INTRODUCTION:Monitoring of cerebral autoregulation (CA) in patients with a traumatic brain injury (TBI) can provide an individual 'optimal' cerebral perfusion pressure (CPP) target (CPPopt) at which CA is best preserved. This potentially offers an individualized precision medicine approach. Retrospective data suggest that deviation of CPP from CPPopt is associated with poor outcomes. We are prospectively assessing the feasibility and safety of this approach in the COGiTATE [CPPopt Guided Therapy: Assessment of Target Effectiveness] study. Its primary objective is to demonstrate the feasibility of individualizing CPP at CPPopt in TBI patients. The secondary objectives are to investigate the safety and physiological effects of this strategy.METHODS:The COGiTATE study has included patients in four European hospitals in Cambridge, Leuven, Nijmegen, and Maastricht (coordinating centre). Patients with severe TBI requiring intracranial pressure (ICP)-directed therapy are allocated into one of two groups. In the intervention group, CPPopt is calculated using a published (modified) algorithm. In the control group, the CPP target recommended in the Brain Trauma Foundation guidelines (CPP 60-70 mmHg) is used.RESULTS:Patient recruitment started in February 2018 and will continue until 60 patients have been studied. Fifty-one patients (85% of the intended total) have been recruited in October 2019. The first results are expected early 2021.CONCLUSION:This prospective evaluation of the feasibility, safety and physiological implications of autoregulation-guided CPP management is providing evidence that will be useful in the design of a future phase III study in severe TBI patients.

Background Several methods have been proposed to measure cerebrovascular autoregulation (CA) in traumatic brain injury (TBI), but the lack of a gold standard and the absence of prospective clinical data on risks, impact on care and outcomes of implementation of CA-guided management lead to uncertainty. Aim To formulate statements using a Delphi consensus approach employing a group of expert clinicians, that reflect current knowledge of CA, aspects that can be implemented in TBI management and CA research priorities. Methods A group of 25 international academic experts with clinical expertise in the management of adult severe TBI patients participated in this consensus process. Seventy-seven statements and multiple-choice questions were submitted to the group in two online surveys, followed by a face-to-face meeting and a third online survey. Participants received feedback on average scores and the rationale for resubmission or rephrasing of statements. Consensus on a statement was defined as agreement of more than 75% of participants. Results Consensus amongst participants was achieved on the importance of CA status in adult severe TBI pathophysiology, the dynamic non-binary nature of CA impairment, its association with outcome and the inadvisability of employing universal and absolute cerebral perfusion pressure targets. Consensus could not be reached on the accuracy, reliability and validation of any current CA assessment method. There was also no consensus on how to implement CA information in clinical management protocols, reflecting insufficient clinical evidence. Conclusion The Delphi process resulted in 25 consensus statements addressing the pathophysiology of impaired CA, and its impact on cerebral perfusion pressure targets and outcome. A research agenda was proposed emphasizing the need for better validated CA assessment methods as well as the focused investigation of the application of CA-guided management in clinical care using prospective safety, feasibility and efficacy studies.

The primary goal of the intensive care management of patients with traumatic brain injury (TBI) is to prevent and treat secondary brain injury by maintaining adequate oxygen delivery and cerebral perfusion pressure. However, non-neurological organ dysfunctions are common after TBI and are an independent factor—but potentially amenable to treatment—related to morbidity and mortality. There is a wide range of systemic complications following TBI. Among these, respiratory, cardiovascular, renal, and liver failure as well as involvement of the hematological system are the most common and can influence early management, mortality, and morbidity. Therefore, prompt recognition, prevention, and treatment of systemic complications represent a modifiable risk after TBI with a potentially important effect on the outcome. In this chapter, we focus on recent evidence on the incidence, features, and treatment of TBI-related complications of systemic organs. Targeted therapy to optimize systemic function may reduce mortality and may improve outcome in TBI survivors.

The assessment of intracranial pressure (ICP) in children with neurological disease remains a cornerstone in their routine management. The quest for a reliable, reproducible and radiation-free non-invasive technique for assessing ICP in children remains somewhat of a holy grail for neurosurgery. This work assesses some of the recent advances in ultrasound-based techniques, addressing both novel processes and modifications aimed at improving the accuracy of existing techniques.

