Ultrasound-based non invasive intracranial pressure

Intracranial pressure (ICP) is an important monitoring modality in the clinical management of several neurological diseases carrying the intrinsic risk of potentially lethal intracranial hypertension (ICH). Considering that the brain is in an enclosed compartment, ICH leads to brain hypoperfusion and eventually ischaemia followed by irreversible neuronal damage. Traumatic brain injury (TBI), for instance, is a condition in which ICH is strongly associated with unfavourable outcome and death. Although ICP can guide patient management in neurocritical care settings, this parameter is not commonly monitored in many clinical conditions outside this environment. The invasive character of the standard methods for ICP assessment and their associated risks to the patient (like infections, brain tissue lesions, haemorrhage) contribute to this scenario. Such risks have prevented ICP assessment in a broad range of diseases like in patients with risk of coagulopathy, as well as in other conditions in which invasive assessment is not considered or outweighed by the risks of the procedure. Provided that knowledge of ICP can be crucial for the successful management of patients in many sub-critical conditions, non-invasive estimation of ICP (nICP) may be helpful when indications for invasive ICP assessment are not met and when it is not immediately available or even contraindicated. Several methods for non-invasive assessment of ICP (nICP) have been described so far. Transcranial Doppler (TCD), for instance, is primarily a technique for diagnosing various intracranial vascular disorders such as emboli, stenosis, or vasospasm, but has been broadly utilised for non-invasive ICP monitoring due to its ability to detect changes in cerebral blood flow velocity derived from ICP variations. Moreover, TCD allows monitoring of these parameters as they may change in time. Optic nerve sheath diameter ultrasonography (ONSD) is another non-invasive tool which gained interest in the last years. The optic nerve sheath is in continuous with the subarachnoid space, and when ICP increased, the diameter of ONSD enlarges proportionally to ICP. The focus of this thesis is on the assessment, applications and development of ultrasoundbased for nICP assessment in different clinical conditions where this parameter is relevant but in many circumstances not considered, including TBI and other neurological diseases ULTRASOUND BASED NON-INVASIVE INTRACRANIAL PRESSURE 17 associated with impairment of cerebral blood flow circulation. As main results, ONSD and TCD-based non-invasive methods could replicate changes in direct ICP across time confidently, and could provide reasonable accuracy in comparison to the standard invasive techniques. These findings support the use of ultrasound based non-invasive ICP methods in a variety of clinical conditions requiring management of intracranial pressure and brain perfusion. More importantly, the low costs associated with nICP methods, ultrasound machines are widely available medical devices, could contribute to its widespread use as a reliable alternative for ICP monitoring in everyday clinical practice

Combined lung and brain ultrasonography for an individualized “brain-protective ventilation strategy” in neurocritical care patients with challenging ventilation needs

When intracranial hypertension and severe lung damage coexist in the same clinical scenario, their management poses a difficult challenge, especially as concerns mechanical ventilation management. The needs of combined lung and brain protection from secondary damage may conflict, as ventilation strategies commonly used in patients with ARDS are potentially associated with an increased risk of intracranial hypertension. In particular, the use of positive end-expiratory pressure, recruitment maneuvers, prone positioning, and protective lung ventilation can have undesirable effects on cerebral physiology: they may positively or negatively affect intracranial pressure, based on the final repercussions on PaO2and cerebral perfusion pressure (through changes in cardiac output, mean arterial pressure, venous return, PaO2and PaCO2), also according to the baseline conditions of cerebral autoregulation. Lung ultrasound (LUS) and brain ultrasound (BUS, as a combination of optic nerve sheath diameter assessment and cerebrovascular Doppler ultrasound) have independently proven their potential in respectively monitoring lung aeration and brain physiology at the bedside. In this narrative review, we describe how the combined use of LUS and BUS on neurocritical patients with demanding mechanical ventilation needs can contribute to ventilation management, with the aim of a tailored “brain-protective ventilation strategy.

