Eficácia e segurança da milrinona no tratamento do vasoespasmo cerebral após hemorragia subaracnóidea: uma revisão sistemática / Efficacy and safety of milrinone in the treatment of cerebral vasospasm after subarachnoid hemorrhage: a systematic review

RESUMO Objetivo: Revisar sistematicamente a evidência atual da eficácia de milrinona no tratamento do vasoespasmo cerebral após hemorragia subaracnóidea. Métodos: Triaram-se as bases de dados Pubmed®, Cochrane e Embase quanto a artigos publicados entre abril de 2001 e fevereiro de 2019. Dois revisores independentes realizaram uma triagem metodológica da qualidade e a extração dos dados dos estudos. Resultados: Encontraram-se 22 estudos considerados relevantes, sendo que apenas um deles era um ensaio randomizado controlado. Os estudos demonstraram acentuada heterogeneidade e debilidade de seus critérios metodológicos. A maioria dos pacientes apresentava vasoespasmo moderado a grave. O principal método para diagnóstico do vasoespasmo foi a angiografia. Em três estudos, realizou-se administração de milrinona por via intra-arterial; em nove estudos, a administração foi endovenosa, e, em seis estudos, utilizaram-se ambas as vias de administração. A via intratecal foi utilizada em dois estudos, em um estudo, a administração foi realizada via cisterna e, em um estudo, a via de administração foi a endovascular. Os efeitos colaterais de milrinona foram descritos em seis estudos. Vinte e um estudos indicaram a resolução do vasoespasmo. Conclusão: A evidência atual indica que o uso de milrinona teve um papel no tratamento do vasoespasmo após hemorragia subaracnóidea aneurismática. Contudo, só foi realizado um ensaio randomizado controlado, com baixo nível de qualidade. Nossos achados indicam a necessidade de futuros estudos randomizados controlados com desfechos centrados no paciente, com o fim de proporcionar recomendações definitivas.

ABSTRACT Objective: To systematically review the current evidence on the efficacy of milrinone in the treatment of cerebral vasospasm after subarachnoid hemorrhage. Methods: The Pubmed®, Cochrane and Embase databases were screened for articles published from April 2001 to February 2019. Two independent reviewers performed the methodological quality screening and data extraction of the studies. Results: Twenty-two studies were found to be relevant, and only one of these was a randomized control trial. Studies showed marked heterogeneity and weaknesses in key methodological criteria. Most patients presented with moderate to severe vasospasm. Angiography was the main method of diagnosing vasospasm. Intra-arterial administration of milrinone was performed in three studies, intravenous administration was performed in nine studies, and both routes of administration in six studies; the intrathecal route was used in two studies, the cisternal route in one study and endovascular administration in one study. The side effects of milrinone were described in six studies. Twenty-one studies indicated resolution of vasospasm. Conclusion: The current evidence indicates that milrinone may have a role in treatment of vasospasm after aneurysmal subarachnoid hemorrhage. However, only one randomized control trial was performed, with a low quality level. Our findings indicate the need for future randomized control trials with patient-centered outcomes to provide definitive recommendations.

Efficacy and safety of milrinone in the treatment of cerebral vasospasm after subarachnoid hemorrhage: a systematic review. / Eficácia e segurança da milrinona no tratamento do vasoespasmo cerebral após hemorragia subaracnóidea: uma revisão sistemática.

OBJECTIVE: To systematically review the current evidence on the efficacy of milrinone in the treatment of cerebral vasospasm after subarachnoid hemorrhage. METHODS: The Pubmed®, Cochrane and Embase databases were screened for articles published from April 2001 to February 2019. Two independent reviewers performed the methodological quality screening and data extraction of the studies. RESULTS: Twenty-two studies were found to be relevant, and only one of these was a randomized control trial. Studies showed marked heterogeneity and weaknesses in key methodological criteria. Most patients presented with moderate to severe vasospasm. Angiography was the main method of diagnosing vasospasm. Intra-arterial administration of milrinone was performed in three studies, intravenous administration was performed in nine studies, and both routes of administration in six studies; the intrathecal route was used in two studies, the cisternal route in one study and endovascular administration in one study. The side effects of milrinone were described in six studies. Twenty-one studies indicated resolution of vasospasm. CONCLUSION: The current evidence indicates that milrinone may have a role in treatment of vasospasm after aneurysmal subarachnoid hemorrhage. However, only one randomized control trial was performed, with a low quality level. Our findings indicate the need for future randomized control trials with patient-centered outcomes to provide definitive recommendations.

OBJETIVO: Revisar sistematicamente a evidência atual da eficácia de milrinona no tratamento do vasoespasmo cerebral após hemorragia subaracnóidea. MÉTODOS: Triaram-se as bases de dados Pubmed®, Cochrane e Embase quanto a artigos publicados entre abril de 2001 e fevereiro de 2019. Dois revisores independentes realizaram uma triagem metodológica da qualidade e a extração dos dados dos estudos. RESULTADOS: Encontraram-se 22 estudos considerados relevantes, sendo que apenas um deles era um ensaio randomizado controlado. Os estudos demonstraram acentuada heterogeneidade e debilidade de seus critérios metodológicos. A maioria dos pacientes apresentava vasoespasmo moderado a grave. O principal método para diagnóstico do vasoespasmo foi a angiografia. Em três estudos, realizou-se administração de milrinona por via intra-arterial; em nove estudos, a administração foi endovenosa, e, em seis estudos, utilizaram-se ambas as vias de administração. A via intratecal foi utilizada em dois estudos, em um estudo, a administração foi realizada via cisterna e, em um estudo, a via de administração foi a endovascular. Os efeitos colaterais de milrinona foram descritos em seis estudos. Vinte e um estudos indicaram a resolução do vasoespasmo. CONCLUSÃO: A evidência atual indica que o uso de milrinona teve um papel no tratamento do vasoespasmo após hemorragia subaracnóidea aneurismática. Contudo, só foi realizado um ensaio randomizado controlado, com baixo nível de qualidade. Nossos achados indicam a necessidade de futuros estudos randomizados controlados com desfechos centrados no paciente, com o fim de proporcionar recomendações definitivas.

