Intra-arterial Nimodipine Infusion Research Articles

Combined stent retriever angioplasty and continuous intra-arterial nimodipine infusion as salvage therapy for cerebral vasospasm and delayed cerebral ischemia after subarachnoid hemorrhage: illustrative case.

Delayed cerebral ischemia (DCI) and cerebral vasospasm (CV) are severe complications of spontaneous subarachnoid hemorrhage (SAH) contributing to an inferior outcome. Rescue therapies include intra-arterial balloon angioplasty and repetitive and finally continuous intra-arterial nimodipine infusion. In the presented case, a young female patient with fulminant refractory DCI and CV, despite induced hypertension and nimodipine application, was treated with three-vessel continuous intra-arterial infusion and additional repetitive angioplasty of the basilar and middle cerebral arteries using a stent retriever, leading to a good clinical outcome. Additional stent retriever dilatation to continuous intra-arterial nimodipine application in three vessel territories may represent a further escalation step in the rescue therapy for severe CV and DCI after SAH. Montreal Cognitive Assessment and SF-36 testing showed satisfactory results 3 months after initial treatment with intra-arterial nimodipine catheters in three vessel territory circulations and additional stent retriever vasodilation of severe CV. We report a unique rescue strategy involving implantation of an additional intra-arterial catheter into the vertebral artery and repetitive stent retriever dilatations of the middle cerebral and basilar arteries as an extra therapy for continuous intra-arterial nimodipine vaspospasmolytic therapy in three vessel territories, resulting in a very good clinical outcome.

Safety Profile and Complication Rates in Emergency Off-label Use of Tirofiban in Interventional Neuroradiology

PurposeTirofiban has been approved for the treatment of acute coronary syndrome. Meanwhile, tirofiban is frequently applied in emergency situations in interventional neuroradiology (INR). The objective of this study was to analyze the risk profile for the off-label use of tirofiban in INR patients.MethodsData of 86 patients, who underwent neurointerventional therapy and were treated with tirofiban at 2 neuroendovascular centers between January 2016 and July 2017 were retrospectively analyzed. Despite off-label use, recent stroke (< 30 days), recent hemorrhage, thrombocytopenia (< 150,000/µl), activated partial thromboplastin time (aPTT) > 1.3-fold, internation normalised ratio (INR) < 1.5, severe liver insufficiency (Child-Pugh C), and preceding intravenous thrombolysis were considered as contraindications.ResultsMedian patient age was 62 years (range 26–88 years). Patients received tirofiban for extracranial (n = 35) or intracranial stenting (n = 35), coiling of ruptured cerebral aneurysms (n = 6), continuous intra-arterial nimodipine infusion via microcatheters for subarachnoid hemorrhage (SAH)-related vasospasm (n = 5), or thrombotic complications during neuroendovascular procedures (n = 5). The desired effect of preventing thrombotic complications when applying tirofiban off-label was achieved in 81 of 86 patients (94.2%). Relevant tirofiban-associated complications occurred in 14 patients (16.3%), of which 9 patients received i.v. thrombolysis for treatment of acute ischemic stroke shortly before starting therapy with tirofiban. Of the 86 patients 12 died, while the overall tirofiban-related mortality was 2.3% (2 patients died due to ICH). Logistic regression analysis revealed age to be the only parameter significantly associated with development of tirofiban-associated complications (p = 0.026).ConclusionWhereas the safety profile of tirofiban when applied off-label in INR is acceptable, the highest risk for relevant tirofiban-associated complications is observed in older patients treated by emergency stenting for acute stroke.

Intracranial stenting as a bail-out option for posthemorrhagic cerebral vasospasm: a single-center experience with long-term follow-up

BackgroundCerebral vasospasm (CVS) is a leading cause of morbidity and mortality in patients after aneurysmal subarachnoid hemorrhage (aSAH). Endovascular treatment, including intraarterial infusion of drugs with vasodilation effects, and balloon- and stentriever angioplasty, are helpful but may achieve only short-term effects. There is a clinical need for long-lasting treatment of refractory recurrent vasospasm. We report our experience in stent implantation as a treatment for recurrent severe post-SAH vasospasm.MethodsA retrospective analysis of our institutional database of 883 patients with SAH, managed between January 2010 and December 2021, was performed. Six patients were identified as having received intracranial stenting in the context of post-SAH cerebral vasospasm. All patients were initially treated with intra-arterial infusion of nimodipine and/or milrinone. Self-expanding intracranial stents were implanted during endovascular aneurysm treatment to enable access despite impaired perfusion (Group 1) or as a bail-out strategy after failed intraarterial drug infusion or mechanical treatment (Group 2). All stented patients received dual antiplatelet therapy (DAPT) for 6 months.ResultsNine vessels in six patients with severe post-SAH vasospasm were stented. The stents were deployed in 16 vessel segments. All attempted implantations were technically successful. All patients demonstrated radiographic and clinical improvement of the vessel narrowing. No recurrent vasospasm or permanent vessel occlusion of the stented vessels was encountered. A thrombus formation in a Group 1 patient resolved under 4 mg eptifibatide IA infusion. During long-term angiographic follow-up, neither in-stent stenosis nor stent occlusion was found.ConclusionsEndovascular implantation of self-expanding stents is a potential ultima ratio strategy for patients with severe refractory post-SAH cerebral vasospasm. Stents with reduced thrombogenicity (avoiding DAPT) and bioabsorbable self-expanding stents might further advance this concept.