Neurocritically ill patients often receive mechanical ventilation. The lung and the brain can affect each other, thus increasing the risk of developing secondary damage, if not properly managed. Ventilator settings are not clear in this group of patients; traditionally, because of the risk of intracranial hypertension, high tidal volume and low levels of positive end-expiratory pressure (PEEP) are applied, whereas rescue strategies such as recruitment maneuvers, prone position, and extracorporeal membrane oxygenation (ECMO) are precluded. However, recent evidence is challenging these concepts. Findings in patients without acute respiratory distress syndrome (ARDS) suggest the application of lower tidal volumes (6 ml/kg predicted body weight [PBW]), in order to reduce the risk of developing ventilator-induced lung injury (VILI) and boost the inflammatory response. PEEP is a key component of mechanical ventilation settings to guarantee alveolar recruitment and to enhance oxygen arterial saturation. It also improves brain tissue oxygen pressure without significantly affecting intracranial pressure or cerebral perfusion. Likewise, recruitment maneuvers should be taken into consideration as rescue treatment when appropriate. Preventive hyperventilation (carbon dioxide partial pressure [PaCO2] ≤25 mmHg) should be avoided. Tracheostomy is frequently performed in this group of patients; the ideal timing of tracheostomy is not clear yet although early tracheostomy seems to have some clinical advantages. In selected cases of severe respiratory failure, prone position and ECMO can also be taken into consideration. The aim of this chapter is to debulk ten false myths concerning ventilatory management in patients with brain injury.

We introduced ‘compensatory-reserve-weighted intracranial pressure (ICP),’ named ‘weightedICP’ for brevity, as a variable that may better describe changes leading to mortality after traumatic brain injury (TBI) over the standard mean ICP.

Objectives: Retrospective data from patients with severe traumatic brain injury (TBI) indicate that deviation from the continuously calculated pressure reactivity-based “optimal” cerebral perfusion pressure (CPPopt) is associated with worse patient outcome. The objective of this study was to assess the relationship between prospectively collected CPPopt data and patient outcome after TBI.