The importance of monitoring cerebral oxygenation in non brain injured patients

Over the past few years, the use of non-invasive neuromonitoring in non-brain injured patients has increased, as a result of the recognition that many of these patients are at risk of brain injury in a wide number of clinical scenarios and therefore may benefit from its application which allows interventions to prevent injury and improve outcome. Among these, are post cardiac arrest syndrome, sepsis, liver failure, acute respiratory failure, and the perioperative settings where in the absence of a primary brain injury, certain groups of patients have high risk of neurological complications. While there are many neuromonitoring modalities utilized in brain injured patients, the majority of those are either invasive such as intracranial pressure monitoring, require special skill such as transcranial Doppler ultrasonography, or intermittent such as pupillometry and therefore unable to provide continuous monitoring. Cerebral oximetry using Near infrared Spectroscopy, is a simple non invasive continuous measure of cerebral oxygenation that has been shown to be useful in preventing cerebral hypoxemia both within the intensive care unit and the perioperative settings. At present, current recommendations for standard monitoring during anesthesia or in the general intensive care concentrate mainly on hemodynamic and respiratory monitoring without specific indications regarding the brain, and in particular, brain oximetry. The aim of this manuscript is to provide an up-to-date overview of the pathophysiology and applications of cerebral oxygenation in non brain injured patients as part of non-invasive multimodal neuromonitoring in the early identification and treatment of neurological complications in this population

Oxygen targets and 6-month outcome after out of hospital cardiac arrest: a pre-planned sub-analysis of the targeted hypothermia versus targeted normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial

Background: Optimal oxygen targets in patients resuscitated after cardiac arrest are uncertain. The primary aim of this study was to describe the values of partial pressure of oxygen values (PaO2) and the episodes of hypoxemia and hyperoxemia occurring within the first 72 h of mechanical ventilation in out of hospital cardiac arrest (OHCA) patients. The secondary aim was to evaluate the association of PaO2 with patients' outcome. Methods: Preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after OHCA (TTM2) trial. Arterial blood gases values were collected from randomization every 4 h for the first 32 h, and then, every 8 h until day 3. Hypoxemia was defined as PaO2 300 mmHg. Mortality and poor neurological outcome (defined according to modified Rankin scale) were collected at 6 months. Results: 1418 patients were included in the analysis. The mean age was 64 ± 14 years, and 292 patients (20.6%) were female. 24.9% of patients had at least one episode of hypoxemia, and 7.6% of patients had at least one episode of severe hyperoxemia. Both hypoxemia and hyperoxemia were independently associated with 6-month mortality, but not with poor neurological outcome. The best cutoff point associated with 6-month mortality for hypoxemia was 69 mmHg (Risk Ratio, RR = 1.009, 95% CI 0.93-1.09), and for hyperoxemia was 195 mmHg (RR = 1.006, 95% CI 0.95-1.06). The time exposure, i.e., the area under the curve (PaO2-AUC), for hyperoxemia was significantly associated with mortality (p = 0.003). Conclusions: In OHCA patients, both hypoxemia and hyperoxemia are associated with 6-months mortality, with an effect mediated by the timing exposure to high values of oxygen. Precise titration of oxygen levels should be considered in this group of patients. Trial registration: clinicaltrials.gov NCT02908308 , Registered September 20, 2016. Keywords: Cardiac arrest; Hyperoxemia; Hypoxemia; Mortality; Neurological outcom

Ventilation management and outcomes in out-of-hospital cardiac arrest: a protocol for a preplanned secondary analysis of the TTM2 trial

