Intravenous Milrinone for Hemodynamic Rescue in Spontaneous Intracerebral Hemorrhage with Intraventricular Extension
-
Mojtaba Mojtahedzadeh
,
Fatemeh Afra
,
Amir Nasrollahizadeh
,
Sepide Javankiani
,
Roya Saedpanah
,
Elahe Shaban
,
Atabak Najafi
,
Amirmahdi Mojtahedzadeh
Abstract
Spontaneous intracerebral hemorrhage (ICH) with intraventricular extension (IVH) is a life-threatening condition associated with high rates of morbidity and mortality. Current management is primarily supportive, with few pharmacologic options available to optimize cerebral perfusion. Milrinone, a phosphodiesterase-3 (PDE-3) inhibitor commonly used in cardiology to boost cardiac output and stabilize hemodynamics, has rarely been explored in neurocritical care. We describe a 70-year-old man with hypertension who experienced a sudden collapse and left-sided paralysis. Imaging revealed a large hemorrhage affecting the right thalamus and basal ganglia with extension into the ventricles. Despite standard interventions, his neurological condition deteriorated. Intravenous milrinone was initiated as a salvage therapy to support mean arterial pressure (MAP) and preserve cerebral perfusion pressure (CPP). Following treatment, his hemodynamics stabilized, intracranial pressure remained controlled, and neurological function improved. At discharge, he had a Glasgow Coma Scale (GCS) of 14, and follow-up imaging confirmed complete resolution of the clot. This case highlights the potential of milrinone to support both systemic and cerebral hemodynamics in patients with ICH/IVH, demonstrating its combined cardiac and neuroprotective effects. To our knowledge, this is among the first documented uses of intravenous milrinone in spontaneous hemorrhagic stroke, suggesting a promising new application for PDE-3 inhibition in critical care beyond traditional cardiology.
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[2] Greenberg SM, Ziai WC, Cordonnier C, Dowlatshahi D, Francis B, Goldstein JN, et al. 2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2022; 53(7):e282-e361.
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[4] Essibayi MA, Ibrahim Abdallah O, Mortezaei A, Zaidi SE, Vaishnav D, Cherian J, et al. Natural History, Pathophysiology, and Recent Management Modalities of Intraventricular Hemorrhage. J Intensive Care Med. 2024; 39(9):813-819.
[5] An SJ, Kim TJ, Yoon BW. Epidemiology, Risk Factors, and Clinical Features of Intracerebral Hemorrhage: An Update. J Stroke. 2017; 19(1):3-10.
[6] Hinson HE, Hanley DF, Ziai WC. Management of intraventricular hemorrhage. Curr Neurol Neurosci Rep. 2010; 10(2):73-82.
[7] Grieb P. Neuroprotective properties of citicoline: facts, doubts and unresolved issues. CNS Drugs. 2014; 28(3):185-93.
[8] Mazaheri S, Darvish M, Pooroalajal J, Fariadras M. A Comparative Study on the Effect of Citicoline on Acute Ischemic and Hemorrhagic Stroke. Avicenna J Clin Med. 2018; 25(1):20-27.
[9] Fouda AY, Newsome AS, Spellicy S, Waller JL, Zhi W, Hess DC, et al. Minocycline in Acute Cerebral Hemorrhage: An Early Phase Randomized Trial. Stroke. 2017; 48(10):2885-2887.
[10] Aspide R, Berselli B, Piazza O, Recchia A, Bilotta F. Statins in Subarachnoid Hemorrhage to Prevent Delayed Cerebral Ischemia: Old Drugs for New Strategies? Neurocrit Care. 2024; 41(1):15-16.
[11] Zheng H, Guo X, Huang X, Xiong Y, Gao W, Ke C, et al. Effect of magnesium sulfate on cerebral vasospasm in the treatment of aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. Front Neurol. 2023; 14:1249369.
[12] Dorhout Mees SM, Rinkel GJ, Feigin VL, Algra A, van den Bergh WM, Vermeulen M, et al. Calcium antagonists for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev. 2007; (3):CD000277.
[13] Packer M, Carver JR, Rodeheffer RJ, Ivanhoe RJ, DiBianco R, Zeldis SM, et al. Effect of oral milrinone on mortality in severe chronic heart failure. N Engl J Med. 1991; 325(21):1468-75.
[14] Baang HY, Reynolds AS, Dangayach NS, Gilmore EJ, Kim JA, Lay C. Treatment effect of early intravenous milrinone for cerebral vasospasm or delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Neurocritical Care. 2025:1-8.
