Evaluation and application of ultra-low-frequency pressure reactivity index in pediatric traumatic brain injury patients.

PURPOSE: While clinical practice suggests that knowing the cerebral autoregulation (CA) status of traumatic brain injury (TBI) patients is crucial in assessing the best treatment, evidence in pediatric TBI (pTBI) is limited. The pressure reactivity index (PRx) is a surrogate method for the continuous estimation of CA in adults; however, calculations require continuous, high-resolution monitoring data. We evaluate an ultra-low-frequency pressure reactivity index (UL-PRx), based on data sampled at ∼5-min periods, and test its association with 6-month mortality and unfavorable outcome in a cohort of pTBI patients. METHODS: Data derived from pTBI patients (0-18 years) requiring intracranial pressure (ICP) monitoring were retrospectively collected and processed in MATLAB using an in-house algorithm. RESULTS: Data on 47 pTBI patients were included. UL-PRx mean values, ICP, cerebral perfusion pressure (CPP), and derived indices showed significant association with 6-month mortality and unfavorable outcome. A value of UL-PRx of 0.30 was identified as the threshold to better discriminate both surviving vs deceased patients (AUC: 0.90), and favorable vs unfavorable outcomes (AUC: 0.70) at 6 months. At multivariate analysis, mean UL-PRx and % time with ICP > 20 mmHg, remained significantly associated with 6-month mortality and unfavorable outcome, even when adjusted for International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT)-Core variables. In six patients undergoing secondary decompressive craniectomy, no significant changes in UL-PRx were found after surgery. CONCLUSIONS: UL-PRx is associated with a 6-month outcome even if adjusted for IMPACT-Core. Its application in pediatric intensive care unit could be useful to evaluate CA and offer possible prognostic and therapeutic implications in pTBI patients. CLINICALTRIALS: GOV: NCT05043545, September 14, 2021, retrospectively registered.

Evaluation and Application of Ultra-Low-Resolution Pressure Reactivity Index in Moderate or Severe Traumatic Brain Injury.

BACKGROUND: The pressure reactivity index (PRx) has emerged as a surrogate method for the continuous bedside estimation of cerebral autoregulation and a predictor of unfavorable outcome after traumatic brain injury (TBI). However, calculation of PRx require continuous high-resolution monitoring currently limited to specialized intensive care units. The aim of this study was to evaluate a new index, the ultra-low-frequency PRx (UL-PRx) sampled at ∼0.0033 Hz at ∼5 minutes periods, and to investigate its association with outcome. METHODS: Demographic data, admission Glasgow coma scale, in-hospital mortality and Glasgow outcome scale extended at 12 months were extracted from electronic records. The filtering and preparation of time series of intracranial pressure (ICP), mean arterial pressure and cerebral perfusion pressure (CPP), and calculation of the indices (UL-PRx, Δ-optimal CPP), were performed in MATLAB using an in-house algorithm. RESULTS: A total of 164 TBI patients were included in the study; in-hospital and 12-month mortality was 29.3% and 38.4%, respectively, and 64% of patients had poor neurological outcome at 12 months. On univariate analysis, ICP, CPP, UL-PRx, and ΔCPPopt were associated with 12-month mortality. After adjusting for age, Glasgow coma scale, ICP and CPP, mean UL-PRx and UL-PRx thresholds of 0 and +0.25 remained associated with 12-month mortality. Similar findings were obtained for in-hospital mortality. For mean UL-PRx, the area under the receiver operating characteristic curves for in-hospital and 12-month mortality were 0.78 (95% confidence interval [CI]: 0.69-0.87; P <0.001) and 0.70 (95% CI: 0.61-0.79; P <0.001), respectively, and 0.65 (95% CI: 0.57-0.74; P =0.001) for 12-month neurological outcome. CONCLUSIONS: Our findings indicate that ultra-low-frequency sampling might provide sufficient resolution to derive information about the state of cerebrovascular autoregulation and prediction of 12-month outcome in TBI patients.

Transcranial Doppler as a screening test to exclude intracranial hypertension in brain-injured patients: the IMPRESSIT-2 prospective multicenter international study.