Increased intracranial pressure (ICP) is an important cause of secondary brain injury and needs to be treated aggressively.1Marmarou A. Anderson R.L. Ward J.D. Choi S.C. Young H.F. Impact of ICP instability and hypotension on outcome in patients with severe head trauma.J Neurosurg. 1991; 75: S59-S66Crossref Scopus (640) Google Scholar The development of clinical protocols for the management of increased ICP has contributed to improved outcomes,2Patel H.C. Menon D.K. Tebbs S. Hawker R. Hutchinson P.J. Kirkpatrick P.J. Specialist neurocritical care and outcome from head injury.Intensive Care Med. 2002; 28: 547-553Crossref PubMed Scopus (294) Google Scholar, 3Clayton T.J. Nelson R.J. Manara A.R. Reduction in mortality from severe head injury following introduction of a protocol for intensive care management.Br J Anaesth. 2004; 93: 761-767Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar and whilst the gold standard for measurement of ICP is invasive, there are times when invasive devices are not available or are contraindicated. Invasive ICP methods also have inherent risks such as bleeding and infection, and as such a non-invasive method would be useful.4Robba C. Bacigaluppi S. Cardim D. Donnelly J. Bertuccio A. Czosnyka M. Non-invasive assessment of intracranial pressure.Acta Neurol Scand. 2016; 134: 4-21Crossref PubMed Scopus (80) Google Scholar Several methods have been studied to assess ICP non-invasively including transcranial Doppler ultrasound (TCD) and ultrasound measurement of optic nerve sheath diameter (ONSD).4Robba C. Bacigaluppi S. Cardim D. Donnelly J. Bertuccio A. Czosnyka M. Non-invasive assessment of intracranial pressure.Acta Neurol Scand. 2016; 134: 4-21Crossref PubMed Scopus (80) Google Scholar The latter technique has been shown to be well correlated with invasive ICP with good sensitivity and specificity.5Hansen H.C. Helmke K. Validation of the optic nerve sheath response to changing cerebrospinal fluid pressure: ultrasound findings during intrathecal infusion tests.J Neurosurg. 1997; 87: 34-40Crossref PubMed Scopus (317) Google Scholar, 6Eisenberg H.M. Gary H.E. Aldrich E.F. Initial CT findings in 753 patients with severe head injury. A report from the NIH Traumatic Coma Data Bank.J Neurosurg. 1990; 73: 688-698Crossref PubMed Scopus (451) Google Scholar A recent study demonstrated that ultrasound assessment of ONSD is able to detect intracranial hypertension (ICP >20 mm Hg) [area under the curve (AUC), 0.91; 95% CI=0.88–0.95] with a sensitivity of 0.98 and a specificity of 0.64 for a threshold of 0.57 cm.7Robba C. Cardim D. Tajsic T. et al.Ultrasound non-invasive measurement of intracranial pressure in neurointensive care: a prospective observational study.PLoS Med. 2017; 14: e1002356Crossref PubMed Scopus (102) Google Scholar Similarly, several TCD-derived formulae including pulsatility index (PI) and a formula based on the flow velocity (nICPFVd) have also shown promise in the non-invasive assessment of ICP.8Rasulo F.A. Bertuetti R. Robba C. et al.The accuracy of transcranial Doppler in excluding intracranial hypertension following acute brain injury: a multicenter prospective pilot study. Traumatic intracranial hypertension.Crit Care. 2017; 21: 44Crossref PubMed Scopus (64) Google Scholar, 9Cardim D. Robba C. Bohdanowicz M. et al.Non-invasive monitoring of intracranial pressure using transcranial Doppler ultrasonography: is it possible?.Neurocrit Care. 2016; 25: 473-491Crossref PubMed Scopus (100) Google Scholar We recently successfully managed a case of raised intracranial pressure using the initial steps of our critical care unit raised ICP protocol (Supplementary material, Appendix S1) using non-invasive ICP (nICP) methods alone. A female in her 30s presented to the Emergency Department with fever, vomiting, and a reduced consciousness level [Glasgow Coma Scale (GCS) E1V2M5]. The patient was intubated, and treatment initiated for suspected meningitis. The head CT with contrast scan revealed cerebral oedema and extensive non-occlusive thrombus in the sagittal sinus, and she was also commenced on unfractionated heparin. Considering her ongoing high risk for intracranial hypertension, it was felt necessary to monitor her ICP to direct further therapy. Because she was receiving a heparin infusion, invasive ICP monitoring was relatively contraindicated. We therefore performed daily sedation holds for assessment of GCS and monitored her ICP non-invasively using repeated ultrasonographic assessments of ONSD, and estimated her ICP using PI and nICPFVd techniques. Ultrasound measurement was performed by a selected group of experienced operators using a standardised insonation technique to reduce inter-operator variability.7Robba C. Cardim D. Tajsic T. et al.Ultrasound non-invasive measurement of intracranial pressure in neurointensive care: a prospective observational study.PLoS Med. 2017; 14: e1002356Crossref PubMed Scopus (102) Google Scholar Ultrasound measurements were performed regularly every 4–6 h and whenever the clinician suspected significant changes in ICP with the patient in the supine position with the head of the bed elevated at 30°. During day 1–3 of her admission, ONSD was 4–5 mm (Fig. 1) and TCD revealed a PI <1 and nICPFVd <20 mm Hg with preserved autoregulation measured by the Mx index.10Czosnyka M. Smielewski P. Piechnik S. et al.Cerebral autoregulation following head injury.J Neurosurg. 2001; 95: 756-763Crossref PubMed Scopus (240) Google Scholar Three days after her admission, a sedation hold was performed and her best GCS recorded as E1VtM1. A repeat CT head scan showed a slight increase in the degree of brain swelling resulting in subtly increased narrowing of perimesencephalic cisterns only, and ONSD measured on CT was 7.1 mm compared with 4.6 mm measured on the initial CT.11Sekhon M.S. Griesdale D.E. Robba C. et al.Erratum to: optic nerve sheath diameter on computed tomography is correlated with simultaneously measured intracranial pressure in patients with severe traumatic brain injury.Intensive Care Med. 2015; 41: 177Crossref PubMed Scopus (6) Google Scholar ONSD values obtained were consistent with raised ICP (7.8 mm) (Fig. 1), and TCD showed a PI >2 and nICPFVd was >20 mm Hg with impaired autoregulation. We therefore escalated therapy, targeting ICP-lowering strategies to achieve ONSD <5.8 mm, PI <1.8 and nICPFVd <20 mm Hg. The patient was re-sedated and 100 ml 5% normal saline administered. Immediately after the administration of hypertonic saline, the ONSD was 5.4 mm, PI 1.4, and the nICPFVd had improved. Since the patient was being cared for on our ICP protocol, all haemodynamic parameters such as carbon dioxide partial pressure remained unchanged before and after hypertonic saline administration, and no other confounders such as patient position were present. The patient continued to be managed for the next 24 h on our ICP management protocol, receiving hypertonic saline boluses when ONSD was >5.8 mm. ONSD measurements remained <5.8 mm, PI <1.8, and nICPFVd <20 mm Hg. The sedation hold performed 24 h later revealed a much improved GCS (E1VtM6). The ICP protocol based on ONSD and TCD was gradually discontinued over the following 72 h, and the patient was successfully extubated. Whilst non-invasive methods have limitations including the need for specialised training, operator variability, and a temporal window not being present in up to 10–20% of patients,7Robba C. Cardim D. Tajsic T. et al.Ultrasound non-invasive measurement of intracranial pressure in neurointensive care: a prospective observational study.PLoS Med. 2017; 14: e1002356Crossref PubMed Scopus (102) Google Scholar, 8Rasulo F.A. Bertuetti R. Robba C. et al.The accuracy of transcranial Doppler in excluding intracranial hypertension following acute brain injury: a multicenter prospective pilot study. Traumatic intracranial hypertension.Crit Care. 2017; 21: 44Crossref PubMed Scopus (64) Google Scholar, 12Robba C. Cardim D. Donnelly J. et al.Effects of pneumoperitoneum and Trendelenburg position on intracranial pressure assessed using different non-invasive methods.Br J Anaesth. 2016; 117: 783-791Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar this case highlights that in the setting of impossible direct ICP measurement, a multimodal approach including clinical examination, nICP estimates, and CT scan findings can demonstrate a rising ICP. We have successfully used ONSD and TCD to estimate ICP for the first time as a target for the early steps of an ICP protocol. Non-invasive methods should not substitute for invasive ICP monitoring when indicated,4Robba C. Bacigaluppi S. Cardim D. Donnelly J. Bertuccio A. Czosnyka M. Non-invasive assessment of intracranial pressure.Acta Neurol Scand. 2016; 134: 4-21Crossref PubMed Scopus (80) Google Scholar but it is becoming increasingly clear that in certain cases when invasive methods are not immediately available or in borderline patients at risk of significant complications (haemorrhage, infection), non-invasive assessment can be a useful approach to guide management in the earlier, less aggressive stages of an ICP protocol. As prevention of pulmonary embolism in hospitalised patients increases, and the prevalence of patients on antiplatelet and anticoagulant medications increases, these techniques may have even broader applicability. We expect that with further research, the clinical application of these techniques will increase into the wider critical care environment. The authors declare that they have no conflicts of interest. 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Dear Editor in chief Dr. Elinor Ben-Menachem, The letter by Pranevicious and colleagues confirms that behind every invention, behind any patent, there are several studies and preliminary theoretical and or practical works that contribute to its practical applicability. The aim of our review (1) was to focus on the main and recent studies, which primarily correlated invasive ICP through a gold standard (mainly bolt or EVD) with non-invasive methods. Thus, this particular study (2) did not meet our search criteria as it was focused mainly on mechanical state of intracranial structures, not non-invasive estimation of ICP. Actually, change in time of flight reported in this paper correlated positively or negatively with direction of change in CSF pressure. It depended on which manoeuvre affecting brain’s venous outflow was used (jugular vein or vena cava compression). The authors suggested that recorded changes in time of flight are secondary to changes in brain elasticity rather than ICP itself. We sincerely thank the authors for this comment and for highlighting their excellent work. Acknowledgements

