Intraventricular Fibrinolysis Research Articles

Cisternal and intraventricular irrigation in subarachnoid and intraventricular haemorrhage

BackgroundSubarachnoid haemorrhage (SAH) and intraventricular haemorrhage (IVH) are associated with poor patient outcomes. Intraventricular fibrinolysis is effective in clearing IVH and improving patient survival and neurological outcome. By similar rationale,...

Prediction of Permanent Shunt Dependency in Patients with Intraventricular Hemorrhage: Outcomes of Early External Ventricular Drainage Weaning Protocol

Hydrocephalus remains a common sequela of intraventricular hemorrhage (IVH) despite adequate drainage of the hematoma, including endoscopic surgery, intraventricular fibrinolysis, and external ventricular drainage (EVD). Moreover, the appropriate timing for conversion from EVD to ventriculoperitoneal shunt (VPS) is uncertain. This study aimed to evaluate the predictors of shunt dependency in patients with IVH based on the early EVD weaning protocol in our institution. We retrospectively reviewed medical records of patients who were diagnosed with primary IVH and secondary IVH from spontaneous intracerebral hemorrhage during the period 2018-2021. Predictors associated with shunt dependency were identified using a logistic regression model. The cutoff point of each variable was selected by receiver operating characteristic curve analysis. Furthermore, shunt complications were reported as a safety measure of our early EVD weaning protocol. The analysis included 106 patients. After IVH treatment, 15 (14%) patients required ventriculoperitoneal shunt, whereas 91 (86%) patients were shunt-free. The diameter of posttreatment temporal horn and the degree of IVH reduction were the significant predictors of shunt dependency. Moreover, patients with IVH reduction of >45% and temporal horn diameter of <9 mm had a lower probability of shunt dependency. Shunt failure was found in 2 (13.3%) patients. This study showed that a large temporal horn diameter and a lower degree of IVH removal were predictors of shunt dependency in patients with IVH. In addition, early conversion from EVD to ventriculoperitoneal shunt is safe and feasible.

Transfrontal External Ventricular Drainage Combined with OMMAYA Sac Implantation under Laser Navigation were Performed: A Technical Note.

Hydrocephalus caused by spontaneous intracerebral hemorrhage (ICH) is an independent risk factor with adverse effects on the progression of the disease. Until now, the choice of intraventricular catheter placement and intraventricular fibrinolysis (IVF) has been mainly based on the personal experience of the neurosurgeon. We will introduce the clinical effect of the new external ventricular drainage (EVD), an independent innovation of our medical center, on ICH patients, hoping to inspire more neurosurgeons to apply our method. In this open retrospective study, We analyzed the clinical data, radiological manifestations, and prognostic scores of 10 patients with the spontaneous intracerebral hemorrhage who received transfrontal lateral ventricle puncture and drainage under laser navigation in our hospital. A total of 10 patients with an average age of 58.10±9.97 years were enrolled for emergency surgery. All operations were completed according to the consensus specifications. It took 11.25±3.81 days for the intracranial pressure to return to normal. On admission, patients had a median GCS of 10. The median preoperative GCS was 8. The median GCS at discharge score was 15. At discharge, the median NIHSS score was 4. After 6 months of follow-up, patients had a median NIHSS score of 4. At discharge, the median ADL score of patients was 85. After 6 months of follow-up, the median ADL score of the patients was 95. In treating patients with ICH, the emergency treatment of transfrontal external ventricular drainage combined with OMMAYA sac implantation under laser navigation is a surgical method worthy of further study.

Outcomes of Combined Endoscopic Surgery and Fibrinolytic Treatment Protocol for Intraventricular Hemorrhage: A Randomized Controlled Trial.