BACKGROUND: Alternative noninvasive methods capable of excluding intracranial hypertension through use of transcranial Doppler (ICPtcd) in situations where invasive methods cannot be used or are not available would be useful during the management of acutely brain-injured patients. The objective of this study was to determine whether ICPtcd can be considered a reliable screening test compared to the reference standard method, invasive ICP monitoring (ICPi), in excluding the presence of intracranial hypertension. METHODS: This was a prospective, international, multicenter, unblinded, diagnostic accuracy study comparing the index test (ICPtcd) with a reference standard (ICPi), defined as the best available method for establishing the presence or absence of the condition of interest (i.e., intracranial hypertension). Acute brain-injured patients pertaining to one of four categories: traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH) or ischemic stroke (IS) requiring ICPi monitoring, were enrolled in 16 international intensive care units. ICPi measurements (reference test) were compared to simultaneous ICPtcd measurements (index test) at three different timepoints: before, immediately after and 2 to 3 h following ICPi catheter insertion. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were calculated at three different ICPi thresholds (> 20, > 22 and > 25 mmHg) to assess ICPtcd as a bedside real-practice screening method. A receiver operating characteristic (ROC) curve analysis with the area under the curve (AUC) was used to evaluate the discriminative accuracy and predictive capability of ICPtcd. RESULTS: Two hundred and sixty-two patients were recruited for final analysis. Intracranial hypertension (> 22 mmHg) occurred in 87 patients (33.2%). The total number of paired comparisons between ICPtcd and ICPi was 687. The NPV was elevated (ICP > 20 mmHg = 91.3%, > 22 mmHg = 95.6%, > 25 mmHg = 98.6%), indicating high discriminant accuracy of ICPtcd in excluding intracranial hypertension. Concordance correlation between ICPtcd and ICPi was 33.3% (95% CI 25.6-40.5%), and Bland-Altman showed a mean bias of -3.3 mmHg. The optimal ICPtcd threshold for ruling out intracranial hypertension was 20.5 mmHg, corresponding to a sensitivity of 70% (95% CI 40.7-92.6%) and a specificity of 72% (95% CI 51.9-94.0%) with an AUC of 76% (95% CI 65.6-85.5%). CONCLUSIONS AND RELEVANCE: ICPtcd has a high NPV in ruling out intracranial hypertension and may be useful to clinicians in situations where invasive methods cannot be used or not available. TRIAL REGISTRATION: NCT02322970 .

Head to toe ultrasound: a narrative review of experts' recommendations of methodological approaches.

Critical care ultrasonography (US) is widely used by intensivists managing critically ill patients to accurately and rapidly assess different clinical scenarios, which include pneumothorax, pleural effusion, pulmonary edema, hydronephrosis, hemoperitoneum, and deep vein thrombosis. Basic and advanced critical care ultrasonographic skills are routinely used to supplement physical examination of critically ill patients, to determine the etiology of critical illness and to guide subsequent therapy. European guidelines now recommend the use of US for a number of practical procedures commonly performed in critical care. Full training and competence acquisition are essential before significant therapeutic decisions are made based on the US assessment. However, there are no universally accepted learning pathways and methodological standards for the acquisition of these skills.Therefore, in this review, we aim to provide a methodological approach of the head to toe ultrasonographic evaluation of critically ill patients considering different districts and clinical applications.

Early management of patients with aneurysmal subarachnoid hemorrhage in a hospital without neurosurgical/neuroendovascular facilities: a consensus and clinical recommendations of the Italian Society of Anesthesia and Intensive Care (SIAARTI).

BACKGROUND: The immediate management of subarachnoid hemorrhage (SAH) patients in hospitals without neurosurgical/neurointerventional facilities and their transfer to a specialized center is challenging and not well covered in existing guidelines. To address these issues, we created a consensus of experts endorsed by the Italian Society of Anesthesia and Intensive Care (SIAARTI) to provide clinical guidance. METHODS: A multidisciplinary consensus panel composed by 19 physicians selected for their established clinical and scientific expertise in the acute management of SAH patients with different specializations (anesthesia/intensive care, neurosurgery and interventional neuroradiology) was created. A modified Delphi approach was adopted. RESULTS: A total of 14 statements have been discussed. Consensus was reached on 11 strong recommendations and 2 weak recommendations. In one case, where consensus could not be agreed upon, no recommendation could be provided. CONCLUSIONS: Management of SAH in a non-specialized setting and early transfer are difficult and may have a critical impact on outcome. Clinical advice, based on multidisciplinary consensus, might be helpful. Our recommendations cover most, but not all, topics of clinical relevance.

How to use cerebral ultrasound in the ICU.