BACKGROUND:The laparoscopic approach is becoming increasingly frequent for many different surgical procedures. However, the combination of pneumoperitoneum and Trendelenburg positioning associated with this approach may increase the patient's risk for elevated intracranial pressure (ICP). Given that the gold standard for the measurement of ICP is invasive, little is known about the effect of these common procedures on ICP.METHODS:We prospectively studied 40 patients without any history of cerebral disease who were undergoing laparoscopic procedures. Three different methods were used for non-invasive estimation of ICP: ultrasonography of the optic nerve sheath diameter (ONSD); transcranial Doppler-based (TCD) pulsatility index (ICPPI); and a method based on the diastolic component of the TCD cerebral blood flow velocity (ICPFVd). The ONSD and TCD were measured immediately after induction of general anaesthesia, after pneumoperitoneum insufflation, after Trendelenburg positioning, and again at the end of the procedure.RESULTS:The ONSD, ICPFVd, and ICPPI increased significantly after the combination of pneumoperitoneum insufflation and Trendelenburg positioning. The ICPFVd showed an area under the curve of 0.80 [95% confidence interval (CI) 0.70-0.90] to distinguish the stage associated with the application of pneumoperitoneum and Trendelenburg position; ONSD and ICPPI showed an area under the curve of 0.75 (95% CI 0.65-0.86) and 0.70 (95% CI 0.58-0.81), respectively.CONCLUSIONS:The concomitance of pneumoperitoneum and the Trendelenburg position can increase ICP as estimated with non-invasive methods. In high-risk patients undergoing laparoscopic procedures, non-invasive ICP monitoring through a combination of ONSD ultrasonography and TCD-derived ICPFVd could be a valid option to assess the risk of increased ICP.