Intraventricular fibrinolysis (IVF) and endoscopic surgery (ES) are the new promising treatment strategies to enhance the rate of hematoma clearance, which might improve functional outcome. This study investigated and compared the outcomes among these interventions. A randomized (1:1) double-blinded trial was carried out between August 2018 and December 2021. The intervention and control groups comprised patients receiving IVF and/or ES and external ventricular drainage (EVD), respectively. All participants had experienced primary or secondary intraventricular hemorrhage (IVH) from spontaneous intracerebral hemorrhage with obstructive hydrocephalus complications. The primary outcome was modified Rankin Scale score 180 days post treatment. Interim assessments were planned for every 50 participants enrolled to ensure safety and efficacy. After enrollment of 110 participants (55 participants in each group), there was a difference in 30-day mortality (2 [3.6%] vs. 13 [32.7%] in the EVD group, P= 0.002), reaching the predetermined boundaries for termination of the trial. We demonstrated a better favorable outcome (modified Rankin Scale score 0-3) at 180 days in the intervention group, compared with the control group (35 [63.6%] vs. 24 [43.6%], P= 0.04). Participants in the intervention group experienced a higher IVH removal rate (91% [9.0] vs. 69.5% [38.0], P < 0.01) and had lower shunt conversion (1 [1.8%] vs. 16 [29.3%], P < 0.01). Treatment complications were comparable between the two groups. This study demonstrated that combined ES and IVF is safe and effective for the treatment of IVH. In addition, it concluded that aggressive but safe procedures used to remove IVH could improve clinical outcome in patients with IVH.

A case of successful intraventricular thrombolysis and external ventricular drain treatment in primary intraventricular hemorrhage

Intraventricular hemorrhage (IVH), accounting for about 45% of acute spontaneous intracranial hemorrhage (ICH), is often associated with obstructive hydrocephalus and poor functional outcomes [1] [2]. Obstructive hydrocephalus and increased intracranial pressure are common after IVH because of an obstruction of normal cerebrospinal fluid (CSF) flow and absorption by blood clots. An external ventricular drain (EVD) - a temporary system that permits drainage of cerebral spinal fluid (CSF) from the ventricles to an external closed system) has been indicated for patients with IVH with hydrocephalus and neurologic decline [3]. However, the treatment with EVD alone is often not sufficiently effective due to a likely potential obstruction of the catheter by blood clots. Intraventricular fibrinolysis (IVF) via the extra-ventricular drain has been known to speed clot resolution and maintain the EVD functionality [4]. However, it is also possible that the risk of hemorrhage, infection, and CFS pleocytosis may be increased with IVF therapy, but these have not been demonstrated so far. We report a clinical case of primary IVH with acute obstructive hydrocephalus, successfully treated with a combination of EVD and direct intraventricular injection of rt-PA into the lateral ventricles. This treatment contributes to confirm that combination of EVD and thrombolysis could be considered as a treatment option for selected patients.

Abstract TP124: Irraflow® Device (ventricular Irrigation And Drainage System) Achieves Optimal Clearance Of Intraventricular Hemorrhage (IVH)

Introduction: IVH clearance of more than 80% with intraventricular fibrinolysis administered via a conventional external ventricular drain (EVD) is associated with improvements in outcomes; however, 80% IVH clearance is difficult to achieve. The IRRAflow® device offers fluid irrigation and drainage in a unique system that is designed to provide efficient drainage and clearance of hemorrhage, which may provide advantages over a conventional EVD. The purpose of this study is to evaluate the radiographic findings and outcomes of patients with IVH associated with intracranial hemorrhage (ICH) or subarachnoid hemorrhage (SAH) who received treatment with the IRRAFlow® device from April 1, 2021, to May 1, 2022. Methods: This was a single center, retrospective review. The primary outcome was change in IVH volume which assessed by modified Graeb Scale (mGS). All endpoints were analyzed using descriptive statistics. Results: Twelve patients were identified during the study period. Four patients were not included in the analysis due to withdrawal of care (n=2) or severe stroke causing death before completion of treatment (n=2). Of the eight patients included in the study, two had IVH associated with SAH, and six had IVH associated with ICH. Four patients received intrathecal boluses of alteplase, and three patients also had a traditional EVD placed in additional to the ventricular flow device. Seven patients had a pre-treatment mGS greater than or equal to 5, and two patients had a pre-treatment mGS of 4. The mean (+/- SD) pre-treatment mGS was 14 (+/- 8), and post-treatment mGS was 2 (+/- 3). The mean (+/- SD) volume clearance, which was calculated using the mGS, was 92% (+/- 12%). All patients had a modified Rankin scale (mRS) of 4 prior to treatment. Mean (+/- SD) mRS was 3 (+/- 1) at post-discharge follow up. All patients achieved IVH clearance, with third and fourth ventricle clearance, except for one patient who removed the device prior to completion of therapy. None of the patients required ventriculoperitoneal shunt placement or died. One patient developed ventriculitis as a complication. Conclusion: In conclusion, the IRRAFlow® device was successful in achieving goal IVH clearance (mGS less than 5) in all patients, which has been associated with improved outcomes.