Cerebral ultrasound is a developing point of care tool for intensivists and emergency physicians, with an important role in the diagnosis of acute intracranial pathology, such as the assessment of cerebrovascular diseases and in the noninvasive intracranial pressure measurement both in the acute clinical settings and in intensive care unit (ICU). The traditional application of transcranial doppler (TCD) by assessing blood flow velocities in the main cerebral arteries, allows the evaluation and follow up of cerebral vasospasm, cerebral perfusion pressure, cerebral autoregulation and intracranial hypertension. The use of TCD, traditionally limited to the neurosonology laboratories settings, has expanded over the last years following the introduction of B-mode ultrasound and color Doppler, the transcranial color-coded duplex ultrasonography (TCCS), opening a new window to the assessment of cerebral anatomy not only in the neurocritical patients, but also in general ICU and emergency room patients. Here we report a brief review with the intent to up-to-date and describe the main applications and use of TCD/TCCS in the setting of Neurointensive Care.

The IN-PANCIA Study: Clinical Evaluation of Gastrointestinal Dysfunction and Failure, Multiple Organ Failure, and Levels of Citrulline in Critically Ill Patients.

PURPOSE: Gastrointestinal dysfunction and failure (GID and GIF) in critically ill patients are a common, relevant, and underestimated complications in ICU patients. The aims of this study were (1) to determine plasmatic levels of citrulline, glutamine, and arginine as markers of GID/GIF in critically ill patients with or without GID/GIF with or without multiple organ failure (MOF) and (2) to assess the role of intra-abdominal hypertension in these patient groups. MATERIALS AND METHODS: This is a 1-year, monocentric (Italian hospital), prospective observational study. Inclusion criteria were adult patients with GID/GIF, with or without MOF. The GIF score was daily evaluated in 39 critically ill patients. Amino acids were measured at the time of GID or GIF. RESULTS: We enrolled 39 patients. Nine patients developed GID and 7 GIF; 6 of patients with GID/GIF developed MOF. Citrulline was lower (P < .001) in patients with GID/GIF (11.3 [4.4] µmol/L), compared to patients without GID/GIF (22.4 [6.8] µmol/L); likewise, glutamine was lower in patients with GID/GIF, whereas arginine was nonstatistically different between the 2 groups. Intra-abdominal pressure was higher in patients affected by MOF (13.0 [2.2] mm Hg) than in patients with GIF/GID without MOF (9.6 [2.6] mm Hg) and compared to patients without GID/GIF (7.2 [2.1] mm Hg). CONCLUSIONS: Both GID and GIF in critically ill patients are associated with low levels of citrulline and glutamine, which could be considered as markers of small bowel dysfunction. The higher the GIF score, the lower the citrulline levels. Patients affected by MOF had higher levels of intra-abdominal pressure.

Transcranial Doppler and Optic Nerve Sonography.

Transcranial Doppler is a bedside procedure that measures linear cerebral blood flow velocity (CBFV) and the pulsatility index through the intracranial circulation. Transcranial color-coded duplex Doppler (TCCD) provides both CBFV and B-mode functions. In this review they are both referred to as brain ultrasound TCCD. Brain ultrasound can be applied in various environments, including out-of-hospital, emergency room, surgery, intensive care, and ward settings. The most common neurologic disease processes evaluated with TCCD are subarachnoid hemorrhage, traumatic brain injury, and ischemic and hemorrhagic stroke. However, TCCD also is used outside the neuroenvironment for diseases such as sickle cell anemia or for cerebral hemodynamic assessment during the cardiovascular perioperative period. In these applications, TCCD can be used for the detection of cerebral vessel occlusion, estimation of cerebrovascular reactivity, right-to-left cardiac shunts, noninvasive estimation of cerebral perfusion and intracranial pressure, optic nerve sheath diameter, midline shift, hydrocephalus, and the presence of foreign objects. Finally, TCCD has a high accuracy in confirming total cerebral circulatory arrest and has been used as an ancillary test to support clinical diagnosis of brain death. Other indications for TCCD include assessment of collateral blood flow and embolization during carotid endarterectomy, assessment of patterns and extent of collateral circulation in severe stenosis or occlusion, assessment of patent foramen ovale/paradoxical embolism, assessment of arteriovenous malformations and studying their supply arteries and flow patterns, assessment of noncardiac right-to-left shunts, assessment of severe stenosis in the arteries of the circle of Willis, and assessment of vertebral artery dissection.

Non-invasive Intracranial Pressure Assessment in Brain Injured Patients Using Ultrasound-Based Methods.