[15] Jaski BE, Fifer MA, Wright RF, Braunwald E, Colucci WS. Positive inotropic and vasodilator actions of milrinone in patients with severe congestive heart failure. Dose-response relationships and comparison to nitroprusside. J Clin Invest. 1985; 75(2):643-9.
[16] Lubis B, Amelia P, Akil M, Viandy V. The Association between Mean Arterial Pressure, Central Venous Pressure, Cerebral Perfusion Pressure, Lung Oxygenation, and Glasgow Coma Scale in Sepsis Patients in the Intensive Care Unit. Open Access Maced J Med Sci. 2022; 10(T7):38-41.
[17] Mutoh T, Mutoh T, Sasaki K, Nakamura K, Tatewaki Y, Ishikawa T, et al. Neurocardiac protection with milrinone for restoring acute cerebral hypoperfusion and delayed ischemic injury after experimental subarachnoid hemorrhage. Neurosci Lett. 2017; 640:70-75.
[18] He Q, Wang W, Zhang Y, Xiong Y, Tao C, Ma L, et al. Global, Regional, and National Burden of Stroke, 1990-2021: A Systematic Analysis for Global Burden of Disease 2021. Stroke. 2024; 55(12):2815-2824.
[19] Al-Kawaz MN, Li Y, Thompson RE, Avadhani R, de Havenon A, Gruber J, et al. Intracranial Pressure and Cerebral Perfusion Pressure in Large Spontaneous Intracranial Hemorrhage and Impact of Minimally Invasive Surgery. Front Neurol. 2021; 12:729831.
[20] Claassen J, Jetté N, Chum F, Green R, Schmidt M, Choi H, et al. Electrographic seizures and periodic discharges after intracerebral hemorrhage. Neurology. 2007; 69(13):1356-65.
[21] Maas MB, Rosenberg NF, Kosteva AR, Bauer RM, Guth JC, Liotta EM, et al. Surveillance neuroimaging and neurologic examinations affect care for intracerebral hemorrhage. Neurology. 2013; 81(2):107-12.
[22] Flaherty ML, Woo D, Haverbusch M, Moomaw CJ, Sekar P, Sauerbeck L, et al. Potential applicability of recombinant factor VIIa for intracerebral hemorrhage. Stroke. 2005; 36(12):2660-4.
[23] Dodd WS, Laurent D, Dumont AS, Hasan DM, Jabbour PM, Starke RM, et al. Pathophysiology of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage: A Review. J Am Heart Assoc. 2021; 10(15):e021845.
[24] Treggiari MM, Rabinstein AA, Busl KM, Caylor MM, Citerio G, Deem S, et al. Guidelines for the Neurocritical Care Management of Aneurysmal Subarachnoid Hemorrhage. Neurocrit Care. 2023; 39(1):1-28.
[25] Delora A, Ezzeldin R, Alderazi Y, Le D, Ezzeldin M. A Rare Case of Cerebral Vasospasm Secondary to Primary Intraventricular Hemorrhage With an Immediate Improvement in Neurological Status Following Intra-arterial Therapy. Cureus. 2022; 14(6):e25697.
[26] Liang F, Wang J, Zhu X, Wang Z, Zheng J, Sun Z, et al. Melatonin Alleviates Neuronal Damage After Intracerebral Hemorrhage in Hyperglycemic Rats. Drug Des Devel Ther. 2020; 14:2573-2584.
[27] Sadan O, Akbik F. Intravenous Milrinone: Are We There yet? Neurocrit Care. 2025; 43(1):1-2.
[28] Fraticelli AT, Cholley BP, Losser MR, Saint Maurice JP, Payen D. Milrinone for the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Stroke. 2008; 39(3):893-8.
[29] Chen Q, Yin Y, Li L, Zhang Y, He W, Shi Y. Milrinone Ameliorates the Neuroinflammation and Memory Function of Alzheimer's Disease in an APP/PS1 Mouse Model. Neuropsychiatr Dis Treat. 2021;17:2129-2139.
[30] Julian N, Gaugain S, Labeyrie MA, Barthélémy R, Froelich S, Houdart E, et al. Systemic tolerance of intravenous milrinone administration for cerebral vasospasm secondary to non-traumatic subarachnoid hemorrhage. J Crit Care. 2024; 82:154807.
[31] Ribeiro E, Vale N. Repurposing Terbutaline and Milrinone for Cancer Therapy: A Comprehensive Review. Future Pharmacology. 2025; 5(3):38.