IntroductionMechanical ventilation is a fundamental component in the management of patients post cardiac arrest. However, the ventilator settings and the gas-exchange targets used after cardiac arrest may not be optimal to minimise post-anoxic secondary brain injury. Therefore, questions remain regarding the best ventilator management in such patients.Methods and analysisThis is a preplanned analysis of the international randomised controlled trial, targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (OHCA)–target temperature management 2 (TTM2). The primary objective is to describe ventilatory settings and gas exchange in patients who required invasive mechanical ventilation and included in the TTM2 trial. Secondary objectives include evaluating the association of ventilator settings and gas-exchange values with 6 months mortality and neurological outcome. Adult patients after an OHCA who were included in the TTM2 trial and who received invasive mechanical ventilation will be eligible for this analysis. Data collected in the TTM2 trial that will be analysed include patients’ prehospital characteristics, clinical examination, ventilator settings and arterial blood gases recorded at hospital and intensive care unit (ICU) admission and daily during ICU stay.Ethics and disseminationThe TTM2 study has been approved by the regional ethics committee at Lund University and by all relevant ethics boards in participating countries. No further ethical committee approval is required for this secondary analysis. Data will be disseminated to the scientific community by abstracts and by original articles submitted to peer-reviewed journals.Trial registration numberNCT02908308

Plasma exchange in the intensive care unit: a narrative review

In this narrative review, we discuss the relevant issues of therapeutic plasma exchange (TPE) in critically ill patients. For many conditions, the optimal indication, device type, frequency, duration, type of replacement fluid and criteria for stopping TPE are uncertain. TPE is a potentially lifesaving but also invasive procedure with risk of adverse events and complications and requires close monitoring by experienced teams. In the intensive care unit (ICU), the indications for TPE can be divided into (1) absolute, well-established, and evidence-based, for which TPE is recognized as first-line therapy, (2) relative, for which TPE is a recognized second-line treatment (alone or combined) and (3) rescue therapy, where TPE is used with a limited or theoretical evidence base. New indications are emerging and ongoing knowledge gaps, notably regarding the use of TPE during critical illness, support the establishment of a TPE registry dedicated to intensive care medicine

Clinical significance of inflammatory markers of bacterial infection in critically ill patients with COVID-19 after treatment with anti-inflammatory and immunomodulatory drugs: a complex new scenario.

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Ventilatory settings in the initial 72 h and their association with outcome in out-of-hospital cardiac arrest patients: a preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial

Purpose: The optimal ventilatory settings in patients after cardiac arrest and their association with outcome remain unclear. The aim of this study was to describe the ventilatory settings applied in the first 72 h of mechanical ventilation in patients after out-of-hospital cardiac arrest and their association with 6-month outcomes. Methods: Preplanned sub-analysis of the Target Temperature Management-2 trial. Clinical outcomes were mortality and functional status (assessed by the Modified Rankin Scale) 6 months after randomization. Results: A total of 1848 patients were included (mean age 64 [Standard Deviation, SD = 14] years). At 6 months, 950 (51%) patients were alive and 898 (49%) were dead. Median tidal volume (VT) was 7 (Interquartile range, IQR = 6.2-8.5) mL per Predicted Body Weight (PBW), positive end expiratory pressure (PEEP) was 7 (IQR = 5-9) cmH20, plateau pressure was 20 cmH20 (IQR = 17-23), driving pressure was 12 cmH20 (IQR = 10-15), mechanical power 16.2 J/min (IQR = 12.1-21.8), ventilatory ratio was 1.27 (IQR = 1.04-1.6), and respiratory rate was 17 breaths/minute (IQR = 14-20). Median partial pressure of oxygen was 87 mmHg (IQR = 75-105), and partial pressure of carbon dioxide was 40.5 mmHg (IQR = 36-45.7). Respiratory rate, driving pressure, and mechanical power were independently associated with 6-month mortality (omnibus p-values for their non-linear trajectories: p < 0.0001, p = 0.026, and p = 0.029, respectively). Respiratory rate and driving pressure were also independently associated with poor neurological outcome (odds ratio, OR = 1.035, 95% confidence interval, CI = 1.003-1.068, p = 0.030, and OR = 1.005, 95% CI = 1.001-1.036, p = 0.048). A composite formula calculated as [(4*driving pressure) + respiratory rate] was independently associated with mortality and poor neurological outcome. Conclusions: Protective ventilation strategies are commonly applied in patients after cardiac arrest. Ventilator settings in the first 72 h after hospital admission, in particular driving pressure and respiratory rate, may influence 6-month outcomes