Continuous Intraarterial Nimodipine Infusion for the Treatment of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: A Retrospective, Single-Center Cohort Trial

BackgroundDelayed cerebral ischemia (DCI) occurs after aneurysmal subarachnoid hemorrhage (aSAH). Continuous intraarterial nimodipine infusion (CIAN) is a promising approach in patients with intracranial large vessel vasospasm (LVV). The objective of this retrospective single-center cohort study was to evaluate the outcome in aSAH-patients treated with CIAN.MethodsCIAN was initiated and ended based on the clinical evaluation and transcranial Doppler (TCD), CT-angiography, CT-perfusion (PCT), and digital subtraction angiography (DSA). Nimodipine (0.5–2.0 mg/h) was administered continuously through microcatheters placed in the extracranial internal carotid and/or vertebral artery. Primary outcome measures were Glasgow Outcome Scale (GOS) at discharge and within 1 year after aSAH, and the occurrence of minor and major (<⅓ and >⅓ of LVV-affected territory) DCI-related infarctions in subsequent CT/MRI-scans. Secondary outcome measures were CIAN-associated complications.ResultsA total of 17 patients underwent CIAN. Median onset of CIAN was 9 (3–13) days after aSAH, median duration was 5 (1–13) days. A favorable outcome (GOS 4–5) was achieved in 9 patients (53%) at discharge and in 13 patients within 1 year (76%). One patient died of posthemorrhagic cerebral edema. Minor cerebral infarctions occurred in five and major infarctions in three patients. One patient developed cerebral edema possibly due to CIAN. Normalization of PCT-parameters within 2 days was observed in 9/17 patients. Six patients showed clinical response and thus did not require PCT imaging.ConclusionThe favorable outcome in 76% of patients after 1 year is in line with previous studies. CIAN thus may be used to treat patients with severe therapy-refractory DCI.

Adverse Events and Complications in Continuous Intra-arterial Nimodipine Infusion Therapy After Aneurysmal Subarachnoid Hemorrhage.

ObjectiveTo determine the frequency and severity of complications associated with the continuous intra-arterial infusion of nimodipine (CIANI) as a new treatment of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH).MethodsPatients from two centers (n = 718) treated for SAH between 2008 and 2016 were included. Demographic and SAH-related parameters were evaluated, and also the frequency of adverse events (AEs) and complications including their severity (mild, moderate, and severe). Clinical outcome was analyzed using Glasgow Outcome Scale (GOS). The unfavorable outcome was defined as GOS 1 to 3, and favorable outcome as GOS 4 to 5. The Short-Form 36 (SF-36) health-related quality-of-life (QoL) questionnaire served as a QoL measurement.ResultsOf 718 patients, 65 (9%) were treated by CIANI and had a higher clinical or imaging grade of bleeding severity. Clinical deterioration while on treatment happened more often in patients who were treated with CIANI than in others. In patients with CIANI, 67% had AEs and/or complications during the treatment. Nimodipine-associated hypotension was seen in 8% (mild). Catheter-associated thrombus occurred in 9% (moderate). New intracerebral hemorrhage was found in 14% (moderate). A total of 6% treated by CIANI died during the treatment period (severe). More than one-third (39%) of patients of CIANI reached at least moderate disability, and 23% showed good recovery. Patients who received CIANI showed reduced QoL, but differences in mental and general health, and also pain were minimal.ConclusionPatients who received CIANI had higher rates of AEs and complications. However, this does not exclude the possibility that the use of CIANI might be helpful in patients with severe and therapy-refractory CV and DCI. Controlled and randomized studies would be helpful to clarify this question but they are methodologically and ethically challenging.