[32] Santos-Teles AG, Ramalho C, Ramos JGR, Passos RDH, Gobatto A, Farias S, et al. Efficacy and safety of milrinone in the treatment of cerebral vasospasm after subarachnoid hemorrhage: a systematic review. Rev Bras Ter Intensiva. 2020; 32(4):592-602.
[33] Williams HG, Ahrens C, Gomes JA, Bain M, Hassett C. Continuous Intrathecal Milrinone Administration via IRRAflow Intraventricular Catheter for Refractory Cerebral Vasospasm in Subarachnoid Hemorrhage: A Case Report. Neurohospitalist. 2025:19418744251362522
[2] Greenberg SM, Ziai WC, Cordonnier C, Dowlatshahi D, Francis B, Goldstein JN, et al. 2022 Guideline for the Management of Patients With Spontaneous Intracerebral Hemorrhage: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2022; 53(7):e282-e361.
[3] Tenny S, Das JM, Thorell W. Intracranial Hemorrhage. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024.
[4] Essibayi MA, Ibrahim Abdallah O, Mortezaei A, Zaidi SE, Vaishnav D, Cherian J, et al. Natural History, Pathophysiology, and Recent Management Modalities of Intraventricular Hemorrhage. J Intensive Care Med. 2024; 39(9):813-819.
[5] An SJ, Kim TJ, Yoon BW. Epidemiology, Risk Factors, and Clinical Features of Intracerebral Hemorrhage: An Update. J Stroke. 2017; 19(1):3-10.
[6] Hinson HE, Hanley DF, Ziai WC. Management of intraventricular hemorrhage. Curr Neurol Neurosci Rep. 2010; 10(2):73-82.
[7] Grieb P. Neuroprotective properties of citicoline: facts, doubts and unresolved issues. CNS Drugs. 2014; 28(3):185-93.
[8] Mazaheri S, Darvish M, Pooroalajal J, Fariadras M. A Comparative Study on the Effect of Citicoline on Acute Ischemic and Hemorrhagic Stroke. Avicenna J Clin Med. 2018; 25(1):20-27.
[9] Fouda AY, Newsome AS, Spellicy S, Waller JL, Zhi W, Hess DC, et al. Minocycline in Acute Cerebral Hemorrhage: An Early Phase Randomized Trial. Stroke. 2017; 48(10):2885-2887.
[10] Aspide R, Berselli B, Piazza O, Recchia A, Bilotta F. Statins in Subarachnoid Hemorrhage to Prevent Delayed Cerebral Ischemia: Old Drugs for New Strategies? Neurocrit Care. 2024; 41(1):15-16.
[11] Zheng H, Guo X, Huang X, Xiong Y, Gao W, Ke C, et al. Effect of magnesium sulfate on cerebral vasospasm in the treatment of aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. Front Neurol. 2023; 14:1249369.
[12] Dorhout Mees SM, Rinkel GJ, Feigin VL, Algra A, van den Bergh WM, Vermeulen M, et al. Calcium antagonists for aneurysmal subarachnoid haemorrhage. Cochrane Database Syst Rev. 2007; (3):CD000277.
[13] Packer M, Carver JR, Rodeheffer RJ, Ivanhoe RJ, DiBianco R, Zeldis SM, et al. Effect of oral milrinone on mortality in severe chronic heart failure. N Engl J Med. 1991; 325(21):1468-75.
[14] Baang HY, Reynolds AS, Dangayach NS, Gilmore EJ, Kim JA, Lay C. Treatment effect of early intravenous milrinone for cerebral vasospasm or delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Neurocritical Care. 2025:1-8.
[15] Jaski BE, Fifer MA, Wright RF, Braunwald E, Colucci WS. Positive inotropic and vasodilator actions of milrinone in patients with severe congestive heart failure. Dose-response relationships and comparison to nitroprusside. J Clin Invest. 1985; 75(2):643-9.
[16] Lubis B, Amelia P, Akil M, Viandy V. The Association between Mean Arterial Pressure, Central Venous Pressure, Cerebral Perfusion Pressure, Lung Oxygenation, and Glasgow Coma Scale in Sepsis Patients in the Intensive Care Unit. Open Access Maced J Med Sci. 2022; 10(T7):38-41.
[17] Mutoh T, Mutoh T, Sasaki K, Nakamura K, Tatewaki Y, Ishikawa T, et al. Neurocardiac protection with milrinone for restoring acute cerebral hypoperfusion and delayed ischemic injury after experimental subarachnoid hemorrhage. Neurosci Lett. 2017; 640:70-75.
[18] He Q, Wang W, Zhang Y, Xiong Y, Tao C, Ma L, et al. Global, Regional, and National Burden of Stroke, 1990-2021: A Systematic Analysis for Global Burden of Disease 2021. Stroke. 2024; 55(12):2815-2824.
