BackgroundUntimely 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.MethodThis 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.ResultsA 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%.ConclusionsThis 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.

Our results demonstrate that among the non-invasive methods studied, ONSD showed the best accuracy in the detection of ICP.

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.

Introduction Critical illness from SARS-CoV-2 infection (COVID-19) is associated with a high burden of pulmonary embolism (PE) and thromboembolic events despite standard thromboprophylaxis. Available guidance is discordant, ranging from standard care to the use of therapeutic anticoagulation for enhanced thromboprophylaxis (ET). Local ET protocols have been empirically determined and are generally intermediate between standard prophylaxis and full anticoagulation. Concerns have been raised in regard to the potential risk of haemorrhage associated with therapeutic anticoagulation. This report describes the prevalence and safety of ET strategies in European Intensive Care Unit (ICUs) and their association with outcomes during the first wave of the COVID pandemic, with particular focus on haemorrhagic complications and ICU mortality. Methods Retrospective, observational, multi-centre study including adult critically ill COVID-19 patients. Anonymised data included demographics, clinical characteristics, thromboprophylaxis and/or anticoagulation treatment. Critical haemorrhage was defined as intracranial haemorrhage or bleeding requiring red blood cells transfusion. Survival was collected at ICU discharge. A multivariable mixed effects generalised linear model analysis matched for the propensity for receiving ET was constructed for both ICU mortality and critical haemorrhage. Results A total of 852 (79% male, age 66 [37–85] years) patients were included from 28 ICUs. Median body mass index and ICU length of stay were 27.7 (25.1–30.7) Kg/m2 and 13 (7–22) days, respectively. Thromboembolic events were reported in 146 patients (17.1%), of those 78 (9.2%) were PE. ICU mortality occurred in 335/852 (39.3%) patients. ET was used in 274 (32.1%) patients, and it was independently associated with significant reduction in ICU mortality (log odds = 0.64 [95% CIs 0.18–1.1; p = 0.0069]) but not an increased risk of critical haemorrhage (log odds = 0.187 [95%CI − 0.591 to − 0.964; p = 0.64]). Conclusions In a cohort of critically ill patients with a high prevalence of thromboembolic events, ET was associated with reduced ICU mortality without an increased burden of haemorrhagic complications. This study suggests ET strategies are safe and associated with favourable outcomes. Whilst full anticoagulation has been questioned for prophylaxis in these patients, our results suggest that there may nevertheless be a role for enhanced / intermediate levels of prophylaxis. Clinical trials investigating causal relationship between intermediate thromboprophylaxis and clinical outcomes are urgently needed.

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