could help individualise the management of neurocritical patients.

Prospective study on non-invasive assessment of ICP in head injured patients: comparison of four methods

DC is supported by a Cambridge Commonwealth, European & International Trust Scholarship, University of Cambridge. JD is supported by a Woolf Fisher Trust Scholarship. XL is supported by a Gates Cambridge Scholarship. GVV is supported by an A. G. Leventis Foundation Scholarship, and a Charter Studentship from St Edmund’s College, Cambridge. SM and GF are supported by the Pan-American Health Organization. DC and MC are partially supported by NIHR Brain Injury Healthcare Technology Co-operative, Cambridge, UK.

Cerebrovascular pressure reactivity monitoring using wavelet analysis in traumatic brain injury patients: A retrospective study

Background After 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 findings Five 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. Conclusions wPRx 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.

Infodemiological data of West-Nile virus disease in Italy in the study period 2004–2015

Google Trends (GT) was mined from 2004 to 2015, searching for West-Nile virus disease (WNVD) in Italy. GT-generated data were modeled as a time series and were analyzed using classical time series analyses. In particular, correlation between GT-based Relative Search Volumes (RSVs) related to WNVD and “real-world” epidemiological cases in the same study period resulted r=0.76 (p<0.0001) on a monthly basis and r=0.80 (p<0.0001) on a yearly basis. The partial autocorrelation analysis and the spectral analysis confirmed that a 1-year regular pattern could be detected. Correlation between GT-based RSVs related to WNVD yielded a r=0.54 (p<0.05) on a regional basis. Summarizing, GT-generated data concerning WNVD well correlated with epidemiology and could be exploited for complementing traditional surveillance.

Effects of Prone Position and Positive End-Expiratory Pressure on Noninvasive Estimators of ICP: A Pilot Study.

Background: Prone positioning and positive end-expiratory pressure can improve pulmonary gas exchange and respiratory mechanics. However, they may be associated with the development of intracranial hypertension. Intracranial pressure (ICP) can be noninvasively estimated from the sonographic measurement of the optic nerve sheath diameter (ONSD) and from the transcranial Doppler analysis of the pulsatility (ICPPI) and the diastolic component (ICPFVd) of the velocity waveform. Methods: The effect of the prone positioning and positive end-expiratory pressure on ONSD, ICPFVd, and ICPPI was assessed in a prospective study of 30 patients undergoing spine surgery. One-way repeated measures analysis of variance, fixed-effect multivariate regression models, and receiver operating characteristic analyses were used to analyze numerical data. Results: The mean values of ONSD, ICPFVd, and ICPPI significantly increased after change from supine to prone position. Receiver operating characteristic analyses demonstrated that, among the noninvasive methods, the mean ONSD measure had the greatest area under the curve signifying it is the most effective in distinguishing a hypothetical change in ICP between supine and prone positioning (0.86±0.034 [0.79 to 0.92]). A cutoff of 0.43 cm was found to be a best separator of ONSD value between supine and prone with a specificity of 75.0 and a sensitivity of 86.7. Conclusions: Noninvasive ICP estimation may be useful in patients at risk of developing intracranial hypertension who require prone positioning.

Individualizing Thresholds of Cerebral Perfusion Pressure Using Estimated Limits of Autoregulation

Objectives: In severe traumatic brain injury, cerebral perfusion pressure management based on cerebrovascular pressure reactivity index has the potential to provide a personalized treatment target to improve patient outcomes. So far, the methods have focused on identifying “one” autoregulation-guided cerebral perfusion pressure target—called “cerebral perfusion pressure optimal”. We investigated whether a cerebral perfusion pressure autoregulation range—which uses a continuous estimation of the “lower” and “upper” cerebral perfusion pressure limits of cerebrovascular pressure autoregulation (assessed with pressure reactivity index)—has prognostic value. Design: Single-center retrospective analysis of prospectively collected data. Setting: The neurocritical care unit at a tertiary academic medical center. Patients: Data from 729 severe traumatic brain injury patients admitted between 1996 and 2016 were used. Treatment was guided by controlling intracranial pressure and cerebral perfusion pressure according to a local protocol. Interventions: None. Methods and Main Results: Cerebral perfusion pressure-pressure reactivity index curves were fitted automatically using a previously published curve-fitting heuristic from the relationship between pressure reactivity index and cerebral perfusion pressure. The cerebral perfusion pressure values at which this “U-shaped curve” crossed the fixed threshold from intact to impaired pressure reactivity (pressure reactivity index = 0.3) were denoted automatically the “lower” and “upper” cerebral perfusion pressure limits of reactivity, respectively. The percentage of time with cerebral perfusion pressure below (%cerebral perfusion pressure < lower limit of reactivity), above (%cerebral perfusion pressure > upper limit of reactivity), or within these reactivity limits (%cerebral perfusion pressure within limits of reactivity) was calculated for each patient and compared across dichotomized Glasgow Outcome Scores. After adjusting for age, initial Glasgow Coma Scale, and mean intracranial pressure, percentage of time with cerebral perfusion pressure less than lower limit of reactivity was associated with unfavorable outcome (odds ratio %cerebral perfusion pressure < lower limit of reactivity, 1.04; 95% CI, 1.02–1.06; p < 0.001) and mortality (odds ratio, 1.06; 95% CI, 1.04–1.08; p < 0.001). Conclusions: Individualized autoregulation-guided cerebral perfusion pressure management may be a plausible alternative to fixed cerebral perfusion pressure threshold management in severe traumatic brain injury patients. Prospective randomized research will help define which autoregulation-guided method is beneficial, safe, and most practical.

Transcranial Doppler: a stethoscope for the brain‐neurocritical care use

Transcranial Doppler (TCD) ultrasonography is a noninvasive bedside monitoring technique that can evaluate cerebral blood flow hemodynamics in the intracranial arterial vasculature.