Although intracranial pressure (ICP) is essential to guide management of patients suffering from acute brain diseases, this signal is often neglected outside the neurocritical care environment. This is mainly attributed to the intrinsic risks of the available invasive techniques, which have prevented ICP monitoring in many conditions affecting the intracranial homeostasis, from mild traumatic brain injury to liver encephalopathy. In such scenario, methods for non-invasive monitoring of ICP (nICP) could improve clinical management of these conditions. A review of the literature was performed on PUBMED using the search keywords ‘Transcranial Doppler non-invasive intracranial pressure.’ Transcranial Doppler (TCD) is a technique primarily aimed at assessing the cerebrovascular dynamics through the cerebral blood flow velocity (FV). Its applicability for nICP assessment emerged from observation that some TCD-derived parameters change during increase of ICP, such as the shape of FV pulse waveform or pulsatility index. Methods were grouped as: based on TCD pulsatility index; aimed at non-invasive estimation of cerebral perfusion pressure and model-based methods. Published studies present with different accuracies, with prediction abilities (AUCs) for detection of ICP ≥20 mmHg ranging from 0.62 to 0.92. This discrepancy could result from inconsistent assessment measures and application in different conditions, from traumatic brain injury to hydrocephalus and stroke. Most of the reports stress a potential advantage of TCD as it provides the possibility to monitor changes of ICP in time. Overall accuracy for TCD-based methods ranges around ±12 mmHg, with a great potential of tracing dynamical changes of ICP in time, particularly those of vasogenic nature.

This study aimed to compare four non-invasive intracranial pressure (nICP) methods in a prospective cohort of hydrocephalus patients whose cerebrospinal fluid dynamics was investigated using infusion tests involving controllable test-rise of ICP.

Non-invasive measurement of ICP (nICP) can be warranted in patients at risk for developing increased ICP during pneumoperitoneum (PP). Our aim was to assess available data on the application of nICP monitoring during these procedures and to present a patient assessed with an innovative combination of noninvasive tools. Literature review of nICP assessment during PP did not find any studies comparing different methods intraprocedurally and only few studies of any nICP monitoring were available: transcranial Doppler (TCD) studies used the pulsatility index (PI) as an estimator of ICP and failed to detect a significant ICP increase during PP, whereas two out of three optic nerve sheath diameter (ONSD) studies detected a statistically significant ICP increase. In the case study, we describe a 52 year old man with a high grade thalamic glioma who underwent urgent laparoscopic cholecystectomy. Considering the high intraoperative risk of developing intracranial hypertension, he was monitored through parallel ONSD ultrasound measurement and TCD derived formulae (flow velocity diastolic formula, FVdnICP, and PI). ONSD and FVdnICP methods indicated a significant ICP increase during PP, whereas PI was not significantly increased. Our experience, combined with the literature review, seems to suggest that PI might not detect ICP changes in this context, however we indicate a possible interest of nICP monitoring during PP by means of ONSD and of TCD derived FVdNICP, especially for patients at risk for increased ICP.

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.