Association of Intraventricular Fibrinolysis With Clinical Outcomes in Intracerebral Hemorrhage: An Individual Participant Data Meta-Analysis.

In patients with intracerebral hemorrhage (ICH), the presence of intraventricular hemorrhage constitutes a promising therapeutic target. Intraventricular fibrinolysis (IVF) reduces mortality, yet impact on functional disability remains unclear. Thus, we aimed to determine the influence of IVF on functional outcomes. This individual participant data meta-analysis pooled 1501 patients from 2 randomized trials and 7 observational studies enrolled during 2004 to 2015. We compared IVF versus standard of care (including placebo) in patients treated with external ventricular drainage due to acute hydrocephalus caused by ICH with intraventricular hemorrhage. The primary outcome was functional disability evaluated by the modified Rankin Scale (mRS; range: 0-6, lower scores indicating less disability) at 6 months, dichotomized into mRS score: 0 to 3 versus mRS: 4 to 6. Secondary outcomes included ordinal-shift analysis, all-cause mortality, and intracranial adverse events. Confounding and bias were adjusted by random effects and doubly robust models to calculate odds ratios and absolute treatment effects (ATE). Comparing treatment of 596 with IVF to 905 with standard of care resulted in an ATE to achieve the primary outcome of 9.3% (95% CI, 4.4-14.1). IVF treatment showed a significant shift towards improved outcome across the entire range of mRS estimates, common odds ratio, 1.75 (95% CI, 1.39-2.17), reduced mortality, odds ratio, 0.47 (95% CI, 0.35-0.64), without increased adverse events, absolute difference, 1.0% (95% CI, -2.7 to 4.8). Exploratory analyses provided that early IVF treatment (≤48 hours) after symptom onset was associated with an ATE, 15.2% (95% CI, 8.6-21.8) to achieve the primary outcome. As compared to standard of care, the administration of IVF in patients with acute hydrocephalus caused by intracerebral and intraventricular hemorrhage was significantly associated with improved functional outcome at 6 months. The treatment effect was linked to an early time window <48 hours, specifying a target population for future trials.

Shunt Dependence after Intraventricular Hemorrhage and Intraventricular Fibrinolysis with uPA versus rt-PA.