BACKGROUND: Non-invasive measurement of intracranial pressure (ICP) can be invaluable in the management of critically ill patients. Invasive measurement of ICP remains the "gold standard" and should be performed when clinical indications are met, but it is invasive and brings some risks. In this project, we aim to validate the non-invasive ICP (nICP) assessment models based on arterious and venous transcranial Doppler ultrasonography (TCD) and optic nerve sheath diameter (ONSD). METHODS: We included brain injured patients requiring invasive ICP monitoring (intraparenchymal or intraventricular). We assessed the concordance between ICP measured non-invasively with arterious [flow velocity diastolic formula (ICPFVd) and pulsatility index (PI)], venous TCD (vPI) and ICP derived from ONSD (nICPONSD) compared to invasive ICP measurement. RESULTS: Linear regression showed a positive relationship between nICP and ICP for all the methods, except PIv. ICPONSD showed the strongest correlation with invasive ICP (r = 0.61) compared to the other methods (ICPFVd, r = 0.26, p value = 0.0015; PI, r = 0.19, p value = 0.02, vPI, r = 0.056, p value = 0.510). The ability to predict intracranial hypertension was highest for ICPONSD (AUC = 0.91; 95% CI, 0.85-0.97 at ICP > 20 mmHg), with a sensitivity and specificity of 85%, followed by ICPFVd (AUC = 0.67; 95% CI, 0.54-0.79). CONCLUSIONS: Our results demonstrate that among the non-invasive methods studied, ONSD showed the best accuracy in the detection of ICP.

Coagulation management in patients undergoing neurosurgical procedures.

PURPOSE OF REVIEW: Management of coagulation in neurosurgical procedures is challenging. In this contest, it is imperative to avoid further intracranial bleeding. Perioperative bleeding can be associated with a number of factors, including anticoagulant drugs and coagulation status but is also linked to the characteristic and the site of the intracranial disorder. The aim of this review will be to focus primarily on the new evidence regarding the management of coagulation in patients undergoing craniotomy for neurosurgical procedures. RECENT FINDINGS: Antihemostatic and anticoagulant drugs have shown to be associated with perioperative bleeding. On the other hand, an increased risk of venous thromboembolism and hypercoagulative state after elective and emergency neurosurgery, in particular after brain tumor surgery, has been described in several patients. To balance the risk between thrombosis and bleeding, it is important to be familiar with the perioperative changes in coagulation and with the recent management guidelines for anticoagulated patients undergoing neurosurgical procedures, in particular for those taking new direct anticoagulants. We have considered the current clinical trials and literature regarding both safety and efficacy of deep venous thrombosis prophylaxis in the neurosurgical population. These were mainly trials concerning both elective surgical and intensive care patients with a poor grade intracranial bleed or multiple traumas with an associated severe traumatic brain injury (TBI). SUMMARY: Coagulation management remains a major issue in patients undergoing neurosurgical procedures. However, in this field of research, literature quality is poor and further studies are necessary to identify the best strategies to minimize risks in this group of patients.

The accuracy of transcranial Doppler in excluding intracranial hypertension following acute brain injury: a multicenter prospective pilot study.

BACKGROUND: Untimely diagnosis of intracranial hypertension may lead to delays in therapy and worsening of outcome. Transcranial Doppler (TCD) detects variations in cerebral blood flow velocity which may correlate with intracranial pressure (ICP). We investigated if intracranial hypertension can be accurately excluded through use of TCD. METHOD: This was a multicenter prospective pilot study in patients with acute brain injury requiring invasive ICP (ICPi) monitoring. ICP estimated with TCD (ICPtcd) was compared with ICPi in three separate time frames: immediately before ICPi placement, immediately after ICPi placement, and 3 hours following ICPi positioning. Sensitivity and specificity, and concordance correlation coefficient between ICPi and ICPtcd were calculated. Receiver operating curve (ROC) and the area under the curve (AUC) analyses were estimated after measurement averaging over time. RESULTS: A total of 38 patients were enrolled, and of these 12 (31.6%) had at least one episode of intracranial hypertension. One hundred fourteen paired measurements of ICPi and ICPtcd were gathered for analysis. With dichotomized ICPi (≤20 mmHg vs >20 mmHg), the sensitivity of ICPtcd was 100%; all measurements with high ICPi (>20 mmHg) also had a high ICPtcd values. Bland-Altman plot showed an overestimation of 6.2 mmHg (95% CI 5.08-7.30 mmHg) for ICPtcd compared to ICPi. AUC was 96.0% (95% CI 89.8-100%) and the estimated best threshold was at ICPi of 24.8 mmHg corresponding to a sensitivity 100% and a specificity of 91.2%. CONCLUSIONS: This study provides preliminary evidence that ICPtcd may accurately exclude intracranial hypertension in patients with acute brain injury. Future studies with adequate power are needed to confirm this result.