Dynamic Autoregulation is Impaired in Circulatory Shock.

BACKGROUND: Circulatory shock is a life-threatening disorder that is associated with high mortality, with a state of systemic and tissue hypoperfusion that can lead to organ failure, including the brain, where altered mental state is often observed. We hypothesized that cerebral autoregulation (CA) is impaired in patients with circulatory shock. METHODS: Adult patients with circulatory shock and healthy controls were included. Cerebral blood flow velocity (CBFV, transcranial Doppler ultrasound) and arterial blood pressure (BP, Finometer or intra-arterial line) were continuously recorded during 5 min in both groups. Autoregulation Index (ARI) was estimated from the CBFV response to a step change in BP, derived by transfer function analysis; ARI ≤ 4 was considered impaired CA. The relationship between organ dysfunction, assessed with the Sequential Organ Failure Assessment (SOFA) score and the ARI, was assessed with linear regression. RESULTS: Twenty-five shock patients and 28 age-matched healthy volunteers were studied. The mean ±â€ŠSD SOFA score was 10.8 ±â€Š4.3. Shock patients compared with control subjects had lower ARI values (4.0 ±â€Š2.1 vs. 5.9 ±â€Š1.5, P = 0.001). Impaired CA was more common in shock patients (44.4% vs. 7.1%, P = 0.003). There was a significant inverse relationship between the ARI and the SOFA score (R = -0.63, P = 0.0008). CONCLUSIONS: These results suggest that circulatory shock is often associated with impaired CA and that the severity of CA alterations is correlated with the degree of multiple organ failure, reinforcing the need to monitor cerebral hemodynamics in patients with circulatory shock.

Intravenous administration of Milrinone, as an alternative approach to treat vasospasm in subarachnoid hemorrhage: A case report of transcranial Doppler monitoring.

This case illustrates the importance and potential of having TCD monitoring in intensive care. This easy-to-use, safe, low-cost, and bedside tool allows evaluation of the safety and feasibility of an alternative treatment of VSP in SCH and demonstrates the potential to avoid the use of angiography, a high cost, invasive procedure.

Effects of somatosensory stimulation on the excitability of the unaffected hemisphere in chronic stroke patients.

INTRODUCTION: Somatosensory stimulation of the paretic upper limb enhances motor performance and excitability in the affected hemisphere, and increases activity in the unaffected hemisphere, in chronic stroke patients. We tested the hypothesis that somatosensory stimulation of the paretic hand would lead to changes in excitability of the unaffected hemisphere in these patients, and we investigated the relation between motor function of the paretic hand and excitability of the unaffected hemisphere. METHODS: Transcranial magnetic stimulation was administered to the unaffected hemisphere of nine chronic stroke patients. Patients were submitted to 2-h somatosensory stimulation in the form of median nerve stimulation and control stimulation using a cross-over design. Baseline Jebsen-Taylor test scores were evaluated. Resting motor threshold, intracortical facilitation, short-interval intracortical inhibition, and visual analog scores for attention, fatigue and drowsiness were measured across conditions. RESULTS: Better pre-stimulation baseline motor function was correlated with deeper SICI in the unaffected hemisphere. We found no overt changes in any physiological marker after somatosensory stimulation. There was increased drowsiness in the control session, which may have led to changes in intracortical facilitation. CONCLUSIONS: Our results do not support an overt effect of a single session of somatosensory stimulation of the paretic hand on motor cortical excitability of the unaffected hemisphere as measured by motor threshold, short-interval intracortical inhibition or intracortical facilitation. It remains to be determined if other markers of cortical excitability are modulated by somatosensory stimulation, and whether repeated sessions or lesion location may lead to different effects.

Effects of somatosensory stimulation on the excitability of the unaffected hemisphere in chronic stroke patients

INTRODUCTION: Somatosensory stimulation of the paretic upper limb enhances motor performance and excitability in the affected hemisphere, and increases activity in the unaffected hemisphere, in chronic stroke patients. We tested the hypothesis that somatosensory stimulation of the paretic hand would lead to changes in excitability of the unaffected hemisphere in these patients, and we investigated the relation between motor function of the paretic hand and excitability of the unaffected hemisphere. METHODS: Transcranial magnetic stimulation was administered to the unaffected hemisphere of nine chronic stroke patients. Patients were submitted to 2-h somatosensory stimulation in the form of median nerve stimulation and control stimulation using a cross-over design. Baseline Jebsen-Taylor test scores were evaluated. Resting motor threshold, intracortical facilitation, short-interval intracortical inhibition, and visual analog scores for attention, fatigue and drowsiness were measured across conditions. RESULTS: Better pre-stimulation baseline motor function was correlated with deeper SICI in the unaffected hemisphere. We found no overt changes in any physiological marker after somatosensory stimulation. There was increased drowsiness in the control session, which may have led to changes in intracortical facilitation. CONCLUSIONS: Our results do not support an overt effect of a single session of somatosensory stimulation of the paretic hand on motor cortical excitability of the unaffected hemisphere as measured by motor threshold, short-interval intracortical inhibition or intracortical facilitation. It remains to be determined if other markers of cortical excitability are modulated by somatosensory stimulation, and whether repeated sessions or lesion location may lead to different effects.