We compare the effect of urokinase (urokinase-type plasminogen activator [uPA]) versus alteplase (recombinant tissue plasminogen activator [rt-PA]) for intraventricular fibrinolysis (IVF) in patients with intraventricular hemorrhage (IVH) on ventriculoperitoneal shunt (VPS) dependence, functional outcome, and complications in the management of IVH. We retrospectively reviewed the patients admitted with IVH or intracerebral hemorrhage (ICH) with IVH within 7 years in three different departments and found 102 patients who met the inclusion criteria. The primary end points were VPS dependence and Glasgow outcome score (GOS) at 3 months. Secondary end points were rate of rebleeding under IVF and incidence of treatment-related complications. Patients were divided into three groups: group I comprised patients treated with external ventricular drain (EVD) and IVF with uPA; group II comprised patients treated with EVD and IVF with rt-PA; and group III comprised patients treated with EVD alone. In all, 9.8% patients needed VPS: 12.2% in group I and 15.0% in group II, with no statistically significant difference. VPS patients had higher values of the modified Graeb score (mGS), IVH score, and IVH volume. We saw a trend for a better outcome in group II, with six patients achieving a GOS of 4 or 5 after 3 months. The mortality rate was higher in groups I and III. We found no statistical difference in the complication rate between groups I and II. Logistic regression analysis revealed that higher mGS and age predicted worse prognosis concerning mortality. The risk for death rose by 7.8% for each year of age. Any additional mGS point increased the chances of death by 9.7%. Our data suggest that both uPA and rt-PA are safe and comparable regarding incidence of communicating hydrocephalus, and age and mGS are predictive for mortality.

The Pathogenesis of Hydrocephalus Following Aneurysmal Subarachnoid Hemorrhage.

Hydrocephalus is a common complication of aneurysmal subarachnoid hemorrhage (aSAH) and reportedly contributes to poor neurological outcomes. In this review, we summarize the molecular and cellular mechanisms involved in the pathogenesis of hydrocephalus following aSAH and summarize its treatment strategies. Various mechanisms have been implicated for the development of chronic hydrocephalus following aSAH, including alterations in cerebral spinal fluid (CSF) dynamics, obstruction of the arachnoid granulations by blood products, and adhesions within the ventricular system. Regarding molecular mechanisms that cause chronic hydrocephalus following aSAH, we carried out an extensive review of animal studies and clinical trials about the transforming growth factor-β/SMAD signaling pathway, upregulation of tenascin-C, inflammation-dependent hypersecretion of CSF, systemic inflammatory response syndrome, and immune dysregulation. To identify the ideal treatment strategy, we discuss the predictive factors of shunt-dependent hydrocephalus between surgical clipping and endovascular coiling groups. The efficacy and safety of other surgical interventions including the endoscopic removal of an intraventricular hemorrhage, placement of an external ventricular drain, the use of intraventricular or cisternal fibrinolysis, and an endoscopic third ventriculostomy on shunt dependency following aSAH were also assessed. However, the optimal treatment is still controversial, and it necessitates further investigations. A better understanding of the pathogenesis of acute and chronic hydrocephalus following aSAH would facilitate the development of treatments and improve the outcome.

Technique of External Ventricular Drainage with Intraventricular Administration of Recombinant Tissue Plasminogen Activator for Patients with Secondary Intraventricular Hemorrhage – Case Series in a Single Institution

Introduction: Intraventricular hemorrhage (IVH) as an extension of spontaneous intracerebral hemorrhage is an independent predictor of mortality. The Clot Lysis: Evaluating Accelerated Resolution of IVH phase 3 (CLEAR III) trial is a randomized, double-blinded, placebo controlled, multiregional trial recently conducted to determine whether external ventricular drainage (EVD) plus intraventricular recombinant tissue plasminogen activator (rtPA, alteplase) improved outcome, in comparison to EVD plus saline. This study is an application of the rationale and principles of management in CLEAR III trial and related literature. Methods: There are five patients described in this case series. Report followed the PROCESS guidelines. Results: 30-day mortality in this series is 2 out of 5 while actual all-cause mortality is 4 out of 5. Modified Graeb scores and IVH scores of all subjects have decreased after the intervention. However, good functional status defined as modified Rankin scale (mRS) score of 0-3 has not been achieved with the intervention. Efficacy of completely resolving IVH and hydrocephalus has been achieved in 2 out of 5 which translated to a benefit of survival to one of the two. Shunt dependence has been avoided by the subjects except for the one with the caudate intracerebral hemorrhage. Complications related to the intervention have been noted and discussed Conclusion: In this single-institution study, patients for which rtPA was used for intraventricular fibrinolysis of IVH clot in addition to EVD as surgical treatment for hydrocephalus resulted to a 30-day survival of 3 out of 5 in this series, while actual survival is 1 out of 5. The intervention was efficacious in decreasing the Modified Graeb scores and IVH scores of all study subjects at end of treatment. Functional status of mRS 5 is the highest score achieved among survivors. Key words: intraventricular hemorrhage, fibrinolysis, external ventricular drainage