Clinical Outcome in Cerebral Vasospasm Patients Treated with and without Intra-Arterial Nimodipine Infusion.

Cerebral vasospasm (CV) after aneurysmal subarachnoid hemorrhage (aSAH) is still a problem. Hypertension, hypervolemia, and hemodilution (triple-H) therapy and oral nimodipine only a modest effect on patients. Intra-arterial treatment, including nimodipine, has been studied, but only as retrospective and single-arm prospective studies. We compared the outcomes between CV patients who received an adjunct intra-arterial nimodipine infusion (IANI) and those who received the standard medical treatment alone in a prospective randomized controlled trial. In this study, patients between the age of 18 and 80 years, who underwent angiography within 14 days after aneurysm obliteration, were recruited and randomized to receive adjunct IANI or not, if they were identified with angiographic vasospasm. All the angiographic and neurologic data were recorded and analyzed during their admission, at the discharge date, and during the 6-month follow-up period. From June 2016 to December 2018, we enrolled 68 patients who were randomized into two groups, 36 in the intervention group and 32 in the control group. The patients' characteristics, aneurysm data, and modalities of treatment were similar between the two groups. Within 24 hours after IANI, Glasgow Coma Scale (GCS) score and motor strength revealed a significant improvement of 33.33 and 38.89%, respectively, in the intervention group versus 12.5 and 9.38%, respectively, in the control group. At discharge, the intervention group still had significant motor improvement (58.33 vs. 21.88%; p = 0.002). IANI could be considered an effective treatment for CV without significant complications. This is the first RCT demonstrating statistically significant motor strength improvement within 24 hours and at discharge.

Continuous intra-arterial nimodipine infusion as rescue treatment of severe refractory cerebral vasospasm after aneurysmal subarachnoid hemorrhage

Severe refractory cerebral vasospasm (CV) is a major cause of disability and death in patients with aneurysmal subarachnoid hemorrhage (SAH). One rescue therapy in selected patients is intra-arterial nimodipine, either given as a single shot or as continuous infusion. To evaluate treatment efficacy, we analyzed outcome factors such as the incidence of craniectomy, ventriculo-peritonial (VP) shunting, and tracheotomy after intra-arterial nimodipine infusion. We retrospectively analyzed the rates of cerebral infarction, decompressive craniectomy, VP shunting, and tracheotomy in patients with severe CV after SAH. Three different patient groups were compared: group 1 had only been treated with oral nimodipine and hypervolemic hypertensive therapy (HHT) (2006–2010), group 2 with a single shot of intra-arterial nimodipine (SSN) in addition to oral conservative treatment (2006–2010), and group 3 with continuous intra-arterial nimodipine (CIAN) (2011–2017). The incidence of cerebral infarction was significantly lower in CIAN group (p = 0.005) than in conservative and SSN group. The indication for consecutive decompressive craniectomy was significantly lower in CIAN group in comparison with the conservative group (p = 0.018). The rates of VP shunting and tracheotomy were significantly higher in the CIAN group than in the conservative group (p = 0.028 for VP, and p = 0.003 for tracheotomy). The significantly lower rate of craniectomy in the CIAN group was most probably attributable to the significantly lower rate of CV-induced infarction. The higher rate of tracheotomy reflects more extensive sedation and the need of longer stays on the intensive care unit. Thus, the effect on long-term neurological outcome and quality of life has to be evaluated separately.

Specifics of endovascular embolization for cerebral aneurysmsin the acute period of subarachnoid hemorrhage

