Blood-brain Barrier Permeability May Influence Vasopressor Effects in Anesthetized Patients With Brain Tumor: An Analysis of Magnetic Resonance Imaging Data.

OBJECTIVE: This is a secondary analysis of data from a previous study of anesthetized brain tumor patients receiving ephedrine or phenylephrine infusions. 18 patients with magnetic imaging verified tumor contrast enhancement were included. We hypothesized that vasopressors induce microcirculatory flow changes, characterized by increased capillary transit time heterogeneity (CTH) and decreased mean transit time (MTT), in brain regions exhibiting BBB leakage. METHODS: This is a secondary analysis of data from a previous study of anesthetized brain tumor patients receiving ephedrine or phenylephrine infusions. 18 patients with magnetic imaging verified tumor contrast enhancement were included. Postvasopressor to prevasopressor ratios of CTH, MTT, relative transit time heterogeneity (RTH), cerebral blood flow (CBF), cerebral blood volume, and oxygen extraction fraction (OEF) were calculated in tumor, peritumoral, hippocampal, and contralateral grey matter regions. Comparisons were made between brain regions and vasopressors. RESULTS: During phenylephrine infusion, ratios of CTH, RTH, and CBF were greater, and ratios of MTT and OEF were lower, in the tumor region with contrast leakage compared with corresponding contralateral grey matter ratios. During ephedrine infusion, ratios of CTH, MTT, RTH, CBF, and cerebral blood volume were higher in the tumor region with leakage compared with contralateral grey matter ratios. In addition, the ratio of CBF was higher in all regions, the ratio of RTH was lower in the leaking tumor region, and the ratio of OEF was lower in peritumoral, hippocampal, and grey matter regions with ephedrine compared with phenylephrine. CONCLUSIONS: Vasopressors can induce distinct microcirculatory flow alterations in regions with compromised brain tumor barrier or BBB. Ephedrine, a combined α and ß-adrenergic agonist, appears to result in fewer flow alterations and less impact on tissue oxygenation compared with phenylephrine, a pure α-adrenergic agonist.

Intraventricular Lavage vs External Ventricular Drainage for Intraventricular Hemorrhage: A Randomized Clinical Trial.

Importance: Intraventricular lavage has been proposed as a minimally invasive method to evacuate intraventricular hemorrhage. There is little evidence to support its use. Objective: To evaluate the safety and potential efficacy of intraventricular lavage treatment of intraventricular hemorrhage. Design, Setting, and Participants: This single-blinded, controlled, investigator-initiated 1:1 randomized clinical trial was conducted at Aarhus University Hospital and Odense University Hospital in Denmark from January 13, 2022, to November 24, 2022. Follow-up duration was 90 days. The trial was set to include 58 patients with intraventricular hemorrhage. Prespecified interim analysis was performed for the first 20 participants. Data were analyzed from February to April 2023. Interventions: Participants were randomized to receive either intraventricular lavage or standard drainage. Main Outcomes and Measures: The main outcome was risk of catheter occlusions. Additional safety outcomes were catheter-related infections and procedure time, length of stay at the intensive care unit, duration of treatment, and 30-day mortality. The main outcome of the prespecified interim analysis was risk of severe adverse events. Efficacy outcomes were hematoma clearance, functional outcome, overall survival, and shunt dependency. Results: A total of 21 participants (median [IQR] age, 67 [59-82] years; 14 [66%] male) were enrolled, with 11 participants randomized to intraventricular lavage and 10 participants randomized to standard drainage; 20 participants (95%) had secondary intraventricular hemorrhage. The median (IQR) Graeb score was 9 (5-11), and the median (IQR) Glasgow Coma Scale score was 6.5 (4-8). The study was terminated early due to a significantly increased risk of severe adverse events associated with intraventricular lavage at interim analysis (risk difference for control vs intervention, 0.43; 95% CI, 0.06-0.81; P = .04; incidence rate ratio for control vs intervention, 6.0; 95% CI, 1.38-26.1; P = .01). The rate of catheter occlusion was higher for intraventricular lavage compared with drainage (6 of 16 patients [38%] vs 2 of 13 patients [7%]; hazard ratio, 4.4 [95% CI, 0.6-31.2]; P = .14), which met the prespecified α = .20 level. Median (IQR) procedure time for catheter placement was 53.5 (33-75) minutes for intraventricular lavage vs 12 (4-20) minutes for control (P < .001). Conclusions and Relevance: This randomized clinical trial of intraventricular lavage vs standard drainage found that intraventricular lavage was encumbered with a significantly increased number of severe adverse events. Caution is recommended when using the device to ensure patient safety. Trial Registration: ClinicalTrials.gov Identifier: NCT05204849.

Cardiac arrest during hyperacute caesarean section due to peripartum cardiomyopathy.

Peripartum cardiomyopathy is a rare and potentially dangerous form of heart failure presenting in women in the last month of pregnancy until five months post partum. The pathogenesis is believed to be multifactorial. This case report describes a young woman with adiposity and preeclampsia who was admitted to hospital and whose clinical condition quickly deteriorated. During the emergency caesarian section, the woman suffered a cardiac arrest and was successfully resuscitated. Echocardiography showed heart failure with an ejection fraction less-than 45% confirming the diagnosis of peripartum cardiomyopathy.

Treatment of Intraventricular Hemorrhage with External Ventricular Drainage and Fibrinolysis: A Comprehensive Systematic Review and Meta-Analysis of Complications and Outcome.