CSF and other interventions

The present talk reviews newer studies with a focus on CSF management in intraventricular hemorrhage and some selected non-surgical interventions in ICH. Intraventricular hemorrhage is a well-established negative prognostic predictor in ICH and different treatment approaches for this condition have been investigated in the recent years. Intraventricular fibrinolysis has been tested in the CLEAR III trial and showed reduced mortality, however no significant difference in clinical outcome as compared to placebo. A subgroup of patients in CLEAR III, namely those with higher IVH volume who were treated until better IVH removal was achieved (>80% of initial volume), benefited from intraventricular tpA. Although IVH removal can be achieved faster with intraventricular fibrinolysis, blood breakdown products still lead to permanent aresorptive hydrocephalus in approximately 15–30% of patients. A recent study (LUCAS-IVH) has investigated a combined approach of intraventricular fibrinolysis and lumbar drainage of CSF after severe IVH, as compared to intraventricular fibrinolysis alone. Lumbar drainage was applied after re-opening of the third and fourth ventricle and led to significantly less shunt surgery. Faster removal of blood degradation products may play a role as a possible mechanism of action in this treatment approach. The only acute treatment in intracerebral hemorrhage that has recently changed based on new results from clinical trials is blood pressure management. After the INTERACT 2 trial showed benefit from intensive BP control, treatment guidelines were adapted. The later published ATACH trial showed no benefit from intensive BP control (110–139 mmHg) as compared to standard treatment (140–179 mmHg systolic BP). Recent subanalyses show that reduction of ICH growth achieved by intensive BP control is somewhat offset by cardio-renal complications. The TICH 2 trial compared treatment with tranexamic acid against placebo in patients with acute ICH within 8h from symptom onset and could not show a significant benefit in clinical outcome. Although there was significantly less ICH growth in the verum group, the absolute difference was small (appr. 1.2 ml less on average). Perihemorrhagic edema is increasingly being recognized as a treatment target after ICH. Non-surgical treatment strategies used in the clinical routine like mannitol and hypertonic saline are presently not based on robust evidence from clinical trials. Deferoxamine did not show promising results in the recently published i-DEF phase II trial. Data on antiinflammatory treatment approaches are still lacking. Hypothermia and machine-based targeted temperature management have only been investigated in small trials on severely affected patients.

Acute treatment of intracerebral hemorrhage

Intracerebral hemorrhage (ICH) represents one of the most severe forms of stroke with high morbidity and mortality; however, effective treatment options to significantly improve patient outcome do not exist so far. This review article evaluates the most recent developments in acute ICH treatment. Analysis and interpretation of currently available evidence regarding ICH treatment, focusing on the most important studies from the last 3years. Hematoma enlargement, perhaps the most important prognostic factor, should be counteracted by aggressive blood pressure management (targeted systolic pressure 140 mm Hg). In cases of ICH under oral anticoagulation, inhibition of coagulation must be immediately antagonized: vitamin K antagonists with prothrombin complex concentrates (PCC), idarucizumab for dabigatran and andexanet if available or high-dose PCC for factor Xa inhibitors. Currently, surgical treatment strategies, both open and minimally invasive, to evacuate the hematoma can currently not be routinely recommended. In patients with intraventricular ICH, treatment with intraventricular fibrinolysis with or without additional lumbar drainage represents apromising treatment option. In recent years, several randomized controlled and observational studies have generated robust evidence regarding ICH treatment; however, there is still no single breakthrough intervention, which significantly improves patient functional outcome. Nevertheless, the sum of various, possibly interacting treatment concepts may potentially improve outcome after ICH.