Aim – to assess the benefits of modern methods for endovascular occlusion of ruptured cerebral aneurysms in the acute period of subarachnoid hemorrhage (SAН). Materials and methods. Medical records of patients undergoing treatment in the acute period of aneurysmal SAН between 2010–2021 were analyzed. 2 groups were formed: I – the use of standard surgical catheters, minimal use of adjunctive techniques for aneurysm embolization (2010–2016), II – routine use of triaxial access systems, intraarterial infusion of nimodipine, active use of adjunctive techniques for aneurysm embolization, intraoperative antiplatelet therapy immediately after aneurysm occlusion – 500 mg of solution Acelysin administrated intravenously (2017–2021). The severity of SAН according to the Hunt–Hess, Fisher scales, the treatment outcome according to the modified Rankin Scale (mSR), the location and size of aneurysms and intraoperative complications were analyzed. Results. There were 156 observations in group I, 91 – in group II. The median age was 48.26 years in group I, 51.44 years – in group II. On the basis of gender status, there was a majority of women in both groups. Aneurysms of the anterior cerebral-anterior communicating artery complex predominated in both groups; the internal carotid artery was the second most frequent localization. The severity of SAН according to the generally accepted scales (Hunt–Hess, Fisher) did not differ significantly. Coil embolization was used in 100 % of cases, balloon-assisted coiling was used in 6.48 % in group I and in 14.80 % – in group II, stent-assisted coiling – in 2.56 % and 9.30 %, respectively, distal access catheter with the triaxial system was not used in group I and it was performed in 57.4 % of cases in group II. Pharmacoangioplasty using nimodipine solution was used in 16.6 % in group I and in 22.2 % in group II. Intravenous drip infusion of 0.5 g Acelysin was performed immediately after aneurysm occlusion in 22.2 % of cases in group II. Intraoperative aneurysm rupture was observed in 5.1 % in group I and in 1.1 % in group II. Distal coil migration or into the maternal artery occurred in 6.41 % in group I and in 2.20 % in group II. Thromboembolic complications were noted in 7.69 % and in 2.20 %, respectively. The mean value of dysfunction degree on mSR amounted to 2.27 in group I and 1.45 – in group II. A good treatment outcome (mRS score 1–2) was defined in 71.2 % of observations in group I and in 87.9 % – in group II. The death rate was 12.82 % and 7.62 %, respectively. Conclusions. Routine use of triaxial access systems and intraarterial pharmacoplasty with nimodipine allow adequate prevention of mechanically induced vasospasm during catheterization of the aneurysm cavity. The triaxial access system stability provides better control of the microguidewire and microcatheters reducing the risk of aneurysmal wall perforation during catheterization. The use of adjunctive techniques for embolization of ruptured cerebral aneurysms in the acute period of SAH and prophylactic infusion of Acelysin solution after aneurysm occlusion significantly reduces the incidence of thromboembolic complications. The earliest possible occlusion of a ruptured cerebral aneurysm is not only the prevention of re-rupture, but also expands the possibilities of intensive care for preventing secondary complications of SAH.

Stellate ganglion block combined with intra-arterial treatment: a "one-stop shop" for cerebral vasospasm after aneurysmal subarachnoid hemorrhage-a pilot study.

Delayed cerebral ischemia (DCI) is a frequent cause of morbidity and mortality in patients with cerebral vasospasm (CV) following aneurysmal subarachnoid hemorrhage (aSAH). Refractory CV remains challenging to treat and often leads to permanent deficits and death despite aggressive therapy. We hereby report the feasibility and safety of stellate ganglion block (SGB) performed with a vascular roadmap-guided technique to minimize the risk of accidental vascular puncture and may be coupled to a diagnostic or therapeutic cerebral angiography. In addition to a detailed description of the technique, we performed a retrospective analysis of a series of consecutive patients with refractory CV after aSAH that were treated with adjuvant roadmap-guided SGB. Clinical outcomes at discharge are reported. Nineteen SGB procedures were performed in 10 patients, after failure of traditional hemodynamic and endovascular treatments. Each patient received 1 to 3 SGB, usually interspaced by 24 h. In 4 patients, an indwelling microcatheter for continuous infusion was inserted. First SGB occurred on average 7.3 days after aSAH. SGB was coupled to intra-arterial nimodipine infusion or balloon angioplasty in 9 patients. SGB was technically successful in all patients. There were no technical or clinical complications. Adjuvant SGB may be coupled to endovascular therapy to treat refractory cerebral vasopasm within the same session. To guide needle placement, using a roadmap of the supra-aortic arteries may decrease the risk of complications. More prospective data is needed to evaluate the therapeutic efficacy, durability, and safety of SGB compared with the established standard of care.

Continous local Intra –arterial Nimodipine administration in severe symptomatic vasospasm after spontanous subarachnoid hemorrhage:a meta-analysis