[19] Al-Kawaz MN, Li Y, Thompson RE, Avadhani R, de Havenon A, Gruber J, et al. Intracranial Pressure and Cerebral Perfusion Pressure in Large Spontaneous Intracranial Hemorrhage and Impact of Minimally Invasive Surgery. Front Neurol. 2021; 12:729831.
[20] Claassen J, Jetté N, Chum F, Green R, Schmidt M, Choi H, et al. Electrographic seizures and periodic discharges after intracerebral hemorrhage. Neurology. 2007; 69(13):1356-65.
[21] Maas MB, Rosenberg NF, Kosteva AR, Bauer RM, Guth JC, Liotta EM, et al. Surveillance neuroimaging and neurologic examinations affect care for intracerebral hemorrhage. Neurology. 2013; 81(2):107-12.
[22] Flaherty ML, Woo D, Haverbusch M, Moomaw CJ, Sekar P, Sauerbeck L, et al. Potential applicability of recombinant factor VIIa for intracerebral hemorrhage. Stroke. 2005; 36(12):2660-4.
[23] Dodd WS, Laurent D, Dumont AS, Hasan DM, Jabbour PM, Starke RM, et al. Pathophysiology of Delayed Cerebral Ischemia After Subarachnoid Hemorrhage: A Review. J Am Heart Assoc. 2021; 10(15):e021845.
[24] Treggiari MM, Rabinstein AA, Busl KM, Caylor MM, Citerio G, Deem S, et al. Guidelines for the Neurocritical Care Management of Aneurysmal Subarachnoid Hemorrhage. Neurocrit Care. 2023; 39(1):1-28.
[25] Delora A, Ezzeldin R, Alderazi Y, Le D, Ezzeldin M. A Rare Case of Cerebral Vasospasm Secondary to Primary Intraventricular Hemorrhage With an Immediate Improvement in Neurological Status Following Intra-arterial Therapy. Cureus. 2022; 14(6):e25697.
[26] Liang F, Wang J, Zhu X, Wang Z, Zheng J, Sun Z, et al. Melatonin Alleviates Neuronal Damage After Intracerebral Hemorrhage in Hyperglycemic Rats. Drug Des Devel Ther. 2020; 14:2573-2584.
[27] Sadan O, Akbik F. Intravenous Milrinone: Are We There yet? Neurocrit Care. 2025; 43(1):1-2.
[28] Fraticelli AT, Cholley BP, Losser MR, Saint Maurice JP, Payen D. Milrinone for the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Stroke. 2008; 39(3):893-8.
[29] Chen Q, Yin Y, Li L, Zhang Y, He W, Shi Y. Milrinone Ameliorates the Neuroinflammation and Memory Function of Alzheimer's Disease in an APP/PS1 Mouse Model. Neuropsychiatr Dis Treat. 2021;17:2129-2139.
[30] Julian N, Gaugain S, Labeyrie MA, Barthélémy R, Froelich S, Houdart E, et al. Systemic tolerance of intravenous milrinone administration for cerebral vasospasm secondary to non-traumatic subarachnoid hemorrhage. J Crit Care. 2024; 82:154807.
[31] Ribeiro E, Vale N. Repurposing Terbutaline and Milrinone for Cancer Therapy: A Comprehensive Review. Future Pharmacology. 2025; 5(3):38.
[32] Santos-Teles AG, Ramalho C, Ramos JGR, Passos RDH, Gobatto A, Farias S, et al. Efficacy and safety of milrinone in the treatment of cerebral vasospasm after subarachnoid hemorrhage: a systematic review. Rev Bras Ter Intensiva. 2020; 32(4):592-602.
[33] Williams HG, Ahrens C, Gomes JA, Bain M, Hassett C. Continuous Intrathecal Milrinone Administration via IRRAflow Intraventricular Catheter for Refractory Cerebral Vasospasm in Subarachnoid Hemorrhage: A Case Report. Neurohospitalist. 2025:19418744251362522
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| Intracranial Hemorrhages Intraventricular Hemorrhage Milrinone Phosphodiesterase Inhibitors | ||
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How to Cite
1.
Mojtahedzadeh M, Afra F, Nasrollahizadeh A, Javankiani S, Saedpanah R, Shaban E, Najafi A, Mojtahedzadeh A. Intravenous Milrinone for Hemodynamic Rescue in Spontaneous Intracerebral Hemorrhage with Intraventricular Extension. Arch Anesth & Crit Care. 2026;.