Effectiveness of Combined External Ventricular Drainage with Intraventricular Fibrinolysis for the Treatment of Intraventricular Haemorrhage with Acute Obstructive Hydrocephalus

Background: Intraventricular haemorrhage (IVH) patients with acute obstructive hydrocephalus (AOH) who require external ventricular drainage (EVD) are at high risk for poor outcomes. Intraventricular fibrinolysis (IVF) with low-dose recombinant tissue plasminogen activator (rtPA) can be used to improve patient outcomes. Here, we evaluated the impact of IVF on the risk of death and the functional outcomes in IVH patients with AOH. Methods: This prospective cohort study included IVH patients with hypertensive intracranial haemorrhage complicated by AOH who required EVD. We evaluated the risk of death and the functional outcomes at 1 and 3 months, with a specific focus on the impact of combined EVD with IVF by low-dose rtPA. Results: Between November 30, 2011 and December 30, 2014, 80 patients were included. Forty-five patients were treated with EVD alone (EVD group) and 35 received IVF (EVD+IVF group). The 30- and 90-day mortality rates were lower in the EVD+IVF group than in the EVD group (42.2 vs. 11.4%, p = 0.003, and 62.2 vs. 20%, p < 0.001, respectively). The Graeb scores were significantly lower in the EVD+IVF group than in the EVD group (p ≤ 0.001) during the first 3 days and on day 7 after assignment. The 30-day good functional outcome (modified Rankin Scale [mRS] score 0–3) was also higher in the EVD+IVF group than in the EVD group (6.7 vs. 28.6%, p = 0.008). However, the 90-day good functional outcome (mRS score 0–3) did not significantly increase in the EVD+IVF group (30.8% in the EVD group vs. 51.6% in the EVD+IVF group, p = 0.112). Conclusions: In our prospective observational study, EVD+IVF was associated with a lower risk of death in IVH patients. EVD+IVF improved the chance of having a good functional outcome at 1 month; however, this result was no longer observed at 3 months.

FIVHeMA: Intraventricular fibrinolysis versus external ventricular drainage alone in aneurysmal subarachnoid hemorrhage: A randomized controlled trial

IntroductionAneurysmal subarachnoid hemorrhage (SAH) is a devastating form of stroke, which often causes acute hydrocephalus requiring the insertion of an external ventricular drain (EVD). A major complication of aneurysmal SAH is delayed cerebral ischemia (DCI). As DCI is linked to the presence of blood within the subarachnoid space, it has been hypothesized that removing this blood may decrease the risk of DCI. This could be achieved by injecting a fibrinolytic agent through the EVD, a strategy called intraventricular fibrinolysis (IVF). Here, we propose to conduct a phase III trial to directly evaluate the impact of IVF after aneurysmal SAH. Materials and methodsWe will perform an open-label randomized controlled trial comparing the standard of care, i.e. EVD alone, to the experimental treatment, i.e. IVF. We plan to include 440 patients to be able to show a 10% increase in the rate of good functional outcomes in the EVD+IVF group compared to the EVD alone group (α=0.05 and β=0.8). To obtain such sample, a multicenter trial is required, and to date 17 research sites in France have agreed to participate. PerspectiveFIVHeMA would be the first phase III trial evaluating the relevance of IVF in aneurysmal SAH. If IVF is shown to be beneficial, then a new therapeutic tool will be available to improve the outcomes of aneurysmal SAH patients.