Aneurysmal Subarachnoid Hemorrhage in Pregnancy-Case Series, Review, and Pooled Data Analysis.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) during pregnancy represents an important cause of maternal and fetal morbidity and mortality. Approaches to diagnostics and treatment are still controversial, and there are only a limited number of cases described in the literature. Our study examines the management of aSAH in pregnant patients, creating a case series by combining patients from our hospital records with those from the limited available literature. METHODS: Data collected from Addenbrooke's Hospital records and cases published between January 1995 and January 2015 were studied. Chi-square test, exact Fisher's test, and chi-square test for trend were used for analyzing categorical data, while the t-test and Mann-Whitney-Wilcoxon test were used for continuous data. RESULTS: Fifty-two patients were included. The mean age was 31.47 ± 5.80, and most patients were in their third trimester. A univariate pooled data analysis suggested that the maternal outcome may depend on the mother's age, mother's Hunt and Hess scale score, Glasgow Coma Scale at arrival, treatment modality for the aneurysm, mode, and timing of delivery. However, at the multivariate analysis only the presence of general complications resulted in a significant impact on maternal outcome. CONCLUSIONS: Ruptured aneurysms in pregnant patients with aSAH may be safely secured in a timely manner. The diagnostic and treatment strategy for each of these patients should consider peculiar maternal and obstetric factors and requires a multidisciplinary assessment involving obstetrics, neurosurgeons, and intensivists. Considering the observed statistical power of our series, our findings should be taken with caution and should be supported by further systematic data collection.

Doppler Non-invasive Monitoring of ICP in an Animal Model of Acute Intracranial Hypertension.

BACKGROUND: In many neurological diseases, intracranial pressure (ICP) is elevated and needs to be actively managed. ICP is typically measured with an invasive transducer, which carries risks. Non-invasive techniques for monitoring ICP (nICP) have been developed. The aim of this study was to compare three different methods of transcranial Doppler (TCD) assessment of nICP in an animal model of acute intracranial hypertension. METHODS: In 28 rabbits, ICP was increased to 70-80 mmHg by infusion of Hartmann's solution into the lumbar subarachnoid space. Doppler flow velocity in the basilar artery was recorded. nICP was assessed through three different methods: Gosling's pulsatility index PI (gPI), Aaslid's method (AaICP), and a method based on diastolic blood flow velocity (FVdICP). RESULTS: We found a significant correlation between nICP and ICP when all infusion experiments were combined (FVdICP: r = 0.77, AaICP: r = 0.53, gPI: r = 0.54). The ability to distinguish between raised and 'normal' values of ICP was greatest for FVdICP (AUC 0.90 at ICP >40 mmHg). When infusion experiments were considered independently, FVdICP demonstrated again the strongest correlation between changes in ICP and changes in nICP (mean r = 0.85). CONCLUSIONS: TCD-based methods of nICP monitoring are better at detecting changes of ICP occurring in time, rather than absolute prediction of ICP as a number. Of the studied methods of nICP, the method based on FVd is best to discriminate between raised and 'normal' ICP and to monitor relative changes of ICP.

Thromboembolic complications of heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is an adverse effect of heparin therapy which can be responsible for thrombotic events with embolic consequences. Although ischemic stroke is a well known consequence of HIT, few cases of cerebral ischemia of arterial origin have been reported so far. A 38-year-old man was admitted because of acute multiple ischemic strokes and pulmonary embolism which occurred during treatment with low molecular weight heparin as prophylactic therapy for orthopedic surgery. Neuroimaging showed occlusion of the right common carotid artery with multiple acute cerebral infarcts. Testing for anti-platelet factor 4 antibodies confirmed the diagnosis. Systematic review of the literature revealed 55 cases of arterial stroke and three cases of carotid artery occlusion caused by HIT. Although arterial ischemic stroke is a rare complication of HIT, a high level of suspicion and a prompt diagnosis of this coagulation disorder are necessary to avoid life-threatening thromboembolic complications.