Splenic Doppler Resistive Index Variation Mirrors Cardiac Responsiveness and Systemic Hemodynamics upon Fluid Challenge Resuscitation in Postoperative Mechanically Ventilated Patients

Objective. To test if splenic Doppler resistive index (SDRI) allows noninvasive monitoring of changes in stroke volume and regional splanchnic perfusion in response to fluid challenge. Design and Setting. Prospective observational study in cardiac intensive care unit. Patients. Fifty-three patients requiring mechanical ventilation and fluid challenge for hemodynamic optimization after cardiac surgery. Interventions. SDRI values were obtained before and after volume loading with 500 mL of normal saline over 20 min and compared with changes in systemic hemodynamics, determined invasively by pulmonary artery catheter, and arterial lactate concentration as expression of splanchnic perfusion. Changes in stroke volume &gt;10% were considered representative of fluid responsiveness. Results. A &lt;4% SDRI reduction excluded fluid responsiveness, with 100% sensitivity and 100% negative predictive value. A &gt;9% SDRI reduction was a marker of fluid responsiveness with 100% specificity and 100% positive predictive value. A &gt;4% SDRI reduction was always associated with an improvement of splanchnic perfusion mirrored by an increase in lactate clearance and a reduction in systemic vascular resistance, regardless of fluid responsiveness. Conclusions. This study shows that SDRI variations after fluid administration is an effective noninvasive tool to monitor systemic hemodynamics and splanchnic perfusion upon volume administration, irrespective of fluid responsiveness in mechanically ventilated patients after cardiac surgery

Neurological and respiratory effects of lung protective ventilation in acute brain injury patients without lung injury: brain vent, a single centre randomized interventional study

Introduction - Lung protective ventilation (LPV) comprising low tidal volume (VT) and high positive end-expiratory pressure (PEEP) may compromise cerebral perfusion in acute brain injury (ABI). In patients with ABI, we investigated whether LPV is associated with increased intracranial pressure (ICP) and/or deranged cerebral autoregulation (CA), brain compensatory reserve and oxygenation. Methods - In a prospective, crossover study, 30 intubated ABI patients with normal ICP and no lung injury were randomly assigned to receive low VT [6 ml/kg/predicted (pbw)]/at either low (5 cmH2O) or high PEEP (12 cmH2O). Between each intervention, baseline ventilation (VT 9 ml/kg/pbw and PEEP 5 cmH2O) were resumed. The safety limit for interruption of the intervention was ICP above 22 mmHg for more than 5 min. Airway and transpulmonary pressures were continuously monitored to assess respiratory mechanics. We recorded ICP by using external ventricular drainage or a parenchymal probe. CA and brain compensatory reserve were derived from ICP waveform analysis. Results - We included 27 patients (intracerebral haemorrhage, traumatic brain injury, subarachnoid haemorrhage), of whom 6 reached the safety limit, which required interruption of at least one intervention. For those without intervention interruption, the ICP change from baseline to “low VT/low PEEP” and “low VT/high PEEP” were 2.2 mmHg and 2.3 mmHg, respectively, and considered clinically non-relevant. None of the interventions affected CA or oxygenation significantly. Interrupted events were associated with high baseline ICP (p  The transpulmonary driving pressure was 5 ± 2 cmH2O in both interventions. Partial arterial pressure of carbon dioxide was kept in the range 34–36 mmHg by adjusting the respiratory rate, hence, changes in carbon dioxide were not associated with the increase in ICP. Conclusions - The present study found that most patients did not experience any adverse effects of LPV, neither on ICP nor CA. However, in almost a quarter of patients, the ICP rose above the safety limit for interrupting the interventions. Baseline ICP, brain compensatory reserve, and mechanical power can predict a potentially deleterious effect of LPV and can be used to personalize ventilator settings