Hémorragies intraventriculaires secondaires à la rupture d’un angiome cérébral : description, suivis et impact de la fibrinolyse

Introduction Arteriovenous malformation (AVM) rupture could lead to intraventricular hemorrhage (IVH), a particularly severe form of intracranial bleeding. The epidemiology, presentation, management and outcomes of IVH related to AVM rupture have not been clearly addressed yet. The aim of the present study was to investigate the characteristics of IVH related to AVM rupture, with particular attention paid to functional outcomes and to the impact of intraventricular fibrinolysis (IVF). Material Between 2011 and 2015, all patients suffering from IVH admitted in two tertiary neurosurgical centers were included in a prospective register. Patient with IVH related to AVM rupture were identified (n = 29) and their data retrospectively collected. Particular attention was paid on patients who received IVF. We also compared them to 29 apparied aneurysmal IVH. Results IVH related to AVM rupture often occurred in young patients. In most cases, intracerebral hemorrhage was associated to IVH. Overall, 17.2% of the patients died and functional outcome at 6 months was similar to those with aneurysmal IVH, with a mean modified Rankin scale of 2.5. Interestingly, 5 patients received IVF and none experienced any rebleeding. Conclusion IVH related to AVM rupture is a severe form of hemorrhagic stroke, with a poor neurologic prognosis. IVF seems to be safe and may be considered in this particular form of IVH.

Intraventricular hemorrhage related to AVM rupture: Description, outcomes and impact of intraventricular fibrinolysis

ObjectivesArteriovenous malformation (AVM) rupture could lead to intraventricular hemorrhage (IVH), a particularly severe form of intracranial bleeding. The epidemiology, presentation, management and outcomes of IVH related to AVM rupture have not been clearly addressed yet. The aim of the present study was to investigate the characteristics of IVH related to AVM rupture, with particular attention paid to functional outcomes and to the impact of intraventricular fibrinolysis (IVF). Patients and methodsBetween 2011 and 2015, all patients suffering from IVH admitted in two tertiary neurosurgical centers were included in a prospective register. Patient with IVH related to AVM rupture were identified (n=29) and their data retrospectively collected. Particular attention was paid on patients who received IVF. We also compared them to 29 apparied aneurysmal IVH. ResultsIVH related to AVM rupture often occurred in young patients. In most cases, intracerebral hemorrhage was associated to IVH. 17% of the patients died, and functional outcome at 6 months was similar to those with aneurysmal IVH. Interestingly, 5 patients received IVF and none experienced any rebleeding. ConclusionIVH related to AVM rupture is a severe form of hemorrhagic stroke, with a poor neurologic prognosis. IVF seems to be safe and may be considered in this particular form of IVH.

Spontaneous Intraventricular Hemorrhage: When Should Intraventricular tPA Be Considered?

Spontaneous intracerebral hemorrhage (ICH) is the most common cause of intraventricular hemorrhage (IVH) in adults. Complicating approximately 40% of ICH cases, IVH adds to the morbidity and mortality of this often fatal form of stroke. It is also a severity factor that complicates subarachnoid hemorrhage and traumatic brain injury, along with other less common causes of intracranial bleeding. Medical and surgical interventions to date have focused on limiting ICH and IVH expansion, controlling intracranial pressure, and relieving obstructive hydrocephalus. The placement of an external ventricular drain (EVD) can achieve the latter two goals but has not demonstrated improvement in clinical outcomes beyond mortality reduction. More recently, intraventricular fibrinolysis, utilizing the EVD, has gained interest as a safe and potentially effective method to maintain catheter patency and facilitate hematoma removal. A recent phase III clinical trial evaluating the efficacy of intraventricular alteplase versus intraventricular saline showed a mortality benefit, but failed to meet the primary endpoint of significant functional improvement. However, planned subgroup analysis focusing on patients with IVH volume > 20 mL, and those with IVH removal > 85% suggest that significant functional benefits may be attainable with this therapy. The practice of intraventricular fibrinolysis for spontaneous IVH is not the standard of care; however, based on 20 years of experience, it meets thresholds as a safe intervention, and in those patients with a high burden of intraventricular blood, aggressive clearance may lead to improved quality of life in survivors of this morbid syndrome.

Local Fibrinolytic Therapy for Intraventricular Hemorrhage: A Meta-Analysis of Randomized Controlled trials.