Abstract Background Subarachnoid hemorrhage (SAH) is bleeding into the subarachnoid space (the area between the arachnoid membrane and the pia mater surrounding the brain). SAH is a potentially life threatening condition. Hemorrhage may occur as a result of a head injury or spontaneously (usually from a ruptured cerebral aneurysm). Spontaneous subarachnoid hemorrhage occurs in about one per 10,000 people per year. Females are more commonly affected than males. While it becomes more common with age, about 50% of people present under 55 years old. It is a form of stroke and comprises about 5 % of all strokes. Disturbed conscious level, specially that associated with cerebral arterial vasospasm, remains a major cause of death and disability in the patients with aneurysmal subarachnoid hemorrhage.The classical modality of management for vasospasm was oral calcium channel blockers (nimodipine) with triple-H therapy (Hypedynamic augmentation therapy). Aim To evaluate the effect of Continous local Intra –arterial nimodipine administration in severe symptomatic vasospasm after spontanous subarachnoid hemorrhage on mortality and morbidity (symptomtic cerebral ischemia). Methodology: Studies and participants In the current meta-analysis, we searched for interventional clinical trials in critically ill adult patients that evaluated to have aneurysmal subarachnoid hemorrhage complicated by severe symptomatic vasospasm (causing delayed cerebral ischemia and neurological deficits) which was refractory to standard hyper dynamic therapy (triple- H therapy) and oral calcium channel blockers (CCBS). Results In the current meta-analysis, the duration of infusion of nimodipine was at least for 72 hours. The onset of occurance of cerebral vasodilation after the infusion in all studies by their different doses was 12 hours detected by transcranial doppler. The time of termination of nimodipine infusion is different from patient to other patient depending on clinical improvement ( improvement of consious level or disappearance of the newly developed neurological deficit) and radiological findings that refers to the relief of vasospasm assesed by transcranial doppler and cerebral angiography. Reinfusion of the nimodipine was done in all included studies in case of recurrence of vasospasm causing new neurological deficit or deterioration in the conscious level . Conclusion It concluded from the current meta-analysis that, intra-arterial nimodipine infusion is effective and safe treatment for syptomatic refractory vasospasm after aneurysmal subarachnoid hemorrhage.

Incidence of Arterial Hypotension in Patients Receiving Peroral or Continuous Intra-arterial Nimodipine After Aneurysmal or Perimesencephalic Subarachnoid Hemorrhage.

Oral nimodipine is used for prophylaxis and treatment of delayed cerebral ischemia in patients with aneurysmal or perimesencephalic subarachnoid hemorrhage (SAH). In cases of serious refractory cerebral vasospasm, a continuous intra-arterial (IA) infusion of nimodipine (CIAN) may be required to avoid cerebral ischemia. Nimodipine can cause arterial hypotension requiring either a dosage reduction or its discontinuation. Aim of the present study was to examine the effect of different nimodipine formulations on arterial blood pressure in aneurysmal or perimesencephalic SAH patients and to measure the plasma levels after both, peroral administration as tablet or solution and IA infusion. In a prospective setting, over a 1-year observation period, data on the course of arterial blood pressure and nimodipine dosage were collected for 38 patients undergoing treatment for aneurysmal or perimesencephalic SAH in an intensive care unit. In addition, plasma concentrations of nimodipine were measured by liquid chromatography-tandem mass spectrometry. The intended full dose of 60mg of nimodipine given orally every 4h could only be administered on 57.2% of the examined days. Ninety-seven episodes of relevant arterial hypotension probably caused by the administration of nimodipine were observed within the first 14days of treatment. Drops in blood pressure occurred about three times as often after administration of nimodipine as oral solution than as tablet. However, there were no differences in nimodipine plasma levels between the two formulations. In patients suffering from higher-grade SAH, arterial hypotension and consequent dosage reduction or discontinuation of nimodipine were more frequent than in patients with lower-grade SAH. Plasma concentrations of nimodipine during CIAN did not exceed those achieved by oral administration. Dosage reduction or discontinuation of oral nimodipine is often necessary in patients with higher-grade SAH. Oral nimodipine solutions cause drops in blood pressure more frequently than tablets. Intra-arterial infusion rates of less than 1mg/h result in venous plasma concentrations of nimodipine similar to those observed after oral application of 60mg every 4 h.

Symptomatic cerebral vasospasm after glioblastoma resection and carmustine wafers implantation. A case report

Abstract Local chemotherapy with carmustine-impregnated wafers showed safe and effective in the treatment of malignant glioma, with infrequent, though sometime serious, adverse effects. We report a rare case of cerebral vasospasm following glioblastoma removal with carmustine wafers implantation in a 57-years-old man. After surgery, the patient awoke with aphasia, due to vasospasm of the left middle cerebral artery. Intra-arterial infusion of nimodipine was performed, with rapid vasospasm resolution and quick recovery. Cerebral vasospasm is an extremely rare adverse effect after carmustine wafers implantation in glioma surgery, with only one case reported. In our case, intra-arterial nimodipine was rapidly effective. Although rare, such a potentially disastrous complication should be considered when a new neurological deficit unexpectedly occurs after carmustine wafers implantation, and vascular investigation should be undertaken.

Complication rate of intraarterial treatment of severe cerebral vasospasm after subarachnoid hemorrhage with nimodipine and percutaneous transluminal balloon angioplasty: Worth the risk?