BACKGROUND: External ventricular drainage (EVD) is a key factor in the treatment of intraventricular hemorrhage (IVH) but associated with risks and complications. Intraventricular fibrinolysis (IVF) has been proposed to improve clinical outcome and reduce complications of EVD treatment. The following review and metaanalysis provides a comprehensive evaluation of IVH treatment with external ventricular drainage (EVD) and intraventricular fibrinolysis (IVF) with regards to complications and clinical outcomes. METHODS: The PRISMA guidelines were followed preparing this review. Studies included in the meta-analysis were compared using forest plots and the related odds ratios. RESULTS: After a literature search, 980 articles were identified and 65 and underwent full-text review. Forty-two articles were included in the review and meta-analysis. We found that bolted and antibiotic-coated catheters were superior to tunnelled/uncoated catheters (P < 0.001) and antibiotic- vs. silver-impregnated catheters (P < 0.001]) in preventing infection. Shunt dependency was related to the volume of blood in the ventricles but unaffected by IVF (P = 0.98). IVF promoted hematoma clearance, decreased mortality (22.4% vs. 40.9% with IVF vs. no IVF, respectively, P < 0.00001), improved good functional outcomes (47.2% [IVF] vs. 38.3% [no IVF], P = 0.03), and reduced the rate of catheter occlusion from 37.3% without IVF to 10.6% with IVF (P = 0.0003). CONCLUSIONS: We present evidence and best practice recommendations for the treatment of IVH with EVD and intraventricular fibrinolysis. Our analysis further provides a comprehensive quantitative reference of the most relevant clinical endpoints for future studies on novel IVH technologies and treatments.

Study protocol for ACTIVE study: safety and feasibility evaluation of external ventricular drainage with ACTIVE fluid exchange in intraventricular hemorrhage-a phase 2, multi-center, randomized controlled trial.

BACKGROUND: Primary intraventricular hemorrhage (IVH) or IVH secondary to intracerebral (ICH) and subarachnoid hemorrhage (SAH) are known to have a very poor prognosis, with an expected mortality between 50 and 80% (Hinson et al. Current Neurology and Neuroscience Reports 10:73-82, 2010). Clearance of IVH might improve patient outcome. METHODS: The study is designed as an investigator-initiated, comparative, prospective, multi-center, 1:1 randomized phase 2 trial evaluating the efficacy and safety of active irrigation in external ventricular drainage (intervention arm-IRRAflow) compared to passive external ventricular drainage (control arm-EVD). The trial will enroll 58 patients with primary or secondary IVH. Major eligibility criteria include age ≥18 years of age, IVH documented on head CT or MRI scan (Graeb score ≥3), need of cerebrospinal fluid drainage, deterioration of consciousness or medical sedation at the time of enrollment, and indication for active treatment evaluated by the treating physicians. Exclusion criteria included patients with fixed and dilated pupils and pregnant or nursing women. The primary endpoint of the study is catheter occlusion evaluated by time to first observed occlusion from VC placement. Secondary endpoints include clearance of ventricular blood as measured by head CT scan, rates of catheter-related infection and shunt dependency, length of intensive care unit stay, functional status-Extended Glascow Outcome Scale (eGOS) and modified Rankin scale (mRS) at discharge to rehabilitation and 90 days-and mortality rates at 30 days and 90 days. DISCUSSION: With no standardized treatment for IVH and a poor prognosis, new treatments are needed. IVH patients often need CSF drainage to treat hydrocephalus and to decrease ICP. Standard treatment with passive external ventricular drainage is related to an increased risk of infections which is found in up to 22% of treated cases. The passive VC is known to have a risk of occlusion and is seen in 19-47% of the cases. We hypothesize that the use of active fluid change using the IRRAflow system will be safe and feasible and will reduce the occlusion and infection rates in patients with IVH. TRIAL REGISTRATION: ClicalTrials.gov NCT05204849. Registered 15 December 2021. Updated 24 January 2022.

Bypassing primary stroke centre reduces delay and improves outcomes for patients with large vessel occlusion.

OBJECTIVE: In large-vessel occlusion, endovascular therapy is superior to medical management alone in achieving recanalisation. Reducing time delays to revascularisation in patients with large-vessel occlusion is important to improving outcome. PATIENTS AND METHODS: A campaign was implemented in the Central Denmark Region targeting the identification of patients with large-vessel occlusion for direct transport to a comprehensive stroke centre. Time delays and outcomes before and after the intervention were assessed. RESULTS: A total of 476 patients (153 pre-intervention and 323 post-intervention) were included. They were treated with either intravenous tissue plasminogen activator or endovascular treatment (alone or in combination with intravenous tissue plasminogen activator). Endovascular therapy patients' median system delay was reduced from 234 to 185 min (adjusted relative risk delay 0.79 (95% confidence interval: 0.67-0.93)). The in-hospital delay was the main driver with an adjusted relative risk delay of 0.76 (confidence interval: 0.62-0.94), while pre-hospital delay was almost significantly reduced with an adjusted relative delay of 0.86 (confidence interval: 0.71-1.04). This was achieved without increasing the intravenous tissue plasminogen activator-treated patients' delay. Significantly more patients treated with endovascular therapy in the post-interventional period achieved functional independence (62% versus 43%), corresponding to an adjusted odds ratio of 3.08 (95% confidence interval: 1.08-8.78). CONCLUSION: Direct transfer of patients with suspected large-vessel occlusion to a comprehensive stroke centre leads to shorter treatment times for endovascular therapy patients and is, in turn, associated with an increase in functional independence. We recorded no adverse effects on intravenous tissue plasminogen activator treatment times or outcome.