The safety and efficacy of intraventricular fibrinolysis (IVF) in patients with intraventricular hemorrhage (IVH) are unclear. We aimed to determine these issues and to evaluate whether there are differences between recombinant tissue-plasminogen activator (rt-PA) and urokinase according to subgroup analyses. A meta-analysis was undertaken of randomized controlled trials in patients with IVH that compared the administration of rt-PA or urokinase through extraventricular drainage (EVD) with normal saline through EVD or EVD placement alone. Six randomized controlled trials involving 607 patients with IVH were included; 2 trials investigated urokinase and 4 rt-PA. IVF reduced death from any cause at the end of follow-up (risk ratio [RR] 0.63, 95% confidence interval [CI] 0.47-0.83), which was driven mostly by rt-PA (RR 0.65, 95% CI 0.48-0.86). Urokinase did not reduce mortality (RR 0.30, 95% CI 0.06-1.53). However, rt-PA did not reduce the proportion of survivors with poor functional outcome (RR 1.36, 95% CI 1.04-1.77), or the composite endpoint of death and poor functional outcome (RR 0.96, 95% CI 0.83-1.11). IVF neither reduced the need for shunt placement (RR 1.06, 95% CI 0.75-1.49) nor increased ventriculitis (RR 0.57, 95% CI 0.35-0.93) and rebleeding (RR 1.65, 95% CI 0.79-3.45). Although the use of IVF in patients with IVH appears generally safe, its benefit is limited to a reduction in mortality at the expense of an increased number of survivors with moderately-severe to severe disability. Subgroup analyses do not suggest an advantage of IVF with urokinase over rt-PA.

Intraventricular hemorrhage and its fibrinolytic treatment: literature review

The review is dedicated to intraventricular hemorrhage (IVH) and its treatment with topical intraventricular fibrinolysis (IVF). We evaluated many clinical factors typical for IVH: etiology, classifications, symptoms, diagnostics, qualitative and quantitative results and in case of re-bleeding the breakdown site where blood enters venricular system.The paper considers main elements of IVF evaluated, namely indications, external ventricular drain (EVD) techniques, fibrinolytic administration through the drainage catheter vs intratecali, fibrinolytic dosage used (urokinase, tissue plasminogen activator).The paper describes the results following IVH: mortality, main complications (re-bleeding, ventriculitis, shunt-dependence ect) and functional outcome. This article reviews the general points associated with IVH and its treatment with topical IVF.

Thrombolysis for non-traumatic intra-ventricular hemorrhage in adults: a critical reappraisal.

Intra-ventricular hemorrhage (IVH) is a critical condition with high rate of morbidity and mortality due to acute hydrocephalus and secondary brain injury. Mechanisms underlying the clinical deterioration are not only related to the appearance of an acute hydrocephalus but also to blood-clot mass effect and the inflammatory effects of blood break-down products which impede local blood flow and exert a direct toxic effect on the peri-ventricular structures leading to chronic hydrocephalus. An effective treatment strategy should aim at IVH fast removal and reduction of blood-clot mass effect. Although external ventricular drainage placement is an intuitive treatment for obstructive hydrocephalus this treatment does not address in total the aforementioned pathophysiological mechanisms underlying secondary brain damage. Intra-ventricular fibrinolysis, with tissue plasminogen activator or urokinase, is a level of evidence B, class IIB treatment which has proved to be beneficial in lowering the mortality rates. Its effectiveness on functional outcome has been assessed on three large meta-analysis and a recent large randomized control trial (CLEAR III). Results from the CLEAR III multicenter trial suggest that a routine extra-ventricular drain, irrigation with alteplase reduced mortality but did not substantially improve functional outcomes compared with irrigation with saline. Protocol-based use of alteplase with extra-ventricular drain seemed safe, therefore such approach may be a potential option in individual cases. Currently no consensus has been reached and extrapolation of data from the literature does not permit to identify a uniform therapeutic approach but merely to outline some rational procedural modalities. Further research and studies are needed to compare the efficacy of the different fibrinolytic agents and protocols on functional outcome.