Background and purposeDelayed cerebral ischemia (DCI) is a complication of aneurysmal subarachnoid hemorrhage (SAH). Arterial cerebral vasospasm (CVS) is discussed as the main pathomechanism for DCI. Due to positive effects of per os nimodipine, intraarterial nimodipine application is used in patients with DCI. Further, percutaneous transluminal balloon angioplasty (PTA) is applied in focal high-grade spasm of intracranial arteries. However, clinical benefits of those techniques are unconfirmed in randomized trials so far, and complications might occur. We analyzed the occurrence of new infarcts in patients with severe CVS treated intra-arterially to assess benefits and risks of those techniques in a large single-center collective. Materials and methodsAll imaging and clinical data of 88 patients with CVS after SAH and 188 procedures of intraarterial nimodipine infusion and additional PTA in selected cases (18 patients, 20 PTA procedures) treated at our institution were reviewed. In the event of new infarcts after endovascular treatment of CVS, infarct patterns were analyzed to determine the most probable etiology. ResultsFifty-three percent of patients developed new cerebral infarction after intraarterial nimodipine and additional PTA in selected cases. Hereunder 47% were caused by persisting CVS. In 6% of patients, 3% of procedures respectively, new infarcts occurred due to complications of the intraarterial treatment including thromboembolism and arterial dissection. Of those, 3% of patients, 2% of procedures respectively, were assigned to thrombembolic complications of digital substraction angiography for intraarterial nimodipine. 17% of all patients treated with PTA (3/18=17%) showed infarction as a complication of PTA (15% of all PTA procedures). In 1% of patients, etiology of new infarction remained unclear. ConclusionIschemic complications occur in about 6% of patients treated intraarterially for CVS, 3% of procedures respectively. Further, to date a benefit for patients treated with this therapy could not be proven. Therefore, intraarterial treatment of CVS should be performed only in carefully selected cases.

Higher dose intra-arterial milrinone and intra-arterial combined milrinone-nimodipine infusion as a rescue therapy for refractory cerebral vasospasm.

Background Cerebral vasospasm (CV) is a major cause of delayed morbidity and mortality in patients with subarachnoid hemorrhage (SAH). Various cerebral protectants have been tested in patients with aneurysmal SAH. We aimed to research the success rate of treatment of CV via intra-arterial milrinone injection and aggressive pharmacological therapy for refractory CV. Methods A total of 25 consecutive patients who received intra-arterial milrinone and nimodipine treatment for CV following SAH between 2014 and 2017 were included in the study. Patients who underwent surgical clipping were excluded. Refractory vasospasm was defined as patients with CV refractory to therapies requiring ≥3 endovascular interventions. Overall, six patients had refractory CV. Long-term neurological outcome was assessed 6-18 months after SAH using a modified Rankin score and Barthel index. Results The median modified Rankin scores were 1 (min: 0, max: 3) and Barthel index scores were 85 (min: 70, max: 100) From each vasospastic territory maximal 10-16 mg milrinone was given to patients; a maximum of 24 mg milrinone was given to each patient in a session and a maximum of 42 mg milrinone was given to a patient in a day. Both milrinone and nimodipine were given to three patients. There was a large vessel diameter increase after milrinone and nimodipine injections. No patient died due to CV; only one patient had motor dysfunction on the right lower extremity. Conclusion Higher doses of milrinone can be used effectively to control refractory CV. For exceptional patients with refractory CV, high dose intra-arterial nimodipine and milrinone infusion can be used as a rescue therapy.

Side Effects of Long-Term Continuous Intra-arterial Nimodipine Infusion in Patients with Severe Refractory Cerebral Vasospasm after Subarachnoid Hemorrhage.

Long-term continuous intra-arterial nimodipine infusion (CIAN) is a rescue therapy option in cases of severe refractory cerebral vasospasm (CV) following acute non-traumatic subarachnoid hemorrhage (SAH). However, CIAN therapy can be associated with relevant side effects. Available studies focus on intracerebral complications, whereas extracerebral side effects are rarely examined. Aim of the present study was to generate descriptive data on the clinical course during CIAN therapy and expectable extracerebral side effects. All patients treated with CIAN therapy for at least 5days between May 2011 and December 2015 were included. We retrospectively extracted data from the patient data management system regarding the period between 2days before the beginning and 5days after the termination of CIAN therapy to analyze the course of ventilation parameters and pulmonary gas exchange, hemodynamic support, renal and liver function, integrity of the gastrointestinal tract, and the occurrence of infectious complications. In addition, we recorded the mean daily values of intracranial pressure (ICP) and intracerebral problems associated with CIAN therapy. Data from 28 patients meeting inclusion criteria were analyzed. The mean duration of long-term CIAN therapy was 10.5±4.5days. Seventeen patients (60.7%) reached a good outcome level (Glasgow Outcome Scale [GOS] 4-5) 6months after SAH. An impairment of the pulmonary gas exchange occurred only at the very beginning of CIAN therapy. The required vasopressor support with norepinephrine was significantly higher on all days during and the first day after CIAN therapy compared to the situation before starting CIAN therapy. Two patients required short-time resuscitation due to cardiac arrest during CIAN therapy. Acute kidney injury was observed in four patients, and one of them required renal replacement therapy with sustained low-efficiency daily dialysis. During CIAN therapy, 23 patients (82.1%) needed the escalation of a previous antiinfective therapy or the onset of antibiotics which was in line with a significant increase of C-reactive protein and white blood cell count. Obstipation was observed in 22 patients (78.6%). Ten patients (35.7%) even showed insufficient defecation on at least seven consecutive days. Compared to the situation before, ICP was significantly higher during the whole period of CIAN therapy. Long-term CIAN therapy is associated with diverse side effects. The leading problems are an impairment of the hemodynamic situation and cardiac problems, an increase in infectious complications, a worsening of the motility of the gastrointestinal tract, and rising ICP values. Teams on neurointensive care units must be aware of these side effects to avoid that the beneficial effects of CIAN therapy on CV reported elsewhere are foiled by the problems this technique can be associated with.

Clinical Course and Monitoring Parameters After Continuous Interventional Intra-Arterial Treatment in Patients with Refractory Cerebral Vasospasm.

In aneurysmal subarachnoid haemorrhage cerebral vasospasm leads to clinical worsening and poor outcome. Interventional treatment with nimodipine might be a therapeutic option. To evaluate the clinical course of patients with different interventional treatment types. A retrospective, observational analysis was performed. Inclusion criteria were aneurysmal subarachnoid haemorrhage, clinical and/or radiologic evidence of vasospasm and interventional intra-arterial treatment. Patients were divided into 3 groups: continuous nimodipine infusion, repetitive nimodipine infusions, and singular nimodipine infusion. Pre- and postinterventional parameters were analyzed to evaluate the efficacy of the procedure in terms of responder status. Outcome was determined using the modified Rankin scale. A total of 163 interventions (97 patients) were examined. Patients with continuous treatment showed a greater World Federation of Neurological Surgeons grade. Response to intra-arterial nimodipine in the continuous group was comparatively worse. Transcranial Doppler monitoring as well as brain tissue oxygenation measuring showed good correlation with imaging results. The rate of intraprocedural complications in the continuous treatment group was significantly greater. We observed a worse clinical outcome in the patients who underwent continuous treatment. None of the patients in the continuous group achieved favorable outcome after 3months. Facing the poor clinical outcome and the greater complication rate, continuous intra-arterial infusion of nimodipine in patients with angiographically refractory cerebral vasospasm has to be indicated strictly. Transcranial Doppler and brain tissue oxygenation monitoring seem to be reliable tools for evaluation of the clinical postinterventional course.

Continuous intra-arterial nimodipine infusion in refractory symptomatic vasospasm after subarachnoid hemorrhage.

IntroductionVasospasm still is a major cause of morbidity after aneurysmal subarachnoid hemorrhage. The purpose of this report is to describe the successful management of severe refractory vasospasm with continuous intra-arterial nimodipine (IAN) treatment.Case descriptionA 72-year old right handed woman was admitted with non-traumatic SAH WFNS grade 1. Cerebral computed tomography demonstrated thick blood filling of the basal cisterns, and intraventricular hemorrhage. Cerebral angiogram failed to detect a vascular abnormality. After an uneventful initial course the patient developed symptomatic left middle cerebral artery vasospasm with aphasia and corresponding restriction in diffusion weighted images in the left frontal lobe. Bolus IAN only transiently improved cerebral circulation and clinical signs and symptoms. Continuous-IAN was started and led to full clinical recovery and normalisation of MRI diffusion restrictions.Discussion and conclusionsContinuous selective intra-arterial infusion of nimodipine may be an option in selected patients with symptomatic vasospasm refractory to conventional treatment after careful consideration of benefits and procedure-related risks.

Continuous intra-arterial nimodipine infusion in patients with severe refractory cerebral vasospasm after aneurysmal subarachnoid hemorrhage: a feasibility study and outcome results.

Severe cerebral vasospasm is a major cause of death and disability in patients with aneurysmal subarachnoid hemorrhage. No causative treatment is yet available and hypertensive hypervolemic therapy (HHT) is often insufficient to avoid delayed cerebral ischemia and neurological deficits. We compared patients receiving continuous intra-arterial infusion of the calcium-antagonist nimodipine with a historical group treated with HHT and oral nimodipine alone. Between 0.5 and 1.2 mg/h of nimodipine were continuously administered by intra-arterial infusion via microcatheters either into the internal carotid or vertebral artery or both, depending on the areas of vasospasm. The effect was controlled via multimodal neuromonitoring and transcranial Doppler sonography. Outcome was determined by means of the Glasgow Outcome Scale at discharge and 6 months after the hemorrhage and compared to a historical control group. Twenty-one patients received 28 intra-arterial nimodipine infusions. Six months after discharge, the occurrence of cerebral infarctions was significantly lower (42.6 %) in the nimodipine group than in the control group (75.0 %). This result was reflected by a significantly higher proportion (76.0 %) of patients with good outcome in the nimodipine-treated group, when compared to 10.0 % good outcome in the control group. Median GOS was 4 in the nimodipine group and 2 in the control group (p = 0.001). Continuous intra-arterial nimodipine infusion is an effective treatment for patients with severe cerebral vasospasm who fail to respond to HHT and oral nimodipine alone. Key to the effective administration of continuous intra-arterial nimodipine is multimodal neuromonitoring and the individual adaptation of dosage and time of infusion for each patient.

Pharmacokinetic Modeling of Intra-arterial Nimodipine Therapy for Subarachnoid Hemorrhage-Related Cerebral Vasospasm.

Intra-arterial (IA) administration of nimodipine has been shown to be an effective treatment for subarachnoid hemorrhage-related cerebral vasospasm. The concentrations achieved in cerebral arteries during this procedure, though, are unknown. Therefore, there are no clinical studies investigating dose-dependent effects of nimodipine. We aimed at providing a pharmacokinetic model for IA nimodipine therapy for this purpose. A two-compartment pharmacokinetic model for intravenous nimodipine therapy was modified and used to assess cerebral arterial nimodipine concentration during IA nimodipine infusion into the internal carotid artery (ICA). According to our simulations, continuous IA nimodipine infusion at 2mg/h and 1mg/h resulted in steady-state cerebral arterial concentrations of about 200ng/ml and 100ng/ml assuming an ICA blood flow of 200ml/min and a clearance of 70l/h. About 85 % of the maximal concentration is achieved within the first minute of IA infusion independent on the infusion dose. Within the range of physiological and pharmacokinetic data available in the literature, ICA blood flow has more impact on cerebral arterial concentration than nimodipine clearance. The presented pharmacokinetic model is suitable for estimations of cerebral arterial nimodipine concentration during IA infusion. It may, for instance, assist in dose-dependent analyses of angiographic results.

Clinical Variables Correlated with Numbers of Intra-arterial Nimodipine Infusion in Patients with Medically Refractory Cerebral Vasospasm.

ObjectiveThe objective of this study was to find out the clinical variables correlated with repeated intra-arterial (IA) nimodipine infusions in patients with medically refractory cerebral vasospasm (CV) following subarachnoid hemorrhage (SAH).Materials and MethodsDuring the 36 months between January 2011 and December 2013, 275 patients were treated at our institute for SAH due to a ruptured intracranial aneurysm. Of the 275 patients, 26 patients (9.5%) met the inclusion criteria. For each patient, a retrospective review of their medical records was conducted.ResultsEleven patients underwent a single IA nimodipine infusion and 15 patients underwent more than two IA nimodipine infusions. Multiple IA nimodipine infusion patients had poor improvement (2 of 15 patients, 13.3%) in Glasgow coma scale (GCS) scores after the first IA nimodipine infusion compared to patients of single IA nimodipine infusion (6 of 11 patients, 54.6%) (p = 0.038). The mean middle cerebral artery (MCA) Lindegaard ratio of multiple IA nimodipine infusion patients was 4.3 ± 1.1 after the first IA nimodipine infusion (p = 0.039). In multiple IA nimodipine infusion patients, CV occurred more often bilaterally (p = 0.035) and distally (p = 0.001). More vessel segments were affected in multiple IA nimodipine infusion patients (3.1 ± 1.0) (p < 0.001).ConclusionThe following factors correlated with multiple IA nimodipine infusions: 1) no improvement in GCS after the IA nimodipine infusion; 2) no decrease of MCA velocity on transcranial doppler over 50 cm/s or Lindegaard ratio over 4.3 after the IA nimodipine infusion; 3) distal, bilateral, or diffuse involvement of CV.